@article {pmid42471352, year = {2026}, author = {Long, K and Liu, Z and Liu, P and Zhang, W and Gao, M and Gan, G and Cao, X and Cheng, Y and Wang, B and Yuan, X and Wang, B and Zhao, D and Xu, A and Sulaiman, JE and Cheng, KK}, title = {Lipodystrophy induces gut microbiota dysbiosis and its related glucose dysmetabolism in mice.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01102-8}, pmid = {42471352}, issn = {2055-5008}, support = {P0056052//Hong Kong Polytechnic University Start-up Fund for RAPs under the Strategic Hiring Scheme/ ; P0059102//RiFood's Interdisciplinary Project Fund/ ; P0059102//RiFood's Interdisciplinary Project Fund/ ; C5044-23G//Hong Kong Research Grant Council Collaborative Research Fund/ ; 92357305//National Natural Science Foundation of China/ ; P0036848//PolyU internal funding/ ; }, abstract = {Both excessive white adipose tissue (WAT) in obesity and insufficient WAT in lipodystrophy disrupt metabolic homeostasis. Although a vicious cycle between WAT dysfunction and gut dysbiosis is known to drive insulin resistance in obesity, whether lipodystrophy impairs gut function and contributes to glucose dysregulation remains unclear. Using adipocyte-specific MDM2 knockout (Adipo-MDM2-KO) mice as a model of lipodystrophy, we identified a direct role of WAT in maintaining intestinal and gut microbiota homeostasis. Progressive adipose tissue loss in Adipo-MDM2-KO mice caused multiple intestinal abnormalities, including gut microbiota dysbiosis, altered microbial metabolism, impaired intestinal barrier integrity, defective immunoglobulin A (IgA) responses, and endotoxemia. These defects were largely reversed by transplantation of healthy subcutaneous WAT (sWAT). Moreover, fecal microbiota transplantation from Adipo-MDM2-KO mice into C57BL/6J recipients reproduced intestinal defects and glucose intolerance, whereas microbiota depletion in Adipo-MDM2-KO mice largely rescued intestinal abnormalities and partially restored glucose homeostasis. Furthermore, sWAT-secreted adipokines, including extracellular vesicles, directly modulated the abundance and growth of specific gut bacterial communities. Multi-omics analyses further linked lipodystrophy-induced microbiota and metabolomic alterations to systemic endotoxemia and impaired glucose metabolism. Altogether, our findings reveal a critical WAT-gut-microbiota axis in the regulation of intestinal homeostasis and host glucose metabolism.}, }
@article {pmid42472818, year = {2026}, author = {Mohammed Abdelhadi, LA and Liang, Y and Liao, Y and Zhu, G}, title = {Current and emerging therapeutic strategies targeting adherent-invasive Escherichia coli in Crohn's disease: a review.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-026-00852-2}, pmid = {42472818}, issn = {1757-4749}, support = {S20250254//The Priority Academic Program of Development Jiangsu High Education Institution, and the High-end Talent Program for International Collaboration/ ; }, abstract = {Considerable evidence has accumulated over the past two decades demonstrating that Escherichia coli, specifically adherent-invasive E. coli, contributes to the pathogenesis of Crohn's disease. Adherent-invasive E. coli can adhere to and invade intestinal epithelial cells, survive, and replicate within macrophages, thereby enabling a key mechanism that induces chronic inflammation. Despite extensive knowledge of the molecular interactions between adherent-invasive E. coli and the host from these studies, translating this knowledge into targeted therapy remains limited.In this review, we summarize current and proposed treatments to prevent or eliminate adherent-invasive E. coli colonization. We provide a theoretical framework that categorizes these strategies into four main pillars: direct pathogen targeting (e.g., antibiotics, phage therapy), blockade of bacterial virulence factors (e.g., anti-adhesive compounds, QseC inhibitors), host-mediated clearance (e.g., autophagy inducers), and ecological intervention/restoration (e.g., fecal microbiota transplantation, Probiotic, Prebiotic and Probiotics). Finally, we discuss new modalities, including predatory bacteria, siderophore immunization, and other approaches. This review identifies the latest weapons against adherent-invasive E. coli, synthesizes experimental and clinical evidence to provide a comprehensive view of this evolving therapeutic arsenal, and offers ideas for future treatment of Crohn's disease.}, }
@article {pmid42473148, year = {2026}, author = {Wang, M and Chen, P and Pei, S and Wang, R and Liu, S and Hou, Z and Liu, Z}, title = {Panax ginseng Extract Alleviates Qi Deficiency Liver Cancer via the Gut-Liver Axis: Insights from Metabolomics and Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.6c00814}, pmid = {42473148}, issn = {1520-5118}, abstract = {Panax ginseng (PG), a valuable functional food known as the "King of Herbs," demonstrates therapeutic potential in the treatment of Qi deficiency liver cancer (QDLC). Regulating the gut-liver axis (GLA) may be an important mechanism of action of PG in the treatment of QDLC; however, its detailed mechanism remains unclear. This study aimed to elucidate this mechanism in QDLC rats using metabolomics and microbiome analysis. Metabolomics and microbiome experiments demonstrate that PG alleviates QDLC by modulating the composition of the gut microbiota, restoring its diversity, improving metabolic disorders, and increasing short-chain fatty acid levels. Antibiotics cocktail treatment, fecal microbiota transplantation, and probiotic colonization experiments further confirmed that PG's role in alleviating QDLC is gut microbiota-dependent. Additionally, PG alleviated GLA damage in QDLC rats by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Collectively, our study provides a novel interpretation of the natural intervention mechanisms for QDLC and confirms the potential value of PG as a functional food.}, }
@article {pmid42473187, year = {2026}, author = {Li, Q and He, R and Wang, X and Long, C and He, Z and Zhang, S and Liu, Y and Zhang, Z and Wu, J and Sun, G and Cui, B and Zhao, F and Zhang, F}, title = {Akkermansia muciniphila enhances washed microbiota transplantation in the treatment of epilepsy.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {42473187}, issn = {2542-5641}, abstract = {BACKGROUND: Refractory epilepsy remains a global clinical challenge. This first-in-human cohort study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of epilepsy.<br><br>METHODS: A prospective, single-center, open-label study of WMT in patients with epilepsy was conducted at the Second Affiliated Hospital of Nanjing Medical University from November 2016 to November 2023. The primary outcome was the clinical response rate (&#x2265;50% reduction in seizure frequency) at one month post-WMT. Parallel experiments using a pentylenetetrazole-induced epileptic mouse model were performed to validate clinical findings and investigate the role of specific core bacterial species.<br><br>RESULTS: Among 21 patients (mean age, 18.9 years), including 18 with refractory epilepsy, the clinical response rates were 43% (9/21), 57% (12/21), and 38% (8/21) at one, three, and six months post-WMT, respectively. A second maintenance WMT course at three months was associated with a higher response rate at six months compared to no maintenance therapy (odds ratio [OR] >999, 95% confidence interval [CI]: [1.12, +infinity], P = 0.080). WMT significantly increased Akkermansia muciniphila (A. muciniphila) levels in responders (P = 0.038). A higher baseline A. muciniphila abundance was associated with improved clinical outcomes (Z = 3.28, P = 0.001). The preclinical study confirmed that A. muciniphila augmented the effects of WMT against seizures, significantly reducing seizure severity and duration, and prolonging seizure latency.<br><br>CONCLUSIONS: Integrating clinical and preclinical findings, this study demonstrates that&#xa0;A. muciniphila&#xa0;synergistically enhances the effects of WMT against epileptic seizures. This study provides evidence for a new concept of microbiome-based therapeutics in epilepsy treatment.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov, NCT02889627.}, }
@article {pmid42474869, year = {2026}, author = {Li, Y and Xiao, X and Jiang, X and Li, X and Wang, W and Lin, R}, title = {Gut microbiota in health and disease.}, journal = {Molecular biomedicine}, volume = {7}, number = {1}, pages = {}, pmid = {42474869}, issn = {2662-8651}, support = {2024ZD0520800//National Major Science and Technology Projects of China/ ; 5003530167//Central University Basic Research Fund of China/ ; 82170571//National Natural Science Foundation of China/ ; 81974068//National Natural Science Foundation of China/ ; 82270586//National Natural Science Foundation of China/ ; 81900580//National Natural Science Foundation of China/ ; 2022YFF1203300//Ministry of Science and Technology of the People's Republic of China/ ; 2023YFC2307000//Key Technologies Research and Development Program/ ; 2022CFA009//Natural Science Foundation of Hubei Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis/microbiology ; Homeostasis ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; Colorectal Neoplasms/microbiology ; }, abstract = {The gut microbiota is integral to host physiology, contributing to metabolic homeostasis, epithelial barrier integrity, immune balance, and bidirectional communication along gut-organ axes. Disruption of this ecosystem, commonly referred to as dysbiosis, is increasingly implicated in a wide range of gastrointestinal and extra-intestinal diseases. Rather than reflecting isolated compositional changes, microbiota-related pathology often involves interconnected disturbances in barrier function, microbial metabolism, immune regulation, genotoxicity, inflammatory and oncogenic signaling, and long-range communication with distal organs. However, key challenges remain, particularly in resolving causality, accounting for interindividual heterogeneity, and translating complex microbiome data into robust clinical tools. In this review, we summarize the role of the gut microbiota in maintaining host homeostasis and outline the concept, drivers, and consequences of dysbiosis. We then discuss the major mechanisms through which the gut microbiota contributes to disease development and progression, using colorectal cancer as a representative gastrointestinal example and gut-organ axes as a framework for extra-intestinal disorders. We further highlight current translational advances in microbiota-based biomarkers, dietary modulation, biotic and postbiotic strategies, fecal microbiota transplantation, and emerging precision microbiota therapies. By integrating mechanistic insights with translational perspectives, this review offers an updated framework for interpreting the gut microbiota in health and disease and may help inform the future development of more precise, mechanism-informed diagnostic and therapeutic strategies.}, }
@article {pmid42476197, year = {2026}, author = {Zhong, Y and Xia, D and Cui, T and Wang, H and Zhai, J and Wu, Z and Zhou, J and Li, Z and Zeng, L and Wu, M and Liu, K and Yang, Z and Song, S and Zeng, G and Chen, Z and Yan, B}, title = {Gut microbiota homeostasis alleviates mycobacterial granuloma pathology in zebrafish.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108723}, doi = {10.1016/j.micpath.2026.108723}, pmid = {42476197}, issn = {1096-1208}, abstract = {Growing evidence links the gut microbiota to host immune regulation and tuberculosis (TB) progressiond; however, its specific impact on the formation and necrosis of TB granulomas remains poorly defined. In this study, we established an adult zebrafish model of antibiotic-induced gut microbiota dysbiosis followed by Mycobacterium marinum (M.m) infection to investigate how gut microbiota perturbation influences host resistance to mycobacterial infection. Our results demonstrated that antibiotic-induced gut microbiota dysbiosis significantly increased the mycobacterial burden in zebrafish, thereby compromising host resistance to mycobacterial infection. Dysbiosis also intensified infection-associated inflammatory responses, as reflected by the elevated expression of the pro-inflammatory cytokines tnf-α and il-1β, resulting in more severe systemic pathology characterized by enhanced granuloma formation and necrosis, together with remodeling of the immune cell composition within granulomatous lesions. Importantly, fecal microbiota transplantation (FMT) from healthy donors effectively reduced the bacterial burden and alleviated granuloma-associated pathological changes in infected zebrafish. These findings demonstrate that the gut microbiota critically modulates the granuloma immune microenvironment, providing a robust platform and mechanistic support for gut microecological interventions as a host-directed therapy for TB.}, }
@article {pmid42476206, year = {2026}, author = {Yang, N and Ye, M and Wang, H and Liang, Y and Huang, K and Zhao, Y and Zhang, X}, title = {Callistephus A from Callistephus chinensis Alleviates DSS-Induced Ulcerative Colitis and Gut-liver Axis Disruption by Targeting the JAK2/STAT1 Pathway and Remodeling Gut Microbiota.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {122213}, doi = {10.1016/j.jep.2026.122213}, pmid = {42476206}, issn = {1872-7573}, abstract = {Callistephus chinensis, a plant belonging to the genus Callistephus in the family Asteraceae, is a traditional Mongolian medicinal herb. In ancient times, it was commonly used for clearing heat, detoxifying, reducing swelling and relieving pain. CA is a 6/7-thickened sesquiterpenoid component isolated from the flowers of Callistephus chinensis, however, its pharmacological mechanism underlying the treatment of intestinal inflammation remains unclear.<br><br>AIM OF THE STUDY: To evaluate the therapeutic effect and mechanism of CA on UC.<br><br>MATERIALS AND METHODS: CA was tested in LPS-stimulated RAW264.7 macrophages and DSS-induced colitis mice. Multi-omics profiling, gut microbiota analysis, fecal microbiota transplantation, inhibitor and knockdown assays were performed.<br><br>RESULTS: CA treatment markedly alleviated colitis and liver injury, reducing the histological score to approximately 0.6 times and key pro-inflammatory cytokines TNF-&#x3b1; and IL-6 to below 0.3 times the levels in the DSS group, while restoring gut barrier integrity. Multi-omics reveals that CA reshapes the gut microbiota by significantly increasing the relative abundance of Firmicutes (1.1-fold) and restoring the Firmicutes/Bacteroidetes ratio compared to the DSS group, while promoting host short-chain fatty acid and amino acid metabolism.Mechanistically, CA directly bound JAK2 and STAT1, suppressing JAK2/STAT1 pathway phosphorylation to under 0.3 times the DSS group level, confirmed by inhibitor and knockdown assays. FMT confirmed that CA's efficacy depends on microbiota modulation. Furthermore, CA reduced gut-derived LPS translocation and alleviated liver injury.<br><br>CONCLUSIONS: CA treats UC by targeting the gut-microbiota-metabolite axis and the JAK2/STAT1 pathway, representing a promising therapeutic lead.}, }
@article {pmid42476661, year = {2026}, author = {Zhang, F and Hu, W and Zhao, X and Fu, B and Lin, Y and Xie, C and Yang, R and Fu, Y and Tan, W and Ye, L}, title = {Comorbid depression exacerbates Gelsemium elegans toxicity via disruption of the Clostridium-LCA-PXR-CYP3A11 metabolic axis.}, journal = {Chinese journal of natural medicines}, volume = {24}, number = {8}, pages = {987-998}, doi = {10.1016/S1875-5364(26)61197-1}, pmid = {42476661}, issn = {1875-5364}, mesh = {Animals ; *Gelsemium/toxicity/chemistry ; Mice ; *Clostridium/metabolism ; Gastrointestinal Microbiome/drug effects ; *Pregnane X Receptor/metabolism/genetics ; Male ; *Depression/metabolism/microbiology/complications ; *Cytochrome P-450 CYP3A/metabolism/genetics ; *Plant Extracts/toxicity ; Indole Alkaloids/toxicity ; Alkaloids ; }, abstract = {Gelsemium elegans (G. elegans) is a toxic medicinal plant traditionally used to treat chronic pain, with its toxicity linked to indole alkaloids such as gelsemine and humantenmine (HMT). Chronic pain often co-occurs with depression, a condition known to disrupt host-microbiota interactions, potentially affecting drug metabolism and toxicity. However, the impact of comorbid depression on the toxicity of G. elegans remains unclear. This study investigates how depression exacerbates the neurotoxicity of G. elegans and explores the role of the gut microbiota-host metabolic axis in this process. Depression-model mice were treated with G. elegans aqueous extract, gelsemine and HMT. Multi-omics approaches, including 16S rRNA sequencing and shotgun metagenomics, were used to analyze microbiota changes under depressive conditions. Functional validation was performed using pseudo-germ-free mice, fecal microbiota transplantation, and supplementation with Clostridium species and lithocholic acid (LCA), as well as pregnane X receptor (Pxr) knockout models. The results showed that depression significantly heightened the neurotoxicity of G. elegans, gelsemine and HMT. Mechanistically, depression reduced Clostridium abundance and LCA levels, impairing PXR activation and downregulating hepatic CYP3A11 expression. This disruption of the Clostridium-LCA-PXR-CYP3A11 axis hindered the detoxification of indole alkaloids, leading to increased systemic exposure and exacerbated neurotoxicity. Restoration of this pathway through Clostridium or LCA supplementation alleviated the toxicity. These findings highlight the role of the Clostridium-LCA-PXR-CYP3A11 axis in the altered toxicity of G. elegans in a depressive state, and suggest that Clostridium species and their metabolites may serve as a potential strategy for mitigating toxicity.}, }
@article {pmid42476727, year = {2026}, author = {Ullern, A and Garborg, KK and Chauhan, SK and Holm, K and Bang, C and Dunn, C and Johnsen, PH and Hov, JER and Kyte, JA}, title = {Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {7}, pages = {}, doi = {10.1136/jitc-2026-015122}, pmid = {42476727}, issn = {2051-1426}, mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; *Neoplasms/therapy/drug therapy ; *Drug Resistance, Neoplasm ; Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has shown promise in overcoming resistance to immune checkpoint inhibitors (ICIs) in early-phase cancer trials. We investigated the safety, feasibility and efficacy of FMT from ICI responders to patients with advanced cancers progressing on ICIs.<br><br>METHODS: This was a single-arm phase IIa basket trial (MITRIC; NCT05286294) including patients with ICI-refractory cancer. Long-term ICI responders were used as FMT donors. Patients received FMTs in combination with ICIs; two FMT administrations (by colonoscopy) were scheduled before the first radiological evaluation after 6 weeks, and up to three later FMTs were allowed (by enema). Co-primary endpoints were the evaluation of FMT-related adverse events and objective response rate. Feasibility, clinical benefit rate, progression-free survival (PFS), overall survival (OS), implant engraftment, immune response and biomarkers were among the secondary objectives.<br><br>RESULTS: The study enrolled 12 patients with melanoma (n=9), head and neck squamous cell carcinoma (HNSCC; n=1), renal cell carcinoma (n=1) or microsatellite instability-high pancreatic cancer (n=1). FMT was well tolerated, whereas immune-related toxicity occurred in 6/12 patients. All patients received the first FMT; 10/12 patients also underwent the second FMT. No objective responses were observed, while 5/12 patients recorded stable disease. Clinical benefit per-protocol (stable disease >6 months) was achieved in a patient with melanoma, who had regression of some lesions and remains alive after 33 months without further systemic treatment. Mixed responses with regression of some lesions were observed in another melanoma patient, and in a patient with HNSCC. The median PFS was 1.5 months, and median OS was 10.1 months. Sequencing of fecal samples indicated engraftment after the first FMT in most patients. Mass cytometry analysis of peripheral blood cells suggested that an activated and differentiated T-cell signature was associated with improved PFS and OS, while a na&#xef;ve T-cell phenotype and a myeloid-dominant environment were unfavorable. CD14[+] monocytes and serum interleukin-8 increased at group level over time.<br><br>CONCLUSION: FMT in combination with ICIs was safe and feasible in patients with advanced cancers, but with limited clinical activity. Further studies are required to clarify the potential benefit of FMT, identify the appropriate patient population and define criteria for donor selection.<br><br>TRIAL REGISTRATION NUMBER: NCT05286294.}, }
@article {pmid42470953, year = {2026}, author = {Chen, Z and Li, W and Wang, M and Li, Y and Gao, J and Xie, Z and Tsering, T and Jia, J and Wang, A}, title = {Lonicera trichosantha alleviates LPS-induced endometritis in mice by modulating the gut microbiota and host metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158577}, doi = {10.1016/j.phymed.2026.158577}, pmid = {42470953}, issn = {1618-095X}, abstract = {BACKGROUND: Endometritis is an inflammatory disorder of the endometrial lining. Conventional antibiotic therapy often fails to control the accompanying disruptive inflammation. The 95 % ethanol-eluted fraction of Lonicera trichosantha (95 %-LT), exhibits potent anti-inflammatory activity in vitro. Nevertheless, its efficacy in vivo and the mechanisms underlying its potential therapeutic effect on endometritis are largely unknown.<br><br>PURPOSE: This study aimed to elucidate the protective effects of 95 %-LT against endometritis and to define its mechanism of action, specifically through the gut microbiota-metabolite axis.<br><br>METHODS: The chemical profile of the 95 %-LT fraction was characterized using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic effects of 95 %-LT were systematically investigated using in vitro cellular inflammation models, a murine endometritis model, 16S ribosomal RNA (16S rRNA) gene sequencing, untargeted metabolomics, pseudo-germ-free (PGF) models, fecal microbiota transplantation (FMT), and in vivo supplementation with key bacterial strains and metabolites.<br><br>RESULTS: Three primary chemical constituents were identified in the 95 %-LT. Dose-dependent mitigation of endometrial pathological injury was achieved following intervention with 95 %-LT. Gut flora reconstruction induced by 95 %-LT was validated through 16S rRNA gene sequencing, among which the commensal beneficial bacterium Lactobacillus murinus exhibited the most remarkable enrichment. Concurrently, untargeted metabolomics showed that 95 %-LT enhanced the production of kynurenic acid (KYNA), a tryptophan-derived metabolite. FMT and PGF model experiments confirmed that the gut microbiota is indispensable for this therapeutic effect. Finally, in vivo supplementation verified that both L. murinus and KYNA function as key mediators underlying the efficacy of 95 %-LT.<br><br>CONCLUSION: Our results demonstrate that 95 %-LT alleviates endometritis by orchestrating a gut microbiota-dependent mechanism, specifically through the "L. murinus-KYNA axis". This study provides a mechanistic foundation for exploiting Tibetan medicine-derived compounds in endometritis therapy.}, }
@article {pmid42468804, year = {2026}, author = {Gong, Z and Wang, Y and Mao, W and Gao, R and Bao, W and Dai, J and Dong, Y and Mu, Z and Fu, Y and Hu, X and Zhang, S and Liu, B}, title = {Gut microbiota alterations are associated with uterine immune homeostasis via microbiota-metabolite interactions.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.07.043}, pmid = {42468804}, issn = {2090-1224}, abstract = {INTRODUCTION: Uterine inflammation is a major cause of infertility and is commonly associated with local bacterial infection. However, the association between gut microbiota and uterine immune homeostasis remains incompletely understood.<br><br>OBJECTIVES: This study aimed to examine the association between gut microbiota dysbiosis and uterine inflammation, and to identify microbiota-associated factors linked to host immune responses.<br><br>METHODS: An antibiotic-induced dysbiosis mouse model was established, followed by fecal microbiota transplantation (FMT), microbial supplementation, metabolite intervention, and acute E. coli challenge to assess inflammation-related outcomes. Uterine inflammation, barrier integrity, and immune responses were evaluated. Gut microbiota and fecal metabolites were profiled by 16S rRNA sequencing and untargeted metabolomics, respectively.<br><br>RESULTS: Gut microbiota dysbiosis was associated with increased uterine inflammation, as indicated by elevated cytokine levels, immune cell infiltration, and impaired epithelial barrier integrity, whereas FMT partially reversed these changes. Taxonomic analysis showed a marked reduction in Prevotellaceae abundance during dysbiosis, which increased following microbial reconstitution. Supplementation with Prevotella copri was associated with reduced uterine inflammation and improved barrier integrity in dysbiotic mice. Integrated microbiome-metabolome analysis revealed that allopregnanolone was strongly associated with Prevotellaceae abundance. Dysbiosis was accompanied by reduced allopregnanolone levels, which increased after FMT. Exogenous administration of allopregnanolone was associated with reduced inflammatory markers and improved epithelial barrier integrity. Importantly, gut microbiota dysbiosis was associated with increased susceptibility to E. coli-induced uterine inflammation, whereas FMT, Prevotella copri, and allopregnanolone were associated with attenuation of infection-related inflammatory responses and tissue injury.<br><br>CONCLUSION: Together, these findings support a microbiota-metabolite-host interaction pattern in which Prevotella copri, together with the host-associated metabolite allopregnanolone, is associated with uterine immune homeostasis. While these results provide functional insights, further studies are required to elucidate the mechanisms linking gut microbiota to uterine inflammation.}, }
@article {pmid42469824, year = {2026}, author = {Song, M and Ping, L and Wang, Y and Zhou, W and Fan, J and Tao, S and Shen, Y}, title = {Gut-derived extracellular vesicle enriched miR-125a-5p mediates cadmium-induced intestinal injury through NF-κB pathway activation.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04809-0}, pmid = {42469824}, issn = {1477-3155}, support = {2662026DKPY001//Fundamental Research Funds for the Central Universities/ ; 2024YFD1300500//Funding for the National Key R&amp;D Program of China/ ; }, abstract = {Cadmium (Cd), as a prevalent environmental heavy metal pollutant, has an incompletely elucidated mechanism of intestinal toxicity following oral ingestion. This study aims to elucidate novel mechanisms underlying cadmium-induced intestinal injury. By establishing a murine model of cadmium exposure, it was found that cadmium not only directly disrupts the intestinal barrier structure but also induces intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) experiments confirmed that the dysbiotic microbiota alone is sufficient to provoke intestinal injury, indicating that microbial dysregulation serves as a critical amplifier of cadmium toxicity. Further investigation revealed that cadmium exposure reshapes the intestinal microenvironment and alters the miRNA profile of gut-derived extracellular vesicles (EVs), with miR-125a-5p being significantly enriched in EVs from the cadmium-exposed group. Mechanistically, miR-125a-5p directly targets and suppresses TNFAIP3, a negative regulator of the NF-κB pathway, thereby relieving the inhibition of this signaling axis and driving sustained inflammation and barrier dysfunction, while inhibition of miR-125a-5p effectively blocks this toxic effect. This study is the first to delineate the axis of "cadmium exposure - intestinal microbiota dysbiosis - gut EV - miR-125a-5p - TNFAIP3 - NF-κB pathway activation - intestinal injury", providing new insights for the development of biomarkers and targeted interventions for cadmium-related intestinal disorders.}, }
@article {pmid42470694, year = {2026}, author = {Yi-Hui, Z and George, S}, title = {Hierarchical Multi-Omics Trajectory Prediction for fecal microbiota transplantation: a novel machine learning framework for small-sample longitudinal multi-omics integration.}, journal = {Briefings in bioinformatics}, volume = {27}, number = {4}, pages = {}, doi = {10.1093/bib/bbag389}, pmid = {42470694}, issn = {1477-4054}, mesh = {Humans ; Multiomics ; *Machine Learning ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; Clostridioides difficile ; Longitudinal Studies ; Predictive Learning Models ; Metagenomics ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective treatment for recurrent Clostridioides difficile infection and is being actively investigated for numerous other conditions. While multi-omics studies have revealed dynamic changes in microbial communities and host metabolism following FMT, existing approaches are primarily descriptive and lack the ability to model individual patient trajectories or identify early biomarkers of treatment response. Small-sample, multi-omics, longitudinal prediction presents unique computational challenges: high dimensionality ($p \gg n$), multi-omics integration, temporal dynamics, and interpretability. Here, we present Hierarchical Multi-Omics Trajectory Prediction (HMOTP), a purpose-built machine learning framework that addresses these challenges through hierarchical feature construction, multilevel attention mechanisms, and patient-specific trajectory prediction. We evaluated HMOTP on 15 patients with recurrent Clostridioides difficile infection who underwent FMT, with lipidomics and metagenomics profiling at four timepoints spanning 6 months. Notably, naively concatenating multi-omics features degraded Random Forest performance ($93.33\%$ to $87.18\%$ accuracy), whereas HMOTP's hierarchical integration benefited from the additional omics layer, demonstrating that its advantage stems from structure, not from access to more data. Through hierarchical interpretability, HMOTP identified key biomarkers and revealed cross-omics associations between host lipid metabolism and microbial energy pathways, demonstrating utility for longitudinal modeling and biological discovery in FMT response. HMOTP provides a generalizable, principled framework for personalized medicine applications across small-sample multi-omics problems. Source code and a demo dataset are publicly available.}, }
@article {pmid42462533, year = {2026}, author = {Ren, H and Zhao, C and Fan, Q and Wang, X and Yan, K and Zhang, H and Jiang, S and Yang, C and Wang, Y and Liu, Y and Wang, N and Fan, S and Xu, X and Li, X}, title = {Paridis rhizoma total saponins ameliorate abnormal uterine bleeding via regulating Proteus mirabilis 2024-mediated estrogen metabolism in the gut-reproductive axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158561}, doi = {10.1016/j.phymed.2026.158561}, pmid = {42462533}, issn = {1618-095X}, abstract = {BACKGROUND AND PURPOSE: Abnormal uterine bleeding (AUB) is a highly prevalent gynecological disorder worldwide, for which first-line steroid hormone therapy is limited by well-documented adverse effects. Paridis rhizoma total saponins (PRS) are the core pharmacodynamic material basis of Gongxuening Capsules, a classic traditional Chinese medicine (TCM) formula with well-validated clinical hemostatic efficacy for AUB. However, its active ingredients and underlying therapeutic mechanisms remain largely unclear, especially the potential regulatory role of the gut-reproductive axis. This study aimed to systematically elucidate the anti-AUB mechanism of PRS.<br><br>METHODS: The therapeutic effect of PRS was evaluated in a rat model of AUB induced by incomplete abortion in early pregnancy. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to characterize the chemical profile and in vivo distribution of PRS. Integrative analysis of uterine transcriptomics, fecal multi-omics, fecal microbiota transplantation, bacterial isolation, gene functional validation, and administration of individual monomeric compound was performed to decipher the mechanism.<br><br>RESULTS: PRS dose-dependently alleviated uterine and ovarian pathological damage, mitigated uterine inflammation and ovarian apoptosis, and restored systemic estrogen homeostasis in AUB rats, characterized by significantly reduced serum estradiol (E2) and elevated estrone (E1). Polyphyllin I (PI) and Paris saponin VII (PVII) were identified as the core active monomers of PRS. We first isolated and identified Proteus mirabilis 2024 (PM_2024) as the key bacterial strain driving the conversion of E2 to E1, and confirmed that the PM_2024_3180 gene was the core functional element encoding short-chain dehydrogenase/reductase (SDR) for estrogen metabolism. Mechanistically, PRS and its active monomers PI/PVII significantly enriched intestinal PM_2024, enhanced its E2 metabolic capacity, upregulated ovarian HSD17B2/HSD17B8 expression, and modulated FKBP5/PGR within the uterine estrogen signaling pathway to exert anti-AUB effects.<br><br>CONCLUSION: This study elucidates a novel estrogen-mediated gut-reproductive axis mechanism of PRS against AUB for the first time, deciphers the scientific connotation of the classic hemostatic TCM Paridis rhizoma, and provides a novel gut microbiota-targeted microecological therapeutic strategy for AUB and other hormone-related gynecological disorders.}, }
@article {pmid42465573, year = {2026}, author = {Dixit, S and Welker, A and Ortiz, D and Athanasouli, M and Stein-Thoeringer, CK}, title = {Microbiome dysbiosis and its modulation in cancer development, prevention and therapy.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1852716}, pmid = {42465573}, issn = {2234-943X}, abstract = {Gut microbiome dysbiosis, a state of microbial imbalance, altered microbial function, and disturbed homeostasis between the gut microbiome and its host, is increasingly recognized as a key contributor to cancer development, progression, and variability in therapeutic response. These microbiome states can facilitate cancer development through chronic inflammation, expansion of microbial genotoxin producers, or disturbances of immune defense mechanisms. In this review, we will discuss current findings on gut microbiome dysbiosis in cancer initiation and progression, emphasizing mechanisms that links dysbiosis to oncogenic transformation and tumor microenvironment remodeling. Furthermore, we will explore microbiome-targeting strategies for cancer prevention and therapeutic support, including dietary modulation, probiotics, prebiotics, and fecal microbiota transplantation. These various microbiome modulations have shown promise in restoring microbial homeostasis, enhancing immunotherapy efficacy, and reducing treatment-associated toxicity. Advances in microbial genomics and metabolomics further enable the identification of biomarkers for predicting cancer risk and therapeutic outcomes. Despite significant progress, translation into clinical settings faces challenges related to interindividual variability, standardization, and mechanistic complexity. Understanding the microbiome-cancer interface provides a platform for personalized, microbiome-informed oncology, paving the way for prevention-driven and precision-guided therapeutics.}, }
@article {pmid42465768, year = {2026}, author = {Zhou, P and Jiang, X and Zhang, H and Jiang, S and Zhang, X and Ma, C and Bai, X}, title = {Gut-lung axis in radiation-induced lung injury: mechanisms and interventions.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1806833}, pmid = {42465768}, issn = {1664-3224}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/radiation effects/immunology ; *Radiation Pneumonitis/therapy/microbiology/etiology/immunology/metabolism ; *Lung/immunology/microbiology/radiation effects/metabolism ; Dysbiosis ; Radiation Injuries ; }, abstract = {Radiation-induced lung injury (RILI) constrains thoracic radiotherapy dosing and includes acute radiation pneumonitis (RP) and chronic radiation-induced pulmonary fibrosis (RPF). This narrative review explores the gut-lung microbiota axis in RILI, synthesizing evidence from preclinical models, clinical cohorts (N = 52-89), and randomized controlled trials (RCTs). Radiotherapy induces gut dysbiosis, barrier breakdown, and metabolite changes [e.g., short-chain fatty acid (SCFA) and desaminotyrosine (DAT) depletion], promoting inflammation and fibrosis via pathways such as Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB), TGF-β/Smad, sphingosine-1-phosphate (S1P)-S1PR, and cGAS-STING in animal studies. Inter-species microbial variations hinder translation, while lung microbiota shifts remain nascent. In non-small cell lung cancer cohorts, lower gut microbiota stability (a marker of dysbiosis) is associated with an increased risk of grade ≥2 RP (multivariable-adjusted models, p < 0.05), with higher baseline Faecalibacterium abundance conferring protection; however, causality remains unproven due to antibiotic confounding. Mechanisms involve lipopolysaccharide (LPS) translocation, interleukin 25 (IL-25)/S1P-driven type 2 innate lymphoid cell (ILC2) migration, regulatory T cell/T helper 17 cell (Treg/Th17) imbalance, and extracellular vesicle (EV) signaling, with biomarkers such as 16S rRNA sequencing and EV-miRNAs (e.g., miR-486-5p). Artificial intelligence models predict RP with 75% accuracy. Phase-specific interventions, such as pre-radiotherapy gut microbiota monitoring, intra-radiotherapy SCFA supplementation, subacute DAT modulation, and RPF-targeted EV therapies, have been explored in preliminary pilot studies [for example, one small study reported approximately 12% FEV1 improvement following fecal microbiota transplantation (FMT)]. Future large-scale, stratified RCTs that properly account for antibiotics, chemotherapy, and immunotherapy are required to establish causality beyond the current largely associative clinical evidence. The integration of immunotherapy and proton therapy in such trials may help clarify gut-lung interactions, including any microbiota-preserving effects of proton therapy; the role of the lung microbiota in fibrosis remains preliminary.}, }
@article {pmid42466149, year = {2026}, author = {Jiao, B and Jiang, S}, title = {Gut microbiota as modulators of obesity and overweight: a registry-based systematic review of clinical trial evidence.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1865785}, pmid = {42466149}, issn = {2296-861X}, abstract = {BACKGROUND: Background: Obesity is a global epidemic that remains inadequately addressed by healthcare systems. The gut microbiota offers a promising metabolic target, yet systematic reviews of clinical trials on microbiome modulators for obesity are scarce.<br><br>METHODS: Using the Trialtrove database (September 16, 2025), we performed a registry-based systematic review with the strategy: "(Disease: Obesity) AND (Mechanism: Microbiome modulator)." We included interventional trials targeting overweight/obese populations with defined microbiome-modulating mechanisms; observational and withdrawn/suspended trials were excluded. Extracted data covered phase, status, intervention type, sponsor, location, and participant characteristics. Descriptive analyses used R software (v4.4.3).<br><br>RESULTS: Among 217 included trials, 131 (60%) were completed and 37 (17%) ongoing., Academic institutions led sponsorship (157 trials), followed by commercial (45) and government (14). Trials rose sharply after 2011, peaking at 34 in 2023 (over 80% of Phase IV trials that year). Probiotics dominated (141 trials), followed by synbiotics (21) and FMT (22). China (52) and the US (24) led research. Probiotics prevailed in Phases III/IV, whereas FMT concentrated in Phases II/IV with a higher termination rate.<br><br>CONCLUSIONS: This study reveals a rapidly growing yet uneven landscape. Probiotics remain the primary focus, academic institutions the main sponsors, and China/US the core hubs. The field has entered a post-marketing evaluation phase dominated by Phase IV studies. Limitations include reliance on a single database and lack of efficacy data, but the study highlights rapid expansion and heterogeneity in this field. Future research should integrate multiple data sources and quality assessments for more comprehensive evidence.}, }
@article {pmid42466885, year = {2026}, author = {Mengoli, M and Boccia, F and Barone, M and Mele, F and Bertolino, L and Della Ratta, EE and De Feo, M and Durante-Mangoni, E and Turroni, S and Brigidi, P and Zampino, R}, title = {Oral, gut, and skin microbiota characterization in patients with heart valve disease with or without infective endocarditis: a pilot study.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0190825}, doi = {10.1128/spectrum.01908-25}, pmid = {42466885}, issn = {2165-0497}, abstract = {The relationship between host microbiota and infective endocarditis (IE) has been investigated by few studies. We compared the oral, gut, and skin microbiota profiles of patients awaiting heart valve replacement, both with and without IE, and correlated the profiles with the patients' clinical data, including the etiological agents and antibiotics received. Thirty-six patients were enrolled in a prospective, observational pilot study: 25 with IE (cases) and 11 with non-infective valve disease requiring surgery (controls). Clinical data and oral, fecal, and skin samples were collected before surgical treatment. Microbiota was profiled using 16S rRNA amplicon sequencing. Cases and controls were comparable, except for inflammatory parameters and prevalence of prosthetic valves, which were higher in cases. Causative IE pathogens were Staphylococcus spp., Streptococcus spp., and Enterococcus spp. Compared to controls, cases showed dysbiotic features in their oral, gut, and skin microbiota, including lower diversity in oral and skin communities and overall community depletion. Only a few bacteria were enriched, such as Oxalobacteraceae in the oral cavity and Bacteroides in the gut. There was low concordance between bacterial changes and blood isolates for most IE-causing pathogens, suggesting that dysbiosis may have effects beyond merely acting as a reservoir for specific pathogens. Dysbiosis may be a relevant yet underexplored factor associated with IE. Further studies are needed to clarify the underlying pathogenetic mechanisms.IMPORTANCEThe relationship between microbiota alterations and infective endocarditis has been explored in the literature, but the majority of available studies focus only on the oral microbiota. In this prospective observational pilot study, we analyzed three microbial ecosystems (oral, skin, and gut) in patients awaiting heart valve replacement with and without infective endocarditis. We observed dysbiotic features that are potentially associated with infective endocarditis. While these findings are preliminary, they suggest that future studies should investigate whether microbiota-targeted interventions, such as a probiotic regimen, could play a preventive role in patients with established IE risk factors, including valve defects, presence of prosthesis, or a history of prior IE.}, }
@article {pmid42304372, year = {2026}, author = {Hiep, ND and Van Nut, L and Vy, TTT and Tin, LD}, title = {Catastrophic pelvic-perineal injuries with traumatic hemipelvectomy following a motorcycle collision: a multidisciplinary reconstruction case report.}, journal = {BMC surgery}, volume = {26}, number = {1}, pages = {}, pmid = {42304372}, issn = {1471-2482}, mesh = {Humans ; Male ; Middle Aged ; *Perineum/injuries/surgery ; *Hemipelvectomy ; *Accidents, Traffic ; *Plastic Surgery Procedures/methods ; Motorcycles ; *Multiple Trauma/surgery ; *Pelvis/injuries/surgery ; Pelvic Bones/injuries/surgery ; Skin Transplantation ; Crush Injuries/surgery ; }, abstract = {BACKGROUND: Catastrophic pelvic and perineal trauma with associated traumatic hemipelvectomy is extremely rare and carries a high mortality risk. These injuries often involve multisystem destruction, including genitourinary, anorectal, musculoskeletal, and vascular structures, presenting extraordinary challenges for surgical management and reconstruction. Reports of survivors, particularly from resource-limited settings, remain limited.<br><br>CASE PRESENTATION: A 52-year-old man presented in 2022 with devastating pelvic-perineal trauma following a high-energy motorcycle crash. He received initial first aid at a district hospital before being urgently transferred to our tertiary care center in Vietnam. Upon arrival, he was in profound hemorrhagic shock, with non-palpable pulses and unrecordable blood pressure. Operative findings revealed complete avulsion of the left hemipelvis, severe crush injury of the left lower limb, full-thickness rectal transection, bladder rupture, and complete loss of the external genitalia. He underwent prompt resuscitation, left hemipelvectomy, and fecal and urinary diversion, followed by staged reconstruction. Definitive wound coverage was achieved using a combination of local rotational flap, right profunda artery perforator (PAP) flap, and autologous skin grafting. The patient recovered well and was discharged after 112 days with stable vital signs and functioning urinary and fecal diversion.<br><br>CONCLUSIONS: This case demonstrates the survivability of catastrophic pelvic-perineal trauma with traumatic hemipelvectomy. It emphasizes the importance of multidisciplinary care, early hemorrhage control and surgical intervention, as well as adaptable reconstruction strategies in low-resource settings.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid42458266, year = {2026}, author = {Zhu, C and Wang, M and Meng, L and Zhao, Z and Han, H and Chang, Y and Zhang, S and Yang, Y}, title = {Gut microbiota dysbiosis in the pathogenesis of ulcerative colitis and the therapeutic efficacy of fecal microbiota transplantation: a meta-analysis.}, journal = {BMC gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12876-026-05091-y}, pmid = {42458266}, issn = {1471-230X}, support = {82560927//the National Natural Science Foundation of China/ ; 2024AAC05095//Natural Science Foundation for Ningxia Province/ ; 2024SF025//the Science and Technology Program of Yinchuan City/ ; 2022LCZX0013//Ningxia Hui Autonomous Region Clinical Medical Research Center for Anorectal Diseases/ ; 2025DPC05028//Science and Technology Basic Condition Construction Project of Ningxia Hui Autonomous Region/ ; 2024BEG02024//Key Research and Development Program of Ningxia Hui Autonomous Region/ ; }, abstract = {OBJECTIVE: To explore the correlation between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), and to provide an evidence-based basis for clinical diagnosis and treatment.<br><br>METHODS: Randomized controlled trials (RCTs) were included through a systematic search of the PubMed, Medline, Web of Science, Cochrane Library, and EMBASE databases. The Cochrane Risk of Bias Tool (RoB 2) was used to evaluate the quality of the literature. RevMan 5.3 software was employed to conduct a Meta-analysis, and the pooled effect size (OR/RR) and 95% confidence interval (CI) were calculated. The primary outcome measures included the associations between gut microbial diversity, changes in the abundance of specific microbial groups and the onset of UC.<br><br>RESULTS: A total of 6 literatures were included, involving 171 study subjects (100 cases in the fecal microbiota transplantation (FMT) group and 71 cases in the control group), all of which were randomized controlled trials. There was no significant difference in the clinical response between the FMT group (ulcerative colitis patients receiving fecal microbiota transplantation intervention) and the control group (ulcerative colitis patients receiving conventional treatment or placebo) (RD&#x2009;=&#x2009;0.17, 95% CI [-0.05-0.40], P&#x2009;=&#x2009;0.14); the clinical remission in the FMT group was significantly better than that in the control group (OR&#x2009;=&#x2009;2.20, 95% CI [1.05-4.59], P&#x2009;=&#x2009;0.04); the changes in the microbiota composition in the FMT group were significantly higher than those in the control group (MD&#x2009;=&#x2009;0.20, 95% CI [0.11-0.28], P&#x2009;<&#x2009;0.001); there was no significant difference in the occurrence of adverse events between the FMT group and the control group (RD=-0.00, 95% CI [-0.15-0.14], P&#x2009;=&#x2009;0.98); there was no significant difference in endoscopic remission between the FMT group and the control group (OR&#x2009;=&#x2009;1.53, 95% CI [0.57-4.11], P&#x2009;=&#x2009;0.40).<br><br>CONCLUSION: This exploratory meta-analysis suggested that gut microbiota dysbiosis may be associated with the onset of UC, manifested as reduced diversity, imbalanced microbiota structure, and changes in the abundance of specific microbial groups. However, given the limited number of included studies, these findings are hypothesis-generating and require validation in larger, well&#x2011;powered trials. Further exploration of the potential value of microbiota intervention in the treatment of UC is needed.}, }
@article {pmid42458949, year = {2026}, author = {Khan, H and Wang, YM and Iftikhar, I and Arif, B and Khan, B and Kiyani, MM and Al-Hussain, F and Bashir, S and Li, HT}, title = {Gut-Brain Axis Mechanisms and Microbiome Abnormalities in Autism Spectrum Disorder and Therapeutic Implications.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X423517260330192710}, pmid = {42458949}, issn = {1875-6190}, abstract = {ASD has been associated with alterations of the microbiota-gut-brain axis, a bidirectional system that links gut microbiota to neural, endocrine, and immune pathways. Multi-omics studies indicate that most of the ASD affected individuals have lower levels of beneficial taxa, including Bifidobacterium, Lactobacillus gemelhinis, Faecalibacterium prausnitzii, and Roseburia species, and also enrichment with potentially pathogenic strains. Dysbiosis likely affects SCFA, especially butyrate, production. Butyrate acts via GPR41 and GPR43, which maintain the gut barrier and reduce inflammation. Lower butyrate and receptor activity can weaken the barrier, leading to systemic and neuroinflammation implicated in ASD. Effects of the microbiota on neurotransmission also seem pertinent, with alteration in tryptophan metabolism being able to affect central nervous system serotonin availability, and imbalance in GABA glutamate signaling potentially playing a role in excitatory inhibitory dysregulation. Immune crosstalk is paramount in these processes, as micro-bial products and SCFAs are able to influence microglial activity and brain-derived neurotrophic factor signaling with consequent impacts on synaptic plasticity and behavior. This narrative review synthesises societal momentum with current understanding and treatment approaches related to the microbiome of ASD. Probiotics, prebiotics, precision nutrition, and faecal microbiota transplanta-tion (FMT) have reported promising evidence of symptom reduction and, in some studies, behavior. Evidence is still mixed because of strain variation, dosing, delivery protocols, and follow-up. We delineate priorities for randomized, adequately powered experiments that incorporate longitudinal multi-omics, immune phenotyping, and standardized neurobehavioral assessments, while taking into account developmental timing and individual variation. Collectively, the current evidence suggests the gut-brain axis as a potential contributor to ASD biology and a potential target of therapy. Customized plans to rehabilitate SCFA production, enhance barrier function, and normalize neuro-immune and neurotransmitter pathways may augment current practice. Establishing causality and determining which patients benefit from which interventions when are the essential next steps.}, }
@article {pmid42459086, year = {2026}, author = {Pérez-Reytor, D and Isla, E and Urrutia, &#xcd;M and Plaza, N and García, K and Karahanian, E}, title = {The Role of Microbiota, Gut Integrity, and Neuroinflammation in Relapse Vulnerability in Alcohol Use Disorder.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X458517260624074839}, pmid = {42459086}, issn = {1875-6190}, abstract = {Alcohol use disorder is a chronic relapsing condition with significant neurobiological, psychological, and social implications. Relapse, defined as the resumption of clinically significant alcohol consumption following abstinence, represents a major barrier to sustained recovery. Emerging evidence indicates that the gut-brain axis may contribute to relapse vulnerability through persistent peripheral and central biological alterations. Chronic alcohol consumption can induce intestinal dysbiosis and disrupt epithelial integrity. This increases intestinal permeability and facilitates the translocation of bacterial endotoxins. These processes may promote systemic inflammation and sustained neuroimmune activation. Also, this can alter glutamatergic, dopaminergic, and GABAergic signaling pathways involved in cravings, negative emotions, and stress sensitivity. Alcohol-related dysbiosis also modifies microbial metabolites, including short-chain fatty acids and tryptophan catabolites, potentially reinforcing inflammatory and neurochemical imbalances. Comorbid depression may further amplify these interactions by enhancing pro-inflammatory signaling and emotional dysregulation. This could increase the risk of relapse. Preclinical studies suggest that microbiota-targeted interventions, such as strain-specific probiotics, fecal microbiota transplantation, and postbiotics including butyrate derivatives, can restore intestinal barrier function, attenuate neuroinflammation, and reduce relapse-like behaviors in experimental models. However, clinical translation remains limited, and longitudinal studies specifically evaluating relapse outcomes are insufficient. This narrative review integrates mechanistic and translational evidence linking gut dysbiosis, intestinal barrier dysfunction, systemic inflammation, and neuroimmune activation to relapse vulnerability in AUD. By situating relapse within an integrated gut-brain framework, we propose that microbiota-informed strategies may represent promising adjunctive approaches to complement existing relapse-prevention treatments.}, }
@article {pmid42459342, year = {2026}, author = {Quan, Y and Chen, M and Cai, Y and Ling, L and Lao, Y and He, X and Wu, L}, title = {Analysis of washed microbiota transplant efficacy for autism and donor-recipient gut microbiota characteristics.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1823988}, pmid = {42459342}, issn = {2235-2988}, mesh = {Child ; Child, Preschool ; Female ; Humans ; Male ; *Autism Spectrum Disorder/therapy/microbiology ; *Autistic Disorder/therapy/microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; Bacteroides/genetics ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Prevotella ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {UNLABELLED: Emerging evidence suggests that washed microbiota transplantation (WMT) can be used to effectively treat autism spectrum disorder (ASD). This study aimed to evaluate the efficacy of WMT, investigate structural changes in the gut microbiota of children with ASD after WMT, and determine the relationship between donor and recipient gut microbiota characteristics in ASD with different treatment efficacies. This study included 38 ASD patients who underwent a full course of WMT from a single donor between July 2019 and December 2024. The clinical rating scale and stool samples were collected before and 4 weeks after WMT. Using 16S rRNA sequencing, patients were stratified by enterotype, Bacteroides (ET-B), or Prevotella (ET-P), to compare gut microbiota features with healthy donors and assess how microbial characteristics influence WMT efficacy. Finally, we found that WMT has statistically significant effects on the scale scores changes of core symptoms, sleep disturbances, and gastrointestinal symptoms in patients with ASD. In addition, the efficacy of WMT for ASD was correlated with donor and recipient gut microbiota characteristics before WMT. Among donors and recipients with Bacteroides as the dominant genus, the closer the recipient gut microbiota was to that of the donor, the better the efficacy of WMT in patients with ASD.<br><br>CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier ChiCTR2400089296.}, }
@article {pmid42459365, year = {2026}, author = {Xu, H and Chen, W and Xiao, Q and Ren, J and Yang, D and Li, S and Cai, Y and Tuerheng, J and Tang, R and He, K and Wu, D}, title = {Microbiota-gut-brain axis imbalance: a promising therapeutic target for preserving brain health in high-altitude environment.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1820153}, pmid = {42459365}, issn = {1662-4548}, abstract = {High-altitude hypobaric hypoxia poses a significant threat to brain function, yet effective neuroprotective strategies remain limited. Emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a key mediator in high-altitude-induced cognitive impairment, positioning it as a potential therapeutic target. This review synthesizes current knowledge on how high-altitude exposure dynamically reshapes gut microbial ecology, characterized by reduced diversity, phylum-level instability, and functional metabolic shifts. Furthermore, we delineate how such altitude-induced dysbiosis has been associated with neural dysfunction through interconnected pathogenic mechanisms that are proposed to link gut ecology to brain outcomes: intestinal barrier disruption with metabolic dysregulation, LPS/TLR4-mediated neuroinflammation, vagal and enteric nervous system alterations, oxidative stress imbalance, and neuroendocrine dysregulation. Most current evidence is correlational, and further research is needed to establish causality. A critical unresolved question is whether short-term, transient gut dysbiosis at high altitude can instigate long-lasting neurological deficits independent of ongoing microbial perturbation. We further evaluate microbiota-targeted neuroprotective strategies, including probiotics, prebiotics, and fecal microbiota transplantation, highlighting their distinct mechanisms and summarizing the current evidence supporting MGBA-targeted interventions for high-altitude brain health. Preclinical studies suggest these approaches hold promise by restoring barrier integrity, attenuating inflammatory signaling, and rebalancing microbial metabolite profiles, while human intervention evidence remains scarce. Finally, we discuss critical challenges and future directions for translating these mechanistic insights into personalized interventions, emphasizing deeper mechanistic exploration and the synergistic interactions among microbial taxa. These insights may inform more effective therapeutic strategies for the growing populations residing in or traveling to high-altitude regions.}, }
@article {pmid42461015, year = {2026}, author = {Dong, W and Yan, C and Korwin-Mihavics, B and Stack, K and Hughes, G and Schmidt, A and Schwartz, KJ and Caballero-Flores, G and Alexander, M}, title = {β-Hydroxybutyrate precursor 1,3-butanediol modulates enteric pathogen susceptibility and Th17 responses via commensal bacteria.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0032426}, doi = {10.1128/msystems.00324-26}, pmid = {42461015}, issn = {2379-5077}, abstract = {T helper 17 (Th17) cells are a critical T lymphocyte subset involved in mucosal immunity and host defense against enteric pathogens. Although ketogenic diets (KD) and the major ketone body β-hydroxybutyrate (BHB) reshape gut microbiota and suppress Th17 responses under defined diet conditions, it remains unclear whether elevation of BHB alone, independent of dietary macronutrient composition and systemic metabolic shifts, is sufficient to remodel Th17-inducing commensals and alter host susceptibility to enteric infection. Here, we used 1,3-butanediol (BD), a precursor metabolized to BHB independently of KD, to elevate systemic BHB levels in mice. BD treatment significantly reduced the frequency of ileal Th17 cells, as assessed by flow cytometry for Th17 markers IL-17A and RORγt. 16S rRNA gene sequencing revealed that BD altered gut microbial community structure, as indicated by beta-diversity analysis based on Bray-Curtis dissimilarity, and reduced Shannon diversity and evenness. Linear discriminant analysis effect size identified segmented filamentous bacteria (SFB) as significantly decreased in the ileum following BD treatment, and SFB abundance positively correlated with Th17 markers. Microbiota transplantation demonstrated that BD-shaped microbiota was sufficient to suppress Th17 responses in recipient mice, accompanied by reduced SFB abundance. In a Citrobacter rodentium infection model, BD treatment was associated with increased pathogen burden, and fecal C. rodentium levels were negatively correlated with SFB abundance. Together, these results support a model in which BD treatment, accompanied by elevated circulating BHB, reshapes the commensal microbiota, including reducing SFB levels, and is associated with dampened Th17 responses as well as increased susceptibility to enteric infection.IMPORTANCEDiet is a key determinant of gut microbial composition and mucosal immune function, yet the microbial mechanisms linking diet-mediated metabolic changes to immune regulation remain incompletely understood. T helper 17 (Th17) cells play central roles in both protective mucosal immunity and inflammatory pathology, making them a critical target of immunometabolic regulation. In this study, we show that 1,3-butanediol (BD) treatment, which leads to elevated circulating β-hydroxybutyrate (BHB) independently of diet, is associated with suppression of intestinal Th17 responses, remodeling of the gut microbiota, and reduced levels of segmented filamentous bacteria (SFB). We further demonstrate that BHB-associated microbiota changes are linked to increased susceptibility to enteric infection. This work provides a mechanistic framework illustrating how metabolic state can influence host immunity through selective effects on commensal microbes. These findings inform future studies of microbiota-mediated immune regulation.}, }
@article {pmid42449149, year = {2026}, author = {Nøhr, AK and Overby, MG and Nielsen, MM and Torp, EA and Jensen, RH and Poulsen, L&#xd8; and Thorlacius-Ussing, O and Rasmussen, SL and Andersen, B and Gögenur, I and Sørensen, E and Pedersen, OBV and Erikstrup, C and Brøns, N and Schwinn, M and Mikkelsen, C and Bruun, MT and Jørgensen, MM and Bertelsen, CA and Hillingsø, JG and Høgdall, E and Ostrowski, SR and ,  and ,  and Bøgsted, M and Brøndum, RF}, title = {Combining genome-wide polygenic scores with registry data for colorectal cancer risk-based screening.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, pmid = {42449149}, issn = {1532-1827}, support = {R374-A2269//Kr&#xe6;ftens Bek&#xe6;mpelse (Danish Cancer Society)/ ; R374-A2269//Kr&#xe6;ftens Bek&#xe6;mpelse (Danish Cancer Society)/ ; }, abstract = {BACKGROUND: Polygenic risk scores (PRS) show potential for risk-based colorectal cancer (CRC) screening, but their utility must be assessed across diverse ancestries and tumour characteristics and compared with the current standard, the faecal immunochemical test (FIT).<br><br>DESIGN: The cohort included 112,204 individuals from the Copenhagen Hospital Biobank (8995 with adenoma and 9246 with CRC), all with linked genetic and health registry data. A subset (N&#x2009;=&#x2009;20,658) also had FIT results. CRC PRSs were evaluated for their association with lifetime adenoma and CRC risk and their predictive value individually and combined with FIT.<br><br>RESULTS: PRS stratified population-calibrated lifetime adenoma and CRC risk independently of ancestry and sex. Individuals with a high PRS reached the incidence of low-PRS individuals up to 10 years earlier, between ages 45-60. PRS stratified risk across tumour location and histologies but showed no association among individuals with deficient mismatch repair tumours (N&#x2009;=&#x2009;623). Combining PRS with FIT did not meaningfully improve prediction of adenoma or CRC at first screening, negative colonoscopy outcomes among FIT-positive participants, or outcomes within 2 years after a negative FIT.<br><br>CONCLUSION: PRS stratifies lifetime adenoma and CRC risk and may inform risk-based screening initiation and intensity but adds limited predictive value when combined with FIT.}, }
@article {pmid42449656, year = {2026}, author = {Clavo, B and Córdoba-Lanús, E and Martínez-Sánchez, G and Cánovas-Molina, &#xc1; and Federico, M and Galván, S and Ramchandani-Vaswani, A and Piñero, JE and Antonilli, C and Benítez, G and Cobiella-Hernández, L and Pérez-Rodríguez, D and Pérez-Santana, C and Martín-Alfaro, R and Fernández-Tagarro, M and Díaz-Garrido, JA and González-Martín, JM and Martínez-Pérez, R and Lorenzo-Morales, J and Rodríguez-Esparragón, F}, title = {Gut Microbiota Dysbiosis and CIPN: State-of-the-Art Evidence and a Microbiota-Ozone Therapeutic Framework.}, journal = {Cancers}, volume = {18}, number = {13}, pages = {}, doi = {10.3390/cancers18132112}, pmid = {42449656}, issn = {2072-6694}, support = {PI23/01324//Institute of Health Carlos III/ ; CIGC/23-24//Cabildo de Gran Canaria/ ; CGC/2025/12551//Cabildo de Gran Canarias/ ; PIFIISC25/52//Fundaci&#xf3;n Canaria Instituto de Investigaci&#xf3;n Sanitaria de Canarias/ ; PIFIISC24/37//Fundaci&#xf3;n Canaria Instituto de Investigaci&#xf3;n Sanitaria de Canarias/ ; }, abstract = {BACKGROUND/OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 85% of patients receiving neurotoxic regimens, often leading to dose reduction and impaired quality of life, yet effective preventive or therapeutic options remain scarce. Emerging evidence implicates chemotherapy-induced gut microbiota dysbiosis in CIPN pathogenesis via a gut-nerve axis. Concurrently, rectal ozone insufflation (ROI) has been shown to modulate the gut microbiota and reduce inflammation in preclinical models. This article critically examines the evidence on the role of gut dysbiosis in CIPN, evaluates the microbiota-modulating capacity of rectal ozone therapy (OT), and assesses the biological plausibility of ozone as a microbiota-targeting intervention for CIPN, while explicitly distinguishing between established evidence and hypothetical mechanisms.<br><br>EVIDENCE SYNTHESIS: Neurotoxic agents induce dysbiosis marked by reduced microbial diversity, loss of short-chain fatty acid-producing bacteria, and expansion of pro-inflammatory taxa. Preclinical models demonstrate a causal role for specific microbial communities in CIPN, with microbiota depletion or fecal transplantation modulating neuropathic phenotypes. In human cohorts, dysbiosis severity correlates with CIPN symptoms. Preclinical studies show that ROI restores microbial balance, enhances short-chain fatty acid levels, and strengthens intestinal barrier function via Nrf2/HO-1 and SIRT1 pathways. Preliminary retrospective data from small case series (n = 7 and n = 15) report sustained symptom improvement in CIPN patients receiving OT. However, no human study has directly linked ozone-induced microbiota changes to clinical outcomes, and the clinical evidence for OT in CIPN remains limited to uncontrolled observations.<br><br>CONCLUSIONS: Convergent preclinical evidence supports a biological rationale for investigating ROI as a microbiota-targeting intervention in CIPN. However, this rationale remains largely hypothetical in the clinical setting. High-quality randomized controlled trials with longitudinal microbiome profiling are urgently needed to establish mechanistic causality and to determine whether the promising preclinical findings translate into clinically meaningful benefits. Until such evidence is available, the framework presented here should be regarded as hypothesis-generating rather than as a basis for clinical practice.}, }
@article {pmid42450578, year = {2026}, author = {Li, J and Cheng, S and Zhang, W and Qiao, S and Zhang, L and Yao, M and Zhang, Y and Wang, B and Wu, C}, title = {Mulberroside A Alleviates Scopolamine-Induced Cognitive Deficits by Suppressing Neuroinflammation and Oxidative Stress via the Dubosiella-Associated Microbiota-Gut-Brain Axis.}, journal = {Biology}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/biology15131030}, pmid = {42450578}, issn = {2079-7737}, support = {262102310255//Henan Provincial Science and Technology Key Project/ ; 26A180030//Key Scientific Research Foundation of Henan Colleges and Universities/ ; 252300423668//Natural Science Foundation of Henan/ ; ZKNUC2024030//Zhoukou Normal University High-level Talent Start-up Foundation/ ; }, abstract = {Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer's disease (AD)-like cognitive impairment through the microbiota-gut-brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice, n = 10/group), we demonstrated that daily administration of MsA (10, 20, and 30 mg/kg/day) for 5 weeks significantly ameliorated cognitive performance in novel object recognition and Morris water maze tests. At the optimal dose (30 mg/kg/day), MsA suppressed hippocampal microglial activation, reduced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and attenuated oxidative stress by decreasing malondialdehyde (MDA) while restoring superoxide dismutase (SOD) and glutathione (GSH) levels. MsA also strengthened intestinal barrier integrity (ZO-1, occludin) and significantly altered the gut microbiota, notably increasing the beneficial genus Dubosiella. Brain metabolomics indicated that MsA reversed scopolamine-induced metabolic disturbances, mainly restoring phospholipid balance. Correlation analysis demonstrated a strong gut-brain connection, with Dubosiella abundance positively associated with neuroprotective phospholipids and negatively with stress markers. Furthermore, fecal microbiota transplantation from MsA-treated donors successfully replicated these behavioral improvements in recipient mice, underscoring the functional involvement of the reshaped microbiome rather than a simple autonomous recovery. These results suggest that MsA alleviates AD-like cognitive impairment by reducing neuroinflammation and oxidative stress through microbiota remodeling, enhancing the intestinal barrier, and modulating the Dubosiella-associated gut-metabolite-brain axis, making MsA a promising multi-target nutraceutical for ameliorating AD-like cognitive deficits.}, }
@article {pmid42451051, year = {2026}, author = {Guo, Y and Wang, C and Dong, H and Li, T and Kang, C and Wang, X and Yu, J}, title = {Lonicerae japonicae flos Polyphenols Attenuate Inflammation-Related Ferroptosis and Gut Microbiota Dysbiosis in LPS-Induced Acute Lung Injury in Mice.}, journal = {Nutrients}, volume = {18}, number = {13}, pages = {}, doi = {10.3390/nu18132048}, pmid = {42451051}, issn = {2072-6643}, support = {2023YFC3503805//National Key Research and Development Project of China/ ; 2060302//Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources/ ; 2025ZDZX07//Science, Education and Industry Major Innovation Pilot Project from Qilu University of Technology (Shandong Academy of Sciences)/ ; }, mesh = {Animals ; *Acute Lung Injury/chemically induced/drug therapy/microbiology ; Male ; *Polyphenols/pharmacology ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; Lipopolysaccharides ; *Dysbiosis/drug therapy ; *Lonicera/chemistry ; Mice ; Lung/pathology/metabolism/drug effects ; Inflammation/drug therapy ; NF-kappa B/metabolism ; Disease Models, Animal ; *Plant Extracts/pharmacology ; }, abstract = {Background/Objectives: Acute lung injury (ALI) currently lacks safe and effective therapeutic strategies with low toxicity. Lonicerae japonicae flos, a traditional herb and functional food, contains polyphenols as its principal active components. This study investigated whether Lonicerae japonicae flos polyphenols (LJP) could exert protective effects against lipopolysaccharide (LPS)-induced ALI in mice. Methods: Eighty-four male C57BL/6J mice were randomly divided into seven groups and treated daily for 7 days with LJP (200, 100, or 50 mg/kg), liproxstatin-1 (10 mg/kg), dexamethasone (5 mg/kg), or saline (control and model groups). Subsequently, another thirty-six mice were used for the fecal microbiota transplantation (FMT) experiment. All groups except the control group received intratracheal instillation of LPS (5 mg/kg) to induce ALI. Results: LJP treatment significantly ameliorated lung histopathological damage and gut microbiota dysbiosis. Lung proteomics analysis revealed the enrichment of the NF-κB and ferroptosis pathways. Mechanistically, LJP downregulated pro-inflammatory factors (IL-6, TNF-α, and IL-1β) by suppressing activation of the TLR4/MyD88/NF-κB pathway. Meanwhile, LJP upregulated SOD and GSH levels, thereby suppressing the accumulation of ROS, GSSG, Fe[2+], and MDA, which were closely related to the activation of the Nrf2/HO-1 and Sirt3/Nrf2/GPX4 pathways. Furthermore, LJP modulated the gut microbiota and promoted short-chain fatty acid (SCFA) production by elevating the relative abundance of Akkermansia muciniphila and Faecalibaculum. Intriguingly, FMT results confirmed that the LJP-derived gut microbiota markedly alleviated lung tissue injury and intestinal barrier damage in ALI mice. Conclusions: This study demonstrated that LJP could reshape the gut microbiota to enhance the production of SCFAs and inhibit inflammation-related ferroptosis in ALI mice.}, }
@article {pmid42451209, year = {2026}, author = {Wu, Y and Wang, J and Kang, L and Wan, X}, title = {The Interactions Between Circadian Rhythm, Gut Microbiota, and Anxiety: From Mechanisms to Intervention Strategies.}, journal = {Nutrients}, volume = {18}, number = {13}, pages = {}, doi = {10.3390/nu18132209}, pmid = {42451209}, issn = {2072-6643}, support = {31960676//National Natural Science Foundation of China/ ; 20242BAB20267//Natural Science Foundation of Jiangxi Province/ ; }, mesh = {Humans ; *Circadian Rhythm/physiology ; *Gastrointestinal Microbiome/physiology ; *Anxiety/microbiology/therapy/physiopathology ; Animals ; Melatonin ; Probiotics ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {The circadian rhythm is an internal timing system formed by the body's adaptation to the Earth's rotation, which helps maintain homeostasis by regulating physiological, metabolic, and behavioral activities. The gut microbiota (GM), the largest microbial ecosystem in the human body, exhibits a bidirectional regulatory relationship with the host circadian clock. Emerging evidence indicates that circadian rhythm disruption (CRD) is linked to disturbances in the diurnal oscillations and compositional balance of the GM, accompanied by reduced short-chain fatty acid levels, increased lipopolysaccharide leakage, and altered tryptophan metabolism. These microbial abnormalities may be involved in anxiety-like behaviors through three major pathways: neuroendocrine (hyperactivation of the HPA axis), immune (microglia-mediated neuroinflammation), and neurotransmitter (imbalance of the serotonergic and dopaminergic systems). Conversely, microbial metabolites such as butyrate and secondary bile acids may reciprocally regulate peripheral clock gene expression, forming a complex "circadian rhythm-GM-anxiety" interaction network. This review summarizes the molecular basis of circadian-GM interactions, potential GM-mediated mechanisms linking CRD with anxiety, and emerging intervention strategies including chrononutrition (time-restricted feeding, sequential nutrient intake), microbiota-targeted therapies (probiotics/prebiotics, fecal microbiota transplantation), and light therapy and melatonin supplementation. Future directions should focus on cell-specific mechanisms using single-cell and spatial transcriptomics, developing personalized interventions that integrate chronotype and microbiome profiling, and conducting large-scale randomized controlled trials to facilitate clinical translation. This review provides a framework for understanding the integrative role of circadian biology and gut microbiota in anxiety and may help develop precision intervention paradigms.}, }
@article {pmid42452591, year = {2026}, author = {Hoferica, J and Budai, BC and Szalai, E&#xc1; and Zolcsák, &#xc1; and Engh, MA and Lenti, K and Hegyi, P and Yu, J and Hegyi, PJ and Banovcin, P}, title = {Fecal Microbiota Transplantation Is Associated with Better Survival Compared to Standard of Care in Severe Alcoholic Hepatitis Not Responding to Corticosteroids: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/jcm15135131}, pmid = {42452591}, issn = {2077-0383}, abstract = {Background: Alcohol-related liver disease (ALD) affects 4.8% of the global population. Among these patients, between 13.4% and 19.6% suffer from alcoholic hepatitis (AH), which, in its severe form, is associated with significant short- and long-term mortality. Current therapeutic options are limited, offering only modest short-term survival benefits. Recent studies suggest that microbiota-based therapies may offer a novel therapeutic opportunity for patients with ALD. Methods: Databases including Embase, Medline, and CENTRAL were searched until 4 February 2026. The pre-registered protocol on PROSPERO (CRD42023467455) was followed without deviation. Studies comparing adult patients with ALD, treated with fecal microbiota transplantation (FMT) or standard of care (SOC), were included. Outcomes investigated included overall survival, alcoholic recidivism, adverse events (AEs), and disease severity scores. Risk of bias (ROB) was assessed using the ROBINS-I and ROB 2 tools. Hazard ratios (HR) were calculated for FMT versus SOC groups. Results: Overall, 10 studies were eligible for inclusion, with 339 patients eligible for synthesis. In these patients, FMT was associated with significantly improved overall survival compared to the SOC, with an HR of 0.50 (95% confidence interval (CI): 0.35-0.72; p = 0.0002). When comparing FMT with pentoxifylline, the HR was 0.45 (95% CI: 0.21-0.96; p = 0.0345), and when FMT was compared with nutritional support alone, the HR was 0.36 (95% CI: 0.19-0.66; p = 0.0001). But FMT did not reach statistical significance when compared to glucocorticoids. ROB analysis showed a moderate to high risk of bias, and the overall certainty of evidence was low. Discussion: FMT is a promising therapeutic option for improving short- and medium-term survival in patients with severe alcoholic hepatitis (SAH), particularly in those who are ineligible or unresponsive to corticosteroid therapy. However, given the risk of bias and low certainty of evidence, clinical significance remains uncertain. Confirmation in well-designed studies is needed.}, }
@article {pmid42453108, year = {2026}, author = {Liang, Y and Zhang, Y and Shi, Y and Zhang, Q and Zhang, H}, title = {Shouhui Tongbian Capsules alleviate constipation by modulating the gut microbiota-tryptophan metabolism-AhR signaling axis: a mechanistic study.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1844612}, pmid = {42453108}, issn = {1664-302X}, abstract = {OBJECTIVE: Constipation is a prevalent functional gastrointestinal disorder characterized by impaired intestinal barrier function, often driven by gut microbiota dysbiosis and metabolic disturbances. Shouhui Tongbian Capsules (SHTB), a traditional Chinese medicine formulation, has demonstrated clinical efficacy in constipation management. This study aimed to elucidate the molecular mechanisms underlying SHTB's anti-constipation effects through modulation of the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor (AhR) signaling axis.<br><br>METHODS: A loperamide-induced murine constipation model was established to evaluate the therapeutic efficacy of SHTB, as assessed by time to first black stool defecation, fecal pellet count, fecal water content, and small intestinal propulsion rate. Colonic histopathology was examined by hematoxylin and eosin (H&amp;E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining. 16S rRNA gene sequencing and metabolomic profiling were used to characterize gut microbiota composition and metabolite alterations in SHTB-treated constipated mice. Key findings were subsequently validated through fecal microbiota transplantation (FMT) and pharmacological AhR inhibition.<br><br>RESULTS: SHTB significantly improved defecation parameters in constipated mice (P < 0.001). Mechanistically, SHTB may promote tryptophan metabolic flux through gut microbiota remodeling, particularly through enrichment of Bifidobacterium (P < 0.05) and Alistipes (P < 0.01), leading to activation of colonic AhR signaling (P < 0.05) and reinforced intestinal barrier integrity. FMT with SHTB-conditioned microbiota restored key bacterial populations and reactivated AhR expression (P < 0.05) in recipient mice. Critically, pharmacological blockade of AhR with CH223191 abolished all SHTB-mediated therapeutic benefits, with no significant differences observed between the CH223191 + Lop and CH223191 + Lop + SHTB groups (P > 0.05), thereby identifying AhR as an indispensable mediator of SHTB's anti-constipation mechanism.<br><br>CONCLUSION: SHTB alleviates constipation in a murine model by enhancing intestinal barrier integrity through modulation of the gut microbiota-tryptophan metabolism-AhR signaling axis, thereby providing mechanistic support for its clinical application in managing constipation.}, }
@article {pmid42453110, year = {2026}, author = {Guo, J and Song, H and Xi, Z and Geng, W and Wang, F}, title = {The role of gut microbiome in antimicrobial resistance transmission between companion animals and livestock: mechanisms, drivers, and One Health implications.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1872946}, pmid = {42453110}, issn = {1664-302X}, abstract = {Antimicrobial resistance (AMR) poses a critical global public health challenge, with animal gut microbiomes serving as significant reservoirs and transmission hubs for antimicrobial resistance genes (ARGs). This review synthesizes current knowledge on the central role of gut microbiomes in companion animals and livestock in facilitating AMR dissemination. It examines key mechanisms that enable horizontal gene transfer within intestinal ecosystems: conjugation, transduction, and transformation. It also highlights how co-selection by heavy metals, disinfectants, and other non-antibiotic agents sustains resistance even without direct antibiotic use. The review analyzes major drivers of AMR, including antimicrobial usage, husbandry practices, and environmental pressures. It critically evaluates microbiome-based interventions such as probiotics, postbiotics, and fecal microbiota transplantation. A distinctive contribution is the integration of these elements into a network-centric One Health framework that explicitly maps cross-species transmission pathways from livestock and companion animals to humans via direct contact, food chains, and environmental dissemination. By moving beyond descriptive cataloging to provide a mechanistic and ecological synthesis, this review aims to guide the development of targeted, microbiome-informed intervention and surveillance strategies.}, }
@article {pmid42453301, year = {2026}, author = {S Afonso, J and Morel, CM and Middelkoop, A and Priem, J and Molist, F and Gloaguen, M and Buchet, A and Sørensen, G and Hansen, SV and Nielsen, JP and Guardabassi, L and Rushton, J}, title = {Impact in production costs resulting from the adoption of interventions to reduce antimicrobials in pig production in Europe: findings from EU-project AVANT.}, journal = {JAC-antimicrobial resistance}, volume = {8}, number = {4}, pages = {dlag131}, pmid = {42453301}, issn = {2632-1823}, abstract = {OBJECTIVES: Antimicrobial resistance is a major global health threat, with antimicrobial use recognized as a key driver. The post-weaning period is one of the most antimicrobial-intensive phases in pig production. This study assessed the impact on production costs of feed-based and immunomodulatory interventions designed to reduce antimicrobial use in European pig production.<br><br>MATERIALS AND METHODS: Within the EU-funded AVANT project, we evaluated feed-based strategies (alfalfa diets and high-fibre/low-protein 'secure' feed) and immunomodulatory interventions (faecal filtrate transplantation and vaccination against Shiga-producing Escherichia coli). Using data from field trials and observational studies conducted in Denmark, the Netherlands and France, we estimated the additional production costs per kilogram of pigmeat associated with each intervention. Cost and production parameters were derived from InterPIG and EU datasets (2019-2023) and adjusted under alternative mortality scenarios (6%-24%).<br><br>RESULTS: Feed-based interventions for piglets accounted for a small share of total feed costs and increased production costs by <0.2% at EU level. Vaccination against Shiga-producing E. coli increased production costs by <1%. By contrast, faecal filtrate transplantation resulted in substantially higher costs under trial conditions, increasing production costs by 9%-11% depending on mortality assumptions. None of the interventions negatively affected pig performance metrics in the trials.<br><br>CONCLUSIONS: Feed-based strategies and vaccination represent accessible and affordable options to reduce antimicrobial use in pig production in Europe. More innovative approaches such as faecal filtrate transplantation remain costly under experimental conditions but may become economically viable through regulatory approval, market development and economies of scale.}, }
@article {pmid42454489, year = {2026}, author = {McCann, JR and Yang, C and Bihlmeyer, NA and Tang, R and Truong, T and Zhou, W and An, J and Jawahar, J and Ilkayeva, O and Muehlbauer, MJ and Hu, Z and Dressman, HK and Poppe, L and Granek, JA and Arnold, JW and David, LA and Oh, J and Shi, P and Gumus Balikcioglu, P and Shah, SH and Armstrong, SC and Newgard, CB and Seed, PC and Rawls, JF}, title = {Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.}, journal = {The Journal of clinical investigation}, volume = {136}, number = {14}, pages = {}, doi = {10.1172/JCI196742}, pmid = {42454489}, issn = {1558-8238}, mesh = {Humans ; Adolescent ; *Amino Acids, Branched-Chain/blood/metabolism ; Female ; Animals ; Male ; Child ; Mice ; *Gastrointestinal Microbiome ; *Weight Loss ; *Pediatric Obesity/therapy/microbiology/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUNDObesity and weight loss in adults have been associated with distinct metabolome and gut microbiome features, but the extent to which those associations apply to adolescent stages remain unclear.METHODSThe Pediatric Obesity Microbiome and Metabolism Study (POMMS) enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 individuals who were healthy weight controls (HWCs). Blood, stool, and clinical measures were collected at baseline and after a 6-month obesity intervention for the OB group. Metabolomic profiling in serum using targeted quantitative mass spectrometry and microbiome profiling in stool were performed, and those features were assessed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants (FMT) were performed on germ-free mice using samples from both groups to assess effects on weight gain and metabolic pathways.RESULTSAdolescents with OB exhibited higher serum branched-chain amino acid (BCAA) but lower branched-chain ketoacid (BCKA) levels compared with HWC. This pattern was sex- and age-dependent and differed from adults with obesity who show elevated levels of both BCAA and BCKA. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from both OB and HWC donors had similar effects on mouse body weight, but specific taxa were linked to weight gain in recipients of FMT.CONCLUSIONAdolescents with OB have unique metabolomic adaptations and microbiome signatures compared with their HWC counterparts and adults with OB.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03139877 (Observational Study) and NCT02959034 (Repository).FUNDING SUPPORTAmerican Heart Association Grants: 17SFRN33670990, 20PRE35180195; National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492.}, }
@article {pmid42455447, year = {2026}, author = {Zakrzewska, Z and Boruta, O and Skupień, D and Skoczeń, S}, title = {Microbiome and peptide alterations in children with acute lymphoblastic leukemia: current insights and future directions.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-026-05551-7}, pmid = {42455447}, issn = {2730-6011}, abstract = {Acute lymphoblastic leukemia (ALL) is the most common type of pediatric leukemia, yet the mechanisms of leukemogenesis remain incompletely comprehended. Since the concept of brain-gut-microbiome has been established, microbiota dysbiosis has been considered to potentially impact on development of this cancer. This review focuses on microbiome and peptide alterations. In ALL pediatric patients during the time of diagnosis significant differences in comparison to healthy children were noted. While treatment and prophylaxis used in this group of patients is known to have an impact on gut microbiome, some changes in bacteria abundances could serve as predictors for infectious complications (e.g. Bifidobacterium longum), however it is not a standard practice. Probiotic supplementation with Bifidobacterium breve or Lactobacillus rhamnosus could reduce adverse symptoms of chemotherapy, but the legitimacy of their use in immunocompromised patients is controversial. Introducing new strategies, such as fecal microbiota transplantation (FMT) could lead to improvement in patients' outcomes in ALL treatment. The interaction between metabolic hormones, peptides and interleukins seems to be crucial for cancer cell metabolism and proliferation as well as immune regulation, inflammation and treatment response. Moreover, gut microbiota does not fully recover in the first year after treatment and even asymptomatic adult survivors of childhood ALL were found to have significantly altered abundances of bacteria species.}, }
@article {pmid42456685, year = {2026}, author = {Steriade, C and Segata, N and Saxena, D}, title = {The role of the gut microbiome in mediating neuroinflammation in immune-based neurological disorders.}, journal = {The Lancet. Neurology}, volume = {25}, number = {8}, pages = {764-780}, doi = {10.1016/S1474-4422(26)00193-6}, pmid = {42456685}, issn = {1474-4465}, abstract = {The gut microbiome can influence brain health by modulating neuroinflammation through various mechanisms, including immune regulation, the production of metabolites that affect neural function, gut and blood-brain barrier integrity, upstream effects via the vagus nerve, upstream migration of gut-resident lymphocytes to the brain, bile acid signalling, and endocrine activity. Changes in gut microbiota have been observed in demyelinating conditions, autoimmune encephalitis, and epilepsy. Gut microbiota composition changes can affect neuroinflammation, disease progression, and treatment outcomes. Advances in microbiome research have improved the potential for clinical translation of findings; but limitations persist, driven by the largely correlational nature of clinical studies and the complexity of microbiome sequencing and interpretation. At present, only the ketogenic diet is routinely recommended by clinicians, whereas other microbiome-based interventions remain investigational. Multiple strategies for manipulating the gut microbiome, including dietary changes, prebiotics, probiotics, postbiotics, and faecal microbiota transplantation, might be used as disease-modifying therapies in the future.}, }
@article {pmid42456784, year = {2026}, author = {Juozas, K and Ianiro, G}, title = {Finding the Signal in the Noise: Can Fecal Microbiota Transplantation Deliver for Irritable Bowel Syndrome?.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2026.07.003}, pmid = {42456784}, issn = {1528-0012}, }
@article {pmid42456880, year = {2026}, author = {Zheng, Y and Li, J and Yu, Y and Wang, W and Fan, X and Sun, L and Tang, L}, title = {The gut-microbiota-brain axis mediates the neuroprotective effects of exercise against microgravity-induced cognitive impairment.}, journal = {Experimental neurology}, volume = {}, number = {}, pages = {115930}, doi = {10.1016/j.expneurol.2026.115930}, pmid = {42456880}, issn = {1090-2430}, abstract = {OBJECTIVE: Prolonged exposure to microgravity is associated with gastrointestinal dysfunction and cognitive decline, both of which are critically regulated by the gut-microbiota-brain axis. This study aimed to investigate whether exercise mitigates microgravity-induced cognitive deficits by restoring gut homeostasis.<br><br>METHODS: The hindlimb unloading (HU) mouse model, a well-established ground-based analog of microgravity, was used in this study. HU mice underwent 4-week weight-loaded treadmill running. After the intervention, gut homeostasis, hippocampal neuroplasticity, and cognitive function were assessed. To establish causality, fecal microbiota transplantation (FMT) from exercised donor mice to HU recipient mice was performed.<br><br>RESULTS: HU mice exhibited gut microbial dysbiosis, increased circulating lipopolysaccharide (LPS) levels, reduced short-chain fatty acids (SCFAs), and impaired learning and memory. Exercise intervention restored intestinal barrier integrity by upregulating zonula occludens-1 (ZO-1) and Occludin, normalized gut microbiota composition and diversity, enhanced hippocampal neuroplasticity by increasing postsynaptic density protein 95 (PSD95), growth associated protein 43 (GAP43), phosphorylated cAMP response element-binding protein (P-CREB), and the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) pathway, and improved cognitive function. FMT from exercised donors to HU recipients recapitulated these benefits.<br><br>CONCLUTION: These results support that physical activity counteracts microgravity-induced neural dysfunction via the gut-microbiota-brain axis, suggesting that microbiome-targeted interventions may help preserve cognitive health in extreme environments such as spaceflight.}, }
@article {pmid42443738, year = {2026}, author = {Carasso, S and Gefen, T and Bakria, R and Bar-Yoseph, H and Geva-Zatorsky, N}, title = {Microbiome changes associated with FMT-mediated clearance of antibiotic-resistant Klebsiella pneumoniae in a murine carriage model.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-05354-4}, pmid = {42443738}, issn = {1471-2180}, support = {grant 1571/17 and 3165/20//Israeli Science Foundation/ ; grant FL-000969/FL-001245/FL-001381//CIFAR Azrieli Global Scholars/ ; grant CDA00025/2019-C//Human Frontier Science Program Career Development Award/ ; ERC, ExtractABact, 101078712//the European Union/ ; }, abstract = {Carbapenem-resistant Enterobacterales (CRE), including Klebsiella pneumoniae (KP), pose a significant public health threat due to their resistance to last-line antibiotics. Eliminating CRE colonization in asymptomatic carriers is crucial to prevent the spread of resistance, as carriage often serves as a reservoir that enables the transmission of resistant strains to vulnerable populations. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to restore gut microbiome balance and eliminate CRE colonization. However, the mechanisms driving successful decolonization warrant further research. This study investigates the impact of FMT on gut microbiome composition, CRE-KP clearance and host response, in a mouse model of CRE-KP carriage. Mice colonized with CRE-KP, were treated with FMT or left untreated. Shotgun metagenomics of fecal samples were used to monitor changes in microbiome composition and function. FMT resulted in substantial changes in the gut microbiome, with successful clearance correlating with an expansion of commensal bacteria including Bifidobacterium and Lactobacillus species. Notably, a reduction in K. pneumoniae was also observed in some untreated control mice as the microbiome recovered naturally, also associated with Bifidobacterium expansion. Phage profiling revealed distinct viral populations that were associated with successful decolonization. Flow cytometry was employed to quantify bacterial populations bound by immunoglobulins, providing insight into host immune modulation. These findings suggest potential mechanisms for CRE carriage eradication using microbiome targeted therapies. The results emphasize the importance of microbiome resilience in combating antibiotic-resistant infections and suggest that phage-microbiome interactions could play a role in restoring microbial balance.}, }
@article {pmid42445250, year = {2026}, author = {Wang, Y and Zheng, Z and Zhang, M and Zhao, J and Xu, Q and Wei, W and Wang, J and Ding, N}, title = {The potential role of lily polysaccharide in mitigating radiation-induced pneumonitis via the gut-lung axis: a comprehensive review.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1863108}, pmid = {42445250}, issn = {1663-9812}, abstract = {Radiation-induced pneumonitis (RIP) is a common and severe complication of thoracic irradiation, for which effective clinical treatments remain limited. Lily polysaccharide (LP), a natural polysaccharide derived from Lilium bulbs, exhibits various biological activities, including anti-inflammatory and tissue-protective effects. However, following oral administration, LP is poorly absorbed from the gastrointestinal tract and thus cannot directly target the lungs. Drawing on the gut-lung axis (GLA) theory, we hypothesize that oral LP may alleviate RIP by remotely inhibiting abnormal activation of the pulmonary cGAS-STING-NLRP3 signaling axis through modulation of the gut microbiota (GM) and its metabolites. Nevertheless, current evidence supporting this hypothesis remains largely indirect. Whether LP metabolites directly inhibit the pulmonary cGAS-STING-NLRP3 pathway, and whether such inhibition is causally linked to changes in the GM, require validation in RIP models. Therefore, this paper systematically reviews the molecular mechanisms underlying RIP, the multi-target pharmacological activities of LP, and the cross-organ regulatory network of the GLA. It also identifies key gaps in current research and provides a theoretical framework for future in-depth investigations, including fecal microbiota transplantation, germ-free animal models, structure-activity relationship analyses, and clinical safety assessments.}, }
@article {pmid42445500, year = {2026}, author = {Yang, W and Liu, Y and Wang, H and Yang, G}, title = {Long-term endurance exercise influences exercise capacity in mice through modulation of the intestinal microbiota by fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1830033}, pmid = {42445500}, issn = {1664-302X}, abstract = {BACKGROUND: Exercise alters intestinal microbiota composition; however, it remains unclear whether these alterations induced by long-term endurance exercise can be transferred by fecal microbiota transplantation (FMT) to improve recipient exercise capacity.<br><br>METHODS: Mice were divided into control (Group C), exercise (Group E), PBS transplantation (Group PT), and FMT (Group MT) groups. Group E underwent 14&#x202f;weeks of treadmill training, and Groups PT and MT were transplanted with PBS or fecal microbiota from Group E, respectively. Subsequently, exhaustive exercise tests and 16S rRNA sequencing were performed, and blood glucose levels, glycogen reserves, and antioxidant indices were assessed.<br><br>RESULTS: Compared with Group C, Group E had significantly higher hepatic/muscle glycogen levels and superoxide dismutase activity, and lower liver malondialdehyde content. After transplantation, Group MT showed significantly higher Firmicutes abundance, alpha diversity (Shannon and Simpson indices), and enrichment of eight beneficial genera (e.g., Bifidobacterium, Dorea) than Group PT, along with lower abundance of two harmful/conditional genera (e.g., Sutterella, Parabacteroides). Forty Kyoto Encyclopedia of Genes and Genomes metabolic pathways (e.g., starch and sucrose metabolism, flavone and flavonol biosynthesis) differed significantly between the PT and MT groups. The exhaustive exercise capacity of Group MT was significantly higher than that of Group PT (p&#x202f;<&#x202f;0.05) but lower than that of Group E (p&#x202f;<&#x202f;0.01). Correlation analysis showed that Sutterella abundance was negatively correlated with exercise capacity (r&#x202f;=&#x202f;-0.42, p&#x202f;<&#x202f;0.05), whereas Dorea abundance was positively correlated (r&#x202f;=&#x202f;0.48, p&#x202f;<&#x202f;0.05).<br><br>CONCLUSION: Exercise-induced increases in glycogen reserves and antioxidant capacity, associated with altered intestinal microbiota composition, can be partially transferred to recipient mice via FMT. The gut microbiota acts as a partial mediator of improvements in exercise capacity, rather than the sole driver.}, }
@article {pmid42448219, year = {2026}, author = {Chai, R and Liu, J and Hu, L and Zheng, P}, title = {Multidimensional Regulatory Mechanisms and Targeted Intervention Strategies of the Gut-Joint Axis in Metabolic Osteoarthritis.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2026.07.003}, pmid = {42448219}, issn = {1878-1810}, abstract = {Osteoarthritis (OA) is increasingly recognized as a heterogeneous disease driven not only by mechanical overload but also by systemic metabolic and inflammatory disturbances, among which metabolic osteoarthritis (Met OA) represents a distinct and highly prevalent subtype. Met OA is closely associated with obesity, insulin resistance, and metabolic syndrome, yet the underlying molecular and immunometabolic mechanisms remain incompletely defined. Emerging evidence supports a pivotal role of the gut-joint axis, whereby gut microbiota (GM) dysbiosis and its metabolites reshape intestinal barrier integrity, systemic immune-inflammatory status, and joint microenvironment homeostasis. In this review, we focus specifically on Met OA as a unique OA subtype and systematically dissect how the gut-joint axis orchestrates disease onset and progression through four interrelated dimensions: metabolic stress, inflammatory stress, immune stress, and oxidative stress. We highlight key GM-derived metabolic pathways-including short-chain fatty acids, tryptophan metabolites, and bile acids/FXR-TGR5-GLP‑1 signaling-as central hubs linking metabolic imbalance to cartilage degeneration and subchondral bone remodeling. On this mechanistic basis, we further summarize current and emerging gut-targeted and immunometabolic interventions, such as dietary modulation, probiotics and prebiotics, fecal microbiota transplantation, and repurposed metabolic drugs. By integrating Met OA subtype concept with a four‑axis stress framework and gut‑directed therapeutic strategies, this review proposes a multidimensional model of the gut-joint axis in Met OA. This model provides a rationale for refined phenotypic classification, biomarker discovery, and the development of precision, gut‑centered interventions for patients with metabolic osteoarthritis.}, }
@article {pmid42448682, year = {2026}, author = {Shi, Y and Sun, J and Chen, L and Xu, S and Guo, S and Xu, A and Ye, Q and Wang, Y and Xu, P}, title = {Black tea ethanol soluble fraction restores intestinal homeostasis by modulating PI3K/AKT signaling and gut microbiota.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00999-x}, pmid = {42448682}, issn = {2396-8370}, support = {32302603//the National Natural Science Foundation of China/ ; B231220.0005-26//Hangzhou Chengxi Sci-tech Innovation Corridor Funds/ ; 2501083737//Ministry of Education Industry-University Cooperative Education Program/ ; }, abstract = {While black tea's oxidized polyphenols hold potential for gut health, the specific protective mechanisms of its ethanol-soluble fraction (BES), particularly regarding host-microbiota interactions, remain poorly defined. This study elucidated the dual mechanisms through which BES ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. By integrating network pharmacology, molecular docking/dynamics simulations, RT-qPCR, and Western blot analysis, we identified the PI3K/AKT signaling axis as a potential host target. Our findings suggest that key flavonoid constituents stably bind to critical nodes, potentially downregulating the expression and activation of pathway components. Concurrently, 16S rRNA sequencing and metabolomics revealed that BES reshaped gut microbiota by suppressing Akkermansia and enriching SCFA producers such as Lactobacillus, restoring fecal SCFA levels. Fecal microbiota transplantation confirmed that BES-modulated microbiota alone transferred protection. Thus, BES acts concertedly through direct PI3K/AKT inhibition and indirect microbiota-SCFA modulation, providing a mechanistic basis for targeted use of black tea fractions in intestinal inflammation.}, }
@article {pmid42448689, year = {2026}, author = {Guo, Z and Zhao, M and Wu, Y and Zhang, P and Li, S}, title = {Microbiota-dependent biotransformation of apiin drives butyrate-associated protection against colitis.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00992-4}, pmid = {42448689}, issn = {2396-8370}, support = {32201393//National Natural Science Foundation of China/ ; }, abstract = {Dietary glycosides represent an important class of microbiota-responsive food components with potential benefits for intestinal health, yet their biotransformation and functional mechanisms remain incompletely understood. Here, we investigated the protective effects of apiin (apigenin-7-O-apiosylglucoside), a naturally occurring flavone glycoside abundant in plant-based foods, against dextran sulfate sodium (DSS)-induced colitis. We demonstrate that apiin is resistant to host digestion but undergoes efficient microbial deglycosylation in the distal intestine, yielding the bioactive aglycone apigenin. Apiin administration was associated with alleviation of colitis severity, as evidenced by improved clinical and histopathological outcomes, reduced pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6), and restoration of intestinal barrier integrity. Integrative multi-omics analyses revealed that apiin reshaped gut microbiota composition and function, leading to enhanced production of the short-chain fatty acid butyrate. This metabolic shift was associated with G protein-coupled receptors (GPR41 and GPR43) and PPARγ signaling, as well as NF-κB-driven inflammatory responses. Importantly, fecal microbiota transplantation recapitulated the protective effects of apiin, confirming a microbiota-dependent mechanism. Collectively, our findings identify apiin as a microbiota-dependent pro-flavonoid whose colonic biotransformation into apigenin and butyrate-associated signaling may contribute to its anti-inflammatory activity.}, }
@article {pmid42448934, year = {2026}, author = {Arora, K and Chowdhary, R and Shenoy, A and Kapadia, C and Paras, F and Vora, N and Arora, A and Chowdhary, R and Arora, A and Goyal, M and Matt-Amaral, L}, title = {Acute myeloid leukemia and gut microbiome: bidirectional effects and opportunities for intervention.}, journal = {Annals of hematology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00277-026-07176-w}, pmid = {42448934}, issn = {1432-0584}, abstract = {Acute myeloid leukaemia (AML) is characterized by substantial treatment-related morbidity that is not fully explained by cytogenetic or molecular risk stratification alone. Emerging evidence implicates the gut microbiome as a critical, modifiable determinant of AML pathogenesis, therapeutic response, and treatment-related complications. Patients with AML exhibit profound gut microbiome disruption at diagnosis, marked by reduced microbial diversity and depletion of short-chain fatty acid-producing commensals, which is further exacerbated by intensive chemotherapy, antibiotic exposure, and hematopoietic stem cell transplantation (HSCT). These perturbations impair intestinal barrier integrity, amplify systemic inflammation, and promote domination by opportunistic and multidrug-resistant organisms, thereby increasing the risks of mucositis, bloodstream infections, graft-versus-host disease, and mortality. Beyond complications, microbiome-derived metabolites modulate immune signalling, hematopoietic homeostasis, and inflammatory pathways relevant to clonal haematopoiesis and leukemogenesis, suggesting bidirectional interactions between the microbiome and AML biology. Observational and translational studies demonstrate that preserved microbial diversity and enrichment of specific taxa are associated with improved survival following HSCT, while dysbiosis correlates with inferior outcomes. Interventions aimed at microbiome preservation and restoration-including antibiotic stewardship, dietary modulation, autologous or donor fecal microbiota transplantation, and emerging postbiotic strategies-have shown feasibility and biologic efficacy, although definitive clinical benefit remains to be established. This review synthesizes current mechanistic, clinical, and translational evidence linking gut microbiome dysregulation with AML outcomes, highlights emerging therapeutic strategies, and outlines key challenges and future directions. Integrating microbiome-focused supportive care into AML management represents a promising avenue to reduce treatment toxicity and improve patient outcomes.}, }
@article {pmid42437603, year = {2026}, author = {Yu, P and He, J and Chen, Y and Zhu, Y}, title = {Circadian Disruption Promotes Epileptic Seizures via the Ruminococcus gnavus-Arginine-NOX4-Ferroptosis Axis.}, journal = {Brain research bulletin}, volume = {}, number = {}, pages = {112037}, doi = {10.1016/j.brainresbull.2026.112037}, pmid = {42437603}, issn = {1873-2747}, abstract = {Circadian rhythm disruption (CRD) exacerbates epileptic seizures, yet the underlying molecular mechanisms remain unclear. Using a pentylenetetrazol (PTZ) kindling rat model combined with continuous light exposure, we found that CRD significantly shortened seizure latency and increased seizure frequency. 16S rRNA sequencing revealed that CRD substantially increased the abundance of Ruminococcus gnavus (R. gnavus) in the gut microbiota. Antibiotic-mediated microbiota depletion, fecal microbiota transplantation (FMT), and R. gnavus monocolonization experiments confirmed that R. gnavus enrichment is a critical factor driving seizure aggravation. Metabolomic analysis demonstrated that elevated R. gnavus suppressed the expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis in the kidney, leading to impaired L-citrulline-to-L-arginine conversion and consequently decreased L-arginine levels in serum and hippocampal tissues. Arginine deficiency subsequently activated NADPH oxidase 4 (NOX4) upregulation in the hippocampus, triggering enhanced oxidative stress (elevated malondialdehyde (MDA) and reduced superoxide dismutase (SOD) activity), which ultimately induced ferroptosis (characterized by mitochondrial cristae reduction, acyl-CoA synthetase long-chain family member 4 (ACSL4) upregulation, and glutathione peroxidase 4 (GPX4) downregulation). Pharmacological intervention with the NOX4-specific inhibitor GLX351322 ameliorated oxidative stress, suppressed ferroptosis, and alleviated seizure severity. Importantly, L-arginine supplementation significantly prolonged seizure latency and reduced seizure frequency by reversing ferroptosis activation through downregulating NOX4-ACSL4 expression and upregulating GPX4 expression. This study unveils a complete signaling axis whereby CRD promotes epileptic seizures through the R. gnavus-ASS1-arginine-NOX4-ferroptosis cascade, providing novel therapeutic targets for clinical intervention.}, }
@article {pmid42439335, year = {2026}, author = {Singh, S and Singh, S and Khandelwal, V and Bharti, U and Singh, PK}, title = {Gut Microbiota in Neuroinflammation, Neurodegenerative Disorders, and Neuropsychiatric Disorders: A Comprehensive Narrative Review.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273455874260702045636}, pmid = {42439335}, issn = {1996-3181}, abstract = {Neurodegenerative and neuropsychiatric illnesses are characterized by neuroinflammation, which is driven by microglial activation, cytokine production, and breakdown of the blood-brain barrier (BBB). It is currently known that the gut microbiota plays an important role in modulating neuroimmune signaling, which in turn may trigger anxiety-like behaviors and depressive phenotypes through the microbiota-gut-brain axis. This review aims to integrate the most recent mechanistic knowledge on treatment strategies targeting the gut microbiota to modulate neuroinflammation. This review article discusses preclinical and clinical studies that investigated microbial composition, metabolite profiles, and host-microbe interactions involved in neuroinflammatory processes. However, special attention was given to signaling via the vagus nerves and bile acids, as well as to tryptophankynurenine metabolism and short-chain fatty acids (SCFAs). To examine the potential connection between the two, researchers used animal models such as germ-free animals and antibiotic-injected mice for fecal microbiota transplantation (FMT). This article defines dysbiosis as amplifying neuroinflammatory responses by altering microglial phenotypes, disrupting the blood-brain barrier, and triggering the production of pro-inflammatory cytokines. In contrast, microbiome diversity rehabilitation through the use of probiotics, prebiotics, synbiotics, and dietary modifications reduces neuroinflammatory markers and enhances cognitive and behavioral status. Clinical trials have shown considerable promise in diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), and depression. However, variability in treatment protocols, treatment resistance, and host-specific factors continue to pose significant challenges. This narrative review integrates mechanistic insights into microglial activation, cytokine signaling, blood-brain barrier regulation, vagal pathways, tryptophan metabolism, and short-chain fatty acids with emerging clinical evidence and therapeutic strategies, including probiotics, prebiotics, dietary modulation, and personalized microbiome-based interventions. Despite promising therapeutic potential, microbiome engineering faces important challenges, including safety concerns, lack of standardized intervention protocols, and substantial inter-individual variability in host-microbiome responses, which currently limit clinical translation. This review focuses on both neurodegenerative and neuropsychiatric disorders, examining shared neuroinflammatory mechanisms mediated by the gut-brain axis and evaluating microbiotatargeted therapeutic strategies across these disease categories. The review discusses both preventive strategies, including dietary modulation, prebiotics, and lifestyle-based microbiome interventions, as well as therapeutic approaches such as microbiota-targeted treatments aimed at mitigating neuroinflammation and disease progression.}, }
@article {pmid42439648, year = {2026}, author = {Parodi, E and Castello, LM and Bottino, P and Gotta, F and Novi, M and Orsello, M and Rocchetti, A and Prenna, S and Cantaluppi, V and Quaglia, M}, title = {Gut Microbiota Dysbiosis Is a Key Driver of Inflammaging in Chronic Kidney Disease.}, journal = {Cells}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/cells15131171}, pmid = {42439648}, issn = {2073-4409}, mesh = {Humans ; *Dysbiosis/microbiology/complications ; *Renal Insufficiency, Chronic/microbiology ; *Gastrointestinal Microbiome ; Animals ; *Inflammation/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The role of gut microbiota and intestinal dysbiosis in promoting inflammaging in chronic kidney disease (CKD) has been the focus of intense research over the last years. Some alterations at the phyla level, such as abundance of Proteobacteria and reduction in Firmicutes/Bacteroidites (F/B) ratio and saccarolytic populations, have been consistently reported in CKD. Other mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (unbalance between T reg and Th17 subsets), and epigenetic interactions. Alterations of metabolic pathways and of bacterial metabolites, such as butyrate and other short chain fatty acids (SCFA), also appear to play a key role in modulating progression of CKD. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, synbiotics, postbiotics and fecal microbiota transplantation (FMT). Modulation of microbiota could correct critical alterations, such as F/B ratio and T reg/Th17 unbalance, blunting inflammaging and potentially reducing progression of CKD and cardiovascular disease. Despite current limitations, gut microbiota is emerging as a powerful environmental factor which could be harnessed to interfere with key mechanisms leading to inflammaging in CKD.}, }
@article {pmid42440795, year = {2026}, author = {Shi, C and Gao, Y and Zhang, L and Chen, C and Su, L and Ren, K and Liu, Z and Liu, J}, title = {Gut-heart axis at high altitude: a dynamic mediator from hypoxic dysbiosis to adaptive cardioprotection.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1861538}, doi = {10.3389/fmicb.2026.1861538}, pmid = {42440795}, issn = {1664-302X}, abstract = {High-altitude hypoxia severely disrupts physiological homeostasis and markedly increases cardiovascular disease (CVD) risk through mechanisms that remain incompletely understood. Emerging evidence regards the gut microbiota as a crucial dynamic regulator within the gut-heart axis, constructing a bridge between the environmental hypoxic stress and the cardiovascular outcomes. This review has summarized the dynamic changes of the gut microbiota in high-altitude environments, from acute dysregulation to adaptive remodeling. We systematically delineate the pathogenic mechanisms whereby acute microbial imbalance drives CVD: at the metabolic level, there is a reduction in the production of short-chain fatty acids (SCFAs), accumulation of trimethylamine N-oxide (TMAO), buildup of hypoxia-induced energy metabolism intermediates (lactic acid and succinic acid), and dysregulation of secondary bile acid metabolism. At the immune inflammatory level, impaired intestinal barrier leads to lipopolysaccharide (LPS) translocation, combined with hypoxia-inducible factor-1α (HIF-1α) overexpression, collectively promoting the development of atherosclerosis, hypertension, and heart failure. The adaptive remodeling reduces vascular injury by enhancing myocardial energy metabolism mediated by SCFA, strengthening the intestinal barrier, regulating anti-inflammatory immunity, stabilizing blood pressure, and also reprogramming uric acid metabolism, thereby playing a role in cardiac protection. Finally, we propose microbiome-targeted intervention strategies, including high-fiber dietary modulation, probiotic/prebiotic/synbiotic supplementation, fecal microbiota transplantation, and metabolite-directed therapies, which provides new theoretical basis and precise therapeutic targets for the prevention of cardiovascular diseases in high-altitude environments.}, }
@article {pmid42441072, year = {2026}, author = {Sun, Y and Zhang, X and Fan, Y and Liu, Y and Yang, D and Chen, X and Li, L}, title = {A chicken-origin Ligilactobacillus agilis R22 exerts probiotic features including growth-promotion and anti-Salmonella infection.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1862425}, doi = {10.3389/fmicb.2026.1862425}, pmid = {42441072}, issn = {1664-302X}, abstract = {INTRODUCTION: In the quest for the development of antibiotic alternatives, this study aimed to systematically evaluate the probiotic potential and mechanism of action of Ligilactobacillus agilis R22, a novel strain isolated from chickens.<br><br>METHODS: The in vitro probiotic properties of L. agilis R22, including growth ability, gastrointestinal tolerance, and antimicrobial activity, were initially assessed. Genomic and untargeted metabolomic analyses were conducted to explore its genetic and metabolic profiles. For in vivo evaluation, dietary supplementation of R22 was performed in broilers to assess growth performance, gut morphology, microbiota, and metabolites. Furthermore, a Salmonella enterica serovar Pullorum infection model in chicks and a fecal microbiota transplantation (FMT) experiment in mice were established to investigate its protective efficacy and underlying mechanisms.<br><br>RESULTS: L. agilis R22 exhibited robust growth, high tolerance to simulated gastrointestinal environments, and significant antimicrobial activity. Omics analyses revealed multiple probiotic-associated genes, an absence of virulence genes, and the capacity to synthesize essential nutrients for the host. In broilers, R22 supplementation significantly improved growth performance, intestinal morphology, and increased the levels of ghrelin and insulin-like growth factor-1. While the overall gut microbiota structure was not significantly altered, beneficial species and specific intestinal metabolites were enriched. In the S. Pullorum infection model, R22 effectively inhibited pathogen colonization in the gut and systemic dissemination to other organs, significantly mitigating pathological changes. Additionally, the FMT mouse model provided evidence that the in vivo protective effects of R22 are mediated by the gut microbiota it remodels.<br><br>DISCUSSION: The affected intestinal metabolites and the remodeled gut microbiota collectively contribute to the in vivo beneficial effects of L. agilis R22. Taken together, L. agilis R22 is a promising probiotic candidate that can be utilized in microbial feed additives.}, }
@article {pmid42442433, year = {2026}, author = {Huang, K and Lu, J and Yu, Y and Xu, X and Wen, H and Wang, C and Xie, H and Sun, X and Tan, M and Han, L}, title = {Ferroptotic Vulnerability Drives Cardiac Fibrosis and Diastolic Dysfunction in Diabetic HFpEF via a Gut-Associated Proline-PPARγ Axis.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2026.07.020}, pmid = {42442433}, issn = {1873-4596}, abstract = {BACKGROUND: Diabetic heart failure with preserved ejection fraction (HFpEF) is a metabolically driven syndrome characterized by diastolic dysfunction and progressive myocardial fibrosis, yet the cellular mechanisms linking metabolic stress to fibroblast maladaptation remain poorly defined.<br><br>RESULTS: Using a high-fat diet combined with low-dose streptozotocin (HFD+STZ)-induced diabetic HFpEF mouse model, we observed significant hyperglycemia, insulin resistance, preserved ejection fraction, and marked diastolic dysfunction accompanied by severe myocardial fibrosis. Notably, diabetic HFpEF mice exhibited gut microbiota remodeling characterized by enrichment of Akkermansia muciniphila and elevated circulating L-proline levels. Broad-spectrum microbiota depletion alleviated cardiac fibrosis and diastolic impairment, whereas fecal microbiota transplantation from diabetic HFpEF donors recapitulated the pathological phenotype. Mechanistically, L-proline supplementation aggravated cardiac remodeling and induced ferroptotic cell death in cardiac fibroblasts, as indicated by decreased GPX4 and SLC7A11 and increased ACSL4 and TFR1 expression. Single-cell transcriptomic analysis revealed that proline-associated metabolic reprogramming preceded ferroptosis activation along the fibroblast trajectory under diabetic stress. Importantly, pharmacological inhibition of ferroptosis or fibroblast-specific activation of PPAR&#x3b3; signaling markedly attenuated myocardial fibrosis and improved diastolic function in diabetic HFpEF mice. Consistently, patients with diabetic HFpEF displayed increased A. muciniphila abundance and elevated serum L-proline levels, supporting translational relevance.<br><br>CONCLUSIONS: Our findings identify cardiac fibroblast ferroptotic vulnerability as a key pathogenic mechanism in diabetic HFpEF and uncover a gut microbiota-associated proline-PPAR&#x3b3;-ferroptosis axis that drives myocardial fibrosis and diastolic dysfunction under diabetic metabolic stress. These results highlight a metabolically driven fibroblast-centered mechanism and provide potential therapeutic targets for diabetic HFpEF.}, }
@article {pmid42436017, year = {2026}, author = {Wang, Q and Zhong, W and Huang, H and Yang, X and Liu, X and Ren, Y and He, F and Li, J}, title = {Harnessing microbial modulators to mitigate antibiotic-induced gut dysbiosis: from phytochemicals to faecal microbiota transplantation.}, journal = {Beneficial microbes}, volume = {}, number = {}, pages = {1-28}, doi = {10.1163/18762891-bja00123}, pmid = {42436017}, issn = {1876-2891}, abstract = {Antibiotics remain indispensable for the management of infectious diseases; however, their use inevitably perturbs the gut microbiota. Advances in metagenomics and multiomics approaches have demonstrated that antibiotic exposure profoundly disrupts microbial diversity and community structure, leading to the depletion of key commensals, the expansion of opportunistic pathogens, metabolic dysfunction, and the emergence of antimicrobial resistance. These alterations are increasingly associated with a broad spectrum of dysbiosis-related diseases (DRDs), encompassing metabolic, neuropsychiatric, and immune-mediated disorders. To mitigate or reverse antibiotic-induced microbial imbalances, various microbiota-targeted interventions have emerged as promising alternatives or complementary approaches. These include dietary phytochemicals (such as polyphenols, alkaloids, and organosulfur compounds), probiotics, prebiotics, synbiotics, postbiotics, bacteriophage therapy, and faecal microbiota transplantation (FMT). Evidence from in vitro and animal studies has provided mechanistic insights into how these interventions modulate microbial composition and function; however, clinical evidence varies across intervention type. This review summarizes the composition and functional roles of the gut microbiota, outlines the consequences of antibiotic exposure, and provides an overview of the underlying mechanisms, recent evidence, and potential applications of microbiota-targeted interventions in preserving intestinal homeostasis. This review aims to provide a theoretical basis and reference framework for the development of safer and more effective alternatives or adjuncts to antibiotic therapy.}, }
@article {pmid42430127, year = {2026}, author = {Du, Z and Yao, H and Xi, C and Yuan, Q and Fu, P and Hu, J and Wu, G and Yang, W}, title = {Oral Lysozyme Attenuates Neuroinflammation and Brain Injury After Traumatic Brain Injury Through Gut Microbiota-Dependent Reprogramming of Tryptophan Metabolism.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {32}, number = {7}, pages = {e71025}, pmid = {42430127}, issn = {1755-5949}, support = {82401618//National Natural Science Foundation of China/ ; 82471407//National Natural Science Foundation of China/ ; 82171382//National Natural Science Foundation of China/ ; 2021QD026//Research Foundation of Huashan Hospital, Affiliated to Fudan University/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; *Muramidase/administration &amp; dosage ; *Brain Injuries, Traumatic/metabolism/drug therapy ; Male ; Administration, Oral ; *Gastrointestinal Microbiome/drug effects/physiology ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Mice ; Humans ; Mice, Inbred C57BL ; *Neuroprotective Agents/administration &amp; dosage ; }, abstract = {AIMS: Traumatic brain injury (TBI) induces secondary neuroinflammation and gut dysbiosis. This study investigated whether oral lysozyme confers neuroprotection after TBI through gut microbiota-dependent metabolic reprogramming of tryptophan metabolism.<br><br>METHODS: In a severe TBI mouse model, neurological function, neuroinflammation, intestinal barrier integrity, and systemic immune homeostasis were assessed following oral lysozyme administration. Fecal untargeted metabolomics, antibiotic-mediated microbiota depletion, and fecal microbiota transplantation (FMT) were used to explore microbiota involvement. Cerebrospinal fluid (CSF) from 10 matched pairs of patients with severe TBI was analyzed for tryptophan pathway metabolites by liquid chromatography-mass spectrometry.<br><br>RESULTS: Lysozyme improved neurological outcomes, attenuated neuronal apoptosis and neuroinflammation, and restored peripheral CD4[+]/CD8[+] T cell homeostasis. Metabolomics revealed enrichment of fecal tryptophan metabolites (indole-3-carboxaldehyde, indolelactic acid, kynurenic acid [KYNA]) and a shift in cerebral kynurenine metabolism toward the KYNA branch. These associations were abolished by microbiota depletion and reproduced by FMT. Favorable clinical outcomes were associated with higher CSF KYNA and an elevated KYNA/QA ratio.<br><br>CONCLUSIONS: Oral lysozyme was associated with attenuated TBI-induced neuroinflammation and brain injury, potentially through gut microbiota-dependent tryptophan metabolism reprogramming. Concordance between preclinical and clinical metabolomic data supports lysozyme as a candidate microbiota-targeted therapeutic strategy. The KYNA/QA ratio warrants further validation as a prognostic indicator in larger, longitudinal cohorts.}, }
@article {pmid42431475, year = {2026}, author = {Liu, S and Chen, Q and Bai, Y and Li, X}, title = {Harnessing the Microbiome for Head and Neck Cancer Therapy: From Mechanistic Insights to Translational Opportunities.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {105484}, doi = {10.1016/j.critrevonc.2026.105484}, pmid = {42431475}, issn = {1879-0461}, abstract = {The human microbiome, particularly the diverse microbial communities in the oral cavity and gut, plays a critical role in the pathogenesis, progression, and treatment response of head and neck squamous cell carcinoma (HNSCC). Emerging evidence indicates that specific microbial communities can bidirectionally modulate cancer therapeutic modalities. Moreover, interventions such as probiotics, prebiotics, and fecal microbiome transplantation have the potential to improve treatment efficacy and alleviate adverse effects. This review outlines the mechanisms underlying oral and gut microbiota in HNSCC development and progression, focusing on their bidirectional regulation of efficacy and toxicity across standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. We emphasize that microbial signatures not only serve as predictive biomarkers and therapeutic targets but also constitute a fundamental component of personalized oncology in HNSCC, providing a comprehensive framework for integrating microbiota-based strategies into clinical practice.}, }
@article {pmid42431711, year = {2026}, author = {Mao, G and Lan, H}, title = {Concomitant medication reporting should accompany fecal microbiota transplantation plus anti-PD-1 therapy in gastric cancer.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {7}, pages = {}, doi = {10.1136/jitc-2026-015908}, pmid = {42431711}, issn = {2051-1426}, mesh = {Humans ; *Stomach Neoplasms/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Combined Modality Therapy ; }, abstract = {This commentary discusses the phase I study of fecal microbiota transplantation plus anti-programmed cell death protein 1 therapy in refractory microsatellite-stable gastric cancer. We suggest that this strategy should be treated as a pharmacomicrobiomic intervention rather than only as an immunotherapy combination. Evidence from fecal microbiota transplantation trials and microbiome immunotherapy studies indicates that antibiotics, proton pump inhibitors, corticosteroids and other microbiome-modifying exposures may affect donor strain engraftment, immune activation, response assessment and safety. In China and other Asian settings, where acid suppression, Helicobacter pylori history, perioperative antibiotic use and nutritional interventions are common, standardized concomitant medication reporting would make future studies more interpretable and transferable.}, }
@article {pmid42432504, year = {2026}, author = {Wang, L and Liu, Z and Fan, F and Zhang, L and Li, J}, title = {Impact of fecal microbiota transplantation on lipid parameters in patients with metabolic syndrome: a meta-analysis.}, journal = {BMC gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12876-026-05037-4}, pmid = {42432504}, issn = {1471-230X}, support = {2023IR35//National High Level Hospital Clinical Research Funding (Interdepartmental Research Project of Peking University First Hospital)/ ; 2021YFC2500600/2021YFC2500601//National Key Research and Development Program of China/ ; National High Level Hospital Clinical Research Funding//State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University/ ; }, abstract = {BACKGROUND: Metabolic syndrome (MetS) is a global health challenge, with impaired lipid metabolism as a key feature. While fecal microbiota transplantation (FMT) shows promise as a MetS therapy, existing meta-analyses have reported conflicting results and focused mainly on glycemic parameters, leaving its impact on lipid metabolism largely unexplored. This meta-analysis systematically assessed the influence of allogenic FMT on lipid parameters in patients with MetS, unraveling its potential as an innovative therapeutic modality for this population.<br><br>METHODS: A meta-analysis was performed to explore the impact of allogenic FMT on lipid parameters (triglycerides, total cholesterol [TCHO], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) in patients with MetS. Terms regarding FMT and MetS were searched in PubMed/Medline, EMBASE, Web of Science, the Cochrane Library, and Scopus from the inception of the databases until 31 August 2023.<br><br>RESULTS: Nine randomized controlled trials (RCTs) were included and subgroup analyses according to follow-up durations were performed. This study was registered in PROSPERO (ID CRD42023389890). A total of 248 patients were included. Patients undergoing allogenic FMT manifested significantly lower TG level compared with control group (receiving placebo or autologous FMT, pooled MD -0.15 [95% CI: -0.29, -0.01]), as well as higher HDL-C level (MD 0.07 [95% CI: 0.02, 0.12]). Subgroup analysis confirmed that these effects were significant at 4 to 6 weeks post-FMT (TG: MD -0.16, 95% CI: -0.32, -0.01; HDL-C: MD 0.08, 95% CI: 0.02, 0.15). No significant difference was observed between allogenic FMT and control group concerning TCHO and LDL-C levels regardless of lengths of follow-up. In subgroup analysis, the results regarding TG and HDL-C remained consistent in the subgroup with 4 to 6 weeks of follow-up.<br><br>CONCLUSIONS: An overall reduction in TG level and elevation in HDL-C level was observed in patients with MetS receiving allogenic FMT. A potential optimal timeframe for FMT efficacy manifestation might be 4 to 6 weeks after first administration.<br><br>TRIAL REGISTRATION: This study is registered in PROSPERO and is available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023389890.}, }
@article {pmid42433272, year = {2026}, author = {Valaei, A and Zahmatkesh, N and Aghaei, R and Maleki, M and Meskini, M and Siadat, SD}, title = {The role of the microbiota in hematological malignancies: A narrative review of mechanisms and therapeutic potential.}, journal = {New microbes and new infections}, volume = {72}, number = {}, pages = {101805}, pmid = {42433272}, issn = {2052-2975}, abstract = {The human microbiota, particularly the gut microbiome, plays a central role in maintaining immune homeostasis, regulating hematopoiesis, and modulating host metabolism through bioactive metabolites such as short-chain fatty acids (SCFAs), bile acids, and tryptophan-derived compounds. Disruption of this microbial ecosystem (dysbiosis) has emerged as a key contributor to the development and progression of hematological malignancies (HMs), including acute and chronic leukemias, lymphomas, and multiple myeloma. This narrative review synthesizes recent evidence (2022-2025) on the complex bidirectional interactions between the microbiota and HMs, highlighting their biological and clinical significance. Current evidence indicates that the microbiota influences hematological malignancies through multiple interconnected mechanisms, including immune regulation, inflammatory signaling, maintenance of hematopoietic homeostasis, and microbial metabolite-mediated modulation of the tumor microenvironment. Dysbiosis has been associated with disease progression, increased susceptibility to infections, impaired treatment tolerance, and inferior clinical outcomes. Conversely, chemotherapy, broad-spectrum antibiotics, and hematopoietic stem cell transplantation profoundly reshape microbial communities, further exacerbating dysbiosis and contributing to complications such as graft-versus-host disease following allogeneic transplantation. Emerging microbiota-targeted interventions, including dietary modulation, probiotics, prebiotics, and fecal microbiota transplantation, show promise for restoring microbial homeostasis and improving therapeutic outcomes. Furthermore, microbiome-derived biomarkers are increasingly being investigated for predicting treatment response, relapse risk, and immunotherapy efficacy. Despite these advances, important challenges remain, particularly in establishing causal relationships, standardizing microbiome profiling, and validating clinical applications through well-designed prospective and randomized studies. Overall, the accumulating evidence supports the microbiota as a critical determinant of hematological cancer biology and treatment response. Integrating microbiome-based diagnostics and therapeutic strategies into precision hematology may offer new opportunities to improve patient management and long-term clinical outcomes.}, }
@article {pmid42434323, year = {2026}, author = {Deshpande, A and Hohmann, EL and Burns, C and Tomeo, NJ and Allegretti, JR}, title = {Practice Variations in the Management of Clostridioides difficile Infection: Findings From a Survey of US Physicians.}, journal = {Gastro hep advances}, volume = {5}, number = {9}, pages = {101025}, pmid = {42434323}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: In 2021, the American College of Gastroenterology and Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America released guidelines for Clostridioides difficile infection (CDI) management, with conflicting recommendations. We surveyed US gastroenterologists (GIs), infectious disease (ID) specialists, and primary care physicians (PCPs) on their use of clinical guidelines and attitudes toward gut microbial therapies for CDI.<br><br>METHODS: We conducted an online survey of 302 physicians (n = 101 GIs, 101 IDs, 100 PCPs; February 24 to March 13, 2023). Included GIs and IDs saw a minimum of 3 to 4 patients and PCPs 1 to 2 patients with CDI per month.<br><br>RESULTS: Physicians working in hospital/academic settings were more familiar with CDI guidelines than those working in independent/group practices. Half of GIs used American College of Gastroenterology guidelines; 98% of IDs followed Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines. More PCPs reported that their institutions did not have set guidelines (40%). More GIs (51%) and IDs (74%) used the recommended multistep algorithm for CDI testing; PCPs were more likely to use a single diagnostic test (49%). GIs and IDs more often prescribed vancomycin taper (93% and 98%, respectively) and fidaxomicin (87% and 97%, respectively); PCPs were more likely to prescribe metronidazole (84%). Less than 10% of physicians felt very knowledgeable about donor-derived microbiome therapies. While 60% of GIs, 53% of IDs, and 50% of PCPs agreed donor-derived microbiome therapies are essential for CDI management, more than 50% cited the need for real-world evidence of safety and efficacy.<br><br>CONCLUSION: Education around CDI guidelines and standardized diagnostic and treatment algorithms are needed to ensure consistent CDI management.}, }
@article {pmid42434548, year = {2026}, author = {Li, H and Wang, X and Yin, L and Li, Y and Fan, S and Zhang, H and Zhang, W and Ou, H and Wang, J}, title = {Abdominal massage alleviates IBS-D by modulating the gut microbiota and suppressing the LPS/TLR4/NF-κB/MLCK pathway.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1730607}, pmid = {42434548}, issn = {1664-302X}, abstract = {BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disorder with complex and incompletely understood pathophysiology. This study aimed to investigate the therapeutic effects and underlying mechanisms of abdominal massage on diarrhea-predominant IBS-D using a rat model.<br><br>METHODS: IBS-D was induced in Sprague-Dawley rats through a combination of maternal separation and chronic stress. The experimental interventions consisted of abdominal massage and fecal microbiota transplantation (FMT) using donor microbiota obtained from IBS-D&#x202f;+&#x202f;abdominal massage rats. Assessments included fecal moisture content (FMC), Bristol stool scores, visceral hypersensitivity, intestinal motility, open field test, gut microbiota, short-chain fatty acids (SCFAs), inflammatory markers (LPS, TLR4/MyD88/NF-&#x3ba;B pathway), and intestinal barrier integrity (TEM, tight junction proteins, FITC-dextran permeability).<br><br>RESULTS: Abdominal massage significantly improved diarrheal symptoms, visceral hypersensitivity, gastrointestinal motility, and anxiety-like behaviors in IBS-D rats. It restored gut microbiota diversity, reduced SCFA levels, and suppressed the TLR4/MyD88/NF-&#x3ba;B pathway, leading to decreased pro-inflammatory cytokines and LPS levels. FMT replicated these effects, suggesting the role of gut microbiota modulation. Moreover, abdominal massage also ameliorated barrier dysfunction in IBS-D rats by restoring ultrastructure, modulating MLCK and junctional proteins, and reducing macromolecular permeability.<br><br>CONCLUSION: Abdominal massage alleviates IBS-D symptoms by modulating gut microbiota, inhibiting the TLR4/MyD88/NF-&#x3ba;B/MLCK signaling pathway, reducing inflammation, and restoring intestinal barrier function. These findings support its potential as a non-invasive therapeutic strategy for IBS-D.}, }
@article {pmid42434742, year = {2026}, author = {Shen, C and Lou, R and Bai, F and Zhang, Y and Xu, T and Huang, Z}, title = {Integrative oncology in colorectal cancer: evidence-based strategies from prevention through survivorship.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1860619}, pmid = {42434742}, issn = {2234-943X}, abstract = {Colorectal cancer (CRC) is a leading global malignancy, with approximately 1.9 million new cases and over 900,000 deaths recorded in 2022, yet evidence-based integrative oncology strategies remain inconsistently incorporated into routine care. This narrative review synthesizes current evidence across the full CRC care continuum, from primary prevention through long-term survivorship. High-fiber diets, Mediterranean dietary patterns, calcium supplementation, regular physical activity, healthy weight maintenance, and berberine each demonstrate reproducible CRC risk reduction in large prospective cohorts and multicenter randomized controlled trials. The CHALLENGE trial (NEJM 2025) provides the first randomized phase 3 evidence that structured exercise after adjuvant chemotherapy reduces disease recurrence (HR 0.72) and death (HR 0.63) in colon cancer. Aspirin chemoprevention requires individualized risk-benefit assessment per 2022 US Preventive Services Task Force guidelines; preliminary CaPP3 trial data (conference presentation, June 2025; not yet peer-reviewed) suggest non-inferiority of low-dose aspirin (75-100 mg/day) to 600 mg/day in Lynch syndrome, pending formal publication. Fusobacterium nucleatum promotes colorectal carcinogenesis through five mechanistically distinct pathways: FadA-mediated Wnt/β-catenin activation, Fap2- and CbpF-mediated immune evasion via TIGIT and CEACAM1, succinate-HIF-1α-EZH2-mediated immune suppression, Hippo pathway-mediated suppression of pyroptosis, and autophagy-induced chemoresistance. Perioperative multi-strain probiotics significantly reduce postoperative infectious complications, and fecal microbiota transplantation shows preliminary promise for sensitizing microsatellite-stable CRC to immunotherapy. The 2022-2024 SIO-ASCO and ASCO-SIO clinical practice guidelines endorse mindfulness-based interventions, yoga, and acupuncture for anxiety, depression, fatigue, and cancer-related pain. Systematic integration of these interventions into multidisciplinary CRC care requires standardized implementation frameworks, CRC-specific clinical trials for mind-body modalities, and bioavailability-optimized phytochemical formulations.}, }
@article {pmid42434798, year = {2026}, author = {Zhai, Z and Ma, S and Shang, S and Liang, X and Yin, S and Lin, H and Ding, R and Jiang, A and Zhang, R and Wu, M and Yu, J and Song, Q and Chen, D}, title = {The use of antibiotic, probiotic, and FMT in modulating Immunotherapy Efficacy and Survival: a systematic review and meta-analysis of clinical outcomes.}, journal = {The oncologist}, volume = {}, number = {}, pages = {}, doi = {10.1093/oncolo/oyag264}, pmid = {42434798}, issn = {1549-490X}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) have been one of the important therapeutic approaches for patients with advanced malignancies; nevertheless, their clinical efficacy remains limited in many patients. Recently, the contribution of intestinal microbiota to improved antitumor immune responses has gradually been recognized.<br><br>METHODS: A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library to identify relevant studies published up to June 15, 2026. We evaluated the influence of microbiota interventions with respect to efficacy and survival in cancer patients receiving ICIs from three perspectives: antibiotics, probiotics, as well as fecal microbiota transplantation (FMT). The main endpoint was objective response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS).<br><br>RESULTS: The final analysis comprised 106 studies and categorized them into three groups: antibiotics (76 studies), probiotics (15 studies), and FMT (15 studies). Antibiotic use was correlated with compromised immunotherapy efficacy and unfavorable survival outcomes. In particular, antibiotics exposure was linked to a reduced ORR (Odds Ratio, OR&#x2009;=&#x2009;0.60, 95% Confidence Interval, CI&#x2009;=&#x2009;0.46-0.77, p&#x2009;<&#x2009;0.001), shorter OS (Hazard Ratio, HR&#x2009;=&#x2009;1.56, 95% CI&#x2009;=&#x2009;1.44-1.69, p&#x2009;<&#x2009;0.001), and shorter PFS (HR&#x2009;=&#x2009;1.50, 95% CI&#x2009;=&#x2009;1.32-1.70, p&#x2009;<&#x2009;0.001). In contrast, probiotics showed a supportive and positive effect on immunotherapy outcomes, with improved ORR (OR&#x2009;=&#x2009;1.95, 95% CI&#x2009;=&#x2009;1.46- 2.62, p&#x2009;<&#x2009;0.001) and better OS (HR&#x2009;=&#x2009;0.56, 95% CI&#x2009;=&#x2009;0.41- 0.78, p&#x2009;<&#x2009;0.001) and PFS (HR&#x2009;=&#x2009;0.53, 95% CI&#x2009;=&#x2009;0.38-0.74, p&#x2009;<&#x2009;0.001). FMT combined with immunotherapy achieved a favorable ORR of 0.30 (95% CI&#x2009;=&#x2009;0.16-0.45, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This meta-analysis synthesized evidence from studies on antibiotics, probiotics, and FMT use, suggesting gut microbiota offering potential approaches to enhance immunotherapy treatment effectiveness and clinical efficacy in individuals with advanced-stage solid cancers.}, }
@article {pmid42435313, year = {2026}, author = {Hu, S and Zhang, X and Jiang, X and Du, L and Gao, X}, title = {Haematococcus pluvialis peptides ameliorated cyclophosphamide-induced immunodeficiency in mice by regulating intestinal barrier function.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.70884}, pmid = {42435313}, issn = {1097-0010}, support = {2024CXPT073//Key R&amp;D Program of Shandong Province/ ; 2024ZLYS02//Key R&amp;D Program of Shandong Province/ ; 2023KJ233//Outstanding Youth Innovation Team of Universities in Shandong Province/ ; WSJK2025MS203//Hainan Province Joint Project of Health and Medical Science and Technology Innovation/ ; }, abstract = {BACKGROUND: Immunodeficiency is a pathological state characterized by impaired functional integrity of the immune system, which contributes to the development of various diseases. Natural bioactive peptides are a promising option for improving immune function.<br><br>RESULTS: This study examined the therapeutic effects and underlying mechanisms of Haematococcus pluvialis peptides (HPP) against CTX-induced immunodeficiency in mice. The results demonstrated that HPP increased bodyweight, immune organ indices, and blood cell count - white blood cells (WBC), red blood cells (RBC), platelets (PLT), hemoglobin (HGB), lymphocytes (Lym), and granulocytes (Gran), as well as serum cytokine levels (interferon-gamma (IFN-&#x3b3;), interleukin-2 (IL-2), and immunoglobulin A (IgA) - in immunodeficient mice. Haematococcus pluvialis peptides improved the villus length and crypt depth of the small intestine and increased intestinal levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and secretory immunoglobulin A (SIgA). Colonic levels of tight junction proteins - zonula occludens-1 (ZO-1) and occludin - were up-regulated. Fecal microbiota analysis suggested that HPP promoted the enrichment of beneficial bacterial genera (Ligilactobacillus, norank_f_Muribaculaceae, Alistipes) and suppressed pathogenic bacteria (Escherichia-Shigella and Klebsiella). Gut microbial metabolites analysis showed that HPP altered various fecal metabolites involved in lipids and lipid-like molecules, organoheterocyclic compounds, phenylpropanoids and polyketides, as well as organic acids and their derivatives. Fecal microbiota transplantation (FMT) experiments also validated the decisive role of gut microbiota in the immunomodulatory function of HPP.<br><br>CONCLUSION: These results offer novel insights into the protective efficacy and underlying mechanisms of HPP for alleviating immunodeficiency, establishing a robust theoretical basis for its application as a promising immunomodulatory agent. &#xa9; 2026 Society of Chemical Industry.}, }
@article {pmid42116227, year = {2026}, author = {Hron, BM and Zhang, YJ and Golden, C and Chalmers, C and Nemec, G and Delaney, E and Ozcan, E and Kim, M and Jalali, L and Solari, T and Brezsny-Feldman, J and Alm, EJ and Bry, L and Rosen, R}, title = {Association between blenderized tube feeds and differential oropharynx, stomach, and stool microbiome signatures relative to conventional formula feeds in children fed via enteral tube: A cross-sectional study.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {50}, number = {5}, pages = {665-675}, doi = {10.1002/jpen.70097}, pmid = {42116227}, issn = {1941-2444}, support = {//Supported by National Institutes of Health R01 DK097112 (PI: Rosen) and K23 DK133679 (PI: Hron), NASPGHAN Astra- Zeneca Research Award (PI: Hron), NIH K12 5K12HD052896 (PI: Fleisher, awarded to Zhang); NASPGHAN Foundation/Reckitt/Mead Johnson Nutrition Young Investigator Development Award (PI: Zhang); AGA Research Scholar Award (PI: Zhang); Harvard Digestive Diseases Center Grants P30 DK034854 (NIH) and Massachusetts Life Sciences Center Capital Grant./ ; }, mesh = {Humans ; *Oropharynx/microbiology ; *Enteral Nutrition/methods ; Female ; Male ; *Stomach/microbiology ; Cross-Sectional Studies ; *Feces/microbiology ; Infant ; Child, Preschool ; Prospective Studies ; *Food, Formulated ; *Gastrointestinal Microbiome ; *Microbiota ; Gastroesophageal Reflux/prevention &amp; control ; Intubation, Gastrointestinal ; }, abstract = {BACKGROUND: Blenderized gastrostomy tube feeds are associated with reduced gastrointestinal symptoms. We hypothesize that patients receiving blenderized tube feeds, compared with standard formula, will have less gastric-oropharyngeal microbial overlap, a possible biomarker of less gastroesophageal refluxate, and differences in beta diversity in the oropharynx, stomach, and stool.<br><br>METHODS: Children requiring enteral tube feeds for >3 months were prospectively recruited to provide saliva via posterior tongue swabs, gastric aspirates, and stool samples. Exclusion criteria were history of cystic fibrosis or solid organ transplant or antibiotic treatment course within 4 weeks. The primary exposure was diet category (formula vs. blenderized feeds). The primary outcome was Jaccard similarity between the gastric and oral microbiomes. Relationships of diet to Jaccard and relative bacterial abundance were analyzed by multivariate linear regression models adjusting for age, sex and proton pump inhibitor use.<br><br>RESULTS: Sixty (60.6%) children received blenderized tube feeds and 39 (39.4%) received formula. Beta diversity in the oral and rectal samples differed significantly between patients on blenderized versus formula feeds. Importantly, gastric and tongue microbiomes had significantly less overlap (by Jaccard distance) in patients receiving blenderized feeds, adjusting for covariates. Several key oral, gastric and stool commensal organisms were present in higher relative abundance in the blenderized versus formula group.<br><br>CONCLUSION: Oropharyngeal microbiomes are more distinct from the gastric microbiomes in patients receiving blenderized feeds, and the oropharyngeal and stool microbiomes demonstrated differential bacterial abundance compared with formula. Overall, these findings suggest a highly favorable microbial profile with blenderized feeds.}, }
@article {pmid42424947, year = {2026}, author = {Zhang, B and Su, S and Lin, H and Zhu, M and Shao, G and Yao, R and Guan, W and Zhang, S}, title = {Brachyspira hyodysenteriae enriched by maternal deoxynivalenol exposure impairs lactation and offspring growth via the bacterial extracellular vesicle-mediated gut-mammary gland axis.}, journal = {Journal of hazardous materials}, volume = {514}, number = {}, pages = {142890}, doi = {10.1016/j.jhazmat.2026.142890}, pmid = {42424947}, issn = {1873-3336}, abstract = {Maternal exposure to deoxynivalenol (DON) disrupts gut homeostasis and impairs offspring health, but the mechanism linking DON to lactation dysfunction remains unclear. Here we show that DON impairs lactation performance in mice, as evidenced by reduced offspring growth, decreased milk fat and milk protein contents, and defective mammary gland function. DON also disrupts intestinal barrier integrity and reshapes the maternal gut microbiota, including enrichment of Brachyspira hyodysenteriae (B. hyodysenteriae), whose abundance is negatively associated with milk quality. Fecal microbiota transplantation (FMT) from DON-exposed dams reproduced the lactation phenotype in recipient mice. Extracellular vesicles (EVs) derived from DON-associated microbiota similarly transferred this defect. Among DON-enriched candidate bacteria, B. hyodysenteriae-derived EVs accumulated in mammary tissue, induced mammary inflammation and were sufficient to impair lactation performance in vivo. Mechanistically, B. hyodysenteriae-derived EVs acted through macrophages to suppress lactation-related programs in mammary epithelial cells. Pharmacological inhibition and genetic ablation experiments showed that NLRP3 and STING signaling contributed to this response, with EV-associated protein and DNA fractions preferentially linked to the NLRP3-IL-1β and STING-IFNB1 pathways, respectively. Together, these findings identify B. hyodysenteriae-derived EVs as microbial mediators of DON-induced gut-mammary communication and reveal a vesicle-dependent mechanism linking mycotoxin-induced dysbiosis to lactation dysfunction.}, }
@article {pmid42426884, year = {2026}, author = {Lei, Y and Xu, Y and Yan, Y and Zhang, J and Zhang, T and Huang, J and Huang, Y and Zhong, J and Wang, X and Zhang, K and Chen, Y}, title = {Multi-omics and functional validation reveal that Methanobrevibacter-derived L-3-aminoisobutyrate alleviates subclinical mastitis in dairy goats via the HSPA1B-p65 signaling pathway.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-026-02464-z}, pmid = {42426884}, issn = {2049-2618}, abstract = {BACKGROUND: Subclinical mastitis (SCM) is prevalent in dairy livestock and compromises milk quality and lactation performance. Although often attributed to bacterial infection, many cases lack identifiable pathogens, suggesting alternative mechanisms. While evidence supports a gut-mammary gland axis, the microbial drivers and microbiota-derived metabolites linking gut dysbiosis to SCM remain unclear. Here, we aimed to identify SCM-associated gut microbial markers, prioritize candidate therapeutic metabolites and define the underlying mechanism.<br><br>RESULTS: Based on differences in somatic cell count (SCC) and inflammatory phenotypes across a cohort of 167 mid-lactation Saanen dairy goats, we selected 6 healthy and 6 SCM goats for downstream analyses. By integrating metagenomics, metabolomics, cross-species fecal microbiota transplantation (FMT) and functional validation in vitro and in vivo, we found that SCM was accompanied by reduced milk yield and heightened inflammatory signatures. Compared with the Healthy group, SCM goats exhibited marked remodelling of the gut microbiota, with enrichment of opportunistic taxa (Eubacterium and Blautia) and a pronounced depletion of archaeal Methanobrevibacter spp. Notably, FMT from SCM donors recapitulated mammary inflammatory phenotypes in mice, supporting a causal contribution of gut dysbiosis to mammary inflammation. Joint metagenomic functional profiling and metabolomics further identified the branched-chain amino-acid-derived metabolite L-3-aminoisobutyrate (BAIBA) as significantly enriched in the gut of healthy goats. Moreover, Methanobrevibacter spp. harboured key enzyme genes (vorA, vorB and vorD) implicated in BAIBA biosynthesis. In an LPS-challenged MAC-T model, BAIBA attenuated mammary epithelial inflammation by activating endoplasmic reticulum protein quality control programmes and restoring HSPA1B expression, thereby suppressing NF-&#x3ba;B activation and reducing pro-inflammatory cytokine production. Finally, in naturally infected goats, intramammary administration of BAIBA lowered SCC, highlighting translational potential.<br><br>CONCLUSIONS: This study identifies BAIBA as a microbiota-derived metabolite that protects against SCM by restraining mammary inflammation via the HSPA1B-NF-&#x3ba;B axis, establishing a mechanistic gut-mammary link and highlighting a potential non-antibiotic intervention strategy. Video Abstract.}, }
@article {pmid42427207, year = {2026}, author = {Huang, C and Chai, P and He, Y and Zhang, Y and Su, S and Liu, Z and Luo, Y and Liu, S and Hou, L and Zhang, J}, title = {Cyclocarya paliurus Polysaccharides Attenuate High-Fat Diet-Induced Metabolic Dysfunction via Gut Microbiota Remodeling.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.70551}, pmid = {42427207}, issn = {1440-1746}, support = {S202117114001//Shanxi Undergraduate Training Program for Innovation and Entrepreneurship/ ; }, abstract = {BACKGROUND AND AIM: Alterations in gut microbiota composition are closely associated with obesity and metabolic disorders. Cyclocarya paliurus polysaccharides (CCPP) have been shown to improve lipid metabolism and modulate the gut microbiota; however, mechanistic evidence remains limited and may vary depending on preparation methods. This study investigated whether a crude polysaccharide-enriched Cyclocarya paliurus preparation alleviates high-fat diet-induced metabolic dysfunction and is associated with gut microbiota remodeling.<br><br>METHODS: Male C57BL/6&#x2009;J mice were randomized into three groups: normal diet (ND), high-fat diet (HFD), and HFD supplemented with CCPP for 12&#x2009;weeks. Serum metabolic parameters were measured; intestinal inflammatory cytokine transcripts were assessed by qRT-PCR; and cecal microbiota composition was analyzed by 16S rRNA gene sequencing. Additionally, fecal microbiota transplantation (FMT) was performed by transferring microbiota from CCPP-treated donors to antibiotic-pretreated HFD-induced recipients for 8&#x2009;weeks.<br><br>RESULTS: CCPP attenuated HFD-induced body weight gain and reduced subcutaneous and visceral adipose tissue mass. CCPP significantly improved serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) and reduced fasting glucose. Cecal 16S rRNA gene profiling showed that CCPP reshaped the gut dysbiosis associated with a HFD and enriched microbial taxa that are commonly linked to carbohydrate fermentation. These taxa specifically include Lachnospiraceae-related microbial taxa and Ileibacterium. Importantly, FMT from CCPP-treated donors recapitulated these metabolic improvements, confirming that the benefits of CCPP were microbiota-dependent.<br><br>CONCLUSION: CCPP mitigates obesity and metabolic dysfunction by remodeling the gut microbiota, particularly by enriching short-chain fatty acid-producing taxa. These findings highlight CCPP as a potential microbiota-targeted therapeutic agent for metabolic disorders.}, }
@article {pmid42427432, year = {2026}, author = {Davar, D and Zarour, HM and Trinchieri, G}, title = {Toward a Dual-Axis Model of Microbiome Modulation in Cancer Immunotherapy: Pathobiont Elimination and Functional Ecosystem Restoration.}, journal = {Cellular and molecular bioengineering}, volume = {}, number = {}, pages = {}, pmid = {42427432}, issn = {1865-5025}, abstract = {PURPOSE: The gut microbiome is increasingly recognized as a modulator of cancer immunotherapy efficacy, including responses to immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy. Recent clinical trials of microbiome-targeted interventions such as fecal microbiome transplantation (FMT) and live biotherapeutic products (LBPs) suggest the potential to enhance antitumor immunity and improve clinical outcomes. Yet responses remain heterogeneous and are not fully explained by engraftment of donor taxa alone.<br><br>METHODS: We integrate evidence from interventional trials, observational cohort studies, and principles from gut microbial ecology to develop a model hypothesis on how microbiome-targeted therapies may shape response to immunotherapy, with potential to inform future trial design, analyses, and interpretation.<br><br>RESULTS: Drawing on the available evidence, we propose that therapeutic perturbation of the gut microbiome may augment immunotherapy efficacy through two parallel axes: (1) elimination of immunosuppressive pathobionts that restrain CD8+ T-cell activation and promote myeloid-mediated immunosuppression, and (2) functional restoration of the gut ecosystem through engraftment of taxa that provide metabolites, structural cues, and immunoregulatory signals required for effective antitumor immunity. The success of both axes appears to depend on ecological processes governed by predator-prey dynamics, including colonization resistance, resilience of the resident microbiota, and the ability of administered organisms to displace entrenched dysbiotic communities. This ecological lens may help to explain discrepancies across trial designs, donor types, and intervention modalities, and suggests that complete donor engraftment is neither necessary nor sufficient for clinical benefit.<br><br>CONCLUSIONS: A dual-mechanism model of pathobiont elimination and functional microbial restoration may help explain microbiome-mediated enhancement of cancer immunotherapy, highlighting a balanced immune permissive gut ecosystem as a key determinant of therapeutic success.}, }
@article {pmid42428309, year = {2026}, author = {Chen, H and Zhang, S and Bai, Y and Yu, L and Gu, Y}, title = {Translating priority effects and niche engineering into rational microbiome therapeutics across the gut-lung axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1871211}, pmid = {42428309}, issn = {1664-302X}, abstract = {The homeostasis of the human microbiome relies on "colonization resistance" governed by complex ecological rules. However, severe perturbations such as broad-spectrum antibiotics can dismantle this defense, shifting the microbial community into a "dysbiotic trap" driven by pathogen niche construction-an alternative stable state that is notoriously difficult to spontaneously reverse. This ecological mechanism explains the frequent failure of empirical therapies like fecal microbiota transplantation (FMT) and blind probiotic supplementation. Crucially, local ecological collapse triggers systemic cascades via the "gut-lung axis." The depletion of core gut metabolites, such as short-chain fatty acids, impairs the metabolic reprogramming and antimicrobial capacity of distal alveolar macrophages. This cascade drastically increases host susceptibility to respiratory infections. To break this clinical deadlock, microbiome medicine must transition from "empirical transplantation" to "rational microbiome engineering." This review systematically outlines the core pillars of this translational framework: achieving "precision niche clearing" via targeted bacteriophages; capturing optimal intervention windows to harness "priority effects"; and ultimately engrafting "synthetic microbial consortia" (SMCs) rationally designed upon metabolic cross-feeding principles. This strategy offers a promising avenue to durably shatter the dysbiotic deadlock and restore host immune homeostasis across the gut and systemic levels.}, }
@article {pmid42428310, year = {2026}, author = {Li, X and Wang, W and Guo, Y and Feng, C and Fan, Y and Lu, Y and Lv, Y and Wang, Y and Pang, X}, title = {Advances in understanding intestinal microbiota mechanisms and intervention strategies for anxiety, depression, sleep disorders, and constipation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1838417}, pmid = {42428310}, issn = {1664-302X}, abstract = {Anxiety, depressive symptoms, sleep disorders, and chronic constipation frequently co-occur and collectively impose a substantial clinical burden. Although these conditions may involve partially overlapping neural, endocrine, immune, and metabolic processes, their shared pathophysiological basis has not been fully established. This narrative review examines the potential role of the microbiota-gut-brain axis in linking affective symptoms, sleep disturbances, and chronic constipation. Evidence from human observational studies, Mendelian randomization analyses, animal models, and preliminary interventional studies suggests that alterations in gut microbial composition and function may contribute to these clinical associations through microbial metabolites, immune signaling, neuroendocrine regulation, and neural pathways. The review also summarizes microbiota-targeted interventions, including probiotics, prebiotics, dietary modification, and fecal microbiota transplantation. However, substantial heterogeneity in study populations, microbial findings, experimental methods, and intervention protocols limits causal interpretation and clinical generalization. A more rigorous distinction among associative, mechanistic, genetic, and interventional evidence is therefore required when evaluating the therapeutic potential of microbiota-based strategies.}, }
@article {pmid42429144, year = {2026}, author = {Wei, L and Kong, X and Li, Y and Wu, H and Gan, Y and Sun, F}, title = {Gut dysbiosis‑derived butyrate loss predicts feeding intolerance: Multiomics evidence guiding nurse‑driven microbiota‑supportive interventions (Review).}, journal = {Molecular medicine reports}, volume = {34}, number = {3}, pages = {}, doi = {10.3892/mmr.2026.13958}, pmid = {42429144}, issn = {1791-3004}, mesh = {Humans ; *Dysbiosis/microbiology/metabolism ; Multiomics ; *Gastrointestinal Microbiome ; *Butyrates/metabolism ; Critical Illness ; }, abstract = {Feeding intolerance (FI) is a common and debilitating challenge among critically ill patients that is linked to a pathway involving the collapse of the gut microbial ecology. The present review synthesizes multiomics evidence supporting a framework whereby critical illness‑associated gut dysbiosis results in a functional deficit of a microbially derived short‑chain fatty acid butyrate, a pivotal metabolite involved in maintaining intestinal barrier integrity, immuneoregulation and gastrointestinal motility. The loss of butyrate‑producing bacteria and their genetic pathways is strongly correlated with FI and may represent a contributory pathogenic mechanism. Key butyrate‑producing organisms diminished during this process include Faecalibacterium prausnitzii and Roseburia spp. Building upon this mechanistic framework, a pragmatic, nurse‑driven intervention model aimed at preserving and restoring microbial health in critically ill patients was proposed. This model is founded on four principal strategies: Minimizing iatrogenic harm (such as antibiotic/proton pump inhibitor stewardship), targeted microbiota nourishment (pre/synbiotics), cautious microbial restoration (probiotics/fecal microbiota transplantation) and innovative monitoring approaches. By integrating principles of microbial ecology with clinical nursing science, the present review provides a framework for developing nurse‑driven protocols designed to address the underlying pathophysiology of FI and improve patient outcomes.}, }
@article {pmid42429615, year = {2026}, author = {Jiang, K and Xiong, F and Peng, Y and Meng, L and Wang, X and Xu, Y and Tang, T and Gao, H}, title = {Intermittent Fasting Restores Cardiac Lipid Homeostasis in Diabetic Cardiomyopathy in Association With Akkermansia Muciniphila and 1-methyl-L-histidine.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e76528}, doi = {10.1002/advs.76528}, pmid = {42429615}, issn = {2198-3844}, support = {22274115//National Natural Science Foundation of China/ ; 21974096//National Natural Science Foundation of China/ ; LZ26C010002//Zhejiang Provincial Natural Science Foundation of China/ ; LQN26C010004//Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes with limited effective interventions. Using a streptozotocin-induced insulin-deficient, type 1 diabetes-like DCM mouse model, we show that intermittent fasting (IF) improves cardiac function and attenuates myocardial remodeling. Antibiotic-mediated microbiota depletion largely abolished these benefits, whereas fecal microbiota transplantation from IF-treated donors recapitulated cardioprotection, supporting a causal role of the gut microbiota. Metagenomic profiling identified Akkermansia muciniphila (A. muciniphila) as a prominent IF-responsive taxon, and A. muciniphila supplementation alleviated cardiac injury without obvious improvement in glycaemia. Integrated serum and heart metabolomics identified 1-methyl-L-histidine as a microbiota-associated metabolite reduced in diabetes but restored by IF and A. muciniphila. In vitro and ex vivo assays further supported an L-anserine-linked microbial route for 1-methyl-L-histidine generation. Importantly, oral 1-methyl-L-histidine supplementation recapitulated key cardioprotective effects, remodeled cardiac lipid homeostasis, and reduced lipid peroxidation and oxidative injury. Together, these findings support a gut microbiota-metabolite-lipid axis associated with IF-related cardioprotection in DCM and highlight microbial metabolites as tractable targets to complement dietary intervention.}, }
@article {pmid42429658, year = {2026}, author = {Wu, G and Wang, H and Zhou, Q and Fu, J and Zhang, F and Duan, Z and Wang, S and Huang, J and Zhou, H and Ma, Z and He, Y and Yin, J and Xu, K}, title = {Effects of gut microbiota on the susceptibility of ischemic stroke in mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0014926}, doi = {10.1128/msystems.00149-26}, pmid = {42429658}, issn = {2379-5077}, abstract = {UNLABELLED: Ischemic stroke is a highly prevalent disease with limited therapeutic options, and emerging evidence suggests that the gut microbiota influences stroke pathophysiology. However, whether the gut microbiota affects individual susceptibility to ischemic stroke remains unclear. Here, middle cerebral artery occlusion was performed to stratify mice into ischemic stroke-sensitive (SEN: reaching humane endpoints within day 1) and ischemic stroke-resistant (RES: surviving to day 7) groups based on post-stroke survival. SEN mice exhibited more severe brain injury than RES mice, accompanied by increased systemic inflammation and elevated intestinal permeability. Fecal microbiota from SEN or RES donors was transplanted into antibiotic-treated recipients. Mice receiving SEN microbiota developed significantly worse outcomes compared with those receiving RES microbiota. Multi-omic analyses of cecal contents, including 16S rRNA gene sequencing and liquid chromatography-mass spectrometry/mass spectrometry-based untargeted metabolomics, identified reduced butyrate-producing bacteria and altered glutathione metabolism as potential contributors to stroke susceptibility. Collectively, these findings demonstrate that gut microbiota and microbial metabolites modulate susceptibility to ischemic stroke.<br><br>IMPORTANCE: The role of the gut microbiota in determining susceptibility to ischemic stroke has remained poorly defined. This study demonstrates that microbiota dysbiosis and metabolite alterations functionally increase vulnerability to stroke injury, highlighting the gut microbiome as a potential target for risk stratification and preventive interventions. Modulating the gut microbiota may therefore represent a novel strategy for reducing stroke susceptibility.}, }
@article {pmid42242200, year = {2026}, author = {Barlow, M and Bailey, S and Alessy, S and Al-Bawardy, B and Aldarweesh, S and Bawaked, RA and Alharith, H and Mahdi, A and Alaklabi, A and Mawardi, M and Althwanay, AM and Althumiri, NA and Alabbad, S and Bzeizi, KI and Rakic, S and Allehebi, A and Zivotic, P and Cetinkaya, V and AlJudaibi, B and Alqahtani, SA}, title = {Novel Technologies for Gastrointestinal Cancer Detection: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000001058}, pmid = {42242200}, issn = {2155-384X}, support = {P179873//World Bank Group/ ; }, abstract = {INTRODUCTION: Gastrointestinal (GI) cancers account for a quarter of all cancers and one-third of cancer-related deaths worldwide. Novel diagnostic approaches are crucial to enhance early detection and improve patient outcomes. This review systematically identified and evaluated novel GI cancer detection approaches.<br><br>METHODS: A systematic review was conducted using PubMed, EMBASE, Scopus, and the Cochrane Library on December 11, 2024, and updated on June 2, 2025. Cohort studies and randomized controlled studies, published in English, that evaluated a novel diagnostic approach for incident GI cancer in a clinical setting, included &#x2265;300 participants, and reported diagnostic accuracy metrics were eligible for inclusion. Two reviewers independently screened studies and assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.<br><br>RESULTS: Of 9,604 records screened, 72 studies were included: by site, 51 on colorectal, 1 on upper GI, 1 on esophageal, 7 on gastric, 9 on pancreatic, and 5 on hepatocellular carcinoma. Stool DNA testing in patients with a positive fecal immunochemical test showed the highest performance for colorectal cancer (area under the receiver operating characteristic curve [AUC] 0.94-0.98). The best performing technologies across other cancer types were Q-Cancer for pancreatic (AUC 0.89-0.92), the GALADUS model for hepatocellular carcinoma in cirrhotic patients (AUC 0.94), and an artificial intelligence model for esophageal cancer (AUC 0.87).<br><br>DISCUSSION: This review highlights several promising novel diagnostic approaches for GI cancer detection. External validation, population-level studies, and health economic evaluation are crucial to establish clinical utility across different settings and populations. Clinicians and policy makers must weigh the added value of novel technologies against current practice, regulatory requirements, clinical understanding, interpretation of results, and public trust.}, }
@article {pmid42420754, year = {2026}, author = {Samulėnaitė, S and Mathis, V and Darcq, E and Burokas, A and Martín-García, E and Maldonado, R}, title = {Gut microbiota as a novel therapeutic target for eating disorders and obesity.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70547}, pmid = {42420754}, issn = {1476-5381}, support = {#2022/18-31//Fundaci&#xf3; la Marat&#xf3; de TV3/ ; #PNSD-2019I006//Plan Nacional Sobre Drogas of the Spanish Ministry of Health/ ; #PNSD-2023I040//Plan Nacional Sobre Drogas of the Spanish Ministry of Health/ ; #2025//ICREA-Acad&#xe8;mia/ ; #PNSD-2017I068//Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas of the Spanish Ministry of Health'/ ; #PNSD-2022//Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas of the Spanish Ministry of Health'/ ; #RD12/0028/0023//Instituto de Salud Carlos III, RETICS-RTA/ ; #2020-SGR//Generalitat de Catalunya, AGAUR/ ; PID2020- 120029GB-I00/MICIN/AEI//Ministerio de Ciencia e Innovaci&#xf3;n (MICIN), Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; PDI2023-1511680B-C21//Ministerio de Ciencia e Innovaci&#xf3;n (MICIN), Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; 01.2.2-LMT-K-718-03-0099//The European Regional Development Fund/ ; PCI2021-122073-2A//Spanish Ministerio de Ciencia e Innovaci&#xf3;n (ERA-NET)/ ; #HR22-00737//Caixa Health/ ; }, abstract = {The gut-brain axis constitutes a bidirectional communication network linking the intestinal microbiota and the central nervous system. Through this communication axis, the gut microbiota exerts a major influence on food intake under physiological and pathophysiological conditions. Exposure to a Western diet has been associated with dysbiosis of the gut microbiota, leading to profound changes in the gut-brain axis and promoting compulsive-like eating patterns. Alterations in the gut microbiota influence brain activity via multiple routes, including activation of vagal afferents, modulation of systemic immune and endocrine responses, and the action of microbiota-derived metabolites. Through these mechanisms, gut microbiota imbalance alters metabolic and reward-related brain processes that govern eating behaviour. Thus, gut microbiota interacts with homeostatic pathways by modulating satiety-related hypothalamic mechanisms, thereby influencing appetite and energy balance. In parallel, microbiota-dependent signalling affects hedonic feeding by shaping mesolimbic dopamine activity. Neuroinflammation is another key mechanistic interface within the gut microbiota-brain axis contributing to the development of metabolic disorders. Gut microbiota dysbiosis can increase intestinal permeability, facilitating the translocation of microbial components that promote systemic inflammation. Given this convergence between metabolic, inflammatory and reward mechanisms, modulation of the gut microbiota has emerged as a potential therapeutic approach for obesity and eating disorders. Prebiotics, probiotics, postbiotics, synbiotics and faecal microbiota transplantation are currently under investigation for their capacity to restore microbial balance and improve these metabolic and behavioural disorders. This review primarily focuses on the neurobehavioural regulation of feeding and its dysregulation, with particular emphasis on gut-brain axis mechanisms.}, }
@article {pmid42421228, year = {2026}, author = {Serrano-García, L and Martínez-Salvador, E and Belda-Marco, A and Herrero-Oliva, C and Cortés, J and Llombart-Cussac, A and Fernández-Murga, L}, title = {Modulation of the response to immunotherapy in triple-negative breast cancer: the role of the microbiota and microbial metabolites in the tumor microenvironment.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2697600}, doi = {10.1080/19490976.2026.2697600}, pmid = {42421228}, issn = {1949-0984}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Triple Negative Breast Neoplasms/therapy/immunology/microbiology ; Female ; *Immunotherapy ; *Gastrointestinal Microbiome/immunology ; Animals ; }, abstract = {Triple-negative breast cancer is an aggressive and heterogeneous breast cancer subtype for which immune checkpoint inhibitors combined with chemotherapy have improved outcomes in selected patients. However, primary and acquired resistance remain common, underscoring the need to identify extrinsic, modifiable determinants of antitumor immunity. Increasing evidence indicates that the gut and tumor-associated microbiota shape systemic and intratumoral immune tone and influence the efficacy of cancer therapies. Beyond microbial composition, microbiota-derived metabolites-including short-chain fatty acids, indole-tryptophan derivatives, bile acids, polyamines, and other small molecules-can act as functional mediators linking microbial ecology to immune-cell programming and tumor biology. These metabolites modulate dendritic cell function, T-cell priming and fitness, myeloid polarization, inflammatory set points, and metabolic pathways within the tumor microenvironment, thereby potentially enhancing or constraining responses to chemoimmunotherapy. Importantly, while some studies propose intratumoral microbial effects, most clinically actionable evidence currently supports systemic gut-derived metabolites and immune tone modulation that secondarily shapes the TNBC tumor microenvironment. In this review, we synthesize current knowledge on (i) the immunobiology of triple-negative breast cancer (TNBC) relevant to microbiota-driven modulation, (ii) mammary and gut microbiome features reported in TNBC, and (iii) mechanistic pathways through which microbial metabolites may regulate antitumor immunity and immune checkpoint inhibitors (ICI) sensitivity. We also discuss methodological considerations for integrating microbiome profiling with metabolomics and immune phenotyping and evaluate emerging opportunities to leverage microbiota-derived metabolites as biomarkers and therapeutic targets. Finally, we highlight translational strategies-including diet, pre/probiotics, antibiotic stewardship, fecal microbiota transplantation, and metabolite-centric ("postbiotic") approaches-and outline priorities for TNBC-focused, prospective multi-omics studies to move from associative signatures toward actionable interventions.}, }
@article {pmid42421565, year = {2026}, author = {Molajafari, A and Ebrahim-Saraie, HS and Moghadam, MT and Hasannejad-Bibalan, M}, title = {A Comprehensive Study of Bidirectional Interactions Between the Human Microbiome and Blood Malignancies and Hematologic Conditions: Focus on Novel Therapeutic Strategies.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e70306}, doi = {10.1002/jcla.70306}, pmid = {42421565}, issn = {1098-2825}, abstract = {BACKGROUND: The human microbiota plays a key role in maintaining host homeostasis by regulating immune responses, metabolism, and hematopoiesis. Microbial dysbiosis has been increasingly associated with immune dysfunction, inflammation, and bone marrow abnormalities that may contribute to hematological diseases. This review summarizes current evidence on the role of the microbiota in normal hematopoiesis and its potential involvement in benign and malignant hematological disorders.<br><br>METHODS: A narrative literature review was conducted through comprehensive searches of major scientific databases without time restrictions using the keywords Microbiome, Dysbiosis, Hematopoiesis, Anemia, Immune Thrombocytopenia, Congenital Neutropenia, Thrombosis, Lymphoma, Leukemia, and Multiple Myeloma. Relevant experimental, clinical, and review articles were screened and synthesized.<br><br>RESULTS: Available evidence suggests that the microbiota may influence hematopoietic stem cell function, immune cell development, and hematopoietic homeostasis. Microbial dysbiosis has been proposed to be associated with benign hematological disorders, including anemia, immune thrombocytopenia, congenital neutropenia, and thrombosis, as well as hematological malignancies such as leukemia, lymphoma, and multiple myeloma. Certain bacterial and viral infections may also influence disease progression and therapeutic responses. Microbiota-targeted interventions, including probiotics, prebiotics, dietary interventions, fecal microbiota transplantation, and other microbiome-based therapies, have shown potential as adjunctive therapeutic strategies.<br><br>CONCLUSIONS: Current evidence suggests that microbiota dysbiosis may contribute to the pathogenesis of various hematological disorders. A better understanding of host-microbiota interactions may support the development of novel biomarkers and microbiota-based therapeutic approaches, although further clinical studies are required to confirm their efficacy and safety.}, }
@article {pmid42422736, year = {2026}, author = {Kaur, P and Rivera-Nieves, J}, title = {A standardized fecal microbiota transplantation protocol enables consistent, microbiota-driven colitis in IL-10-deficient mice.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1842264}, pmid = {42422736}, issn = {1664-302X}, abstract = {Gut microbiota dysbiosis is a central feature of inflammatory bowel disease (IBD), yet experimental systems that enable controlled investigation of microbiota-driven inflammation remain limited. In interleukin-10-deficient (Il10[-/-]) mice, intestinal inflammation is strictly dependent on the presence of commensal microbiota; however, disease onset and severity are highly variable, reflecting differences in microbial composition across environments. To overcome this limitation, pharmacologic approaches such as piroxicam administration have been widely used to synchronize disease, but these methods introduce epithelial injury and non-microbiota-dependent inflammatory pathways that confound mechanistic interpretation. Here, we describe a standardized fecal microbiota transplantation (FMT) protocol that enables controlled microbiota-driven induction of colitis in Il10[-/-] recipient mice without the use of chemical triggers. In this model, recipient mice aged 8-10 weeks receive fecal microbiota via oral gavage from either colitic Il10[-/-]; Itgb7[-/-] double knockout (DKO) donor mice or non-colitic young Il10[-/-] controls. The DKO donors exhibit impaired mucosal immune regulation and reduced IgA responses, features associated with the emergence of a colitogenic microbial community. Repeated FMT administration over 9 weeks promotes uniform disease induction and reduces variability in disease kinetics across experimental cohorts. Importantly, this approach preserves microbiota-driven disease mechanisms while improving experimental consistency compared with conventional spontaneous Il10[-/-] models and avoids the confounding effects of pharmacologic synchronization. The protocol is compatible with downstream histological, immunological, and microbiome analyses and provides a practical platform for investigating host-microbiota interactions and microbiome-targeted therapeutic strategies in IBD.}, }
@article {pmid42422874, year = {2026}, author = {Jiang, Q and Zhu, X and Yin, L}, title = {The role of gut microbiota dysbiosis in the pathogenesis of hyperuricemic nephropathy.}, journal = {Frontiers in molecular biosciences}, volume = {13}, number = {}, pages = {1872377}, pmid = {42422874}, issn = {2296-889X}, abstract = {Hyperuricemic nephropathy (HN) is a renal complication associated with sustained hyperuricemia and urate-related renal injury. Emerging evidence suggests that gut microbiota dysbiosis may participate in HN pathogenesis by influencing uric acid metabolism, intestinal urate excretion, gut barrier integrity, microbial metabolite production, and gut-kidney immune crosstalk. However, the strength of evidence varies substantially across proposed mechanisms, with many findings derived from animal models, in vitro experiments, CKD studies, or human studies of hyperuricemia and gout rather than HN-specific clinical cohorts. This review summarizes current clinical and experimental evidence linking gut microbiota dysbiosis with HUA, gout, CKD, and HN, critically evaluates proposed mechanistic pathways, and discusses microbiota-targeted interventions including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and metabolite-based approaches. Particular emphasis is placed on distinguishing association from causality and identifying translational gaps that should be addressed in future HN-specific studies.}, }
@article {pmid42412955, year = {2026}, author = {Lv, J and Waza, AA}, title = {Recurrent urinary tract infections in older adults: A systematic review of current challenges and emerging therapeutic strategies.}, journal = {Acta pharmaceutica (Zagreb, Croatia)}, volume = {76}, number = {2}, pages = {1-25}, doi = {10.2478/acph-2026-0017}, pmid = {42412955}, issn = {1846-9558}, mesh = {Humans ; *Urinary Tract Infections/diagnosis/epidemiology/therapy/microbiology/drug therapy ; Aged ; Recurrence ; *Anti-Bacterial Agents/therapeutic use/administration &amp; dosage ; Female ; Prevalence ; Age Factors ; Risk Factors ; }, abstract = {As global life expectancy continues to rise, urinary tract infections (UTIs) have become an increasing concern in older adults. The higher prevalence in this population is attributed to anatomical and physiological changes of the urinary tract, hormonal imbalances, immunosenescence, and the presence of comorbidities. These factors, combined with a distinct microbiological profile and rising antimicrobial resistance, create significant clinical challenges in diagnosis and treatment. We conducted a systematic review of clinical trials and observational studies on the epidemiology, pathogenesis, diagnosis, and management of recurrent urinary tract infections (rUTIs) in older adults. The prevalence of rUTIs increases with age, disproportionately affecting women, with 53 % of those over 55 years experiencing recurrences within one year. Healthcare-associated UTIs (HAUTIs) account for 20-30 % of nosocomial infections, primarily impacting older adults. The host microbiome seemed crucial in UTI pathogenesis, with Escherichia coli being the leading causative agent due to its ability to adhere, colonise, and evade the immune response. In elderly patients, atypical presentations - such as delirium, functional decline, or nonspecific abdominal symptoms - complicate diagnosis, underscoring the critical need to differentiate symptomatic infections from asymptomatic bacteriuria (ASB) to prevent misdiagnosis and overtreatment. Effective management requires accurate diagnosis, appropriate antibiotic selection, and careful monitoring of adverse effects, especially in patients with comorbidities. Emerging therapies, including faecal microbiota transplantation, bacteriophages, probiotics, and proanthocyanidins, offer promising adjuncts. While long-term antibiotic prophylaxis is effective, it increases the risk of bacterial resistance, particularly in catheterised patients. Behavioural modifications, such as increased fluid intake, aid pathogen clearance, and topical estrogen therapy in postmenopausal women provides additional preventive benefit. Managing recurrent UTIs in ageing populations requires addressing microbiological, diagnostic, and antimicrobial resistance challenges. Despite resistance levels, the first-line treatment, nitrofurantoin, remains a viable therapeutic option, particularly in developed countries. An integrated approach combining individualised care, healthcare provider training, and rational antimicrobial use is essential to improving patient outcomes and quality of life. Future strategies should focus on novel antimicrobials targeting bacterial virulence factors, vaccines against uropathogens, and advanced diagnostic technologies.}, }
@article {pmid42413478, year = {2026}, author = {Newsome, RC and Jobin, C}, title = {Microbiota and immunotherapy: The birth of a new paradigm?.}, journal = {Cell metabolism}, volume = {38}, number = {7}, pages = {1269-1272}, doi = {10.1016/j.cmet.2026.06.007}, pmid = {42413478}, issn = {1932-7420}, mesh = {Humans ; *Immunotherapy/methods ; *Fecal Microbiota Transplantation ; *Neoplasms/therapy/immunology/microbiology ; Animals ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {Emerging data suggest fecal microbiota transplantation (FMT) may improve cancer patients' responses to immune checkpoint blockade not only by enriching beneficial bacteria but also by depleting harmful taxa. Here, we discuss the "supplementation" and new "depletion" FMT paradigms in cancer management and highlight key knowledge gaps to be addressed to move this field forward.}, }
@article {pmid42413716, year = {2026}, author = {Gu, M and Wang, Z and Huang, F and Li, Y and Liu, Z and Huang, Z and Chang, P}, title = {Gut microbiota and metabolites in remodeling the tumor microenvironment and regulating immunotherapeutic efficacy in colorectal cancer.}, journal = {Life sciences}, volume = {}, number = {}, pages = {124581}, doi = {10.1016/j.lfs.2026.124581}, pmid = {42413716}, issn = {1879-0631}, abstract = {AIMS: Immune checkpoint inhibitors (ICIs) benefit patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), but efficacy remains limited in proficient mismatch repair/microsatellite-stable (pMMR/MSS) tumors. This review evaluates how the gut microbiota and microbial metabolites influence CRC development, the tumor microenvironment, and immunotherapy responses, with emphasis on strategies for pMMR/MSS CRC.<br><br>MATERIALS AND METHODS: We reviewed and critically evaluated recent preclinical, translational, and clinical evidence on microbiota-associated metabolic regulation, chronic inflammation, DNA damage, epigenetic reprogramming, microbial biomarkers, and microbiota-targeted interventions.<br><br>KEY FINDINGS: Microbial effects are context dependent and cannot be classified simply as beneficial or harmful. Short-chain fatty acids, tryptophan derivatives, and secondary bile acids influence epithelial integrity, immune-cell function, tumor metabolism, and epigenetic regulation. Akkermansia muciniphila, Bifidobacterium, and Lactobacillus strains are promising candidates for improving ICI responses. Notably, tumor-associated bacteria, including Fusobacterium nucleatum and selected Bacteroides taxa, may exert context-dependent and potentially opposing effects depending on strain, metabolite output, host background, and treatment setting. Emerging strategies include dietary modulation, fecal microbiota transplantation, probiotics, engineered bacteria, and rational combination therapies.<br><br>SIGNIFICANCE: The gut microbiota is a modifiable component of ICI resistance rather than a sole determinant. Future studies should establish causal mechanisms and develop reproducible, function-based biomarkers through longitudinal multi-omics analyses and prospective clinical validation.}, }
@article {pmid42413732, year = {2026}, author = {Paul, P and Kaul, R and Ayyan, M and Lakshmanan, AP and Chaari, A}, title = {Gut Microbiome-Modulating Therapeutics and Lipid Profile in Metabolic Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.}, journal = {Clinical nutrition ESPEN}, volume = {}, number = {}, pages = {103461}, doi = {10.1016/j.clnesp.2026.103461}, pmid = {42413732}, issn = {2405-4577}, abstract = {OBJECTIVES: To evaluate the effects of gut microbiome-modulating interventions (probiotics, prebiotics, synbiotics, and fecal microbiota transplantation) on lipid profile parameters in adults with metabolic syndrome (MetS).<br><br>DESIGN AND DATA SOURCES: Systematic review and random-effects meta-analysis with univariate meta-regression of controlled clinical trials indexed in PubMed, Web of Science, and Scopus through June 2025.<br><br>ELIGIBILITY CRITERIA: Controlled clinical trials in adults with MetS diagnosed according to ATP III, IDF, or WHO criteria reporting at least one lipid outcome (total cholestrol (TC), low-density lipoprotein cholestrol (LDL-C), high desntiry lipoprotein cholestrol (HDL-C), or triglycerdies (TG)). Studies without control groups, insufficient data, or populations not meeting full MetS criteria were excluded.<br><br>DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted data. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analysis (DerSimonian-Laird) generated pooled mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I[2] statistics. Meta-regression evaluated moderators including age, baseline BMI, intervention dose, duration, and geographic region.<br><br>RESULTS: Nineteen studies comprising 21 trial comparisons and 897 participants were included. Microbiome-modulating interventions were associated with reductions in TC (MD -8.97 mg/dL; 95% CI -12.55 to -5.38) and TG (MD -11.33 mg/dL; 95% CI -19.25 to -3.40), while HDL-C showed no significant change. LDL-C was also reduced in the primary pooled analysis (MD -5.05 mg/dL; 95% CI -9.57 to -0.53); however, this finding should be interpreted cautiously because of substantial between-study heterogeneity (I[2] = 73.8%) and loss of statistical significance in sensitivity analyses. Greater lipid reductions were generally observed in trials using higher probiotic doses and longer intervention durations, although moderator effects were not consistent across all lipid outcomes.<br><br>CONCLUSIONS: Microbiome-modulating interventions are associated with modest improvements in selected lipid parameters in adults with metabolic syndrome, particularly TC and TG. Evidence for LDL-C reduction is less robust because of substantial heterogeneity and sensitivity to analytical assumptions. Larger, well-standardized clinical trials are required to confirm lipid-specific effects, identify responsive populations, and determine the clinical relevance of these interventions.}, }
@article {pmid42414020, year = {2026}, author = {Clister, D and Chandra, QM and Tan, MW and Gunawan, MC and Bibi, A and Ahmed, A and Bastian, M and Meesakul, P and Cao, S and Kim, B and Nurkolis, F and Syahputra, RA}, title = {Microbiome-Based Precision Interventions in Type 2 Diabetes Mellitus: Mechanisms, Modulators, and Translational Opportunities.}, journal = {The Journal of nutrition}, volume = {156}, number = {7}, pages = {101596}, doi = {10.1016/j.tjnut.2026.101596}, pmid = {42414020}, issn = {1541-6100}, mesh = {*Diabetes Mellitus, Type 2/therapy/microbiology ; Humans ; *Precision Medicine ; Probiotics ; *Gastrointestinal Microbiome ; Prebiotics ; Fecal Microbiota Transplantation ; Synbiotics ; Dysbiosis ; Animals ; *Microbiota ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a complex metabolic disease driven by insulin resistance, chronic low-grade inflammation, and impaired glucose regulation. Although pharmacological options have advanced, sustained glycemic control remains elusive due to heterogeneity in disease progression and therapeutic response. Precision medicine offers a framework to individualize interventions, with the gut microbiota emerging as a central determinant of host metabolic and immune regulation. Dysbiosis has been implicated in T2DM through altered microbial metabolites-including short-chain fatty acids, bile acids, branched-chain amino acids, and indole derivatives-that shape insulin sensitivity, inflammatory pathways, and glucose homeostasis. This review critically examined microbiome-targeted strategies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and personalized nutrition, alongside advances in metagenomics and machine learning for biomarker discovery. By integrating mechanistic and translational insights, we highlight opportunities and challenges in implementing microbiome-based precision interventions, underscoring their potential to transform T2DM management.}, }
@article {pmid42414480, year = {2026}, author = {Nieri, R and Severino, A and Foglio, E and De Maio, F and Santoni, D and Sardaro, MLS and Fancello, G and Masucci, L and D'Aiello, A and Morini, S and Tarquini, D and Gervasoni, J and Santucci, L and Leoni, O and Mammi, C and Pedicino, D and Mangoni, A and Amato, KR and Russo, MA and Crea, F and Liuzzo, G and Limana, F}, title = {Human gut microbiota from acute coronary syndrome patients promotes plaque vulnerability in a mouse model of atherosclerosis.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-61047-y}, pmid = {42414480}, issn = {2045-2322}, support = {2017WJBKKW//Ministero dell'Universit&#xe0; e della Ricerca, PRIN 2017/ ; 2017WJBKKW//Ministero dell'Universit&#xe0; e della Ricerca, PRIN 2017/ ; }, abstract = {Gut microbiota has been implicated in atherosclerosis and plaque destabilization. However, the relationship between microbiota composition and plaque vulnerability remains incompletely understood. This study tested whether fecal microbiota from patients with acute coronary syndrome (ACS) versus chronic coronary syndrome (CCS) differentially associates with atherosclerotic plaque phenotype in a fecal microbiota transplantation (FMT) model. Female ApoE[-]/[-] mice underwent antibiotic-mediated microbiota depletion followed by repeated FMT from ACS (n = 9) or CCS (n = 11) donors. Mice were fed a standard diet or a 1% choline-enriched diet for 12 weeks. Atherosclerosis burden and plaque vulnerability were assessed by Oil Red O morphometry (necrotic core area, fibrous cap thickness, cap-to-core ratio) and immunostaining (including MMP2). Serum trimethylamine N-oxide (TMAO) levels were quantified by UPLC-MS/MS, and fecal microbiota composition was analyzed by 16 S rRNA gene sequencing at study end. Choline supplementation increased circulating TMAO levels in all experimental groups. However, TMAO concentrations did not differ between ACS- and CCS-FMT recipient mice and did not correlate with lesion size or plaque vulnerability parameters. Despite comparable TMAO levels, choline-fed ACS-FMT recipient mice developed a more vulnerable plaque phenotype than CCS-FMT recipients, characterized by larger necrotic cores, thinner fibrous caps, a reduced cap-to-core ratio, increased intraplaque MMP2 expression, and elevated pro-inflammatory cytokines and chemokines. In addition, 16 S rRNA gene sequencing identified distinct microbial taxa associated with plaque vulnerability-related features. In this ApoE[-]/[-] FMT model, donor coronary syndrome status is associated with differential plaque vulnerability features and distinct gut microbiota signatures, independently of circulating TMAO levels.}, }
@article {pmid42415721, year = {2026}, author = {Hou, H and Li, Y and Tang, W and Gao, Y and Tian, Y and Chen, F and Zhang, L and Zhang, J and Xu, X and Li, Y and Li, Y and Wang, Q and Liu, L and Teng, T and Wu, H and Zhou, X}, title = {Gut microbiota-targeted interventions for depression in adolescents and young adults: Mechanisms, evidence strength and clinical strategies-A narrative review.}, journal = {General psychiatry}, volume = {39}, number = {4}, pages = {e70036}, pmid = {42415721}, issn = {2517-729X}, abstract = {Depression in adolescents and young adults is common, associated with substantial functional impairment and characterised by limited treatment efficacy. The microbiota-gut-brain (MGB) axis has emerged as a potential therapeutic target for depression. This narrative review synthesises preclinical and clinical evidence on a range of MGB axis interventions aimed at alleviating depressive symptoms in youth, including probiotics, prebiotics, synbiotics, postbiotics, faecal microbiota transplantation (FMT) and lifestyle strategies such as dietary modification and structured exercise. In animal models, these interventions consistently produce antidepressant effects, accompanied by reduced inflammatory signalling, normalisation of hypothalamic-pituitary-adrenal axis activity and upregulation of neurotrophic and serotonergic pathways. In humans, particularly among younger cohorts, the evidence is heterogeneous. Some probiotic or synbiotic regimens have yielded modest improvements in depressive symptoms in preliminary trials, whereas stand-alone prebiotics have shown inconsistent or null effects; clinical evidence for postbiotics and FMT remains preliminary. Lifestyle interventions that target the MGB axis, such as Mediterranean-style diets and structured exercise programmes, have been associated with improved mood and, in some studies, reductions in inflammatory biomarkers. Compared with studies in adults, research in this population remains limited by small sample sizes, greater methodological heterogeneity and less consistent findings and also suggests the presence of age-specific pathways. Current evidence indicates that interventions targeting the MGB axis should be approached cautiously and considered only as adjunctive strategies for the treatment of depression in this population. Future work requires rigorously designed, strain- and protocol-specific clinical trials with standardised procedures, careful safety monitoring and biomarker-guided personalised approaches.}, }
@article {pmid42418807, year = {2026}, author = {Tahmasebi, H and Bahar, A and Khazaei, M and Arabestani, MR}, title = {The Dual Role of the Gut Microbiota in Cancer Chemoresistance.}, journal = {MicrobiologyOpen}, volume = {15}, number = {4}, pages = {e70357}, doi = {10.1002/mbo3.70357}, pmid = {42418807}, issn = {2045-8827}, mesh = {Humans ; *Drug Resistance, Neoplasm ; *Neoplasms/drug therapy/microbiology ; *Gastrointestinal Microbiome ; *Antineoplastic Agents/therapeutic use/metabolism/pharmacology ; Probiotics ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Chemoresistance is one of the primary reasons that cancer chemotherapy fails to deliver successful treatment outcomes and contributes to poor overall survival rates for patients with cancer. New research has begun to shed light on the effects of the gut microbiome (GM). This new research will examine how certain microorganisms (referred to as "bad bacteria") can contribute to cancer treatment failure, as well as how others (such as Bifidobacterium, Akkermansia, and Lactobacillus) can enhance treatment success. This review will focus on the molecular mechanisms underlying these effects, including drug metabolism by microorganisms, modulation of the immune system by microorganisms, regulation of cellular apoptosis by microorganisms, and metabolic crosstalk between tumor tissue and the microbiome. Finally, we will look at new therapies under development that leverage knowledge of the microbiome to combat chemoresistance, including fecal microbiota transplantation, targeted probiotic and prebiotic supplementation, and dietary modifications. By studying the complex interactions among the host, the microbiome, and chemotherapeutic agents, we hope to demonstrate how microbiome-centered approaches can tailor and enhance an individual's cancer treatment while transforming the GM from a passive participant to an active target in cancer therapy.}, }
@article {pmid42418904, year = {2026}, author = {Yu, J and Wan, Y and Peng, Y and Liang, S and Chan, FKL and Ng, SC and Tun, HM}, title = {Multi-cohort evidence for impaired microbial support of the methionine cycle in children with autism spectrum disorder.}, journal = {Psychiatry research}, volume = {364}, number = {}, pages = {117317}, doi = {10.1016/j.psychres.2026.117317}, pmid = {42418904}, issn = {1872-7123}, abstract = {The contribution of gut microbiota to outcomes of autism spectrum disorders (ASD) has been increasingly appreciated in recent years. With the accumulating evidence on ASD-driven alterations of the gut microbiota, heterogeneities arise across different reports. To account for variabilities in gut microbiota, clinical representations of ASD and data processing approaches, as well as limitations in sample sizes among the existing gut microbiota studies for ASD, the present multi-cohort analysis applied a standard bioinformatic and statistical pipeline on the publicly available gut metagenomic sequencing data for 674 samples, including 326 TD and 348 ASD individuals, collected from eight studies across three main geographical regions. Throughout the analysis, we identified taxonomic profiles of the gut microbiota exhibited more pronounced dysbiosis associated with ASD and between-study variations compared to functional profiles. Differentially abundant taxonomic and pathway markers were identified and validated for their consistent response to ASD across different studies. Co-occurring deficits in microbial pathways for salvaging adenosylcobalamin and S-adenosyl-L-methionine and biosynthesis of methionine in children with ASD point to a reduced microbial support for the host methionine cycle. Species from Faecalibacterium, Bacteroides, Blautia and Bifidobacterium were identified as microbial contributors to ASD-deficient microbial pathways, particularly those related to the methionine cycle. Therefore, the generalisable ASD-deficient contributors to the methionine cycle, such as Blautia wexlerae, Bacteroides stercoris and Streptococcus thermophilus, could be further investigated for their role in therapeutic applications for ASD.}, }
@article {pmid42419261, year = {2026}, author = {Valles-Colomer, M and Foster, JA}, title = {Decoding the microbiome: Insights into FMT for depression.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {7}, pages = {1154-1156}, doi = {10.1016/j.chom.2026.06.004}, pmid = {42419261}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Major Depressive Disorder/therapy/microbiology ; *Microbiota ; Animals ; }, abstract = {While fecal microbiota transplantation (FMT) emerges as a promising microbiome-targeted treatment approach, its application in major depressive disorder (MDD) remains investigational. In this issue of Cell Host &amp; Microbe, Wang et al. provide insights into the potential underpinnings of FMT in MDD and offer a step toward decoding the molecular pathways accompanying clinical response.}, }
@article {pmid42419268, year = {2026}, author = {Sen, P and Kaulmann, D and Youngster, I and Abdeen, SK and Elinav, E}, title = {Advances and challenges in microbiome transplantation.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {7}, pages = {1202-1219}, doi = {10.1016/j.chom.2026.06.006}, pmid = {42419268}, issn = {1934-6069}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects/trends ; *Clostridium Infections/therapy/microbiology ; *Microbiota ; Animals ; Clostridioides difficile ; Gastrointestinal Microbiome ; }, abstract = {Over the past two decades, the microbiome has emerged as a central modifier of host health, whose manipulation may prevent or treat disease. Fecal microbiome transplantation (FMT) transfers stool from healthy donors to recipients to restore microbial structure and function. It is universally accepted as therapy for recurrent Clostridioides difficile infection (rCDI) and is studied across metabolic, neurological, oncological, and autoimmune disorders. However, challenges remain, including donor selection, possible transmission of infectious or non-communicable risks, and limited understanding of mechanisms driving benefits. This review summarizes FMT designs, mechanisms, indications, and obstacles. It discusses emerging strategies such as the use of microbial consortia and extra-intestinal microbiome transplantation and suggests that a better understanding of FMT functions, limitations, and off-target effects may enable safer, more generalizable modulation of microbiome-regulated diseases. Such a mechanistic understanding may manifest as refined donor screening, standardized protocols, tracked outcomes, and identified microbes and metabolites inducing durable clinical benefits.}, }
@article {pmid42419269, year = {2026}, author = {Engevik, MA and Hecht, AL and Allegretti, JR and Kashyap, PC}, title = {Ecological and dietary strategies to constrain Clostridioides difficile.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {7}, pages = {1220-1240}, doi = {10.1016/j.chom.2026.05.023}, pmid = {42419269}, issn = {1934-6069}, mesh = {Humans ; *Clostridioides difficile/physiology/pathogenicity/growth &amp; development ; *Clostridium Infections/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation ; *Diet ; Animals ; Gastrointestinal Microbiome ; Microbiota ; Feces/microbiology ; Biofilms/growth &amp; development ; }, abstract = {Clostridioides difficile exemplifies a pathogen that leverages its metabolic plasticity to exploit nutrients that become available during community disruption, including host and microbiota-derived metabolites and substrates enriched in modern diets. These ecological dynamics underpin the high and growing burden of C. difficile infection (CDI), including recurrent disease and the rising prevalence of community-associated CDI. Fecal microbiota transplantation and standardized stool-derived products consistently re-establish colonization resistance through convergent functions that include secondary bile acid restoration, nutrient niche exclusion, and suppression of opportunistic pathogens. These principles have provided a valuable roadmap for rational consortia design. In this review, we synthesize current ecological mechanisms governing C. difficile colonization, persistence, and recurrence, highlight missing dimensions in diet intervention studies and mucosal colonization by C. difficile, and propose an ecology-informed, artificial intelligence-enabled precision framework that integrates host susceptibility, exposures, diet, community function, and pathogen features to guide personalized prevention and treatment.}, }
@article {pmid42419591, year = {2026}, author = {Kim, S and Seo, H and Jo, S and Rahim, MA and Hossain, MS and Shuvo, MSH and Jeong, SY and Lee, MY and Kim, KH and Lee, N and Won, JH and Song, HY and Yoon, SY}, title = {Oral Sodium Butyrate Supplementation, Gut Microbiome Modulation, and Reduced Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2026.07.006}, pmid = {42419591}, issn = {2666-6367}, abstract = {BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Disruption of the gut microbiome during transplantation has been implicated in the pathogenesis of aGVHD, yet clinically applicable strategies to modulate the microbiome in immunocompromised patients remain limited.<br><br>OBJECTIVES: To evaluate the association between oral sodium butyrate supplementation and the incidence and severity of aGVHD, and to investigate its impact on gut microbiome recovery following allo-HSCT.<br><br>STUDY DESIGN: In this prospective, single-center study, 39 consecutive patients undergoing allo-HSCT received oral sodium butyrate (1,200 mg/day) from neutrophil engraftment to day +100. Outcomes were compared with 18 historical controls treated at the same institution without butyrate supplementation. The primary endpoint was the cumulative incidence of grade II-IV aGVHD by day +100. Secondary endpoints included lower gastrointestinal aGVHD and microbiome characteristics assessed using shotgun metagenomic sequencing. Competing risk analyses were performed to account for death as a competing event.<br><br>RESULTS: Butyrate supplementation was associated with a lower incidence of grade II-IV aGVHD (30% vs 53%, p=0.028) and grade III-IV aGVHD (5% vs 34%, p=0.002). Lower gastrointestinal aGVHD occurred in 5% of the butyrate group compared with 40% of historical controls (p<0.001). In multivariable competing risk analysis, butyrate supplementation remained independently associated with reduced grade II-IV aGVHD (adjusted HR 0.31, 95% CI 0.11-0.89; p=0.029) and lower gastrointestinal aGVHD (adjusted HR 0.07, 95% CI 0.02-0.30; p<0.001). Microbiome analysis demonstrated improved recovery of gut microbial diversity at day +100 in the butyrate group, with enrichment of commensal taxa and restoration of fecal butyrate levels.<br><br>CONCLUSIONS: Oral sodium butyrate supplementation was associated with reduced incidence and severity of aGVHD, particularly involving the gastrointestinal tract, along with improved microbiome recovery. These findings suggest a potential role for postbiotic-based microbiome modulation in GVHD prevention and warrant validation in randomized controlled trials.}, }
@article {pmid42420318, year = {2026}, author = {Nie, H and Wang, N and Mao, H and Wei, Y and Qian, J and Chen, R and Yuan, Q and Xiao, Y and Zhang, L and Yan, F}, title = {Periodontitis aggravates bone loss through gut microbiota alterations in ovariectomized mice.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01084-7}, pmid = {42420318}, issn = {2055-5008}, support = {0224C032//High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University/ ; 82270979//National Natural Sciences Foundation of China/ ; JSDW202246//Jiangsu Province Key discipline cultivation unit/ ; }, abstract = {Epidemiological evidence suggests a bidirectional relationship between periodontitis and osteoporosis, yet the underlying mechanisms remain unclear. In this study, using a mouse model combining ovariectomy-induced osteoporosis and ligature-induced periodontitis, we demonstrated that periodontitis significantly aggravated both alveolar and femoral bone loss, impaired intestinal barrier integrity, and elevated systemic inflammation. Gut microbiota and metabolomic analyses revealed that periodontitis induced distinct alterations in gut microbial composition and intestinal metabolic profiles, potentially contributing to systemic inflammation and bone metabolic dysregulation. Furthermore, fecal microbiota transplantation demonstrated that gut microbiota from periodontitis donors aggravated bone loss and inflammation in recipient mice, whereas microbiota from donors that received periodontal treatment partially alleviated inflammatory responses and skeletal deterioration. Collectively, these findings suggest that periodontitis may aggravate osteoporosis via gut microbiota-mediated mechanisms, highlighting the importance of maintaining oral health to mitigate the adverse impact of periodontitis on systemic bone metabolism.}, }
@article {pmid42420462, year = {2026}, author = {Desharnais, L and Swaby, A and Messaoudene, M and Doré, S and Yu, MW and Fiset, B and Breton, V and Ponce, M and Hu, Y and Wilson, L and Sorin, M and Wang, Y and Dewar, K and Pollak, M and Elkrief, A and Routy, B and Walsh, LA and Quail, DF}, title = {Diet-microbiome synergy underlies obesity-associated immunotherapy efficacy.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {42420462}, issn = {1476-4687}, abstract = {Physiological host factors, such as the gut microbiome and obesity, independently influence anti-tumour immunity and responses to immune checkpoint inhibitors (ICIs)[1], with high body mass index (BMI) having an unexpected link with greater ICI efficacy[2-6]. However, how these factors interact across diverse dietary contexts remains unclear. Here, using 12 mouse diet models that reflect a spectrum of obesity biology, we characterize diet-driven metabolic, immune and gut microbiota features associated with ICI sensitivity. We find that obesity-associated ICI responses are poorly correlated with metabolic dysfunction and are instead dependent on the diet-gut axis. Obesogenic diets promote a robust and persistent gut microbial ecosystem that is capable of restoring ICI sensitivity following a short-term diet switch or fecal microbiota transplants (FMTs) from non-responder models. Monocolonization of germ-free mice with favourable bacteria such as Lactobacillus johnsonii, together with an obesogenic diet, synergistically promotes tumour regression through an enrichment of microbiota-derived aromatic amino acid metabolites. Moreover, human-to-mouse FMT from donors with a high BMI enhanced ICI efficacy compared with donors with a normal BMI, and an obesogenic diet restored sensitivity following FMT from a non-responder patient. Our study provides insight on epidemiological associations between BMI and ICI efficacy, and suggests that immunomodulatory synergy between diet and the gut microbiota could be leveraged to improve ICI outcomes and FMT interventions.}, }
@article {pmid42128989, year = {2026}, author = {Takata, E and Lee, JJ and Lightner, AL}, title = {Needles for healing: stem cells, platelet-enriched plasma, and fat injection in perianal fistulizing Crohn's disease.}, journal = {Techniques in coloproctology}, volume = {30}, number = {1}, pages = {}, pmid = {42128989}, issn = {1128-045X}, mesh = {Humans ; *Crohn Disease/complications ; *Rectal Fistula/therapy/etiology ; *Wound Healing ; *Platelet-Rich Plasma ; *Mesenchymal Stem Cell Transplantation/methods ; *Adipose Tissue/transplantation ; }, abstract = {Perianal fistulizing Crohn's disease affects a third of patients with Crohn's disease and represents one of the most challenging complications to manage. This severe phenotype is characterized by aggressive disease behavior, high recurrence rates, frequent hospitalizations and surgical interventions, and profound impairment of quality of life, particularly affecting social and sexual function. The complex pathophysiology involves genetic susceptibility, immune dysregulation with elevated inflammatory cytokines, epithelial-to-mesenchymal transition, myofibroblast activation, and impaired wound healing mechanisms. Despite advances in anti-inflammatory and immunomodulatory therapies, current medical and surgical approaches achieve long-term fistula healing in only approximately 50% of patients. More than 90% of patients undergo multiple operative interventions, often with limited efficacy and risk of fecal incontinence. Anti-tumor necrosis factor agents, particularly infliximab, remain the cornerstone of medical therapy, yet more than 50% of patients lose response over time. Combination approaches with setons and biologics improve outcomes but remain suboptimal for many patients.These persistent limitations have prompted increasing interest in regenerative strategies aimed at restoring tissue integrity and enhancing local healing mechanisms. Mesenchymal stem cell therapy, particularly adipose-derived stem cells, has emerged as a promising approach, with clinical trials demonstrating complete fistula healing in the majority of cases and a favorable safety profile, but there are limitations with logistics of cell handling and negative late phase pivotal trials. This review evaluates the current landscape of novel regenerative therapies for perianal fistulizing Crohn's disease, including mesenchymal stem cell preparations, extracellular vesicle-based approaches, and adjunctive techniques.}, }
@article {pmid42407345, year = {2026}, author = {Shi, Y and Xue, Q and Yuan, Y and Li, Y and Zhu, X and Niu, D and Jin, C}, title = {WD-3 improves anti-PD-L1 therapy by remodeling the tumor immune microenvironment through gut microbiota.}, journal = {Immunobiology}, volume = {231}, number = {4}, pages = {153215}, doi = {10.1016/j.imbio.2026.153215}, pmid = {42407345}, issn = {1878-3279}, abstract = {BACKGROUND: Gastric cancer (GC) ranks as the fifth most prevalent malignancy globally. Emerging evidence implicates gut microbiome as a key modulator of anti-tumor immunity and immunotherapy response. Traditional Chinese Medicine (TCM) presents a promising yet underexplored avenue for microbiome modulation.<br><br>METHODS: 16S rDNA sequencing of fecal samples was used to detect changes of gut microbiota in advanced GC patients. GC models were established in huPBMC-NOG-dKO mice after fecal microbiota transplantation (FMT) to investigate the potential synergy between Number 3 Prescription (WD-3) and anti-PD-L1 monoclonal antibody (mAb) in treatment of non-responders.<br><br>RESULTS: In this study, WD-3 combined with &#x3b1;PD-L1 showed additive benefit after the FMT of non-responders in the humanized mouse model model. WD-3 combination therapy correlated with reduced proportion of Treg cell infiltration in tumors. WD-3 combination was also associated with increased species richness and improved gut microbiota community structure compared to &#x3b1;PD-L1 alone, with increased relative abundances of Enterobacteriaceae and Lachnospiraceae.<br><br>CONCLUSION: Our data provide correlative evidence that WD-3 supplementation combined with &#x3b1;PD-L1 treatment may attenuate GC progress in the FMT mouse model, indicating association with the modulation of gut microbiota. These findings aim to provide treatment strategies for the clinical treatment of advanced GC.}, }
@article {pmid42410815, year = {2026}, author = {Liao, DX and Zhang, S and Cao, D and Cai, X and Sun, HL and Jin, WD and Fu, T}, title = {Fecal microbiota transplantation for chronic constipation following bowel surgery in an elderly patient: A case report.}, journal = {Medicine}, volume = {105}, number = {27}, pages = {e49600}, doi = {10.1097/MD.0000000000049600}, pmid = {42410815}, issn = {1536-5964}, mesh = {Humans ; *Constipation/therapy/etiology ; Male ; *Fecal Microbiota Transplantation/methods ; Aged ; Chronic Disease ; Treatment Outcome ; Dysbiosis/therapy ; Colorectal Surgical Procedures ; *Postoperative Complications/therapy ; }, abstract = {RATIONALE: Chronic constipation is a common gastrointestinal disorder traditionally managed with laxatives and surgical interventions. Nevertheless, a subset of elderly patients remains unresponsive to conventional treatments. Additionally, chronic constipation is linked to an increased risk of mortality from cardiovascular events and a heightened incidence of colorectal cancer.<br><br>PATIENT CONCERNS: A 65-year-old male with a medical history of sigmoidostomy, enterostomy, and jejunostomy presented with an 11-year history of intermittent abdominal distension, pain, and constipation refractory to standard treatments including lactulose, castor oil, and glycerin enemas.<br><br>DIAGNOSES: The patient was diagnosed with severe chronic constipation associated with surgically altered anatomy and intestinal dysbiosis.<br><br>INTERVENTIONS: After thorough discussion, fecal microbiota transplantation (FMT) was implemented as a therapeutic intervention.<br><br>OUTCOMES: The patient's abdominal distension and pain were significantly alleviated within 1 week and completely resolved 6 months post-FMT. No recurrence was observed during the subsequent follow-up period.<br><br>LESSONS: This case demonstrates that FMT can serve as an effective therapeutic intervention for elderly patients with surgically altered anatomy and intestinal dysbiosis, particularly those showing reduced response to conventional laxative treatments for chronic constipation.}, }
@article {pmid42410982, year = {2026}, author = {Alanazi, A}, title = {Organ-Specific Human Microbiomes and Dysbiosis: Mechanistic Links to Disease and Emerging Therapeutic Strategies.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e70307}, doi = {10.1002/jcla.70307}, pmid = {42410982}, issn = {1098-2825}, abstract = {BACKGROUND: The human microbiome is a dynamic and diverse community of microorganisms that affects susceptibility to illness and promotes wellness. Dysbiosis, or disruption of this delicately regulated microbial ecology, has been identified as a major factor in the emergence and development of systemic and organ-specific disorders.<br><br>OBJECTIVE: With an emphasis on dysbiosis-driven illness processes and therapeutic intervention implications, this study attempts to critically analyze host-microbiome interactions across key human organ systems.<br><br>METHODS: Using predetermined microbiome-related keywords, a systematic literature search (2001-2025) was carried out in PubMed, Scopus, Web of Science, and Google Scholar. To assess microbiome formation, organ-specific distribution, disease correlations, and therapeutic implications, English-language peer-reviewed original papers, meta-analyses, and clinical or validated animal studies were chosen and methodically compiled.<br><br>RESULTS: Microbiome dysbiosis is linked to cardiovascular, metabolic, inflammatory, neurological, hepatic, renal, and cancer-related illnesses by interfering with immune modulation, metabolic balance, and epithelial barrier integrity, according to evidence from human and verified animal research. Modified production of short-chain fatty acids, immunological signaling imbalance, chronic inflammation, and communication between the gut-organ axis are examples of mechanistic linkages. Immune and metabolic indicators improved condition-specifically with interventions such as probiotics, fecal microbiota transplantation, and diet-based regulation.<br><br>CONCLUSION: Collectively, current evidence supports the microbiome as a modifiable determinant of disease risk and therapeutic response, underscoring its translational potential for precision medicine.}, }
@article {pmid42411731, year = {2026}, author = {Liang, B and Zou, J and Mao, X and Xie, N and Liang, Z}, title = {Systematic Review and Meta-Analysis of the Efficacy of Fecal Microbiota Transplantation in Parkinson's Disease: An Exploration Based on UPDRS and Cognitive Scores.}, journal = {Revista de neurologia}, volume = {81}, number = {6}, pages = {50106}, doi = {10.31083/RN50106}, pmid = {42411731}, issn = {1576-6578}, mesh = {Humans ; *Parkinson Disease/therapy/psychology ; *Fecal Microbiota Transplantation ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Cognition ; Severity of Illness Index ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that has been increasingly linked to gut-brain axis dysfunction. Fecal microbiota transplantation (FMT), a microbiome-targeted intervention, has shown theoretical and preliminary clinical potential in PD, but randomized clinical evidence remains limited. This review aimed to systematically evaluate the effects of FMT on motor, non-motor, and cognitive outcomes in patients with PD.<br><br>METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review and meta-analysis of randomized controlled trials (RCTs) comparing FMT with placebo or conventional care in PD was conducted. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Pooled analyses were performed using a random-effects model, and the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.<br><br>RESULTS: Five RCTs involving 226 participants were included. No statistically significant differences were observed between the FMT and control groups in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III, Montreal Cognitive Assessment (MoCA), or Mini-Mental State Examination (MMSE) scores at any assessed follow-up time, with heterogeneity generally low to moderate across outcomes.<br><br>CONCLUSIONS: Based on current evidence from five small RCTs, FMT did not demonstrate a statistically significant benefit for motor, daily living, or cognitive outcomes in PD. However, these findings should be interpreted cautiously, given the limited sample size, short follow-up duration, and between-study differences in intervention protocols. Larger, well-designed RCTs with standardized FMT protocols and longer follow-up are needed. The PROSPERO Registration: This systematic review was registered in the PROSPERO database under registration number CRD420251121443, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251121443.}, }
@article {pmid42412324, year = {2026}, author = {Adiga, U and Vasishta, S and Adiga, S and Augustine, AJ}, title = {Targeting the Gut-Heart Axis in Atherosclerosis: Microbial Metabolites, Molecular Mechanisms, and Precision Therapeutics.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {42412324}, issn = {1867-1314}, abstract = {Despite advances in lipid-lowering and anti-inflammatory medications, atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of morbidity and mortality worldwide. Recent studies have identified the gut microbiota as a key modulator of cardiovascular health via the gut-heart axis. This review investigates the molecular processes by which microbial metabolites affect atherogenesis. Proatherogenic substances like trimethylamine-N-oxide (TMAO), which are produced from dietary precursors through gut microbial and hepatic metabolism, aggravate foam cell production, platelet aggregation, and vascular inflammation. Short chain fatty acids (SCFAs), such as butyrate and propionate, have been shown to protect against atherosclerosis by activating G-protein-coupled receptors, regulating gene expression, and improving endothelial function. Additionally, secondary bile acids, tryptophan derivatives, and phenylacetylglutamine have emerged as important microbial metabolites involved in vascular disease. The review also summarizes various therapeutic strategies such as use of probiotics, prebiotics, postbiotics, precision microbiome editing (using bacteriophages and CRISPR-Cas systems), and fecal microbiota transplantation (FMT) for targeting gut-heart axis. Multi-omic systems combined with artificial intelligence can now detect disease-specific microbial signatures, improving risk stratification and paving the way for precision microbiome-based therapeutics. However, challenges such as determining causality, regulatory intricacies, and inter-individual variability in host-microbiome interactions remain. Despite these obstacles, the gut-heart axis provides a disruptive paradigm in preventive cardiology by emphasizing tailored microbiome therapies as a complement to traditional ASCVD care.}, }
@article {pmid42402612, year = {2026}, author = {Cao, L and Zhang, G and Zhang, G and Zhang, F and Li, W and Song, Q and He, J and Zhao, J and Zhang, Z}, title = {Cichorium intybus L. polysaccharide improves growth performance and colonic barrier function in weaned piglets via the microbiota-HDCA-TGR5-Akt-NF-κB signaling axis: validation by FMT and in vitro models.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {}, pmid = {42402612}, issn = {1674-9782}, support = {32302766//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Weaning stress predisposes piglets to intestinal barrier disruption and gut dysbiosis, which contribute to post-weaning diarrhea and poor feed efficiency. Chicory (Cichorium intybus L.) polysaccharide (CLP) is a fructan-rich prebiotic candidate; however, how CLP reshapes the microbiota-metabolite network to protect the colon remains unclear.<br><br>METHODS: In Exp. 1, 96 weaned piglets [Duroc&#x2009;&#xd7;&#x2009;(Landrace&#x2009;&#xd7;&#x2009;Yorkshire), 28&#xa0;days old, 8.03&#x2009;&#xb1;&#x2009;0.2&#xa0;kg] were fed a basal diet (CON group) or a 0.5% CLP supplemented diet (CLP group). In Exp. 2, fecal microbiota from piglets were transplanted into dextran sulfate sodium (DSS)-induced mice to confirm the causal role of the CLP-remodeled microbiota. Metagenomic and untargeted metabolomic analyses were employed to identify key microbial species and functional metabolites. In Exp. 3, Caco-2 cells were treated with varying concentrations of hyodeoxycholic acid (HDCA) for 24&#xa0;h to functionally validate the regulatory effects on TGR5&#xa0;and FXR&#xa0;expression levels.<br><br>RESULTS: The results showed that dietary CLP significantly decreased the feed to gain ratio, diarrhea rate and histology index (P&#x2009;<&#x2009;0.05), but increased goblet cell numbers (P&#x2009;<&#x2009;0.05). Metagenomic sequencing revealed that CLP significantly increased microbial &#x3b1;-diversity and remodeled the community structure, specifically enriching beneficial microbes, such as Blautia sp., Eubacterium sp., and Ruminococcus sp. To test microbiota causality, fecal microbiota from CON or CLP piglets was transplanted into antibiotic treated mice followed by DSS challenge. The CLP modified microbiota alleviates DSS induced colitis, upregulated Occludin and ZO-1 expression, and reduced colonic IL-1&#x3b2; and TNF-&#x3b1; levels. Mechanistically, the CLP remodeled microbiota promoted the accumulation of HDCA, which functioned as a signaling ligand to activate the colonic TGR5 receptor. This activation subsequently suppressed the phosphorylation of Akt (P&#x2009;<&#x2009;0.05), leading to the inhibition of the NF-&#x3ba;B signaling pathway through the reduced phosphorylation of I&#x3ba;B&#x3b1; and the p65 subunit (P&#x2009;<&#x2009;0.05), thereby effectively abrogating the inflammatory response.<br><br>CONCLUSION: Dietary CLP supplementation mitigates weaning induced intestinal injury and inflammation by remodeling the colonic microbiota, specifically enriching HDCA-producing species. The subsequent activation of the HDCA-TGR5-Akt signaling axis inhibits the NF-&#x3ba;B pathway, thereby improving host immune responses and intestinal barrier function.}, }
@article {pmid42403915, year = {2026}, author = {Wang, T and Chen, L and Lei, C and Song, X and Tuohongerbieke, A and Feng, J and Gasparetto, R and Zhang, X and McClain, CJ and Tan, Y and Deng, Z}, title = {Intestinal neutral ceramidase exacerbates MASH pathogenesis.}, journal = {eGastroenterology}, volume = {4}, number = {2}, pages = {e100417}, pmid = {42403915}, issn = {2976-7296}, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease and its more severe manifestation, metabolic dysfunction-associated steatohepatitis (MASH), are intimately linked to genetic factors, gut microbiota and barrier alteration. Ceramidases and ceramides are associated with MASH, yet the role of intestinal neutral ceramidase in MASH development remains unclear.<br><br>METHODS: Murine models with intestinal epithelial cell (IEC)-specific depletion of neutral ceramidase (Asah2[&#x394;IEC]) or aryl hydrocarbon receptor (AhR [&#x394;IEC]) were subjected to either a Western diet (WD) at 6 weeks old for 10-12 months to induce MASH, or a hydrogenated vegetable oil, sucrose, palmitate and cholesterol (HSPC) diet to accelerate MASH progression. Fecal microbiota transplantation was performed in germ-free mice.<br><br>RESULTS: MASH is associated with the induction of neutral ceramidase, which reshapes the intestinal microbiota and metabolite profiles, leading to increased production of 2-hydroxyhippuric acid (2-HHA). We identified 2-HHA as an inhibitor of AhR signalling, a pathway that normally promotes intestinal fucosylation. Elevated 2-HHA suppresses AhR activity, reduces fucosylation and contributes to MASH and associated airway inflammation in mice fed WD or HSPC diet. Notably, IEC-specific deletion of neutral ceramidase decreases 2-HHA levels, restores AhR signalling, enhances fucosylation and protects against MASH. Consistently, intestinal AhR deficiency exacerbates MASH by reducing intestinal fucosylation, whereas supplementation with fucoidan increases fucosylation, improves barrier function and attenuates MASH.<br><br>CONCLUSIONS: These findings identify intestinal neutral ceramidase as a key driver of MASH through a microbiota-2-HHA-AhR axis that impairs intestinal fucosylation and barrier function, highlighting a potential therapeutic target.}, }
@article {pmid42404763, year = {2026}, author = {Wang, X and Piao, Y and Xia, B and Chu, W and Yao, X and Li, W}, title = {Diet, gut microbiota, and the gut-brain axis: mechanistic interactions and therapeutic implications in neuropsychiatric disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1834069}, pmid = {42404763}, issn = {2235-2988}, mesh = {Humans ; *Diet ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders/therapy/microbiology ; *Brain ; Animals ; Dysbiosis ; *Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota is a dynamic trans-kingdom ecosystem that contributes to host immunological, metabolic, and neuroendocrine homeostasis through the microbiota-gut-brain axis (MGBA). Diet is one of the major environmental factors shaping this axis, as it influences microbial composition, microbial production of neuroactive metabolites, and intestinal barrier integrity. Dysbiosis has been increasingly associated with neurological, psychiatric, and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Experimental studies have identified several potential mechanisms linking gut microbiota to brain function, including immune modulation, vagus nerve signaling, microbial metabolite production, and blood-brain barrier regulation. However, translating these findings into clinical practice remains challenging because human studies are affected by genetic heterogeneity, dietary variation, medication use, lifestyle factors, and disease-specific confounders. In this review, we summarize current evidence on the interactions among diet, gut microbiota, and brain function, with particular emphasis on microbial metabolites, immune mediators, and barrier-related mechanisms. We also critically discuss microbiota-targeted interventions, including precision nutrition, probiotics, and fecal microbiota transplantation, highlighting both their therapeutic potential and their current limitations. A more cautious and mechanistically integrated understanding of the MGBA may support the development of personalized strategies for neuropsychiatric disease prevention and management.}, }
@article {pmid42404795, year = {2026}, author = {Tang, J and Chen, L and Wang, Q and He, X and Hang, D and Chen, G and Feng, L}, title = {Optimized fecal microbiota transplantation using membrane-filtered bacterial concentrates as adjunctive therapy for mild-to-moderate ulcerative colitis: a retrospective cohort study.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1805799}, pmid = {42404795}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for ulcerative colitis (UC). This single-center retrospective cohort study evaluated the clinical effectiveness and safety of an optimized FMT protocol, in which donor bacteria were concentrated by tangential-flow micropore membrane filtration and delivered after pre-FMT antibiotic preconditioning, as adjunctive therapy in adults with mild-to-moderate UC.<br><br>METHODS: We analyzed prospectively collected data from 156 patients with mild-to-moderate active UC treated between December 2022 and December 2024. Treatment allocation was determined by a shared clinical decision between the gastroenterologist and patient based on disease severity, prior medication exposure, and patient preference. Patients were grouped into four pre-specified treatment strata: aminosalicylates alone (Group A, n = 42), aminosalicylates plus corticosteroids/immunosuppressants (Group B, n = 38), aminosalicylates plus FMT (Group FMT1, n = 40), and aminosalicylates plus corticosteroids/immunosuppressants plus FMT (Group FMT2, n = 36). Donor stools were processed using a validated tangential-flow 0.22-&#x3bc;m membrane filtration workflow that retains and concentrates viable bacteria in the retentate while clearing soluble metabolites and host debris in the permeate. Confounding was addressed using multivariable logistic regression and inverse probability of treatment weighting (IPTW) as a sensitivity analysis. The primary outcome was clinical response at 12 weeks; effect sizes are reported as risk differences with 95% confidence intervals.<br><br>RESULTS: Clinical response rates at 12 weeks were 31.0% (Group A), 52.6% (Group B), 72.5% (Group FMT1), and 77.8% (Group FMT2). Clinical remission rates were 19.0%, 34.2%, 55.0%, and 61.1%, respectively. FMT-containing regimens were associated with higher response and remission than aminosalicylates alone (risk difference for response: 41.5%, 95% CI 22.7-60.3% for FMT1 vs. A; 46.8%, 95% CI 28.0-65.6% for FMT2 vs. A; both P < 0.001). Microbiome analysis using 16S rRNA gene sequencing showed that responders had increased Bacteroides-related amplicon sequence variants and increased alpha diversity comparable to donor profiles, while non-responders maintained dysbiotic profiles. Adverse events were mild and comparable across all groups.<br><br>CONCLUSIONS: In this retrospective cohort, an optimized FMT protocol using membrane-filtered bacterial concentrates was associated with higher rates of clinical response, clinical remission and endoscopic improvement at 12 weeks compared with conventional therapy, with an acceptable short-term safety profile. Given the observational design, these findings should be interpreted as hypothesis-generating and require confirmation in randomized controlled trials.}, }
@article {pmid42404992, year = {2026}, author = {Szilagyi, A and Galiatsatos, P and Margolese, N and Hilzenrat, N}, title = {Microbiome alternative treatments for hepatic encephalopathy: Reassessment of the potential use of lactose in lactase non-persistent cirrhosis patients.}, journal = {Canadian liver journal}, volume = {9}, number = {2}, pages = {319-327}, pmid = {42404992}, issn = {2561-4444}, abstract = {BACKGROUND: Hepatic encephalopathy is secondary to liver failure and is prevalent in 20%-40% of cirrhosis patients. The cause involves ammonia toxicity, gut-brain interactions, and inflammation usually involving the microbiome. The aim was to review succinct management of microbiome disturbances. The purpose includes an argument for further research into the possible selective benefit of lactose and dairy products in managing chronic hepatic encephalopathy in lactose maldigesters.<br><br>METHODS: Articles from 1970 to June 2025 were sought on PubMed and Google Scholar, as well as individual articles, regarding using altered microbiome and hepatic encephalopathy management.<br><br>RESULTS: Non-digestible disaccharides and synthetic polymers, often combined with non-absorbable antibiotic rifaximin, have been found to benefit hepatic encephalopathy. It is of note that after a few reports, lactose was abandoned as a potential treatment in lactase non-persistent cirrhotic patients. After abandonment for unclear reasons, colonic adaptation in lactase non-persistent populations was clearly defined to be associated with microbiome changes similar to other non-absorbable disaccharides.<br><br>CONCLUSIONS: While current treatment is acceptable to most patients, the potential role of lactose and dairy products likely deserves further studies in patients with lactase non-persistence. The process of colonic adaptation may favour improvement in hepatic encephalopathy by altering the bacterial milieu. Use of dairy foods could also improve nutrition in cirrhosis. As such, use of lactose or dairy products could have a wide application since cirrhosis is common in parts of the world where lactose maldigestion is also widespread.}, }
@article {pmid42405758, year = {2026}, author = {Zhang, S and Tu, J and Hong, W and Liu, J and Xue, C and Dong, N}, title = {Gut microbiota as key mediators of animal acclimation to temperature changes: mechanisms and interventions.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0241225}, doi = {10.1128/aem.02412-25}, pmid = {42405758}, issn = {1098-5336}, abstract = {With the intensification of global climate change, temperature fluctuations profoundly affect animal physiology and health. Research has shown that the gut microbiota, as a critical bridge between the host and its environment, helps animals adapt to temperature changes by regulating intestinal barrier stability, immune function, and energy metabolism. This adaptive capacity underscores the indispensable role of gut microbiota in temperature change responses. In cold environments, animals increase food intake and activate brown adipose tissue to maintain body temperature, but prolonged exposure causes metabolic overload and gut microbiota imbalance. Chronic cold reduces beneficial bacteria and increases pro-inflammatory species, impairing intestinal barrier integrity and inducing systemic inflammation, ultimately leading to metabolic disorders and immunosuppression. Similarly, heat exposure leads to pathogenic overgrowth and immune dysfunction, reducing microbial diversity and increasing the abundance of harmful bacteria, ultimately impairing animal health. Furthermore, the gut-brain axis plays a central role in coping with environmental stress, as temperature change alters microbial composition and metabolites, impacting neurotransmitter synthesis and release, thereby regulating physiological states and emotional responses. Finally, targeted microbial interventions-such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and postbiotics-are discussed as effective strategies to restore gut microbiota homeostasis, enhance host resilience to temperature change, and improve animal health under temperature fluctuations.}, }
@article {pmid42405768, year = {2026}, author = {Berryhill, BA and Gil-Gil, T and Burke, KB and Fontaine, J and Brink, CE and Harvill, MG and Goldberg, DA and Navas, JN and Grabowicz, M and Konstantinidis, KT and Levin, BR and Woodworth, MH}, title = {Enteric populations of Escherichia coli are likely to be resistant to phages due to O antigen expression.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0038626}, doi = {10.1128/msphere.00386-26}, pmid = {42405768}, issn = {2379-5042}, abstract = {Metagenomic data provide evidence that bacteriophage (phage) abound in the enteric microbiomes of humans. However, the contribution of these viruses in shaping the bacterial composition of the gut microbiome and how these phages are maintained remain unclear. We performed experiments with 756 combinations of 54 Escherichia coli and nine phage isolates from four fecal microbiota transplantation (FMT) doses and five laboratory phages as samples of non-dysbiotic human enteric microbiota. We also developed a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our experiments predict that as a consequence of the production of the O antigen, most of the E. coli in the human enteric microbiome will be resistant to infections with the array of co-occurring phages. Our modeling suggests that phages are maintained in these enteric communities due to the high rates of transition between the O antigen-resistant and -sensitive states. Based on our observations and predictions from this theory, we postulate that the phage found in the human gut are likely to play a little role in shaping the strain composition of E. coli of healthy individuals. Although we only investigated E. coli, the mechanism of resistance described here is shared among most of the gram-negative bacteria. Evidence is provided that, as a consequence of O antigen-mediated resistance, the genetically diverse array of bacteriophage in the gut microbiome of humans plays little or no role in determining the densities and distribution of the genetically diverse strain E. coli in this habitat. Our mathematical model predicts and our experiments support the hypothesis that the phage present in the gut microbiome are maintained by replication on the minority of sensitive bacteria generated by the leakiness of O antigen-mediated resistance.IMPORTANCEBacteriophages (phages) are abundant in the human gut, yet whether these viruses shape the bacterial communities living there remains unresolved. Using Escherichia coli and phages isolated from the stool of healthy fecal microbiota transplantation (FMT) donors, together with a mathematical model, we show that the vast majority of gut E. coli are resistant to co-occurring phages because they express the O antigen, a surface structure that masks the receptors phages use to attach. Despite this widespread resistance, phages persist by replicating on a small, continually regenerated subpopulation of sensitive cells, a phenomenon we term leaky resistance. These findings suggest that phages play a little role in determining which E. coli strains dominate the healthy human gut. Because the O antigen is broadly expressed across gram-negative bacteria, this mechanism likely extends well beyond E. coli and helps explain why isolating therapeutic phages against many pathogens is difficult.}, }
@article {pmid42401711, year = {2026}, author = {Huang, L and Lu, C and Hu, Y and Chen, J and Chen, A and Zhong, C and Chen, D and Qin, Z and He, X and Wu, L}, title = {Washed microbiota transplantation is associated with short-term changes in selected spirometric parameters in patients with abnormal spirometry.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-60829-8}, pmid = {42401711}, issn = {2045-2322}, support = {2026P-ZD004//Guangzhou Clinical High-Tech Major and Specialized Technology Project/ ; 82505713//the National Natural Science Foundation of China/ ; 2025A1515011113//the Basic and Applied Basic Research Fund of Guangdong Province/ ; 2025KTSCX058//the Characteristic Innovation Project of Regular Colleges and Universities in Guangdong Province/ ; }, abstract = {Gut microbiota may modulate pulmonary inflammation through the gut-lung axis. This study investigated the association between washed microbiota transplantation (WMT) and short-term changes in pulmonary function, inflammatory markers, and gut microbiota in patients with abnormal spirometric patterns. A total of 110 patients who underwent fecal microbiota transplantation, also referred to as WMT, were consecutively screened between March 2023 and January 2025. Of these, 47 patients with paired baseline and post-WMT spirometric data were included in the primary spirometric analysis. According to baseline spirometric patterns, WMT recipients were classified into an abnormal spirometric-pattern group (DG, n = 19) and a normal spirometric-pattern WMT-recipient group (HC, n = 28; HC denotes WMT recipients with normal spirometry rather than healthy community controls). In addition, 43 patients receiving conventional treatment without WMT were included as a non-WMT comparison group (CON). The WMT group underwent multi-course interventions with longitudinal monitoring of pulmonary function parameters, inflammatory markers, breath-holding time (BHT), and 36-Item Short Form Health Survey scores (SF-36). Gut microbiota composition and predicted functional profiles were analyzed using 16S rRNA gene sequencing. After one WMT course, DG patients showed increases in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Compared with the non-WMT comparison group, the change in FVC was greater in WMT recipients, whereas the between-group difference in FEV1 change was not statistically significant. Other spirometric indices, BHT, inflammatory markers, SF-36 scores, and microbiome-related findings were considered exploratory. Exploratory 16S rRNA gene sequencing identified differences in selected gut microbial taxa between WMT recipients with abnormal and normal spirometric patterns, including differences in Firmicutes, Faecalibacterium, and Alistipes. Predicted functional profiling suggested changes in glycerolipid metabolism-, Nod-like receptor signaling-, and bacterial chemotaxis-related functional potentials. WMT was associated with short-term changes in selected spirometric parameters, particularly FVC and FEV1, in patients with abnormal spirometric patterns. Changes in inflammatory markers, BHT, SF-36 scores, and microbiome-related findings were exploratory and hypothesis-generating. Further randomized, disease-specific studies with standardized pulmonary function testing and mechanistic validation are needed.}, }
@article {pmid42398209, year = {2026}, author = {Zhang, C and Jiang, Y and Li, X and Wan, Z and Li, M and Xu, Q and Wang, W and Huo, J}, title = {Run Chang Tong Mi tea alleviates functional constipation through regulating gut microbiota and SCF/c-kit pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158519}, doi = {10.1016/j.phymed.2026.158519}, pmid = {42398209}, issn = {1618-095X}, abstract = {BACKGROUND: Functional constipation (FC) is a gastrointestinal motility disorder related to intestinal transit function and hormonal imbalance and has been reported to be associated with an imbalance in the gut microbiota. Clinically, Run Chang Tong Mi tea (RCTM) can effectively alleviate the constipation symptoms of patients with FC. However, the mechanism by which RCTM improves FC and its regulation of intestinal homeostasis remain unclear.<br><br>PURPOSE: This study aims to investigate the potential mechanism of RCTM alleviates FC by improving intestinal motility and mucosal secretion function through gut microbiota and its metabolites.<br><br>METHOD: The FC rat model was established by loperamide hydrochloride. The treatment effect of RCTM was evaluated by assessing stool frequency, fecal water content, time to first black stool, and small bowel transit rate. The histological changes of colon were observed by HE staining. Serum and colonic hormone levels were measured by ELISA. Immunohistochemistry was performed to assess the expression of tight junction proteins associated with the intestinal barrier. Western blotting and RT-qPCR were used to analyze the expression of SCF/c-kit pathway and intestinal barrier related proteins and mRNA, 16S rDNA sequencing was used to analyze the composition of intestinal microbiota, and GC/MS was used to detect SCFAs levels. By transplanting RCTM-treated fecal bacteria into FC rats, the relationship between the disturbance of gut microbiota, the onset of FC and the effect of RCTM intervention was further clarified.<br><br>RESULTS: RCTM can effectively restore the gastrointestinal motility and repair the damaged intestinal barrier in FC rats. RCTM promoted the secretion of excitatory hormones and neurotransmitters in the gastrointestinal tract, and regulated the mRNA and protein content of SCF/c-kit pathway. Furthermore, RCTM restored gut microbiota disorder and SCFAs content. More importantly, RCTM-FMT effectively alleviated constipation symptoms and increased gastrointestinal hormone and neurotransmitter levels, effects that were associated with alterations in the abundance of Lachnospiraceae and Lactobacillus as well as enhanced SCFA production. Moreover, RCTM-FMT improved intestinal barrier function, which was associated with decreased abundances of Escherichia-Shigella and Dubosiella.<br><br>CONCLUSION: Our findings indicate that RCTM alleviated constipation in rats with FC, and this amelioration was associated with modulation of the gut microbiota, elevation of SCFAs, and restoration of the SCF/c-kit pathway.}, }
@article {pmid42401355, year = {2026}, author = {El-Sehrawy, AAMA and Farah, H and Oripov, F and Shakhmurova, G and Hussein, FM and Maharana, L and Singh, R and Tailor, NK}, title = {Estrobolome and the Endocrine-Microbiome Axis in Breast and Endometrial Carcinogenesis.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {105471}, doi = {10.1016/j.critrevonc.2026.105471}, pmid = {42401355}, issn = {1879-0461}, abstract = {The estrobolome, the community of gut microbial genes involved in estrogen metabolism, may influence hormone bioavailability and cancer risk, although human evidence remains largely associative. This review summarizes evidence that bacterial β-glucuronidases, sulfatases, and hydroxysteroid dehydrogenases regulate enterohepatic estrogen recycling, while microbial metabolism also shapes receptor signaling, genotoxic estrogen metabolites, inflammation, and immune responses. Observational studies link gut microbial composition and function with breast and endometrial cancer, but causality remains unproven. Early dietary, probiotic, antibiotic, and fecal microbiota transplantation studies show biological effects, yet they are not sufficient for clinical application. We propose a functional framework that prioritizes microbial enzymatic activity over taxonomy and highlight multiparametric biomarkers and selective β-glucuronidase inhibition as promising research directions for prevention and adjunct therapy in hormone-driven cancers.}, }
@article {pmid42393343, year = {2026}, author = {Wang, S and Hu, S and Yan, Y and Wu, L and Tang, L and Hu, Y and Wang, W}, title = {Docosahexaenoic acid alleviates DSS-induced colitis by regulating the gut microbiota and restoring the gut barrier.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {}, number = {}, pages = {}, pmid = {42393343}, issn = {1618-1905}, abstract = {Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has well-recognized anti-inflammatory activity; however, the mechanisms underlying its protective effects in inflammatory bowel disease (IBD) remain incompletely understood. In this study, we investigated the effects of DHA in a dextran sulfate sodium (DSS)-induced mouse model of colitis and examined whether these effects were mediated by the gut microbiota. DHA administration markedly alleviated DSS-induced colitis, as indicated by reduced body weight loss, disease activity, mortality, colon shortening, histological injury, intestinal barrier disruption, and colonic inflammatory responses. 16 S rRNA gene sequencing showed that DHA reshaped the gut microbial community and increased the abundance of beneficial taxa, including Bifidobacterium. Antibiotic cocktail (ABX)-mediated microbiota depletion largely abolished the protective effects of DHA, whereas fecal microbiota transplantation (FMT) from DHA-treated donors transferred resistance to DSS-induced colitis to recipient mice. DHA also restored tight junction protein expression and increased the frequency of colonic regulatory T cells in a microbiota-dependent manner. These findings indicate that DHA alleviates experimental colitis by modulating the gut microbiota, restoring intestinal barrier integrity, and regulating mucosal immune homeostasis. DHA may therefore represent a promising dietary strategy for the prevention or adjunctive treatment of ulcerative colitis (UC).}, }
@article {pmid42394968, year = {2026}, author = {Hu, Q and Jin, H and Hu, L and Li, X}, title = {The role of mitochondria in the gut-kidney axis: implications for kidney health.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1851705}, pmid = {42394968}, issn = {1663-9812}, abstract = {Mitochondria, multifunctional organelles that regulate cellular energy metabolism and signaling pathways, play a pivotal role in maintaining the physiological functions of the gut and kidneys, as well as influencing the progression of chronic kidney disease (CKD). Through the gut-kidney crosstalk, gut microbiota modulate gut and renal pathophysiology and also influence mitochondrial activity in intestinal and renal cells. This review explores the regulatory roles of mitochondria in preserving epithelial barrier integrity, regulating intestinal metabolism, and maintaining gut microbiota homeostasis. It also examines the contributions of mitochondrial biogenesis, dynamics, autophagy abnormalities, and mitochondrial DNA (mtDNA) damage to renal pathological progression. Moreover, we highlight the bidirectional interactions between intestinal and renal mitochondria via the microbiota-mitochondria-kidney axis and mechanisms involving inflammation, oxidative stress, and ferroptosis. Therefore, targeting mitochondrial regulation through non-pharmacological interventions such as dietary adjustments, probiotic supplementation and fecal microbiota transplantation (FMT) emerges as a promising therapeutic strategy for maintaining renal health by optimizing mitochondrial function. In conclusion, elucidating the mechanisms of mitochondrial involvement in the gut-kidney axis will lay the foundation for novel therapeutic approaches to CKD and other gut-kidney axis-related disorders.}, }
@article {pmid42395662, year = {2026}, author = {Kashiv, P and Balwani, MR and Pasari, A and Saxena, K and Kute, VB}, title = {Trimethylamine N-oxide as a key microbial mediator in the progression of diabetic kidney disease.}, journal = {World journal of nephrology}, volume = {15}, number = {2}, pages = {117355}, pmid = {42395662}, issn = {2220-6124}, abstract = {In this editorial, we comment on the article by Song et al published in the recent issue of the World Journal of Nephrology, which investigates the mechanistic role of gut microbiota-derived trimethylamine N-oxide (TMAO) in accelerating diabetic kidney disease through renal fibrotic pathways. Diabetic kidney disease is increasingly recognised as a disorder influenced not only by intrinsic renal metabolic and inflammatory pathways. In the Zucker diabetic fatty model, the investigators demonstrate a reproducible pattern in which progression of renal injury is accompanied by distinct alterations in gut microbial composition and a marked rise in circulating TMAO concentrations. The incorporation of fecal microbiota transplantation further shows that the dysbiotic microbial environment characteristic of diabetic kidney disease possesses an intrinsically enhanced capacity to generate TMAO and can transfer this metabolic profile to recipient animals, establishing functional evidence that gut microbial changes can modify host metabolite production. Partial improvement in renal biochemical parameters, fibrotic protein expression, and histological abnormalities following inhibition of trimethylamine formation reinforces the mechanistic relevance of this pathway within the gut-kidney axis and supports the concept that therapeutic strategies targeting microbial metabolism may offer a promising direction for altering the clinical trajectory of diabetic kidney disease.}, }
@article {pmid42395675, year = {2026}, author = {Almuhanna, AA and Vatte, C and Guo, Q and Elsalamouni, TS and Al-Muhanna, FA and Aboalrihy, AM and Alhabib, HA and Almomen, MF and Alali, RA and Habara, AH and Alrubaish, MA and Alfalah, KM and Cyrus, C and Abdul-Rahman, IS and Keating, BJ and Al-Ali, AK and Wang, C}, title = {Gut microbiota in a Saudi population with chronic kidney disease.}, journal = {World journal of nephrology}, volume = {15}, number = {2}, pages = {118343}, pmid = {42395675}, issn = {2220-6124}, abstract = {BACKGROUND: The gut microbiota (GM) plays an important role in chronic kidney disease (CKD) progression, and dialysis modalities can differentially impact the GM composition and function. There is also limited information on the GM in Arab populations.<br><br>AIM: To investigate the distinct microbial profiles and functional alterations associated with hemodialysis (HD) and peritoneal dialysis (PD) in a Saudi Arabian cohort.<br><br>METHODS: We performed whole-genome metagenomic sequencing on fecal samples from 189 participants (controls and CKD, HD, and PD patients).<br><br>RESULTS: We detected distinct microbial profiles across all patient groups compared with that of the controls. Microbial risk scores derived from differentially abundant taxa accurately distinguished CKD, PD, and HD patients from controls, with area under the curves exceeding 0.9. Compared with HD patients, PD patients exhibited reduced species richness, an increased abundance of opportunistic pathogens (particularly Proteobacteria), and increased virulence. Functional analysis revealed suppressed energy metabolism and activated proinflammatory pathways in PD patients. Cooccurrence network analysis demonstrated decreased microbial community resilience in PD patients, with increased Proteobacteria interactions. Conversely, the HD group showed partial recovery of microbial balance and beneficial metabolic functions, including increased short-chain fatty acid metabolism and reduced lipopolysaccharide biosynthesis.<br><br>CONCLUSION: The findings of this study highlight the potential of the microbial profile as a robust biomarker for CKD classification and underscore the differential impacts of different dialysis modalities.}, }
@article {pmid42397471, year = {2026}, author = {Li, X and Li, H and Wang, Q and Gao, X and Gao, J and Du, M and Zhang, W and Liu, S and Liang, Y and Li, Q and Gan, Y and Tu, H}, title = {Enriched environment inhibits melanoma by reshaping gut microbiota and enriching Parabacteroides distasonis.}, journal = {Cellular oncology (Dordrecht, Netherlands)}, volume = {}, number = {}, pages = {}, doi = {10.1007/s13402-026-01249-8}, pmid = {42397471}, issn = {2211-3436}, support = {82003249//the National Natural Science Foundation of China/ ; 82203173//the National Natural Science Foundation of China/ ; 82173381//the National Natural Science Foundation of China/ ; 24ZR1465400//Natural Science Foundation of Shanghai/ ; ZZ94-2307//the State Key Laboratory of Systems Medicine for Cancer/ ; }, abstract = {PURPOSE: The role of psychological factors in the holistic regulation of cancer has garnered significant attention. Psychological eustress induced by an enriched environment (EE) inhibits various cancers including melanoma, but underlying mechanisms remain largely unknown. The brain-gut axis may play a key role in modulating psychological factors and cancer progression. This study investigates the role of gut microbiota in EE-induced anti-melanoma effects.<br><br>METHODS: C57BL/6 mice were housed in EE or standard environment (SE). Longitudinal fecal samples from EE and SE mice underwent 16S rRNA gene sequencing. SE melanoma-bearing mice received fecal microbiota transplantation (FMT) from EE or SE donors to assess the microbiota's causal role in EE's anti-tumor effects. Bacterial species upregulated by EE in tumor-bearing mice were identified;Parabacteroides distasonis (Pd) was selected for therapeutic administration. Immune cells in spleen and tumor were quantified by flow cytometry. Natural killer (NK) cell function was tested using anti-NK1.1 depletion.<br><br>RESULTS: EE increased the alpha diversity of the gut microbiota and alleviated the dysbiosis caused by melanoma. FMT from EE mice to SE mice inhibited melanoma growth, suggesting that the gut microbiota contributes to EE's anti-tumor effects. EE upregulated seven bacterial species in tumor-bearing mice, including Pd. Oral administration of Pd inhibited melanoma growth and increased intratumoral NK/NKT cell proportions and NK cell granzyme B expression. NK cell depletion abrogated Pd's anti-tumor effect.<br><br>CONCLUSION: This study underscores the interconnectedness of psychological eustress, gut microbiota, and cancer, providing preclinical insights into holistic cancer treatments. Leveraging the brain-gut-cancer axis, targeting psychological factors and gut microbiota could offer a potential adjunctive strategy for melanoma management.}, }
@article {pmid42398208, year = {2026}, author = {Yi, Y and Li, D and Li, Y and Wang, H and Yang, D and Yang, S and Xing, S and Wei, S and Yang, J and Guo, H and Luo, Z}, title = {Abrus cantoniensis α-glucan-like polysaccharide alleviates influenza via gut microbial acetate to activate free fatty acid receptor 2/ mitochondrial antiviral signaling protein/interferon-beta pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158533}, doi = {10.1016/j.phymed.2026.158533}, pmid = {42398208}, issn = {1618-095X}, abstract = {BACKGROUND: The gut microbiota is critical for host defense against influenza. Polysaccharides are known for their microbiota-modulating and immunomodulatory activities; however, the anti-influenza efficacy of homogeneous Abrus cantoniensis polysaccharides (ACP) remains unexplored.<br><br>PURPOSE: The present study seeks to clarify the protective role of ACP in influenza and explore its underlying molecular mechanisms.<br><br>METHODS: Initially, crude polysaccharides were extracted via ethanol precipitation and subsequently purified by gel chromatography. Systematic structural characterization of ACP was then performed using carbohydrate chemistry techniques, including scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), ultraviolet (UV) spectroscopy, and nuclear magnetic resonance (NMR). The therapeutic efficacy of ACP was assessed by monitoring various indicators such as body weight, survival rate, viral load, and pulmonary pathological changes in mouse models. Furthermore, to elucidate the biological mechanism underlying ACP's anti-influenza activity via regulation of pulmonary interferon-beta (IFN-&#x3b2;) immune networks by intestinal acetate-producing microbiota, multi-omics analyses integrating metagenomics, metabolomics, gene knockout, immunofluorescence, and Western blot were conducted. Finally, the potential anti-influenza effects of ACP via the gut-lung axis were evaluated based on in vivo and in vitro detection of protein expression of IFN-&#x3b2;, free fatty acid receptor 2 (FFAR2), and mitochondrial antiviral signaling protein (MAVS), as well as antiviral interferon-stimulated genes (ISGs).<br><br>RESULTS: In this study, we purified a novel polysaccharide, ACP-A1, with a backbone of&#x2192;4)-&#x3b1;-D-Glcp-(1&#x2192;,&#x2192;4)-&#x3b2;-D-Galp-(1&#x2192;, and &#x2192;4,6)-&#x3b1;-D-Glcp-(1&#x2192; linkages and &#x3b1;-D-Glcp-(1&#x2192; branches at O-6. In H1N1-infected mice, oral ACP-A1 alleviated weight loss, increased survival, and reduced lung inflammation and viral load. Metagenomic and targeted metabolomic analyses showed that ACP-A1 enriched Limosilactobacillus reuteri and elevated acetate levels. Fecal microbiota transplantation, FFAR2 inhibition, and MAVS knockout experiments demonstrated that ACP-A1 enhances the FFAR2/MAVS/IFN-&#x3b2; antiviral pathway via microbial-derived acetate.<br><br>CONCLUSION: Collectively, our findings elucidate that ACP mitigates influenza virus-induced lung dysfunction by promoting the proliferation of acetate-producing gut microbiota, particularly Limosilactobacillus reuteri, and activating the FFAR2/MAVS/IFN-&#x3b2; antiviral axis in pulmonary immune cells. These findings establish ACP-A1 as a natural polysaccharide regulating IFN-&#x3b2; homeostasis, highlighting its potential for influenza prevention.}, }
@article {pmid42387047, year = {2026}, author = {Qi, XY and Wang, MY and Wei, TC and Shao, FB and Liu, SH and Han, D and Cheng, JW and Zhao, YH and Shi, L and Luo, J and Cheng, T and Zhang, SX}, title = {Microbiome immune crosstalk in Sjögren's syndrome: mechanistic insights and translational perspectives.}, journal = {Immunologic research}, volume = {74}, number = {1}, pages = {}, pmid = {42387047}, issn = {1559-0755}, support = {No. 202203021221269//Natural Science Foundation of Shanxi Province/ ; No. 82001740//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Sjogren's Syndrome/immunology/microbiology/therapy/etiology ; *Dysbiosis/immunology ; Animals ; *Microbiota/immunology ; Multiomics ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Sjögren's syndrome (SS) is a systemic autoimmune disorder driven by interactions among genetic susceptibility, environmental factors, and alterations in mucosal microbial ecosystems. Emerging evidence from studies of the gut, oral cavity, and ocular surface indicates that microbial dysbiosis is closely associated with SS. Patients frequently exhibit reduced beneficial commensals and expansion of potentially pathogenic taxa, accompanied by epithelial barrier disruption, imbalance of T helper 17 and regulatory T cells, abnormal B-cell responses, and sustained activation of type I interferon signaling. Several mechanisms may contribute to disease development, including molecular mimicry, exosome-mediated immune communication, and alterations in microbiota-derived metabolites. Integrated multi-omics approaches, particularly high-throughput sequencing and metabolomics, have revealed SS-associated microbial signatures and metabolic pathway changes, offering insights for biomarker discovery and therapeutic targeting. Microbiota-directed strategies, such as probiotic supplementation, fecal microbiota transplantation, and investigations of drug-microbiome interactions, have shown potential to restore immune homeostasis. However, current evidence remains limited by small cohort sizes, methodological heterogeneity, and insufficient clarification of causal relationships. This review summarizes microbial alterations in SS, their roles in immune dysregulation, and the therapeutic potential of microbiome-based interventions within the framework of personalized medicine.}, }
@article {pmid42387077, year = {2026}, author = {Chen, J and Chen, L and Cai, G and Chen, Y and Zeng, Y and Zhang, Y and Huang, J and Xia, G and Wang, C and Feng, A and Nie, X}, title = {The involvement of Anaeroplasma, caproic acid, and interleukins through the brain-gut axis may contribute to IgAV with neurological involvement.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {42387077}, issn = {1530-0447}, abstract = {BACKGROUND: Immunoglobulin A vasculitis (IgAV), the most prevalent pediatric systemic vasculitis, may involve central nervous system (CNS) manifestations with unknown mechanisms.<br><br>METHODS: To investigate gut-brain axis interactions, human gut microbiota from IgAV with or without neurological involvement and healthy children were transplanted into specific pathogen-free mice. The recipients' microbiota, fecal short-chain fatty acids (SCFAs), and serum cytokines were analyzed alongside electroencephalogram (EEG) monitoring.<br><br>RESULTS: Spike waves emerged exclusively in the EEGs of mice receiving transplants from neurologically affected IgAV children. Comparative analyses demonstrated: enrichment of Anaeroplasma in the IgAV with neurological involvement (IgAVNI) group compared to IgAV controls (P&#x2009;<&#x2009;0.05); elevated caproic acid in IgAVNI versus controls (P&#x2009;<&#x2009;0.05); reduced IL-1&#x3b1; in IgAVNI versus controls (P&#x2009;<&#x2009;0.05); and a positive correlation between Anaeroplasma and IL-17A (r&#x2009;=&#x2009;0.94, P&#x2009;=&#x2009;0.004).<br><br>CONCLUSION: Gut microbiota, notably Anaeroplasma, may trigger IgAV-related CNS involvement via the gut-brain axis, co-mediated through regulation of caproic acid, IL-1&#x3b1;, and IL-17A.<br><br>IMPACT: First evidence that Anaeroplasma drives IgAV CNS manifestations via the gut-brain axis by regulating caproic acid, IL-1&#x3b1;, and IL-17A, with EEG spike waves as a specific marker. The Anaeroplasma-caproic acid-IL-17A axis fills a mechanistic gap in IgAV neurological complications, transcending current immunoinflammatory paradigms. Provides combined EEG/microbiota/metabolite biomarkers for early prediction and suggests Anaeroplasma, IL-17A, and caproic acid may represent therapeutic targets for neuroprotective interventions.}, }
@article {pmid42388391, year = {2026}, author = {Fernandez, MF and Stricker, A and Bottero, A and Busquet, L and Waldbaum, C and Mingorance, FL and Patetta, RM and Toer, I and Juliá, A and Mangano, A}, title = {Correction: Fecal microbiota transplantation promotes gut microbiome recovery in pediatric hematopoietic stem cell transplant recipients.}, journal = {Frontiers in microbiomes}, volume = {5}, number = {}, pages = {1904862}, doi = {10.3389/frmbi.2026.1904862}, pmid = {42388391}, issn = {2813-4338}, abstract = {[This corrects the article DOI: 10.3389/frmbi.2026.1849762.].}, }
@article {pmid42388392, year = {2026}, author = {Zhao, J and Fan, Y and Yang, K and Gao, H}, title = {Fecal microbiota transplantation: from empirical remedy to precision medicine.}, journal = {Frontiers in microbiomes}, volume = {5}, number = {}, pages = {1863308}, pmid = {42388392}, issn = {2813-4338}, abstract = {Fecal microbiota transplantation (FMT) has evolved from an empirical remedy for recurrent Clostridioides difficile infection (rCDI) into a foundational platform for precision microbiome-based therapeutics. This comprehensive review details FMT's journey, analyzing its multifaceted mechanisms of action-including restoration of colonization resistance, metabolic reprogramming via short-chain fatty acids and bile acids, and profound immunomodulation-which extend far beyond simple microbial replacement. We critically evaluate its established, high efficacy in rCDI and its expanding, albeit more variable, applications across a wide spectrum of gastrointestinal diseases (such as inflammatory bowel disease, irritable bowel syndrome, and constipation), neurological disorders (including Parkinson's and Alzheimer's disease), metabolic conditions, autoimmune diseases, and oncology (particularly in modulating response to immune checkpoint inhibitors and treating graft-versus-host disease). The review further discusses the critical challenges of donor-recipient variability, safety, and the lack of standardized protocols that have driven the field's technical evolution. This progression encompasses refined processing methods like washed microbiota transplantation (WMT), diverse delivery routes including oral capsules, and the exploration of non-bacterial components like bacteriophages through fecal filtrate transplantation (FVT). Ultimately, we highlight the field's trajectory toward next-generation, defined live biotherapeutic products (LBPs) and engineered microbial consortia, aiming to transition from the complex "black box" of whole stool to safer, more consistent, and rationally designed precision therapies that target the specific dysbiotic networks underlying diverse human diseases.}, }
@article {pmid42388393, year = {2026}, author = {Fernandez, MF and Stricker, A and Bottero, A and Busquet, L and Waldbaum, C and Mingorance, FL and Patetta, RM and Toer, I and Juliá, A and Mangano, A}, title = {Fecal microbiota transplantation promotes gut microbiome recovery in pediatric hematopoietic stem cell transplant recipients.}, journal = {Frontiers in microbiomes}, volume = {5}, number = {}, pages = {1849762}, pmid = {42388393}, issn = {2813-4338}, abstract = {INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) profoundly disrupts the gut microbiome and may contribute to adverse post-transplant outcomes. Fecal microbiota transplantation (FMT) has emerged as a strategy to restore microbial diversity; however, data in pediatric HSCT recipients remain limited.<br><br>METHODS: We conducted a longitudinal analysis of 17 pediatric HSCT recipients who received FMT. Fecal samples were collected before FMT and at days 7, 14, and 30 after treatment. Gut microbiome composition was analyzed using 16S rRNA gene sequencing.<br><br>RESULTS: Baseline samples showed reduced microbial diversity and a dysbiotic microbial profile. Following FMT, microbial diversity increased progressively, with recovery evident from day 7 and stabilization by day 30. Taxonomic analyses demonstrated depletion of dysbiosis-associated genera and enrichment of beneficial short-chain fatty acid-producing taxa, including Faecalibacterium, Blautia, Subdoligranulum, and Akkermansia. Distinct microbial configurations were observed according to gastrointestinal involvement by acute graft-versus-host disease.<br><br>CONCLUSIONS: FMT was associated with progressive restoration of gut microbiome diversity and structure in pediatric HSCT recipients, supporting its potential role as a microbiota-based strategy to promote ecological recovery after HSCT.}, }
@article {pmid42388848, year = {2026}, author = {Yang, K and Peng, G and Zhang, X and Yang, D and Wang, Y and Chen, R}, title = {Host genotype is associated with selective colonization of human fecal microbiota in NCG and SGM3 mice: implications for microbiota-based therapies.}, journal = {Bioscience of microbiota, food and health}, volume = {45}, number = {3}, pages = {188-196}, pmid = {42388848}, issn = {2186-6953}, abstract = {Humanized mouse models are widely used to investigate host-microbiota interactions, yet the extent to which host background contributes to engraftment fidelity remains incompletely defined. In this study, we transplanted fecal microbiota from healthy human donors into NCG and SGM3 mice and characterized engraftment using 16S rRNA sequencing. Both models exhibited reduced diversity relative to donors, but their colonization trajectories diverged. NCG recipients appeared closer to donors in β-diversity space, a pattern largely associated with the expansion of a limited set of opportunistic Proteobacteria such as Escherichia-Shigella and Citrobacter. In contrast, SGM3 mice displayed modestly higher α-diversity and retained a broader set of donor-associated genera, with selective enrichment of Bacillus, yet exhibited greater predicted functional divergence, with reductions in pathways related to ABC transport and carbohydrate metabolism. Several strictly anaerobic commensals, including Faecalibacterium, failed to colonize in either genotype. Collectively, these findings suggest that host genotype is associated with selective colonization of human fecal microbiota and support the utility of integrating compositional and functional criteria when selecting experimental models for translational microbiome research.}, }
@article {pmid42389273, year = {2026}, author = {Guo, Y and Hu, F and Zhao, AZ and Zeng, Y and Chen, H and Wang, A and Li, X and Cong, L}, title = {Omega-3 polyunsaturated fatty acids are associated with microbiota-related 18β-glycyrrhetinic acid alterations and M2 macrophage polarization in type 1 diabetes mellitus.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1871892}, pmid = {42389273}, issn = {1663-9812}, abstract = {INTRODUCTION: Omega-3 polyunsaturated fatty acids (PUFAs) have been widely reported to exert beneficial effects in type 1 diabetes mellitus (T1DM). However, the mechanisms by which Omega-3 PUFAs influence pancreatic islet function through the gut-islet axis remain incompletely understood. This study aimed to investigate whether Omega-3 PUFAs-associated alterations in gut microbiota composition and their metabolites are involved in the modulation of the pancreatic islet microenvironment in T1DM, and to explore the potential immunological mechanisms underlying these effects.<br><br>METHODS: Fecal microbiota transplantation (FMT) was performed to evaluate the effects of Omega-3 PUFAs-associated gut microbiota in non-obese diabetic (NOD) mice. Immune cell composition and inflammatory status within pancreatic islets were analyzed using transcriptomic profiling, flow cytometry, and immunohistochemistry. Metabolomics analysis was performed to investigate the association among Omega-3 PUFAs, gut microbiota, and microbiota-related metabolites. In vitro co-culture systems were further established to evaluate the effects of selected metabolites on macrophage polarization and insulin production and secretion in pancreatic &#x3b2;-cells.<br><br>RESULTS: Omega-3 PUFAs treatment and FMT were associated with reduced islet inflammation and a marked enrichment of the Eubacterium coprostanoligenes group (E. coprostanoligenes). Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18&#x3b2;-glycyrrhetinic acid (18&#x3b2;-GA) showed a strong association with E. coprostanoligenes, and in vitro experiments suggested a potential involvement of E. coprostanoligenes in the metabolic conversion process related to 18&#x3b2;-GA. In co-culture systems, 18&#x3b2;-GA promoted macrophage polarization toward an M2-like phenotype, which was accompanied by increased insulin production and secretion in pancreatic &#x3b2;-cells.<br><br>CONCLUSION: These findings suggest that Omega-3 PUFAs-associated alterations in gut microbiota composition and 18&#x3b2;-GA-related metabolic changes may contribute to the modulation of the pancreatic immune microenvironment and &#x3b2;-cells function in T1DM. This study provides additional insights into lipid-microbiota-immune interactions relevant to T1DM and supports further investigation of microbiota-associated immune regulation.}, }
@article {pmid42389275, year = {2026}, author = {Zhang, P and Zhuang, YD and Lv, WW and Zhao, Y and Wang, JH and Zhang, JY and Wu, LL}, title = {Role of gut microbiota in melanosis coli: from anthraquinone biotransformation to mucosal homeostasis dysbiosis.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1791164}, pmid = {42389275}, issn = {1663-9812}, abstract = {Melanosis coli (MC) is a benign and usually reversible condition characterized by brownish-black pigmentation of the colonic mucosa and is commonly associated with chronic exposure to anthraquinone laxatives (ALs). The best-established histopathological sequence involves AL-related epithelial apoptosis, phagocytosis of apoptotic bodies by macrophages, and subsequent lipofuscin deposition. Emerging evidence suggests that the gut microbiota (GM) may contribute to this process by converting pharmacologically inactive anthraquinone glycosides into active anthrone metabolites, including rhein anthrone. This narrative review summarizes available MC-specific findings and clearly distinguishes them from mechanistic hypotheses extrapolated from constipation, intestinal barrier, and microbiome literature. We discuss microbial β-glucosidases and reductases involved in AL biotransformation, reported changes in microbial diversity and SCFA-producing taxa in MC or constipation-associated cohorts, and plausible links with barrier dysfunction, bile-acid metabolism, tryptophan-derived metabolites, and LPS-TLR4 signaling. We therefore present the "Microbiota-Apoptosis Axis" as a proposed framework rather than a validated causal pathway. Finally, we review GM-targeted strategies, including probiotics, synbiotics, and fecal microbiota transplantation, while emphasizing that direct clinical evidence in MC remains limited and that cessation of anthraquinone laxatives remains the primary management strategy.}, }
@article {pmid42389522, year = {2026}, author = {Qian, N and Zhu, S and Song, Y and Yang, Y and Wang, H and Han, H and Xu, G and Hao, W and Jiang, H and Yang, Y and Xi, H and Ding, Y and He, W and Wei, T and Yang, W and Cheng, T}, title = {The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1840716}, pmid = {42389522}, issn = {1664-3224}, mesh = {*Hepatolenticular Degeneration/metabolism/therapy ; *Copper/metabolism ; Animals ; Humans ; *Liver/metabolism ; *Kidney/metabolism ; *Blood-Brain Barrier/metabolism ; *Brain/metabolism ; Intestinal Barrier Function ; Copper-Transporting ATPases/genetics ; Gastrointestinal Microbiome ; Intestinal Mucosa/metabolism ; Cuproptosis ; Mice ; }, abstract = {Wilson disease (WD) has long been framed as a hepatocentric disorder of copper accumulation. That view is now giving way to a broader model centered on the gut-liver-kidney-brain axis. In WD, copper is not simply stored in tissues as an inert burden. It circulates in dynamic, bioactive pools-particularly relative exchangeable copper (REC)-that disrupt barrier structures, including the intestinal epithelium and blood-brain barrier, and spread toxicity through measurable biochemical mediators. Major pathogenic processes include copper-induced suppression of autophagy, disruption of FXR-regulated bile acid signaling, and direct injury to the intestinal barrier. Gut dysbiosis, supported by fecal microbiota transplantation (FMT) studies in ATP7B-deficient mice, further amplifies hepatic inflammation and favors copper retention. Renal tubular dysfunction and neurotoxicity appear to reflect copper species-dependent passage across biological barriers together with secondary metabolic disturbances, including the recently described pathway of cuproptosis. In the clinic, this shift has been accompanied by greater use of copper-species biomarkers such as ceruloplasmin oxidase activity and REC, along with advanced imaging approaches such as [64]Cu-PET/CT. Treatment is also moving beyond conventional chelation alone, with increasing attention to biliary copper excretion, epithelial barrier repair, and microbiome-directed interventions. Viewed in this way, the axis model helps explain the marked phenotypic heterogeneity of WD and offers a mechanistic basis for more precise interventions aimed at breaking pathogenic feedback loops across organs.}, }
@article {pmid42391840, year = {2026}, author = {Yi, X and Zhang, Y and Yang, K and Li, B and Liu, F and Tian, G and Zhang, J and Yan, T and Li, J and Li, W and Li, L and Jing, R and Zhang, Z and Qiu, X and Xiao, J and Zhang, W}, title = {6PPD-Q exposure disrupts intestinal homeostasis and impairs skeletal muscle function in mice.}, journal = {Ecotoxicology and environmental safety}, volume = {321}, number = {}, pages = {120470}, doi = {10.1016/j.ecoenv.2026.120470}, pmid = {42391840}, issn = {1090-2414}, abstract = {6PPD-Q is an emerging tire-derived contaminant, but its mammalian toxicological mechanisms and inter-organ effects remain poorly understood. Because oral exposure directly interfaces with the intestine, we investigated whether 6PPD-Q disrupts intestinal homeostasis and is associated with skeletal muscle dysfunction through a microbiota-related gut-muscle axis, and whether post-exposure sodium butyrate (NaB) intervention can alleviate these alterations. Male C57BL/6 mice were orally exposed to 6PPD-Q at 0.1, 1, or 10 μg/kg/day, and NaB intervention was evaluated after high-dose exposure. Toxic effects were mainly observed at 1 and 10 μg/kg/day. 6PPD-Q accumulated predominantly in the intestine and induced villus-crypt disruption, microvillus damage, increased permeability, inflammatory activation, and oxidative imbalance. These alterations were accompanied by reduced exercise performance, smaller myofiber cross-sectional area, and impaired myogenic differentiation. Low residual 6PPD-Q levels in perfused skeletal muscle and tissue-equivalent C2C12 exposure results suggested that intestinal dysfunction may contribute to muscle impairment. 6PPD-Q also altered gut microbial composition and fecal short-chain fatty acid profiles, with reduced butyrate emerging as a candidate metabolic alteration associated with muscle dysfunction. Fecal microbiota transplantation from 6PPD-Q-exposed donors partially transferred intestinal barrier dysfunction, inflammatory and oxidative disturbances, reduced butyrate levels, and muscle-related abnormalities to recipients, whereas microbiota from NaB-treated donors attenuated these effects. Post-exposure NaB intervention partially alleviated intestinal, microbial, metabolic, and skeletal muscle alterations without substantially reducing tissue 6PPD-Q burden.These findings suggest that oral 6PPD-Q exposure disrupts intestinal homeostasis and microbiota-SCFA profiles, which may contribute to gut-muscle axis-associated skeletal muscle dysfunction in mice.}, }
@article {pmid42391938, year = {2026}, author = {Yi, L and Shi, W and Jia, H and Song, G and Zhang, W and Bai, G and Zhu, J and Zhao, S}, title = {From composition to function: Translating porcine gut microbiota research into strategies for improving intestinal health.}, journal = {Microbiological research}, volume = {311}, number = {}, pages = {128612}, doi = {10.1016/j.micres.2026.128612}, pmid = {42391938}, issn = {1618-0623}, abstract = {The gut microbiota plays a pivotal role in regulating host physiology, metabolism, and overall health. The diverse geographical landscape of China has contributed to the development of rich indigenous pig genetic resources, which exhibit stronger disease resistance than commercial breeds, largely attributed to the composition of their gut microbiota. Given the substantial anatomical and physiological similarities between pigs and humans concerning intestinal structure, and the fact that human-derived microorganisms can effectively colonize the porcine gut, pigs serve as excellent models for intestinal diseases. This review summarizes the geographical and spatial ecological niches of gut microbiota in Chinese indigenous pig breeds, the influences of age and environment on microbial composition, and the beneficial roles of certain microbial taxa from these local breeds in preventing intestinal disorders, including diarrhea associated with impaired intestinal barrier function, pathogen-induced diarrhea, porcine epidemic diarrhea virus infection, intestinal inflammation models, human rotavirus infection, and necrotizing enterocolitis. Their gut microbiota is characterized by the enrichment of Akkermansia, Lactobacillus, Prevotella, Bacillus, Bifidobacterium, Faecalibacterium, and Bacteroides, which have been implicated in maintaining intestinal barrier integrity and reducing inflammatory cytokine levels during pathogen-induced intestinal inflammation. In the context of gastrointestinal disease prevention and treatment, strategies have largely centered on fecal microbiota transplantation, fecal suspension transplantation, or supplementation with single bacterial strains. However, research on multi-strain combinatorial therapeutics remains limited. Future studies should expand to underexplored indigenous breeds and prioritize the development of composite microbial consortia informed by existing findings.}, }
@article {pmid41575630, year = {2026}, author = {Weirauch, T and Yahav, D and Zahavi, I and Würstle, S and Vehreschild, MJGT}, title = {A review on antibiotic and non-antibiotic decolonization strategies of multidrug-resistant bacteria in the gastrointestinal tract.}, journal = {Infection}, volume = {54}, number = {3}, pages = {1041-1062}, pmid = {41575630}, issn = {1439-0973}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Drug Resistance, Multiple, Bacterial ; *Gastrointestinal Tract/microbiology ; *Bacterial Infections/microbiology/therapy/drug therapy ; *Bacteria/drug effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Probiotics ; }, abstract = {The escalating global threat of antimicrobial resistance represents a critical challenge for contemporary medicine. Intestinal colonization by multidrug-resistant organisms (MDROs) is increasingly identified as a primary driver of hospital-acquired infections across various patient cohorts. While localized eradication via non-absorbable antibiotics was once viewed as a viable strategy, clinical evidence has failed to demonstrate its efficacy. Consequently, attention has shifted toward microbiome-modulating interventions, such as fecal microbiota transfer (FMT), probiotics, and live biotherapeutic products (LBPs), which have shown potential in preliminary studies. However, current evidence remains fragmented and lacks the support of large-scale randomized controlled trials (RCTs). This review critically assesses both traditional and novel decolonization methods and features a comprehensive summary of clinical studies to highlight existing research gaps. A notable limitation of this analysis is the absence of a formal methodological quality assessment for the included studies. Ultimately, definitive conclusions remain elusive, necessitating future large-scale, pathogen-specific RCTs to validate these emerging approaches.}, }
@article {pmid42375606, year = {2026}, author = {Fu, S and Liao, W and He, B and Wu, H and Huang, J and Jiang, W}, title = {Hylocereus undatus flower inhibits lipopolysaccharide-induced acute lung injury in mice by regulating the gut-lung axis and inflammatory response.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1803336}, pmid = {42375606}, issn = {1663-9812}, abstract = {BACKGROUND: Hylocereus undatus flower (HUF), the dried flower of H. undatus (Haw.) Britton and Rose, was first recorded in the Lingnan Record of Medicinal Herbs and is now listed in the Dictionary of Traditional Chinese Medicines. As an established traditional remedy, HUF is primarily used to treat various pulmonary conditions, including pneumonia, asthma, and tuberculosis. Acute lung injury (ALI) represents a critical and common pathological manifestation underlying severe respiratory disorders. However, the potential protective effects of HUF against ALI, and the specific mechanisms involved, remain unelucidated.<br><br>PURPOSE: To systematically evaluate the protective effects of HUF extract on ALI and the pharmacological mechanisms involved.<br><br>METHODS: Using a lipopolysaccharide-induced mouse model of ALI, we investigated the effects of HUF on the intestinal microbiota of ALI mice via microbial sequencing, metabolomics sequencing, and fecal microbiota transplantation (FMT). We explored the targets and signaling pathways of HUF intervention using transcriptomics and network pharmacology methods and then validated our results using immunological experiments and polymerase chain reaction analysis (PCR).<br><br>RESULTS: HUF reduced lung indices and wet-dry ratios associated with pulmonary edema, alleviated inflammatory responses, and mitigated the severity of pulmonary pathological damage. HUF also increased the expression of intestinal tight junction protein (ZO-1), modulated the structure and relative abundance of the gut microbiota, and elevated the levels of certain short-chain fatty acids (SCFAs). FMT experiments confirmed that the HUF-mediated remodeling of the microbiota played a significant role in alleviating ALI. Transcriptomics and network pharmacology analyses suggested that the mechanism underling the interventional effect of HUF on ALI is related to inflammatory pathways. Immunological and PCR experiments further confirmed an association with the P38 mitogen-activated protein kinase (MAPK) pathway.<br><br>CONCLUSION: HUF is associated with attenuation of ALI, correlating with modulation of the gut-lung axis and the inflammatory pathways, and HUF may be a candidate for the treatment of ALI.}, }
@article {pmid42379287, year = {2026}, author = {Brett Moreau, G and Petri, WA}, title = {The Impact of Fecal Microbiota Transplantation on Host Immunity and Epithelial Restoration Following Clostridioides difficile Infection.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {103060}, doi = {10.1016/j.anaerobe.2026.103060}, pmid = {42379287}, issn = {1095-8274}, abstract = {Fecal microbiota transplantation (FMT) has emerged as an effective therapy for the prevention of recurrent Clostridioides difficile infection (rCDI). Despite this therapeutic success, questions remain about safety and standardization of protocols, leading to calls for more defined biotherapeutics. While FMT-mediated protection is associated with restoration of the intestinal microbiota and metabolome, our understanding of its impact on host immune responses and restoration of colonic homeostasis remains incomplete. In this review, we focus on our current knowledge regarding the effects of FMT on host responses, including immune responses, colonic barrier restoration, and host metabolism. FMT is associated with restoration of immune signaling, which is depleted following antibiotic therapy. Restoration is associated with a shift towards type 2 and regulatory immune responses that limit intestinal inflammation and promote repair. FMT also modifies non-immune cells, promoting enhanced barrier integrity and significantly modifying host metabolism within the gut. FMT studies utilize a variety of experimental protocols and FMT formulations, and more mechanistic studies are required to understand how this variation impacts microbiota and host-directed changes. Better understanding of the immune and metabolic changes associated with protection against rCDI will allow for the design of more targeted therapeutics.}, }
@article {pmid42382190, year = {2026}, author = {Duan, R and Wang, K and Duan, L}, title = {Mother-to-offspring microbial vertical transmission: timing, determinants, and impact on offspring susceptibility to gastrointestinal diseases.}, journal = {Medical review (2021)}, volume = {6}, number = {3}, pages = {243-261}, pmid = {42382190}, issn = {2749-9642}, abstract = {The establishment of the early-life microbiota is profoundly shaped by microbial vertical transmission from mother to offspring. This review synthesized the current understanding of the timing, determinants, and health implications of mother-to-offspring microbial vertical transmission. We detailed the contentious evidence regarding prenatal microbial transmission and highlighted the well-established roles of intrapartum and postnatal transmission via birth and breastfeeding, respectively. Multiple factors, including delivery mode, gestational age, feeding patterns and antibiotic exposure, are critical modulators of microbial transmission, shaping the initial microbial community. Emerging intervention strategies, such as breastfeeding, probiotic supplementation, vaginal microbiota transplantation, and fecal microbiota transplantation, offer promising avenues for restoring a healthy microbial trajectory when natural transmission is disrupted. This review underscores that vertical transmission is the cornerstone of intergenerational microbiome inheritance and a potential therapeutic target for preventing early-life dysbiosis and associated diseases.}, }
@article {pmid42382341, year = {2026}, author = {Zhang, S and Zhang, T and Zhang, Y and Ye, C and Mu, L and He, Q and Huang, T and Wang, G and Li, Y and Xie, S and Tang, X}, title = {Correction: Akkermansia muciniphila regulates the gut microenvironment and alleviates periodontal inflammation in mice with periodontitis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1892163}, doi = {10.3389/fmicb.2026.1892163}, pmid = {42382341}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2025.1643691.].}, }
@article {pmid42382646, year = {2026}, author = {Peng, Z and Hu, Y and Wang, S and Liu, C and Zhou, Q and Xie, S and Huang, S and Liu, N and Wang, Y}, title = {Case Report: Allergic reaction following fecal microbiota transplantation in children with autism spectrum disorder: a report of two cases.}, journal = {Frontiers in pediatrics}, volume = {14}, number = {}, pages = {1847568}, pmid = {42382646}, issn = {2296-2360}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in children with autism spectrum disorder (ASD) and is generally considered to have an acceptable safety profile. However, the risk and mechanisms of severe adverse events in the high-risk subgroup of children with ASD complicated by multiple food intolerances (FI) have not been reported, and clinical strategies for risk prevention and management remain lacking.<br><br>CASE REPORT: This article reports two cases of children with ASD and multiple FIs who developed anaphylactic shock following FMT, representing the first such report in the pediatric field. Case 1 presented with early-stage shock, which was considered to be associated with IgG-mediated type III hypersensitivity. Case 2 developed classic anaphylactic shock with a biphasic course characterized by relapse after initial resolution, raising the possibility of biphasic anaphylaxis. Both children improved after standardized anti-allergy and anti-shock treatment, and one child successfully completed subsequent FMT using a low-dose regimen.<br><br>CONCLUSION: FMT carries a risk of anaphylactic shock in children with ASD and multiple FIs, who have underlying susceptibility due to impaired intestinal barrier function and immune dysregulation. Refined risk stratification, close monitoring throughout the procedure, individualized transplantation protocols, and standardized emergency procedures can effectively enhance the safety and feasibility of FMT in this high-risk subgroup.}, }
@article {pmid42382671, year = {2026}, author = {Liu, Y and Mei, D}, title = {The gut microbiome in colorectal cancer: molecular paradigms and translational frontiers.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {14}, number = {}, pages = {1864299}, pmid = {42382671}, issn = {2296-4185}, abstract = {The gut microbiome is now recognized as a causal driver of colorectal cancer (CRC) rather than a mere commensal ecosystem. This review elucidates the molecular mechanisms of keystone pathogens, specifically Fusobacterium nucleatum, pks [+] Escherichia coli, and enterotoxigenic Bacteroides fragilis, which induce DNA interstrand crosslinks, hyperactivate Wnt/β-catenin signaling, compromise the epithelial barrier, and reshape the tumor immune microenvironment. We discuss how bioengineered human organoids and microfluidic Organ-on-a-Chip platforms resolve the aerobic-anaerobic co-culture paradox, enabling patient-specific mechanistic dissection of host-microbe crosstalk. From a clinical perspective, we evaluate multi-omics signatures for noninvasive screening, intratumoral bacterial load as a prognostic indicator, and emerging therapeutic strategies including narrow-spectrum antimicrobials, bacteriophage-guided drug delivery, fecal microbiota transplantation for immunotherapy sensitization, and engineered living probiotics. By integrating mechanistic paradigms, organoid-guided validation, and translational applications, we delineate actionable trajectories for precision microbiome targeting in CRC management.}, }
@article {pmid42382782, year = {2026}, author = {Kim, S and Lee, S and Ju, S and Bae, J and Ryu, JS and Heo, Y and Choi, WJ and Shin, KJ and Kim, SJ and Kim, N and Choi, H and Park, J and Lee, E and Yoon, CH and Kwon, S and Chung, J and Kim, MK}, title = {Gut microbiota transfer from autoimmune dry eye mice imprints stereotypic B cell receptor repertoires in the lacrimal gland and induces disease.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1827057}, pmid = {42382782}, issn = {1664-3224}, mesh = {Animals ; *Lacrimal Apparatus/immunology/metabolism ; Mice ; *Gastrointestinal Microbiome/immunology ; Disease Models, Animal ; *Sjogren's Syndrome/immunology/microbiology ; *Receptors, Antigen, B-Cell/immunology/genetics/metabolism ; Female ; Mice, Inbred NOD ; *B-Lymphocytes/immunology/metabolism ; *Autoimmune Diseases/immunology/microbiology ; Fecal Microbiota Transplantation ; *Dry Eye Syndromes/immunology/microbiology ; Mice, Inbred C57BL ; }, abstract = {Gut microbiota and humoral immunity have been suggested as key players in the pathogenesis of Sjögren disease (SjD), but their mechanisms remain unclear. In this study, we transferred the gut microbiota of SjD-like autoimmune dry eye disease model mice to B6 mice, then characterized the resulting gut microbiome composition, clinical ocular phenotype, and B cell receptor (BCR) repertoire. Notable changes were observed in the gut microbiome of NOD-FMT mice, accompanied by SjD-like clinical features, including elevated corneal fluorescein staining scores, reduced tear production, increased IL-6 mRNA levels, and decreased MUC5AC mRNA levels. Additionally, stereotypic B cell receptor (BCR) clonotypes were shared at significantly higher frequencies in NOD-FMT mice than in controls. The majority of B cell clones encoding these stereotypic clonotypes developed and expanded locally in the lacrimal gland, and some also achieved systemic presence. These results uncover a gut-ocular immune axis in which microbiota transfer induces stereotyped, systemically disseminating BCR clonotypes that contribute to the immunopathogenesis of autoimmune dry eye disease.}, }
@article {pmid42383626, year = {2026}, author = {Xiao, Y and Chen, B and Zhang, X and Sun, H and Wang, H and Du, P and Yang, X and Fan, G}, title = {Multiomics Integration Reveals AFB1 Causes Liver Damage Involving the Gut-Microbiota-Lipid Metabolism Axis in Piglet.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c17707}, pmid = {42383626}, issn = {1520-5118}, abstract = {Prolonged exposure to aflatoxin B1 (AFB1) poses a significant threat to livestock production. The liver is the main target, but the role of the gut-liver axis and lipid metabolism in pig hepatic toxicity is not well understood. This study evaluates the impact of AFB1 on piglet liver injury via the gut-liver axis using multiomics analysis. Chronic AFB1 exposure significantly impaired the piglet growth and induced liver injury. Meanwhile, AFB1 caused gut microbiota dysbiosis and intestinal barrier damage in the piglets. Fecal microbiota transplantation (FMT) demonstrated that AFB1-altered microbiota causally contribute to hepatic inflammation in mice. Multiomics analysis revealed systemic disruption of lipid metabolism pathways, which might be involved in the intestinal flora imbalance caused by AFB1. Abnormal lipid metabolism subsequently leads to the accumulation of inflammatory lipid mediators in the plasma, ultimately causing severe liver damage. The findings highlight the crucial roles of gut microbiota and lipid metabolism in AFB1-induced liver toxicity.}, }
@article {pmid42383946, year = {2026}, author = {Fischer, M and Vaughn, BP and Peery, AF and Kelly, CR}, title = {AGA Clinical Practice Update on Management of Clostridioides difficile Infection in Adults: Expert Review.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2026.05.007}, pmid = {42383946}, issn = {1542-7714}, abstract = {DESCRIPTION: Clostridioides difficile infection is a common cause of clinically significant diarrhea, often becomes recurrent, and can be fatal when severe or fulminant. The purpose of this America Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide best practice advice for C difficile infection management.<br><br>METHODS: This expert review was commissioned by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The review was developed from expert opinion and a review of the published literature. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. The review underwent internal peer review by the Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. BEST PRACTICE ADVICE STATEMENTS BEST PRACTICE ADVICE 1: Prevention of C difficile infection should include proper barrier protection and disinfection with United States Environmental Protection Agency-approved sporicidal agents in health care settings. Patients should be counseled on the importance of handwashing and to consider disinfecting areas of the home potentially contaminated with C difficile spores, to prevent reinfection. Reassurance should be provided that C difficile infection transmission to unaffected family members is uncommon. BEST PRACTICE ADVICE 2: C difficile infection is a clinical diagnosis that requires compatible symptoms (typically acute diarrhea, following antibiotics) in combination with supportive laboratory testing. Multistep testing is preferred for best diagnostic accuracy; however, patients with discordant testing who have a high clinical suspicion for C difficile infection should be treated. BEST PRACTICE ADVICE 3: Clinicians should classify hospitalized patients with C difficile infection as having nonsevere, severe, or fulminant disease at diagnosis. White blood cell count >15,000 cells/uL and/or creatinine >1.5 &#xd7; baseline are indicative of severe C difficile infection and increased risk for recurrence and poor outcomes. Patients with additional findings of shock, ileus, or megacolon have fulminant C difficile infection, which can be fatal. BEST PRACTICE ADVICE 4: Fidaxomicin (200 mg twice daily oral for 10 days) is a narrower spectrum agent, and given lower recurrence rates, is favored as first-line therapy for nonfulminant C difficile infection. However, given practical considerations, vancomycin (125 mg 4 times daily oral for 10 days) is also acceptable therapy. Metronidazole should not be used outside of fulminant disease. BEST PRACTICE ADVICE 5: Cholestyramine and other bile acid-binding agents should not be used as monotherapy or concurrently with oral vancomycin or fidaxomicin. Psyllium fiber can be used to bulk stools in patients who have recovered from the infection. BEST PRACTICE ADVICE 6: Following treatment of C difficile infection, clinicians should not perform routine test of cure. Stool testing should only be performed for persistent worsening of diarrheal symptoms. BEST PRACTICE ADVICE 7: First C difficile infection recurrence (second episode) within 8 weeks of completing anti-C difficile infection therapy should be treated with either a tapering course of vancomycin or fidaxomicin. Treatment of C difficile infection should include a risk assessment for C difficile infection recurrence and consideration of microbiota restoration therapy to prevent recurrence. BEST PRACTICE ADVICE 8: Fecal microbiota-based therapies (fecal microbiota spores, live-brpk, fecal microbiota, live-jslm, or conventional fecal microbiota transplant) should be offered after treatment of a second recurrence (third C difficile infection episode). Microbiota restoration therapy may be considered after treatment of an initial infection or first recurrence in patients who are at high risk for further recurrence or in patients whose initial C difficile infection episode was particularly morbid or difficult to treat. BEST PRACTICE ADVICE 9: Prolonged, low dose, suppressive vancomycin regimen (125 mg daily) for secondary prophylaxis may be considered in patients with multiple recurrent episodes who are not candidates for fecal microbiota-based therapies due to ongoing comorbidities, limited life expectancy, or ongoing/frequent systemic antibiotics or who have failed multiple courses of fecal microbiota-based therapy. BEST PRACTICE ADVICE 10: Fulminant C difficile infection should be managed by a multidisciplinary team (gastroenterology/infectious disease, surgery, medicine/critical care) and treated with high-dose vancomycin 500 mg every 6 hours (oral or enteral), with metronidazole 500 mg intravenously every 8 hours, and if ileus is present, rectal vancomycin 500 mg every 6 hours should be added. BEST PRACTICE ADVICE 11: Multi-dose fecal microbiota transplantation (fresh-directed donors, or institutional stool banks) delivered via lower endoscopy, should be considered in individuals with fulminant C difficile infection. Fecal microbiota, live-jslm (Rebyota), and fecal microbiota spores, live-brpk (Vowst) have not been studied and are not approved for treatment of severe and/or fulminant C difficile infection. Due to high risk of C difficile infection recurrence, patients who recover from severe or fulminant C difficile infection should be maintained on a suppressive vancomycin regimen until a final fecal microbiota transplantation can be administered as an outpatient. BEST PRACTICE ADVICE 12: Use of vancomycin is not advised during systemic antibiotic administration to prevent C difficile infection. Probiotics are not advised to prevent an initial or recurrent C difficile infection. To promote restoration of healthy gut microbiota, patients should be instructed to consume a healthy diet including a variety of fruits and vegetables, rich in both soluble and insoluble fiber. BEST PRACTICE ADVICE 13: During the treatment of C difficile infection or the prevention of its recurrence, the use of proton pump inhibitors should be evaluated. If a legitimate indication exists for their use, proton pump inhibitor discontinuation is not necessary. BEST PRACTICE ADVICE 14: Individuals with a history of C difficile infection should be specifically counseled to avoid unnecessary antibiotic therapy.}, }
@article {pmid42384640, year = {2026}, author = {Zhang, X and Fu, Y and Chen, J and Shen, H and Du, Y and Wu, J and Lai, H and Liu, Y and Chen, J and Hou, X and Chang, W and Hu, X}, title = {An exercise-associated gut microbiota signature enhances endurance performance: A study combining a human cohort and a mice FMT model.}, journal = {PloS one}, volume = {21}, number = {7}, pages = {e0351316}, doi = {10.1371/journal.pone.0351316}, pmid = {42384640}, issn = {1932-6203}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation ; Male ; Young Adult ; *Physical Endurance/physiology ; RNA, Ribosomal, 16S/genetics ; Adult ; Female ; *Exercise/physiology ; Feces/microbiology ; Cohort Studies ; }, abstract = {BACKGROUND: The gut microbiota is closely related to exercise, but the interrelationship between the two remains elusive. In this study, we aimed to explore differences in the gut microbiota between young adults with exercise and sedentary lifestyles. In addition, we evaluated the effects of gut microbiota from these different lifestyle populations on endurance exercise capacity.<br><br>METHODS: The exercise status and nutritional characteristics of young adults were evaluated by PARS-3 and food frequency questionnaires. The gut microbiota of young adults from exercise and sedentary lifestyle groups was analyzed by 16S rRNA analysis. Subsequently, we performed fecal bacteria transplantation (FMT) from the human donors into mice and evaluated the effects on their endurance exercise capacity.<br><br>RESULTS: The exercise group exhibited significantly higher gut microbiota diversity compared to the sedentary group. Several beneficial bacteria, including Veillonella, Faecalibacterium, and Bacteroides, were enriched in the exercise group. The FMT experiment confirmed that mice receiving microbiota from the exercise group showed significantly improved endurance exercise capacity.<br><br>CONCLUSION: Young people who exercise regularly possess a more diverse gut microbiota enriched with beneficial bacteria. This exercise-associated microbiota has the potential to directly improve exercise capacity.}, }
@article {pmid41919665, year = {2026}, author = {Kataria, S and Singla, A and Mamoria, VP and Sharma, I}, title = {The burden of cyclosporiasis in immuno-compromised patients: A growing public health issue lessons from case studies.}, journal = {Tropical doctor}, volume = {56}, number = {3}, pages = {514-520}, doi = {10.1177/00494755261437456}, pmid = {41919665}, issn = {1758-1133}, mesh = {Humans ; *Cyclosporiasis/epidemiology/parasitology/diagnosis ; *Cyclospora/isolation &amp; purification ; Male ; *Immunocompromised Host ; Middle Aged ; Female ; Feces/parasitology ; Oocysts ; Animals ; Risk Factors ; Public Health ; Diarrhea/parasitology ; }, abstract = {Cyclospora cayetanensis is an emerging notifiable food-and-water-borne coccidian parasite causing gastro-intestinal-disease in humans. Detailed information about its biology-associated risk-factors and routes of transmission remain poorly understood; the lack-of-comprehensive epidemiological data underlines a critical need for targeted research into effective prevention and control. Acid variable (pink to brilliant red colour) oocysts of Cyclospora spp. were observed in 16/162 samples, predominantly in 51-60 years males in October. Most cases were among transplant recipients presenting with diarrhoea, therapeutic options among whom remains limited.}, }
@article {pmid42373816, year = {2026}, author = {Yang, J and Ling, Z and Zhou, M and Tao, M and Mao, J and Guo, H and Wang, J and Qu, X and Wang, Y and Zhu, Y and Zhang, K and Yan, X}, title = {Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-10546-9}, pmid = {42373816}, issn = {2399-3642}, support = {81902422//National Natural Science Foundation of China (National Science Foundation of China)/ ; BK20250559//Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)/ ; }, abstract = {Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.}, }
@article {pmid42375360, year = {2026}, author = {Zhou, K and Lu, P and Xu, H and Wang, L and Liang, X}, title = {Molecular studies on the impact of microbiome on anticancer drug resistance.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1848345}, pmid = {42375360}, issn = {1664-3224}, mesh = {Humans ; *Drug Resistance, Neoplasm/immunology ; Animals ; *Antineoplastic Agents/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/immunology/drug effects ; *Neoplasms/drug therapy/microbiology/immunology ; Tumor Microenvironment/immunology ; Probiotics ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {Cancer remains a leading global health challenge, with drug resistance posing a critical barrier to the durable efficacy of anticancer therapies, including chemotherapy, immunotherapy, and targeted treatments. Growing evidence highlights the gut microbiome as a key modulator in this resistance process. The gut microbiome-a dynamic and diverse microbial ecosystem-can influence drug efficacy through multiple mechanisms, including the biotransformation of chemotherapeutics, modulation of immune responses, alteration of host drug-metabolizing enzymes, and reshaping of the tumor microenvironment. Notably, specific bacterial taxa can enzymatically inactivate chemotherapeutic drugs, while microbial metabolites and signaling pathways further promote resistance by rewiring cellular survival and immune-regulatory programs. In this review, we synthesize recent molecular insights into microbiome-driven anticancer drug resistance and discuss emerging microbiome-targeted strategies, such as dietary intervention, probiotics and prebiotics, fecal microbiota transplantation, and advanced drug delivery systems. A deeper understanding of host-microbiome-drug interactions may provide new opportunities to overcome therapeutic resistance and advance precision oncology.}, }
@article {pmid42365572, year = {2026}, author = {Abebaw, D and Adugna, A and Tegegne, BA and Teffera, ZH and Selabat, B and Kindie, Y and Tilahun, M and Belew, H and Baylie, T and Mengistu, G and Jemal, M and Atnaf, A}, title = {Harnessing the gut microbiome for improved immune checkpoint inhibition in colorectal cancer immunotherapy: a narrative Review.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10238-026-02222-3}, pmid = {42365572}, issn = {1591-9528}, abstract = {Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune checkpoint inhibitors (ICIs) have shown efficacy mainly in mismatch repair-deficient (dMMR) CRC, while responses in mismatch repair-proficient (pMMR) microsatellite-stable (MSS) cases remain limited. Emerging evidence highlights the gut microbiome as a critical factor influencing CRC development, progression, and therapeutic response. In particular, the gut microbiota has been shown to affect the efficacy of ICIs, with dysbiosis contributing to treatment resistance and specific microbial taxa enhancing antitumor immune responses. Preclinical and clinical studies have demonstrated that microbiome-based interventions, including probiotics, fecal microbiota transplantation (FMT), dietary modulation, and traditional medicines, can restore immune function by modulating immune cell populations and producing immunoregulatory metabolites. These effects may enhance responsiveness to ICIs and contribute to the suppression of tumor growth. However, we also address key limitations in this field, including inconsistent findings and safety concerns, such as infection risks, to guide future translational efforts. Overall, while microbiome-based interventions represent a promising adjunct to CRC immunotherapy, rigorous clinical trials and mechanistic validation are required before their routine clinical implementation.}, }
@article {pmid42366511, year = {2026}, author = {Yin, Y and Gao, J and Zhang, K and Meng, F and Feng, T}, title = {Novel treatments for Parkinson's disease.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {42366511}, issn = {2542-5641}, abstract = {Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a rapidly rising global disease burden and a substantial decline in patients' quality of life. Although currently approved therapies offer symptomatic relief, their clinical efficacy inevitably wanes over time. This review provides a comprehensive summary of recent advancements in both symptomatic treatments and experimental therapies focused on neuroprotection and disease modification. These novel treatments for PD include continuous dopaminergic stimulation, adaptive deep brain stimulation, transcranial temporal interference stimulation, anti-α-synuclein immunotherapies, oral anti-α-synuclein therapies, non-receptor tyrosine kinase inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, iron chelators, fecal microbiota transplantation, glucosylceramide synthase inhibitors, as well as stem cell therapies and gene therapies. However, the majority of these novel treatments are still in the investigational phase and necessitate additional validation via randomized controlled trials. Future research should also focus on optimizing trial methodologies, including the timing of intervention, stratification of PD subjects, and selection of treatment endpoints.}, }
@article {pmid42366893, year = {2026}, author = {Chen, J and Su, S and Zhang, X and Xiong, F and Zheng, H and Zhang, W and Shen, Y and Lin, P and Gao, H and Li, Y}, title = {Vancomycin Protects Against Lung Injury and Promotes Butyrate Metabolism.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {13}, pages = {e72084}, pmid = {42366893}, issn = {1530-6860}, support = {81970066//National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; *Vancomycin/pharmacology ; Mice ; *Butyrates/metabolism ; Mice, Inbred C57BL ; Humans ; *Acute Lung Injury/metabolism/microbiology/drug therapy/prevention &amp; control ; Male ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology ; Lung/metabolism/drug effects ; *Lung Injury/metabolism/prevention &amp; control ; }, abstract = {Lung injury is one of the most common clinical respiratory diseases, caused by the exposure of lung tissue to various stimuli (including hypoxia, ischemia-reperfusion, and foreign substances). Among them, chronic lung injury is characterized by continuous inflammation in the lungs, which damages the endothelial and epithelial cell barriers within the lungs. Clinically, it presents as severe hypoxia and diffuse functional impairment, and on imaging, it shows diffuse alveolar damage, accompanied by varying degrees of inflammation and airway obstruction. Several studies have highlighted the role of gut microbiota in modulating immune responses and pathological features of respiratory diseases through the gut-lung axis. However, the precise metabolic mechanism remains unknown. A lung injury model was generated by transplanting microbiota from acute lung injury (ALI) patients into healthy C57BL/6J mice. The changes in the gut microbiota and metabolic phenotypes of the feces samples from ALI patients and lung-injured mice were analyzed using 16S rRNA sequencing technology and metabolomics based on [1]H-nuclear magnetic resonance ([1]H-NMR), respectively. The effect of gut microbiota on lung injury was also explored after giving an oral vancomycin treatment to lung-injury mice. The data presented here show that Firmicutes formed the vital species of microbiota that was different in lung-injury mice. Moreover, butyrate (produced by Firmicutes) was the most crucial metabolite in the feces samples of ALI patients and lung-injury mice. ELISA and Hematoxylin-Eosin results showed aggravated functional disturbances in the intestinal barrier of ALI patients and lung inflammation in the lung-injured mice. These phenomena were significantly alleviated after the oral administration of vancomycin. Besides, the utilization of butyrate in the colon of mice was increased considerably. Thus, vancomycin can affect the metabolism of butyrate in the colon by influencing the intestinal microbiota, and it can help in the treatment of lung injury.}, }
@article {pmid42367132, year = {2026}, author = {Qu, J and Fu, J and Wang, Y and Jiang, X and Ma, Y and Yi, J and Wu, J and Liu, Y and Huang, K and Wang, J and Yuan, Z and Wen, L and Liu, S}, title = {Chronic Exposure to NaAsO2 Induces Renal Fibrosis by Modulating Gut Microbiota-Mediated AhR/NLRP3 Inflammasome Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.6c05585}, pmid = {42367132}, issn = {1520-5118}, abstract = {Arsenic is an environmental contaminant with potent renal toxicity. Accumulating evidence has indicated that gut microbiota dysbiosis plays an important role in kidney disease. However, the role of gut microbiota in arsenic-exposure-induced renal injury remains unclear. In our study, chronic exposure to NaAsO2 and fecal microbiota transplantation (FMT) from NaAsO2-exposed mice increased intestinal permeability and elevated renal indoxyl sulfate (IS), a key metabolite of gut microbiota, which promoted renal fibrosis and activated the AhR/NLRP3 inflammasome signaling pathway. Moreover, AST-120, a non-specific adsorbent, alleviated chronic NaAsO2 exposure-induced renal fibrosis by reducing the IS level in mice. In HK-2 cells, IS mediated NaAsO2-induced fibrosis via the AhR/NLRP3 inflammasome signaling pathway. Collectively, we confirmed that chronic exposure to NaAsO2 caused renal fibrosis and intestinal barrier dysfunction. Meanwhile, the gut-kidney axis plays a significant role in the mechanism of NaAsO2-induced renal fibrosis, providing a new therapeutic target for the prevention and treatment of arseniasis.}, }
@article {pmid42367194, year = {2026}, author = {Abaakil, K and Liu, Z and Wang, M and Kuznecova, E and Sung, MSC and Marchesi, JR and Mausz, MA and Li, JV}, title = {Antibiotic course frequency and recovery strategies alter gut microbial composition and metabolism.}, journal = {ISME communications}, volume = {6}, number = {1}, pages = {ycag145}, pmid = {42367194}, issn = {2730-6151}, abstract = {Antibiotics profoundly alter the gut microbiome, but how exposure frequencies shape microbial recovery remains unclear. The effectiveness of post-antibiotic interventions, e.g. probiotics or autologous fecal microbiota transplantation, (aFMT) requires further exploration. This study investigated how antibiotic course timing and recovery strategies influence gut microbiome and metabolism in male Wistar rats. A single oral dose of vancomycin-ciprofloxacin (VC) caused rapid urinary and fecal metabolic shifts within 8-12 h and reduced bacterial α-diversity in cecal and colonic contents. When three VC courses were administered at regular (every 3 weeks; VCr) or irregular (1-3 weeks; VCi) intervals, VCr showed greater suppression of fecal α-diversity and stronger disruption of amino acid and host-microbial co-metabolism than VCi. Over the 3-week recovery period, VCr exhibited slower fecal α-diversity restoration; at week 3, β-diversity remained significantly different between groups, and cecal butyrate levels were persistently reduced in VCr. Both groups showed elevated levels of 5-aminovalerate in feces and colon compared with controls, whereas only VCi showed reductions in jejunal and ileal amino acids. Probiotics or aFMT had limited influence on small intestinal alterations, though aFMT accelerated fecal α-diversity recovery, and both interventions promoted partial normalization of fecal amino acids and 5-aminovalerate, without achieving complete restoration. Overall, shorter antibiotic intervals exerted stronger effects on the small intestinal luminal chemical environment, whereas longer intervals led to greater suppression of colonic and fecal microbial metabolism. Probiotics and aFMT supported selective metabolic recovery without fully reversing antibiotics-induced disturbances, highlighting the need for more targeted restoration strategies across gastrointestinal regions.}, }
@article {pmid42367597, year = {2026}, author = {Gilroy, R and Chaloner, G and Wedley, A and Richards-Rios, P and Pottenger, S and Wigley, P}, title = {Caecal microbiome transplant inhibits transmission and intestinal colonisation of Campylobacter jejuni in broiler chickens.}, journal = {Poultry science and management}, volume = {3}, number = {1}, pages = {13}, pmid = {42367597}, issn = {3005-0715}, abstract = {Campylobacter jejuni is the most frequent cause of foodborne bacterial gastroenteritis with poultry products the most frequent source of infection. C. jejuni can colonise the intestinal tract of the chicken and in particular the large blind caeca to a high level accompanied by faecal shedding and rapid transmission in flocks. As such, reducing transmission and intestinal colonisation in poultry meat production is considered a key target to reduce human infection. Whilst vaccines and feed-based approaches including modulation of the microbiome are considered most likely to reduce numbers in the chicken caeca, neither have yet shown the capacity to lead to significant reductions. We have previously shown that administration of a caecal microbiome transplant (CMT) at hatch acts to modify the microbiome, increasing diversity and reducing Enterobacteriacae levels associated with poor gut health and increased Campylobacter susceptibility. When challenged at 21 days old with C. jejuni M1 in a seeder bird infection model, birds in groups receiving CMT showed reduced transmission and significantly lower levels of C. jejuni at post-mortem examination at 35 days of age than control birds or birds treated with a commercial microflora competitive exclusion product (Aviguard). These data show that a microbiome-based intervention has the potential to inhibit C. jejuni transmission and decrease levels in the caeca at slaughter age. This is modelled to lead to a significant reduction in human cases. CMT offers a valuable tool to determine protective taxa in the chicken gut, aiding rational development of microbial interventions as well as a low-cost platform to help understand immunological development in the chicken gut.}, }
@article {pmid42367812, year = {2026}, author = {Wu, Y and Liu, L and You, D and Mao, T and Zheng, X and Dai, X and Xu, X and Wu, X and Zhou, H}, title = {Deoxycholic acid promotes anxiety- and depression-like behaviors in mice via modulation of the gut microbial metabolite indole-3-propionic acid.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1840574}, pmid = {42367812}, issn = {1664-3224}, mesh = {Animals ; *Depression/metabolism/chemically induced/etiology ; *Deoxycholic Acid/adverse effects ; Mice ; *Anxiety/metabolism/etiology/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Male ; *Indoles/metabolism ; *Behavior, Animal/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; Brain-Gut Axis ; Propionates ; }, abstract = {BACKGROUND: High-fat diet (HFD)-associated anxiety- and depression-like behaviors are closely linked to disturbances in the gut-brain axis; however, the peripheral signaling mechanisms and key metabolites involved remain to be elucidated. Deoxycholic acid (DCA), a bile acid elevated by a HFD, has been reported to be associated with abnormal cognitive behaviors in mice. This study aimed to investigate whether HFD-induced anxiety- and depression-like behaviors are regulated by intestinal DCA and its underlying mechanisms.<br><br>METHODS: Four mouse models were established with different interventions: a low-fat diet (LFD), a HFD, a LFD plus DCA, and a HFD plus the bile acid binder cholestyramine. We performed behavioral phenotyping, brain tissue transcriptome sequencing, fecal 16S rRNA gene sequencing, fecal and serum metabolomics, and intestinal barrier function assessment to clarify the phenotypes and underlying mechanisms. In vitro cell experiments, ileal organoid assays, and in vivo fecal microbiota transplantation (FMT) were further used for validation.<br><br>RESULTS: DCA intervention induced HFD-like anxiety- and depression-like behaviors in the mice, accompanied by reduced levels of the key gut bacterium Clostridium_sensu_stricto_1 and its metabolite indole-3-propionic acid (IPA) in the gut and serum. IPA supplementation restored circulating IPA levels, upregulated the expression of key genes (Cyp3a11 and Abcb1a) in the cerebral pregnane X receptor (PXR) signaling, ameliorated DCA-induced emotional and behavioral abnormalities, and reversed related gut-brain axis impairments, including downregulated brain barrier-related proteins, morphological changes associated with microglial activation, intestinal barrier damage (reduced goblet cells, downregulated Claudin-1/Occludin), intestinal epithelial oxidative stress and injury, and impaired ileal organoid budding. FMT induced behavioral phenotypes, barrier impairments, reduced serum IPA, and cerebral pathological changes in recipient mice similar to those observed in DCA model mice.<br><br>CONCLUSIONS: These findings support a potential gut-brain pathway linking HFD-associated luminal DCA elevation to anxiety- and depression-like behaviors in mice. The reduction in IPA levels resulting from the remodeling of gut microbiota triggered by DCA might be the key mediating factor. Targeting abnormal bile acid metabolism or restoring IPA function is a promising intervention strategy for HFD-related emotional and behavioral abnormalities.}, }
@article {pmid42368286, year = {2026}, author = {Ruttenberg, DP}, title = {Commentary: Safety and efficacy of a novel fecal microbiota transplantation method using hydrogen nanobubble water without antibiotics or bowel cleansing in children with autism spectrum disorder.}, journal = {Frontiers in pediatrics}, volume = {14}, number = {}, pages = {1838225}, pmid = {42368286}, issn = {2296-2360}, }
@article {pmid42370690, year = {2026}, author = {Dietz, M and Subramanian, S and Staley, C}, title = {The gut microbiome and colorectal cancer.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0033225}, doi = {10.1128/cmr.00332-25}, pmid = {42370690}, issn = {1098-6618}, abstract = {SUMMARYColorectal cancer (CRC) is a significant global health concern that is growing in prevalence, especially in younger populations. The gut microbiome is an increasingly recognized factor in the development and progression of numerous diseases, including CRC. This review explores the current research on the causal relationship between the microbiome and CRC, including the strengths and limitations of the current models for studying this complex interaction. We then delve into key microbial metabolites and their effects on host signaling pathways in the context of CRC and highlight specific bacterial species with direct links to CRC development and progression. Existing microbiota-targeted therapies such as pre- and pro-biotics and fecal microbiota transplantation are described, as well as innovative microbiome-focused strategies that are currently in development, like quorum quenching. Finally, we address the major challenges in the field, such as conflicting research findings and the need for a systems-level, multi-omic approach to describe the intertwined and bidirectional host-microbe interactions.}, }
@article {pmid42370841, year = {2026}, author = {Dang, J and Lee, Y and Wills, MV and Brown, JM and Madsen, K and Mocanu, V}, title = {The Gut Microbiome in Surgical Oncology: Mechanisms, Perioperative Outcomes, and Therapeutic Opportunities.}, journal = {The British journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjs/znag082}, pmid = {42370841}, issn = {1365-2168}, abstract = {INTRODUCTION: The gut microbiome is a fundamental determinant of gastrointestinal physiology. It is essential in maintaining host homeostasis while also implicated in cancer pathogenesis and alteration in physiological response to surgical stress. This narrative review evaluates the microbiome's mechanistic role in surgical oncology, assessing it as a biomarker for risk stratification and an emerging therapeutic target.<br><br>METHOD: The current literature was synthesized to examine microbial impacts on tumourigenesis and perioperative surgical outcomes across the lower and upper gastrointestinal tracts (including the gut-lung axis), the hepatopancreatobiliary system, and extra-abdominal malignancies (breast cancer and melanoma).<br><br>RESULTS: Dysbiotic microbial signatures, termed the oncobiome, actively drive tumour progression and immune evasion. Perioperative interventions induce acute microbial shifts linked to serious complications such as anastomotic leaks and pneumonia. Clinically, targeted modulation yields significant benefits as demonstrated by: perioperative synbiotics reducing infectious complications by 45% in colorectal surgery and 64% in major liver surgery. Furthermore, preoperative oral care reduces post-esophagectomy pneumonia by up to 50%, while Helicobacter pylori eradication halves metachronous gastric cancer risk. However, a detrimental "antibiotic paradox" exists in melanoma, where pre-treatment antibiotic exposure severely impairs immune checkpoint inhibitor efficacy. Conversely, faecal microbiota transplantation can reverse this immunotherapy resistance, achieving up to 80% response rates in trials.<br><br>CONCLUSION: The microbiome is a critical, modifiable determinant of both short-term surgical recovery and long-term oncologic survival. Future surgical oncology practice will need to integrate precision surgical microbiome-mediated biotherapeutics to optimise outcomes in multidisciplinary cancer care.}, }
@article {pmid42371176, year = {2026}, author = {Shen, Z and Xu, D and Wang, K and Chen, Y and Dou, Q and Jin, S and Hu, B}, title = {Gut-brain axis modulation by fecal microbiota transplantation improves dual-organ injury after cerebral ischemia-reperfusion via Caspase-8 dependent inhibition of necroptosis.}, journal = {Metabolic brain disease}, volume = {41}, number = {1}, pages = {}, pmid = {42371176}, issn = {1573-7365}, support = {B20252733//Hangzhou Health Science and Technology Plan Project/ ; }, mesh = {Animals ; *Caspase 8/metabolism ; *Necroptosis/physiology ; *Reperfusion Injury/metabolism/therapy ; Male ; Rats ; *Fecal Microbiota Transplantation/methods ; *Brain Ischemia/metabolism/therapy ; Rats, Sprague-Dawley ; *Brain-Gut Axis/physiology ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Gastrointestinal Microbiome/physiology ; Intestinal Barrier Function ; Infarction, Middle Cerebral Artery/metabolism ; *Brain/metabolism ; }, abstract = {The pathological features of cerebral ischemia-reperfusion (CIR) include necroptosis activation. This study investigated how healthy fecal microbiota transplantation (H-FMT) improves CIR and intestinal barrier damage. Rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) were treated with H-FMT and/or a Cysteine-aspartic acid protease-8 (Caspase-8) inhibitor. Survival and body weight were monitored throughout the experiment. Neurological function, tissue damage, inflammatory cytokines, and Caspase-8/Receptor-interacting protein kinase 1 (RIPK1)-Receptor-interacting protein kinase 3 (RIPK3)-Mixed lineage kinase domain-like protein (MLKL) expression were assessed. Ultrastructural changes were examined by transmission electron microscopy (TEM), p-RIPK1/p-RIPK3 expression by immunohistochemistry (IHC), and gut microbiota by 16 S sequencing. H-FMT significantly ameliorated neurological deficits and intestinal barrier disruption, reduced infarct volume and neuronal loss, and attenuated mitochondrial damage. These effects were accompanied by reduced apoptosis and inflammation, increased Caspase-8 activation, and suppressed RIPK1-RIPK3-MLKL phosphorylation. IHC confirmed reduced p-RIPK1/p-RIPK3 signals after H-FMT. 16 S sequencing revealed that H-FMT restored microbial diversity, reduced pathogenic Proteobacteria, and enriched beneficial Lactobacillus, which positively correlated with Caspase-8 activation. Our findings suggest that H-FMT alleviates CIR injury by activating Caspase-8 and suppressing necroptosis. However, due to the small sample size, these results should be considered preliminary.}, }
@article {pmid42371558, year = {2026}, author = {Zhong, S and Guo, F and Chen, Q and Zhang, S}, title = {Microbiota-oriented strategies to mitigate parenteral nutrition-related complications in intestinal failure: A narrative review.}, journal = {Intestinal Failure (New York, N.Y.)}, volume = {10}, number = {}, pages = {100355}, pmid = {42371558}, issn = {2950-4562}, abstract = {BACKGROUND: Parenteral nutrition (PN) is essential for patients with intestinal failure (IF) but is associated with complications such as dysbiosis, small intestinal bacterial overgrowth, catheter-related infections, and intestinal failure-associated liver disease (IFALD). Growing evidence indicates that gut microbiota alterations contribute to the pathogenesis of these complications, supporting microbiota-oriented interventions as potential adjunctive therapies.<br><br>METHODS: Data sources: A structured literature search was conducted in PubMed, Web of Science, and Scopus from inception to December 2025.Study eligibility criteria: Clinical trials, observational studies, mechanistic studies, and relevant reviews evaluating gut microbiota features or microbiome-targeted interventions in IF or PN-dependent populations were included.Participants: Pediatric and adult patients with intestinal failure or short bowel syndrome, as well as relevant animal models.Interventions: Microbiota-oriented strategies, including probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT).Statistical analysis: Due to substantial heterogeneity in study design, interventions, and outcomes, meta-analysis was not performed; findings were synthesized qualitatively.<br><br>RESULTS: PN dependence was consistently associated with reduced microbial diversity, enrichment of Proteobacteria and Lactobacillaceae, and depletion of obligate anaerobes and short-chain fatty acid-producing taxa. Microbiota-oriented interventions demonstrated biological plausibility and microbiome modulation in selected studies; however, clinical benefits were variable and generally modest. Safety concerns, limited microbial engraftment, small sample sizes, and patient heterogeneity limited generalizability.<br><br>CONCLUSION: Gut microbiota dysbiosis plays a contributory role in PN-related complications of IF. Microbiota-oriented interventions are promising but remain unproven, underscoring the need for well-designed, stratified clinical studies to define efficacy, safety, and responsive patient subgroups.}, }
@article {pmid42372605, year = {2026}, author = {Yuan, S and Hong, J and Zhang, H and Gao, P and Yang, P and Lei, J and He, Y and Fang, X and Lu, Y and Wang, B and Tu, P and Zhang, X and Jiang, Y}, title = {Total glycosides of Cistanche deserticola ameliorate alcohol-induced oligoasthenozoospermia via the modulation of gut microbiota-mediated spermidine metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158483}, doi = {10.1016/j.phymed.2026.158483}, pmid = {42372605}, issn = {1618-095X}, abstract = {BACKGROUND: Oligoasthenozoospermia is a major cause of male infertility, with chronic excessive alcohol consumption being a prevalent etiology. Cistanche deserticola Ma., a traditional Chinese medicine historically employed for reproductive improvement. However, the role and mechanism in alcohol-induced reproductive dysfunction remains unexplored.<br><br>PURPOSE: This study aimed to elucidate the protective effect and underlying mechanism of total glycosides of C. deserticola (TGCD) against alcohol-induced oligoasthenozoospermia.<br><br>METHODS: The effects of TGCD were evaluated using a NIAAA mouse model. Mechanisms were elucidated through multi-omics, fecal microbiota transplantation, Lactobacillus reuteri supplementation, spermidine supplementation, and so on. Translational relevance was assessed by patients with alcohol-induced sperm abnormalities and a public single-cell transcriptome dataset.<br><br>RESULTS: TGCD administration significantly improved alcohol-impaired sperm quality, restored testosterone levels and testicular architecture. Mechanistically, TGCD selectively enriched L. reuteri, which enhanced spermidine production. Spermidine activated the Nrf2-mediated antioxidant pathway, thereby reducing ROS accumulation and reinstating the expression of key steroidogenic enzymes. Critically, these findings are corroborated by clinical data showing reduced fecal L. reuteri abundance in patients with alcohol-related sperm abnormalities, as well as human testicular single-cell transcriptomic evidence of concurrent downregulation of spermidine and Nrf2 pathways in infertile patients.<br><br>CONCLUSION: TGCD alleviates alcohol-induced oligoasthenozoospermia via a gut microbiota-dependent mechanism involving L. reuteri-enhanced spermidine production and subsequent activation of the Nrf2 antioxidant pathway. This study not only highlights the therapeutic potential of TGCD for male infertility but also underscores the gut-testis axis as a promising target. Fecal abundance of L. reuteri emerges as a potential biomarker for clinical translation in this context.}, }
@article {pmid42373460, year = {2026}, author = {Li, Y and Yang, Z and Liu, YQ and Liu, Q and Niu, YR and Cai, W and Hu, Y}, title = {[Role of gut-derived immune cells and the gut-lung axis in acute respiratory distress syndrome].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {49}, number = {7}, pages = {805-809}, doi = {10.3760/cma.j.cn112147-20260126-00059}, pmid = {42373460}, issn = {1001-0939}, support = {2024AFB412//Natural Science Foundation of Hubei Province/ ; 2025020701020248//Wuhan Municipal Health Commission Research Fund/ ; }, mesh = {*Respiratory Distress Syndrome/immunology/physiopathology ; Humans ; *Lung/immunology ; *Gastrointestinal Microbiome ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Acute respiratory distress syndrome (ARDS) is a critical illness with high incidence and mortality in the intensive care unit (ICU). Recent studies have demonstrated that the "gut-lung axis", a bidirectional regulatory network between the gut and the lungs, plays a pivotal role in the pathophysiology of ARDS. This review focuses on the "homing" mechanisms underlying the directed migration of gut-derived immune cells, particularly ILC2s, ILC3s, and γδ T17 cells, from the gut to the lungs. It also discusses the critical mediating role of the "gut-lymph-lung" pathway in gut-derived lung injury. Furthermore, this article summarizes interventional strategies targeting the gut-lung axis, including modulation of the gut microbiota (probiotics and fecal microbiota transplantation), supplementation with metabolites (such as short-chain fatty acids), and novel nanoparticle-based drug delivery systems. A deeper understanding of this immunoregulatory network will provide new insights and therapeutic targets for precision treatment and clinical translation of ARDS.}, }
@article {pmid42373713, year = {2026}, author = {Liu, H and Zhi, J and Li, Z and Fan, S and Zhang, N and Liu, M and Xie, R and Wang, W and Feng, N and Wu, Y and Xu, Z and Liu, F}, title = {A nurse-led peer support intervention to enhance decision-making for fecal microbiota transplantation in recurrent UTI: a pilot study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-58218-2}, pmid = {42373713}, issn = {2045-2322}, support = {2021BYGT-006//Open Fund of Gansu Provincial Key Laboratory of Functional Genomics and Molecular Diagnosis/ ; }, abstract = {To examine the preliminary effects and feasibility of peer support on decision-making regarding fecal microbiota transplantation (FMT) among patients with recurrent urinary tract infections (rUTIs). This was a prospective, two-arm pilot study conducted from September 2023 to April 2024 in the urology outpatient departments of two tertiary hospitals in China using convenience sampling. Patients were assigned to either a peer support group or a control group. The intervention consisted of weekly WeChat-based interactions between trained peer supporters and patients for four weeks. Decision-making was assessed using validated tools including the Decisional Conflict Scale, Preparation for Decision Making Scale, Decision Self-Efficacy Scale, Choice Predisposition Scale, and Decisional Satisfaction Scale, all derived from the Ottawa Decision Support Framework. Anxiety and depression were measured using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). A total of 24 patients were assigned to a peer support group (n = 12) and a control group (n = 12). Compared with the control group, the peer support group showed higher FMT-related knowledge, stronger choice predisposition toward FMT, higher decision-making self-efficacy, and lower decisional conflict after the intervention. No significant between-group differences were observed in preparation for decision making, decisional satisfaction, anxiety, or depression. In this small exploratory pilot study, nurse-led peer support showed preliminary potential to improve selected decision-related outcomes among women with rUTIs considering FMT. Rather than confirming efficacy, this study supports the feasibility of a structured nurse-led peer support protocol and provides a basis for future larger-scale research. Given the small sample size, convenience sampling, and single cultural context, these findings should be interpreted cautiously and require confirmation in larger studies. Future studies should also assess whether these preliminary improvements are sustained and translate into actual treatment decisions and long-term decisional satisfaction.}, }
@article {pmid42365269, year = {2026}, author = {Fassarella, M and Smidt, H}, title = {Translational human gut microbiome research: What are the missing pieces of the puzzle?.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08490-7}, pmid = {42365269}, issn = {1479-5876}, abstract = {BACKGROUND: Human gut microbiome research has expanded remarkably over the past two decades, revealing the fundamental role of gut microbes in human health and disease. Despite these advances, translation into evidence-based clinical practice and public health implementation remains exceptionally limited. This integrative translational perspective review evaluates human gut microbiome research across four critical aspects: translational successes, barriers to effective translation, applicability of frameworks from other medical disciplines, and strategies to enhance translational progress.<br><br>MAIN TEXT: Human gut microbiome research was evaluated through the lens of translational medical research principles, as summarised below. (1) Translational successes in human gut microbiome research are explored by analysing the developmental pathways of major microbiome-based or microbiome-targeted approaches, including faecal microbiota transplantation, probiotics, postbiotics, prebiotics, and dietary interventions, despite overall limited clinical and public health translation. (2) Established translational medical research frameworks served as a foundation to identify missing elements in current human gut microbiome research, including progression through T0-T4 phases, bidirectional knowledge flow, prioritization of unmet patient and societal health needs, patient-centric approaches, stakeholder engagement, and interdisciplinary collaboration. Integration of these principles is discussed in light of the specific characteristics, challenges, and limitations of human gut microbiome research. (3) Translational barriers in human gut microbiome research were analysed beyond limited integration of translational medical principles. These arise from the inherent complexity and high-dimensional nature of the gut microbiome, temporal and inter-individual variability, confounding factors, inconsistent methodological standardization and validation, and fragmentation across research efforts. Collectively, these barriers hinder causal inference, resulting in a low-quality evidence base and limiting effective translation. (4) A framework to advance translational human gut microbiome research is proposed based on the previous findings, including strategic priorities such as education and training in translational research principles for gut microbiome researchers.<br><br>CONCLUSIONS: Human gut microbiome research remains largely confined to early translational phases, with progression toward effective translation limited by intrinsic and methodological barriers that hinder causal inference and high-level evidence generation. Integration of core translational medical research principles offers a pathway to bridge these gaps, with education and training of gut microbiome researchers emerging as a key priority for advancing translational progress.}, }
@article {pmid41580587, year = {2026}, author = {Fiedorová, K and Obručová, H and Grombiříková, H and Vaněrková, M and Blaštíková, E and Štěpánková, S and Husová, L and Freiberger, T}, title = {Longitudinal analysis of gut bacterial and fungal dynamics after solid organ transplantation.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {132}, pmid = {41580587}, issn = {1471-2180}, support = {e-INFRA CZ (ID:90254)//the Ministry of Education, Youth and Sports of the Czech Republic/ ; IG 201802//the Centre of Cardiovascular and Transplantation Surgery (CKTCH)/ ; Programme EXCELES, ID Project No. LX22NPO5104//the European Union, Next Generation EU/ ; MUNI/A/1716/2024//Masarykova Univerzita/ ; }, mesh = {Humans ; *Bacteria/classification/genetics/isolation &amp; purification ; *Organ Transplantation/adverse effects ; Longitudinal Studies ; *Fungi/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; Female ; *Mycobiome ; Male ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Dysbiosis/microbiology ; Adult ; Feces/microbiology ; Aged ; }, abstract = {BACKGROUND: Solid-organ transplantation and related medical treatments can significantly alter the gut microbiome. While disruptions in bacterial communities (dysbiosis) have been associated with infections, rejection, and increased mortality in transplant recipients, research on gut fungal communities (the mycobiome) remains limited. To our knowledge, no study has yet concurrently characterized the bacterial and fungal microbiota or quantified the fungal load longitudinally in patients following solid-organ transplantation. This study aimed to describe temporal changes in these microbial communities and explore associations with clinical outcomes. RESULTS: We analysed the gut microbiota dynamics in 21 solid-organ transplant recipients and 10 healthy volunteers across six timepoints, processing 184 samples using both bacterial (16 S rRNA) and fungal (ITS) amplicon sequencing. Bacterial diversity significantly decreased shortly after transplantation but partially recovered during the later post-transplant phase. In contrast, fungal diversity was consistently lower after transplantation and showed greater temporal variability. Quantitative PCR revealed a transient increase in the fungal load at approximately two weeks post-transplant, which was negatively correlated with bacterial diversity. Patients who experienced clinical complications presented reduced microbial richness, especially during the early post-transplant period. Additionally, we identified correlations between selected fungal taxa and bacterial genera previously linked to dysbiosis, suggesting potential interkingdom interactions that may influence microbiome dynamics after transplantation. CONCLUSIONS: Our study provides a longitudinal overview of both bacterial and fungal microbiota following solid-organ transplantation. The association between fungal load and bacterial diversity indicates possible interkingdom interactions affecting microbiome recovery, but the clinical implications remain to be elucidated. These findings highlight the importance of including fungal communities alongside bacterial microbiota in future research and clinical monitoring.}, }
@article {pmid41933306, year = {2026}, author = {Adamczak, M and Pokora, P and Kaczmarczyk, M and Gojowy, D and Wierzbicka-Woś, A and Cembrowska-Lech, D and Kolonko, A and Łoniewski, I and Więcek, A}, title = {Intestinal microbiome and acute transplanted kidney rejection - results of a single-center, case-control study.}, journal = {BMC nephrology}, volume = {27}, number = {1}, pages = {}, pmid = {41933306}, issn = {1471-2369}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Graft Rejection/microbiology ; Female ; Male ; Case-Control Studies ; *Gastrointestinal Microbiome ; Retrospective Studies ; Adult ; Middle Aged ; Feces/microbiology ; Acute Disease ; }, abstract = {BACKGROUND: Kidney transplantation (KTx) is the preferred form of renal replacement therapy. Acute rejection of the transplanted kidney (AR) may impair long-term outcomes. The gut microbiota influences immune system activity; however, its relationship with AR remains underexplored. This study aimed to investigate the relationship between the gut microbiome and risk of AR shortly after KTx. METHODS: In this single-center, retrospective case-control study, 10 patients with consecutive biopsy-proven AR shortly after KTx (median age 43 (38, 48) years) were matched by sex and age with 20 patients without AR (median age 42 (37, 48) years) during a one-year follow-up after KTx. Stool samples were collected 4–7 days after KTx for microbiome analysis using Illumina shallow shotgun sequencing. Bioinformatics analysis included taxonomic and functional profiling, with predictive modeling performed using a random forest model (RF). Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). RESULTS: No significant differences in gut microbiota diversity were observed between the groups. The differential abundance analysis did not identify any taxonomic features that remained significant after adjusting for possible covariates. The predictive RF models varied in performance, with functional KEGG pathway profiles showing the highest predictive value (AUC = 0.73). Key metabolic pathways implicated in such profiles included lipid metabolism, glycan biosynthesis and metabolism, and terpenoid and polyketide metabolism. CONCLUSION: No universal taxonomic gut microbiota markers for AR have been identified. The functional profile of the gut microbiome may be related to AR with specific metabolic pathways potentially involved in the underlying mechanisms. These findings suggest a role of immunomodulation, inflammation, and metabolic regulation in AR.}, }
@article {pmid42362695, year = {2026}, author = {Saensupha, T and Jirahiranpat, A and Pratumwan, N and Bubpamala, T and Jamnongkan, W and Kulthawatsiri, T and Suksawat, M and Thaiwatcharamas, K and Auiewiriyanukul, W and Attapong, M and Sritong, N and Mullish, BH and Phetcharaburanin, J}, title = {Bile reinfusion is associated with shifts in host-microbiota metabolic profiles following cholangiocarcinoma-associated microbiota transplantation.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-58698-2}, pmid = {42362695}, issn = {2045-2322}, support = {651H114-C//Graduate School, Khon Kaen University, Thailand/ ; MR/Z504002/1//Medical Research Council Clinician Scientist Fellowship/ ; B13F670075//Program Management Unit for Human Resources &amp; Institutional Development, Research and Innovation/ ; }, abstract = {Cholangiocarcinoma (CCA) is a heterogeneous group of malignant tumours originating along the biliary tract. Previous studies have demonstrated that CCA is characterised by altered gut microbial composition and disrupted bile acid metabolism, both of which are critical determinants of host metabolic homeostasis. Although bile reinfusion (BR) has been proposed to improve surgical outcomes in CCA patients, its systemic metabolic effects and interaction with gut microbiota remain poorly understood. Here, we employed faecal microbiota transplantation (FMT) from CCA patients, with or without BR, into Wistar rats to investigate host-microbiota metabolic interactions using integrated [1]H NMR-based metabolomics and full-length 16S rRNA gene sequencing. Rats receiving CCA-derived microbiota displayed altered systemic metabolic phenotypes, characterised by lower levels of glucose, lactate, and succinate compared to normal microbiota recipients, whilst no significant differences in faecal metabolites were observed between these groups. Notably, BR was associated with shifts in gut microbial composition, marked by enrichment of Lactobacillaceae, altered intestinal fermentation metabolites (decreased short-chain fatty acids and increased succinate), and a convergence of peripheral plasma metabolite profiles towards those observed in healthy microbiota recipients. These findings reveal associations between bile reinfusion and shifts in microbial composition and systemic metabolic phenotypes, providing a basis for investigating microbiota-bile acid-host metabolic crosstalk and potential therapeutic implications for managing CCA-associated dysbiosis.}, }
@article {pmid42364737, year = {2026}, author = {Hajjar, C and Saint-Criq, V and Thomas, M and Butel, MJ and Bazarbachi, A and Abifadel, M}, title = {The Lung Microbiome in Hematopoietic Stem Cell Transplantation: Immune Interactions, Clinical Consequences, and Emerging Interventions.}, journal = {Respiratory medicine}, volume = {}, number = {}, pages = {109004}, doi = {10.1016/j.rmed.2026.109004}, pmid = {42364737}, issn = {1532-3064}, abstract = {Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Traditionally attributed to immune suppression and graft-versus-host disease (GvHD), these complications are increasingly recognized to involve disruption of pulmonary microbial communities. A growing body of clinical and experimental evidence indicates that HSCT-associated perturbations in the lung microbiome, driven by conditioning, antimicrobials, immune injury, and infection, are associated with distinct post-transplant pulmonary phenotypes and, in some cohorts, with mortality risk. Whether these microbial shifts represent causal contributors to lung injury or contextual biomarkers of immune vulnerability remains unresolved, and this distinction carries direct implications for microbiome-targeted intervention. Dysbiotic shifts in the lung have been associated with both infectious and non-infectious complications, including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and fibrotic lung disease. Gut-lung microbial crosstalk may amplify or reflect systemic immune dysfunction, though the directionality of this relationship remains incompletely characterized. Multi-omics approaches, integrating metagenomics, metatranscriptomics, and metabolomics, are beginning to define the host-microbiome interaction signatures that distinguish injury subtypes and predict outcomes. This review synthesizes mechanistic insights into lung microbiome-immune interactions after HSCT, critically appraises the methodological constraints on the current evidence base, and evaluates microbiome-based interventions, including fecal microbiota transplantation, inhaled postbiotics, and precision antimicrobials, as candidate strategies for respiratory protection in transplant recipients, while acknowledging that prospective interventional evidence in this population remains limited.}, }
@article {pmid42350644, year = {2026}, author = {Suissa, D and Fidelle, M and Reich, E and Pham, TN and Thomas, S and Björk, JR and Liu, P and Zhao, L and Kitaoka, K and Piard, E and Lebhar, I and Tian, AL and Thelemaque, C and Alves Costa Silva, C and Deutsch, E and Loriot, Y and Segata, N and Piccinno, G and Hospers, GAP and Maleki Vareki, S and Silverman, MS and Lenehan, JG and Bataille, V and Boulate, D and Kuznetsova, T and Weersma, RK and Messaoudene, M and Durand, S and van der Aalst, CM and de Koning, HJ and Schuler-Thurner, B and de Vries, IJM and Rafie, E and Saliby, RM and Machaalani, M and Haferkamp, S and Schilling, B and Porcari, S and Ciccarese, C and Iacovelli, R and Cremolini, C and Choueiri, TK and Elkrief, A and Kroemer, G and Heinzerling, L and Chamoto, K and Ianiro, G and Routy, B and Derosa, L and Paragios, N and Zitvogel, L}, title = {Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {42350644}, issn = {1546-170X}, abstract = {Immune-checkpoint inhibitors benefit a subset of patients with advanced cancer, and the metabolic determinants of response remain unclear. Here, using targeted metabolomics and metagenomics, we profiled 4,336 plasma samples from 1,714 patients across five tumor types and 16 cohorts spanning Europe and North America, longitudinally sampled during five immune-checkpoint inhibitor-based treatment modalities, including fecal microbiota transplantation. A multimodal machine-learning framework integrating 154 metabolites with clinical variables identified five metabolites, age, body mass index and renal function as predictors of 12-month progression-free survival. The model achieved areas under the curve of 0.88 in training and 0.73 in validation cohorts of 105 and 30 patients, respectively and generalized across seven external cohorts. Histidine was a favorable prognostic feature of survival, whereas long-chain fatty acids and succinate were negatively associated with outcome. Histidine supplementation enhanced antitumor immunity in mice. Histidine-rich diets improved progression-free survival in patients lacking dysbiotic microbiome signatures associated with histidine catabolism.}, }
@article {pmid42351636, year = {2026}, author = {Loguercio, M and Giamundo, DM and Giglio, A and Buda, E and Ambrosetti, M and Perone, F}, title = {Gut Microbiota: Cardiovascular Disease Prevention and Targeted Therapies.}, journal = {Biomedicines}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/biomedicines14061210}, pmid = {42351636}, issn = {2227-9059}, abstract = {The gut microbiota has emerged as a key regulator of cardiovascular health, influencing metabolic, inflammatory, and vascular pathways. Growing evidence indicates that gut dysbiosis, characterized by reduced microbial diversity, depletion of beneficial short-chain fatty acid-producing bacteria, and enrichment of pro-inflammatory taxa, is associated with major cardiovascular risk factors and disease progression. Microbial-derived metabolites, including trimethylamine/trimethylamine N-oxide, short-chain fatty acids, amino acids and bile acids, may play a central role in modulating lipid metabolism, endothelial function, inflammation, and thrombosis, although the underlying mechanisms remain incompletely understood. Recent multi-omics approaches have expanded this understanding by identifying personalized microbiome-metabolome signatures linked to cardiovascular risk, supporting a shift toward precision medicine. In this review, we summarize current evidence on the composition and functional role of the gut microbiota in cardiovascular disease and critically discuss emerging microbiota-targeted strategies. These include dietary interventions, prebiotics, probiotics, synbiotics, antibiotics, enzyme inhibitors, and fecal microbiota transplantation, which may contribute to both the prevention and adjunctive treatment of cardiovascular conditions. In addition, we address the challenges of integrating gut microbiota management into clinical practice and highlight the importance of tailored strategies, including exercise-based interventions, microbial enzyme inhibitors, and postbiotics. Despite promising preclinical and early clinical data, the translation of microbiome-based therapies into routine practice remains limited by heterogeneity in study design, the lack of standardized protocols, and incomplete mechanistic understanding. Overall, targeting the gut microbiota represents a novel and potentially complementary approach for cardiovascular disease prevention and management, warranting further well-designed clinical studies.}, }
@article {pmid42351694, year = {2026}, author = {Hijová, E and Bertková, I and Benetinová, V}, title = {Gut Microbiota as an Innovative Therapeutic Target in Cardiovascular Diseases from a Metabolic and Inflammatory Perspective.}, journal = {Biomedicines}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/biomedicines14061267}, pmid = {42351694}, issn = {2227-9059}, abstract = {The gut microbiome plays a key role in the pathogenesis of cardiovascular disease through systemic inflammation, impaired lipid metabolism, and proatherogenic gut metabolites like trimethylamine N-oxide. Gut dysbiosis contributes to decreased level of microbial metabolites such as short-chain fatty acids, bile acids, coprostanol, and phenylacetylglutamine, as well as increased intestinal permeability and platelet hyper-reactivity, and exacerbating cardiovascular risk. New microbiome-focused treatments such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation are showing potential to help reduce cardiovascular diseases. However, bringing these therapies into clinical settings is difficult because they vary by strain and individual response. The gut-heart connection offers an innovative approach to preventing and treating heart condition, but additional research is needed to ensure lasting effectiveness and safety.}, }
@article {pmid42353350, year = {2026}, author = {Trifonova, EA and Ivanov, RA and Kochetov, AV and Lashin, SA}, title = {The Microbiota in the Diagnosis and Treatment of Autism Spectrum Disorder.}, journal = {International journal of molecular sciences}, volume = {27}, number = {12}, pages = {}, doi = {10.3390/ijms27125636}, pmid = {42353350}, issn = {1422-0067}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/diagnosis/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Animals ; Signal Transduction ; Brain/metabolism ; Diet, Ketogenic ; }, abstract = {Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and repetitive behaviors. Recent research highlights the role of the gut microbiota in ASD pathophysiology, particularly through the microbiota-gut-brain axis. The microbiota may influence neurodevelopment via multiple signaling pathways, including the GABAergic and serotonergic systems, as well as the mTOR signaling pathway. This analytical review examines current evidence on microbiota alterations in ASD and evaluates microbiota-targeted strategies for diagnosis and treatment, focusing on fecal microbiota transplantation (FMT), probiotics, and diet-based therapeutic approaches. The review also provides a critical appraisal of the microbiota-gut-brain axis in the context of autism spectrum disorder.}, }
@article {pmid42353674, year = {2026}, author = {Vashishtha, K and Borah, P and Sonowal, R}, title = {The ESKAPE Challenge: Understanding Resistance and Exploring Alternative Treatments.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/antibiotics15060550}, pmid = {42353674}, issn = {2079-6382}, abstract = {Antimicrobial resistance (AMR) constitutes a critical and escalating global public health challenge, severely limiting the potential of existing antimicrobial drugs and escalating infection-associated morbidity and mortality rates. This analysis focuses on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are prioritized by the World Health Organization (WHO) and represent a significant cause of nosocomial infections due to their extensive drug resistance. We provide an in-depth review of the global prevalence and specific antibiotic-resistant mechanisms of these pathogens. Due to the decline in the traditional antibiotic development pipeline, accelerated development of alternative therapeutic strategies is essential. The review comprehensively discusses innovative non-traditional therapies currently being explored to bypass traditional antibiotic limitations, such as phage therapy, antimicrobial peptides (AMPs), anti-virulence therapies, fecal microbiota transplantation (FMT), and targeted CRISPR-based approaches. Addressing the ESKAPE challenge requires a concerted, multi-sectoral strategy guided by the One Health principle, focusing on enhancing public awareness, improving surveillance and research, optimizing judicious antibiotic use, and cultivating sustainable investment in novel interventions.}, }
@article {pmid42354799, year = {2026}, author = {Wu, L and Li, Z and Zhu, J and Sun, Z and Yan, L and Luo, M and Chen, H and Yin, Y}, title = {Engineering the Gut Microbiome: Emerging Genome-Editing Strategies and Therapeutic Applications.}, journal = {Microorganisms}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/microorganisms14061174}, pmid = {42354799}, issn = {2076-2607}, support = {No. 32460015//National Natural Science Foundation of China/ ; No. 2025LT0103004//Guangxi Science and Technology Department/ ; }, abstract = {The gut microbiome, often termed the human "second genome", profoundly influences host physiology through metabolic interactions, immune modulation, and gut-brain axis signaling. Dysbiosis is implicated in the pathogenesis of obesity, inflammatory bowel disease (IBD), malignancies, and neuropsychiatric disorders. However, traditional gut microbiota interventions, such as probiotic supplementation and fecal microbiota transplantation (FMT), still exhibit significant limitations in precision therapeutics. Probiotic intervention fails to achieve precise regulation at the strain or genetic level, and although FMT demonstrates definitive efficacy against recurrent Clostridioides difficile infection (rCDI), its therapeutic outcomes and safety profiles show marked interindividual variability in ulcerative colitis (UC), metabolic syndrome, and other diseases, with insufficient treatment specificity to meet the practical demands of clinical precision intervention. Recent advancements in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) proteins systems and base editors, have enabled targeted functional manipulation of specific gut commensals and optimization of community architectures. These engineered strategies, combined with sophisticated delivery systems, demonstrate substantial potential in disease treatment, diagnostic monitoring, and immune modulation. This review systematically examines core editing methodologies, innovative delivery platforms, and targeted design strategies, elucidating their applications in metabolic disorders, IBD, cancer immunotherapy, and neuropsychiatric conditions. We critically analyze current technical bottlenecks and biosafety concerns while prospecting future directions, including in situ editing, artificial intelligence (AI)-driven design, and personalized engineering. Collectively, these insights aim to facilitate the clinical translation of gut microbiome engineering from bench to bedside.}, }
@article {pmid42354867, year = {2026}, author = {Zambelli, G and Masetti, M and Rasmi, S and Addati, I and Bonacorsi, L and Diona, S and Esposito, S}, title = {Restoring Microbial Balance: Clinical Applications, Challenges, and Future Directions of Fecal Microbiota Transplantation in Pediatric Disorders.}, journal = {Microorganisms}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/microorganisms14061241}, pmid = {42354867}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance-particularly during early life-restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications-including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders-remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit.}, }
@article {pmid42354994, year = {2026}, author = {Bao, S and Xu, S and Wang, Z and Chai, S and Wang, S and Dai, D and Wang, X and Lv, J}, title = {Fecal Microbiota Transplantation Improves Biota and Hepatic Metabolism, Promoting Growth in SD Rats Under Hypobaric Hypoxia Exposure.}, journal = {Microorganisms}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/microorganisms14061370}, pmid = {42354994}, issn = {2076-2607}, abstract = {Hypobaric hypoxia poses a serious threat to growth and development and can induce pronounced inflammatory responses. These effects are closely associated with the gut microbiota. However, the underlying mechanisms, particularly the role of gut microbiota in regulating hepatic metabolism under chronic hypoxic conditions, remain poorly understood. In this study, SD rats were used as recipients and assigned to three groups: a hypobaric hypoxia group (H), an antibiotic-treated group (HA), and an antibiotic-treated group receiving fecal microbiota transplantation from plateau zokors (HAM). All rats were maintained in a hypobaric hypoxia chamber simulating an altitude of 6000 m for 30 days. Subsequently, growth performance, routine hematological parameters, and multi-omics profiles were evaluated. Compared with the H group, both the HAM and HA groups showed significantly increased average daily gain (ADG) (p < 0.05), while the ADG/ADFI ratio was significantly higher in the HAM group than in the H group (p < 0.05). Monocyte count (Mon#) and monocyte percentage (Mon%) were significantly higher in the HA group than in both the H and HAM groups (p < 0.05). Microbiota analysis revealed significant enrichment of Lachnospiraceae_NK4A136_group in the HAM group, whereas Desulfovibrio was significantly enriched in the HA group (p < 0.05). Fecal metabolomics showed that ursodeoxycholic acid (UDCA) was significantly increased in the HAM group (p < 0.05). In the liver metabolome, the anti-inflammatory lipid FAHFA 18:1/20:3 was significantly elevated in the HAM group, whereas pro-inflammatory factors, including uric acid and leukotriene D4, were significantly reduced (p < 0.05). Correlation analysis further demonstrated that the abundance of Lachnospiraceae was positively correlated with FAHFA 18:1/20:3 and negatively correlated with uric acid and creatinine (p < 0.05). Collectively, these findings indicate that the gut microbiota can modulate gut-liver metabolism, alleviate inflammatory responses, and enhance the adaptation of rats to hypoxic environments. This study provides valuable insights into potential strategies for promoting sustainable animal health and adaptation under hypoxic conditions.}, }
@article {pmid42355348, year = {2026}, author = {Piquer-Esteban, S and Pérez-Brocal, V and Domínguez-Santos, R and Latorre, A and García-Ferris, C and Moya, A}, title = {Blattella germanica Selects Microbiota Taxa from Feces and Environmental Inputs.}, journal = {Insects}, volume = {17}, number = {6}, pages = {}, doi = {10.3390/insects17060615}, pmid = {42355348}, issn = {2075-4450}, support = {Prometeo/2018/133//Conselleria d'Educaci&#xf3;, Generalitat Valenciana (Spain)/ ; CIPROM/2021/042//Conselleria d'Educaci&#xf3;, Generalitat Valenciana (Spain)/ ; FPU20/05756//Spanish Ministry of Universities/ ; }, abstract = {Cockroaches display a double symbiosis: an obligate intracellular one with Blattabacterium spp., and a complex extracellular non-vertically transmitted gut microbiota, that may be affected by horizontally transmitted factors. Four experiments using 16S rRNA gene amplicon sequencing were conducted to analyze the microbiota of the hindgut and feces of adult cockroaches. They aimed to understand the influence of the environment and feces on the acquisition and development of the hindgut microbiota. We observed that sample type (hindgut vs. feces), rearing conditions (environment, i.e., place and diet), coprophagy, and host influenced microbiota composition. Cockroaches initially germ-free, placed in non-sterile conditions and with blocked parental coprophagy, were unable to develop the normal microbiota of the control population, demonstrating that coprophagy is essential for acquiring a normal microbiota. This also showed that, in the absence of parental fecal input, the cockroach gut microbiota is strongly diminished. Moreover, when exploring fecal microbiota differences among three cockroach species, the greatest divergence was observed between Periplaneta americana and Blattella germanica, with Blatta orientalis occupying an intermediate position. Therefore, P. americana was selected for fecal transplantation on B. germanica. This transplantation experiment indicates that different species select different gut microbes, and that even when they receive feces from other species, only some of those bacteria are retained. Overall, these results suggest that beyond other factors, the host species had the strongest influence on shaping the cockroach gut microbiota.}, }
@article {pmid42356344, year = {2026}, author = {Ciurea, NA and Mahdi, L and Graziani, A and Di Ciaula, A and Portincasa, P and Khalil, M}, title = {Targeting the Human Gut Microbiota-Between Conventional Therapy and Precision Genetic Engineering.}, journal = {Nutrients}, volume = {18}, number = {12}, pages = {}, doi = {10.3390/nu18121958}, pmid = {42356344}, issn = {2072-6643}, support = {CUP H93C22000950001; HORIZON-HLTH-2022-STAYHLTH-01-05; Project 101080329//PRIMA Programme (Partnership for Research and Innovation in the Mediterranean Area/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/genetics ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Genetic Engineering/methods ; *Precision Medicine/methods ; Prebiotics ; }, abstract = {The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson's disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation.}, }
@article {pmid42356496, year = {2026}, author = {Zhang, W and Guo, X and Zhang, J and Zhang, YW and Li, C}, title = {Microbiota-Derived SCFAs Mediate the Synergistic Antidepressant Effects of Dajianzhong Decoction and Ketamine via FFAR2-NLRP3-IL-1β Signaling.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ph19060877}, pmid = {42356496}, issn = {1424-8247}, support = {32371304//National Natural Science Foundation of China/ ; 2023A1515110683//Guangdong Academy of Sciences/ ; 2024A1515011695//Guangdong Academy of Sciences/ ; }, abstract = {Background: Ketamine is a rapid-acting antidepressant for major depressive disorder; however, its effects are short-lasting and associated with neurotoxic side effects. Thus, identifying strategies to prolong its antidepressant effects is of critical importance. It has been shown that Dajianzhong Decoction (DJZT) prolongs the antidepressant effects of ketamine through modulation of the gut microbiota, but the underlying mechanisms remain unclear. Method: Fecal microbiota transplantation, metabolomic profiling, pharmacological interventions, and behavioral approaches were employed together with a chronic unpredictable mild stress (CUMS) mouse model to investigate how microbiota-derived signals mediate the combined effects of DJZT and ketamine. Results: Microbiota from CUMS mice induced depressive-like behaviors in recipient mice, accompanied by reduced levels of short-chain fatty acids (SCFAs), decreased FFAR2 expression in the medial prefrontal cortex, and increased neuroinflammation and synaptic deficits. These alterations were reversed by microbiota from DJZT-plus-ketamine-treated donors. Notably, acetic acid and isobutyric acid were identified as key SCFAs restored by the combined treatment and were significantly associated with behavioral outcomes. Moreover, SCFA supplementation recapitulated these effects by activating FFAR2 and suppressing NLRP3-IL-1β signaling. Importantly, pharmacological inhibition of FFAR2 using GLPG0974 abolished the antidepressant-like, anti-inflammatory, and synaptic protective effects of the microbiota from DJZT-plus-ketamine-treated donors. Conclusions: These findings demonstrate that microbiota-derived SCFAs mediate the synergistic antidepressant effects of DJZT and ketamine via a central FFAR2-dependent mechanism involving suppression of neuroinflammation. This work highlights a potential role of the SCFA-FFAR2-NLRP3- IL-1β axis in influencing ketamine efficacy and points to microbiota-modulating strategies as a possible avenue for improving antidepressant therapy.}, }
@article {pmid42357401, year = {2026}, author = {Liu, X and Hu, J and Chen, Y and Shi, B and Shang, Z and Liang, Y}, title = {Pharmacokinetics, Excretion, and Metabolite Profiling of Leonurine in Rats: Evidence for Extensive Phase II Conjugations.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {12}, pages = {}, doi = {10.3390/molecules31122002}, pmid = {42357401}, issn = {1420-3049}, mesh = {Animals ; *Gallic Acid/analogs &amp; derivatives/pharmacokinetics/administration &amp; dosage/chemistry/urine/metabolism ; Rats ; Male ; Administration, Oral ; Feces/chemistry ; Tandem Mass Spectrometry ; Rats, Sprague-Dawley ; Chromatography, Liquid ; Metabolome ; Biological Availability ; }, abstract = {Leonurine, a bioactive alkaloid from Leonurus japonicus, has attracted considerable pharmacological interest, yet its in vivo disposition remains insufficiently defined. In the present study, the pharmacokinetics, excretion, and metabolic profile of leonurine were systematically investigated in rats after intravenous (IV), oral (PO), and intraperitoneal (IP) administration. A validated LC-MS/MS method was used to quantify leonurine in plasma, urine, and feces, and high-resolution MS was applied for metabolite profiling. Following IV administration, leonurine exhibited rapid systemic disposition, with a half-life of 2.48 h and a clearance of 152 mL/min/kg. Oral exposure was negligible, with an absolute bioavailability of 0.14%, whereas IP administration produced markedly higher systemic exposure (66.6%). Recovery of unchanged leonurine in urine and feces remained low across all dosing routes, with total excretory recovery below 6% of doses. The results indicated that metabolic conversion, rather than parent drug excretion, was the dominant elimination pathway. A total of 30 leonurine-related components were characterized in vivo, including 24 previously unreported metabolites. The metabolic profile was dominated by phase II conjugation, comprising 12 glucuronidated and 12 sulfated metabolites, together with hydrolysis, methylation/demethylation, and other transformation products. Notably, ester bond cleavage was identified as one of the major primary biotransformation routes, and several glucuronide and sulfate conjugates were also formed on hydrolysis-derived fragments. These findings provide a more comprehensive view of leonurine disposition in rats and offer a mechanistic basis for its rapid clearance and limited systemic availability after oral administration.}, }
@article {pmid42358262, year = {2026}, author = {Ji, Y and Zhao, L and Wang, L and Wang, A and Zhang, C and Xie, Y and Luo, X}, title = {Fecal microbiota transplantation in obesity: a comprehensive overview from basic research to clinical application.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1840517}, pmid = {42358262}, issn = {1664-302X}, abstract = {BACKGROUND: Obesity involves microbiota dysbiosis, low-grade inflammation, and insulin resistance, which interacts with multiple metabolic disorders. Fecal microbiota transplantation (FMT) is an emerging therapeutic approach in obesity that enhances intestinal barrier function and regulates energy metabolism.<br><br>AIM: To provide a comprehensive overview of publication trends, research collaborations, hotspots, future directions, and the current clinical application status of FMT in obesity.<br><br>METHODS: Literature searches were conducted in the Web of Science (WoS) and PubMed databases. The primary analysis was performed using the WoS database for bibliometric analysis, while PubMed was searched to supplement the clinical research landscape, ensuring data comprehensiveness and methodological rigor.<br><br>RESULTS: A total of 517 papers were finally included, of which 116 (22.44%) were published in the top 10 academic journals. Most publications originated from China (n = 246, 47.6%) and Zhejiang University contributed the most publications (n = 18, 3.5%). Gut Microbes ranked first (21 publications, IF 10.931), followed by Frontiers in Microbiology (19, IF 4.504) and Nutrients (14, IF 4.919). Research hotspots have shifted toward "targeting the gut microbiota." "Oral supplementation" and targeted "prebiotics" may be more accessible in the future. The mini literature review of 21 clinical trials revealed that metabolic improvements following FMT are often transient and highly variable across individuals. No standardized protocol for donor selection, delivery route, or outcome measurement currently exists, and most trials had small sample sizes.<br><br>CONCLUSION: Although FMT shows promise, its clinical benefits remain transient and variable across individuals. Current evidence does not yet support routine clinical application. Targeted oral microbiota supplementation may represent a future direction, but high-quality, large-scale clinical trials are urgently needed to establish standardized protocols and evaluate long-term safety and efficacy.}, }
@article {pmid42358304, year = {2026}, author = {Mei, X and Yang, Y and Wen, Y and Zhang, X and Li, Z and Yang, T and Li, L}, title = {Perinatal phlorizin alleviates maternal high-fat diet-induced metabolic syndrome in female mouse offspring and is associated with modulation of the gut microbiota.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1799829}, pmid = {42358304}, issn = {2296-861X}, abstract = {INTRODUCTION: Maternal obesity induces transgenerational metabolic syndrome (MS). The role of phlorizin (PHZ) in improving MS has been confirmed; however, the transgenerational metabolic benefits of PHZ in female offspring remain unclear. This study aimed to investigate whether perinatal PHZ intake could mitigate the adverse metabolic effects of maternal high-fat diet (HFD) in female offspring and to elucidate the role of the gut microbiota in mediating these transgenerational effects.<br><br>METHODS: C57BL/6 mice with maternal HFD &#xb1; perinatal PHZ (0.8 g/kg diet) intervention were used. After weaning, Female offspring's glucolipid metabolism, gut barrier, gut microbiota, and SCFAs were analyzed. Obesogenic dietary challenge and fecal microbiota transplantation (FMT) were implemented to verify microbiota mediation.<br><br>RESULTS: Maternal HFD induces metabolic abnormalities in female offspring, characterized by disrupted glucolipid metabolism during weaning and mild obesity. In adulthood, although these offspring did not display overt obesity, they exhibited gut microbial dysbiosis (increase Firmicutes/Bacteroidetes ratio and pro-inflammatory bacteria), accompanied by insulin resistance and impaired intestinal barrier function, along with a significantly increased obesity susceptibility. Maternal PHZ co-intervention ameliorated MS and restored gut microbial balance in adulthood, increased the abundance of SCFA-producing bacteria (Akkermansia muciniphila and Blautia sp.), elevated fecal SCFAs and serum GLP1/2 levels, improved gut barrier integrity, alleviated inflammatory conditions, and reduced obesity susceptibility. To eliminate the protective effect of estrogen metabolism, antibiotic-treated (ABX) male mice were selected as the recipients for FMT. ABX male mice receiving FMT from PHZ-intervened female offspring could attenuate MS induced by receiving FMT from maternal HFD offspring via the gut microbiota-SCFA pathway.<br><br>CONCLUSION: Our findings suggested that maternal PHZ alleviates maternal HFD-induced transgenerational metabolic dysfunction in female offspring and is associated with modulation of the gut microbiota, positioning PHZ as a promising functional food component with transgenerational metabolic protective potential.}, }
@article {pmid42358596, year = {2026}, author = {Kent, J and Chao, J and Liao, W and Singla, S}, title = {Exploring the Gut Microbiome's Association in Psoriasis and Psoriatic Arthritis: A Scoping Review.}, journal = {Journal of psoriasis and psoriatic arthritis}, volume = {}, number = {}, pages = {24755303261464171}, pmid = {42358596}, issn = {2475-5311}, abstract = {INTRODUCTION: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic inflammatory conditions treated with primarily immune-modulating medication. However, interest is growing in gut microbiome therapies. Studies have reported altered gut microbiota in PsO/PsA and explored probiotics and fecal microbiota transplantation (FMT) as potential therapies. This review synthesizes global studies on the microbiome's associations in PsO/PsA.<br><br>METHODS: We conducted a scoping literature review to understand the association between gut microbiota in PsO and PsA patients. Pubmed was used to identify 4,126 published manuscripts between 2015-2025. Thirty studies were included, encompassing 749,275 participants, with balanced gender representation and ages ranging from 18 to 76&#xa0;years. These studies included 21 case-control studies, 1 case-series, 2 genome-wide analyses, 5 clinical trials, and 1 retrospective review.<br><br>RESULTS: Eighteen studies reported significant gut microbiome differences in PsO/PsA vs healthy controls. Variation in the Firmicutes/Bacteroides (F/B) ratio was of interest, with one study suggesting a low F/B ratio and five studies suggesting an elevated F/B ratio in PsO. A higher F/B ratio was linked to increased acetate production. Acetate and propionate, key short-chain fatty acids (SCFAs), were associated with modulation of the IL-23/Th17 axis in psoriasis and activation of keratinocytes. The role of therapeutics targeting the gut microbiome was explored. Ustekinumab and tofacitinib altered gut microbiome composition. Probiotic and FMT interventions showed mixed outcomes. Six of eight probiotic studies reported increased SCFA producing species and/or reduced inflammatory markers. FMT improved immune markers in mice but had no significant benefit in human trials.<br><br>CONCLUSION: Alterations in the microbiome linked to inflammation and immune response, suggest the microbiome as a potential therapeutic target for PsO/PsA.}, }
@article {pmid42359346, year = {2026}, author = {Wu, L and Fang, J and Chen, M and Si, YC}, title = {Acupuncture modulates the microbiota-gut-brain axis to treat irritable bowel syndrome: a mechanistic exploration.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1820371}, pmid = {42359346}, issn = {1662-4548}, abstract = {Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder involving dysregulation of the microbiota-gut-brain (MGB) axis. Acupuncture effectively alleviates IBS symptoms, yet its underlying mechanisms remain incompletely understood. This review synthesizes current evidence to propose a mechanistic framework by which acupuncture treats IBS through MGB axis modulation. We systematically examine: (1) MGB axis dysfunction in IBS pathophysiology across neural, endocrine, and immune pathways; (2) acupuncture's modulation of gut microbiota structure (alpha/beta diversity, specific bacterial genera); (3) functional consequences including enhanced short-chain fatty acid production and tryptophan metabolism; (4) causal evidence from fecal microbiota transplantation; (5) correlations between microbiota changes and clinical improvement. Key findings reveal that acupuncture induces "convergent remodeling" of microbial structure toward a healthy profile, exerts "bidirectional regulation" on beneficial and harmful bacteria, and establishes a "niche selection" mechanism via neuro-immune pathways. These microbiota-mediated effects integrate with neural, endocrine, and immune pathways, forming a "point-to-surface" networked regulatory pattern that explains acupuncture's dual efficacy in alleviating both gastrointestinal and psychological symptoms. This review provides a novel theoretical framework for understanding acupuncture's therapeutic mechanisms and supports its clinical application in IBS management.}, }
@article {pmid42359605, year = {2026}, author = {Feng, J and Liu, X and Zhu, H and Yang, Y and Liu, W and Jiang, X and Yang, Z}, title = {Early diabetes-like phenotypes in germ-free mice induced by gut microbiota from patients with type 2 diabetes.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70229}, pmid = {42359605}, issn = {2576-2095}, support = {2022YFF0710600//National Key Research and Development Program of China/ ; 2021-1-I2M-035//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2023-PT180-01//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; 20250333//National High-level Innovation and Entrepreneurship Talents Program for Young Backbone Talents (SpringBuds Project)/ ; }, abstract = {BACKGROUND: The contribution of gut microbiota to the early stage of type 2 diabetes (T2D) remains incompletely understood. This study established a germ-free mouse model colonized with gut microbiota from donors with T2D to determine whether diabetes-associated microbiota could induce early diabetes-like phenotypes.<br><br>METHODS: Human fecal samples were collected from 18 healthy donors and 14 donors with T2D for microbiota profiling. Based on these features, samples from 12 healthy donors and 3 donors with T2D were selected, pooled within each group, and transplanted into germ-free mice, generating a healthy microbiota recipient group (HM, n&#x2009;=&#x2009;14) and a diabetes-associated microbiota recipient group (DM, n&#x2009;=&#x2009;13). Glucose homeostasis was assessed over 10&#x2009;weeks using fasting blood glucose and intraperitoneal glucose tolerance tests. Gut microbial succession was analyzed by 16S rRNA sequencing. Fecal and plasma metabolomics were performed to identify metabolic and their associations with microbial changes.<br><br>RESULTS: DM mice developed an early diabetes-like phenotype characterized by progressive impairment of glucose tolerance, reduced insulin levels, and mild renal alterations, without sustained overt fasting hyperglycemia. Microbial divergence emerged before stable metabolic dysfunction and was accompanied by persistent dysbiosis in DM mice. Integrated metabolomic analysis identified coordinated alterations in fecal and plasma metabolites, with cholic acid and L-Dopa decreased in both compartments. L-Dopa showed consistent associations with altered genera, particularly Ruminococcus and Sellimonas.<br><br>CONCLUSIONS: Transplanting diabetes-associated human gut microbiota effectively induced early glucose dysregulation in germ-free recipient mice. This model provides a framework for studying microbiota-associated events during early T2D-related metabolic deterioration.}, }
@article {pmid42361932, year = {2026}, author = {Ying, Y and Zheng, X and Yang, J and Ye, H and Dong, Z and Ji, Y and Li, S and Tan, X and Zhang, W}, title = {Tong-Xie-Yao-Fang Ameliorates IBS-D: Potential Role of Alistipes finegoldii-associated Gut Tryptophan Indole Metabolism.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {122061}, doi = {10.1016/j.jep.2026.122061}, pmid = {42361932}, issn = {1872-7573}, abstract = {Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent chronic gastrointestinal condition characterized by visceral hypersensitivity, low-grade mucosal inflammation, and impaired epithelial barrier integrity. Current therapies remain limited, highlighting the need for more alternative strategies. Tong-Xie-Yao-Fang (TXYF), a classical Chinese herbal formula, has shown clinical efficacy in IBS-D, however, the mechanisms underlying its therapeutic effects remain unclear.<br><br>AIM OF THE STUDY: This study aimed to investigate whether and how TXYF exerts therapeutic effects by modulating colonic tryptophan metabolism, with a particular focus on the gut microbiota.<br><br>MATERIALS AND METHODS: IBS-D model was induced by combining chemical irritation and wrap restraint stress in C57BL/6J mice, and multi-omics approaches were employed to identify specific microbiota and metabolites modulated by TXYF. The multi-omics findings were further verified in vivo and in vitro.<br><br>RESULTS: TXYF treatment significantly alleviated IBS-D symptoms in our model. Non-targeted metabolomics identified the tryptophan-indole pathway as a key axis modulated by TXYF, with indole-3-acetic acid (IAA) emerging as a prominent differential metabolite in colonic tissue. Western blot analysis showed that TXYF activated the aryl hydrocarbon receptor (AhR) in the colon. Integrative metagenomic and metabolomic analyses revealed a strong association between Alistipes finegoldii and colonic indole and IAA levels. Consistent with these findings, transplantation of A. finegoldii combined with tryptophan supplementation, or administration of IAA alone, recapitulated the therapeutic effects of TXYF against IBS-D. In vitro, both IAA and faecal supernatant from TXYF-treated mice protected against tumour necrosis factor-induced epithelial barrier disruption in an AhR-dependent manner.<br><br>CONCLUSION: Collectively, the present study suggests that the therapeutic efficiency of TXYF against IBS-D is closely associated with its ability to modify microbiota-derived colonic IAA production, with gut microbiota member Alistipes finegoldii playing a key role in this effect.}, }
@article {pmid42361952, year = {2026}, author = {Guo, Y and Liu, A and Hao, X and Cao, X and Li, Y and Liu, X}, title = {The gut microbiota, neurodevelopment and autism spectrum disorder: A close connection.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {}, number = {}, pages = {111811}, doi = {10.1016/j.pnpbp.2026.111811}, pmid = {42361952}, issn = {1878-4216}, abstract = {The gut microbiota plays a crucial role in early neurodevelopment, particularly during the highly adaptable prenatal and postnatal stages. Dysbiosis in these periods can disrupt the microbiota-gut-brain axis, hinder neural development, and increase the risk of autism spectrum disorder (ASD). This review examines how maternal and infant gut microbiota dysbiosis affects neurodevelopment, explores microbial differences in ASD children and their neurotypical siblings, and analyzes the link between microbial patterns and ASD severity. It also summarizes current microbiota-targeted therapies for ASD and their mechanisms. Overall, the review aims to connect maternal-infant gut microbiota, neurodevelopment, and ASD, providing insights for microbiota-based prevention and intervention strategies for ASD.}, }
@article {pmid42362557, year = {2026}, author = {Shuai, Y and Xing, J and Liu, X and Song, Z and Lin, S and Lu, C and Zeng, W and Wang, G}, title = {Atractylodes macrocephala polysaccharide orchestrates anti-tumor immunity via a dual-network mechanism targeting the gut microbiota and spleen.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {42362557}, issn = {2055-5008}, support = {81873225//National Natural Science Foundation of China/ ; }, abstract = {Colorectal cancer (CRC) is a common global malignancy, and its advanced stage is closely linked to a gut microbiota-metabolism-immunity vicious cycle requiring early intervention. In this study, anti-CRC effects of PAMK in CT26 tumor-bearing mice were explored. Results showed that PAMK significantly inhibited tumor growth and improved the quality of life of tumor-bearing mice by enhancing antitumor immunity, including increased NK cell infiltration and NKG2D expression, elevated CD4[+]:CD8[+] ratios, and higher serum IFN-γ levels. However, therapeutic effects of PAMK were not observed in antibiotic‑induced microbiota depletion (AIMD) mice. Notably, following fecal microbiota transplantation (FMT), therapeutic effects of PAMK were largely restored. PAMK alleviated tumor-induced gut microbiota dysbiosis characterized by enriched g_Alistipes, and remodeled fatty acid and steroid metabolism, which was closely associated with enhanced antitumor immunity and a potential microbiota-metabolism-immunity axis. Meanwhile, PAMK modulated multiple metabolic, circadian and immune pathways in the spleen as verified by transcriptomics and qPCR. Integrative multi-omics analysis indicated that the gut microbiota-metabolite-spleen gene axis may act synergistically to mediate anti-CRC effects of PAMK in tumor-bearing mice. This study highlights the potential of PAMK in CRC tumor immune adjuvants, providing experimental and theoretical support for its clinical translation and novel tumor immunotherapies.}, }
@article {pmid41729343, year = {2026}, author = {Bénard, MV and Zonneveld, R and Haaften, PB and Wentink-Bonnema, EMS and Matamoros, S and Ponsioen, CY}, title = {Lower prevalence of Blastocystis spp. and Dientamoeba fragilis in ulcerative colitis and association with disease activity.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {41729343}, issn = {1435-4373}, abstract = {AIM: To evaluate the prevalence of intestinal protozoan parasites Blastocystis spp. and Dientamoeba fragilis in ulcerative colitis (UC) patients and healthy controls, and to assess their association with UC disease activity. METHODS: Fecal samples were collected from 103 UC patients and 95 healthy volunteers during the screening of the TURN2 trial, a randomized controlled trial on the efficacy of anoxic-prepared fecal microbiota transplantation (FMT) in active UC. The presence and load of protozoa were assessed by microscopy and PCR. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score and fecal calprotectin (FCP). RESULTS: The prevalence of Blastocystis spp. was significantly higher in healthy controls (33% by microscopy and 34% by PCR, respectively) compared to UC patients (6% by both methods, p < 0.001). Similarly, D. fragilis was more common in healthy controls (34% by microscopy and 37% by PCR) than UC patients (9% and 12% respectively, both p < 0.001). Microscopic detection of D. fragilis was significantly associated with lower disease activity, as measured by the Simple Clinical Colitis Activity Index (median [IQR]: 4 [4] vs. 6 [4], p = 0.023) and the Partial Mayo Score (median [IQR]: 4 [2] vs. 6 [2], p = 0.009). Amongst the D. fragilis positive samples, higher D. fragilis loads, as assessed by either microscopy or PCR, were significantly associated with lower FCP levels (p = 0.010 and p = 0.040). PCR detection of D. fragilis showed similar but non-significant associations with disease activity scores. No associations were found between Blastocystis spp. and disease activity. CONCLUSION: Our findings show a higher prevalence of Blastocystis spp. and D. fragilis in healthy individuals compared to UC patients, challenging their pathogenicity in the context of UC and in general. The reported association between D. fragilis presence and load and lower UC disease activity warrants further investigation in larger cohorts.}, }
@article {pmid41739244, year = {2026}, author = {Long Depaquit, T and Michel, F and Madec, FX and Peyrottes, A and Chiron, P and Mohammad, S and Bruyere, F and Savoie, PH and Karsenty, G}, title = {Comparison of rectourethral fistula repairs: york mason vs. transperineal repair with gracilis flap interposition.}, journal = {World journal of urology}, volume = {44}, number = {1}, pages = {}, pmid = {41739244}, issn = {1433-8726}, abstract = {INTRODUCTION: Rectourethral fistulas (RUFs) are rare but severe complications of prostate or rectal cancer treatment. The York Mason (YM) procedure and transperineal repair with gracilis muscle flap interposition (TPGF) are the two most frequently used approaches, but direct comparative data are limited. METHODS: We conducted a multicenter retrospective cohort study including all patients who underwent RUF repair with either YM or TPGF at four French tertiary referral centers between 2011 and 2024. Fistulas were classified using the Rivera and Mundy–Andrich systems. The primary endpoint was reintervention-free survival (RFS), assessed by Kaplan–Meier analysis and Cox regression. Secondary endpoints were first-attempt and overall closure rates, perioperative complications, and postoperative urinary and fecal continence. RESULTS: Fifty-seven patients were included (YM = 27, TPGF = 30). Median follow-up was 39 months (YM 27 vs. TPGF 53). Kaplan–Meier analysis showed superior RFS after TPGF (12-month estimates: 94.7% vs. 68.2%; log-rank p = 0.038). First-attempt success was higher with TPGF (77% vs. 44%; p = 0.013), as was overall success at last follow-up (94% vs. 70%; p = 0.046). Operating time and hospital stay were longer after TPGF, but complication rates were comparable (50% vs. 37%; p = 0.12). Stress urinary incontinence occurred in 53% of TPGF and 41% of YM patients (p = 0.34). No de novo fecal incontinence was observed. On Cox regression, complex fistula morphology predicted YM failure (HR 6.5, 95% CI 1.15–36.8), whereas no predictive factor for failure was identified in the TPGF group. CONCLUSION: In this multicenter cohort, TPGF achieved higher RFS than YM without increased morbidity. TPGF appears particularly suitable for complex or irradiated RUFs, while YM may remain appropriate for selected simple, nonirradiated cases.}, }
@article {pmid41774360, year = {2026}, author = {Fawzy, MN and Fathy, MK}, title = {Targeting the Gut-Brain-Ferroptosis Axis: Molecular Mechanisms and Therapeutic Potential in Alzheimer's Disease and Epilepsy.}, journal = {Journal of molecular neuroscience : MN}, volume = {76}, number = {1}, pages = {}, pmid = {41774360}, issn = {1559-1166}, abstract = {Alzheimer’s disease (AD) and epilepsy share underlying mechanisms of oxidative stress and neuroinflammation, yet effective targeted therapies remain limited. This review presents a novel integrative model linking gut microbiota dysbiosis to ferroptosis, an iron-dependent form of regulated cell death. We propose a vicious cycle in which dysbiosis promotes systemic inflammation and disrupts cerebral iron homeostasis, impairing the glutathione/GPX4 antioxidant system and sensitizing neurons to lipid peroxidation and ferroptotic death. This neuronal damage further fuels neuroinflammation and may exacerbate gut barrier dysfunction. Evidence from both conditions reveals altered gut microbiota alongside ferroptosis markers such as iron accumulation, reduced GPX4, and elevated lipid peroxides. Therapeutically, we examine two complementary approaches: central inhibition of ferroptosis using specific inhibitors and iron chelators, and peripheral modulation of the gut-brain axis via probiotics, prebiotics, or fecal transplantation. Preclinical studies indicate that targeting either pathway can reduce pathology and improve outcomes. We conclude that the most promising strategy involves combined therapies that simultaneously inhibit ferroptosis and restore gut microbial balance, offering a novel, multi-target approach to disrupt the pathogenic cycle in AD and epilepsy.}, }
@article {pmid41838338, year = {2026}, author = {Hu, M and Xiao, Y and Zhang, X and Guo, J and Shen, T and Wang, Y and Deng, J and Liu, D}, title = {The role of gut microbiota in the development, diagnosis, and treatment of gastric cancer.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41838338}, issn = {1874-9356}, support = {AD23026316//Guangxi Science and Technology Base and Talent Special Project/ ; 2021KY0106//Guangxi Young and Middle-aged University Teachers' Scientific Research Ability Enhancement Project/ ; }, abstract = {Gastric cancer (GC) remains a significant global health challenge, and the relationship between the gut microbiota and GC has garnered increasing attention. A growing body of research has demonstrated that the gut microbiota plays a key role in the development and progression of GC through a complex network of mechanisms. This review analyzes key factors such as microbial dysbiosis, urease-assisted colonization, and the formation of nitrosamines and other carcinogenic metabolites, highlighting their influence on GC. Additionally, we emphasize the roles of chronic inflammation and immune dysregulation, which are driven by microbial activities, in gastric carcinogenesis. The recent advances in microbiota-based biomarkers for GC are summarized. The clinical value of microbial-related therapies, including probiotics, antibiotic therapy, and fecal microbiota transplantation is also explored. This review discusses the complex and close relationship between the gut microbiota and GC, along with its clinical implications. It aims to provide deeper insights into dysbiosis-related GC research, the development of microbiota-based diagnostic biomarkers, and the advancement of treatment strategies.}, }
@article {pmid41963684, year = {2026}, author = {Mc Closkey, C and El-Hakeem, AA and Gafar, ME and Slattery, E}, title = {Trends in Clostridioides Difficile Hospitalisations in Ireland (2009-2022).}, journal = {Irish journal of medical science}, volume = {}, number = {}, pages = {}, pmid = {41963684}, issn = {1863-4362}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infection associated with significant morbidity, mortality and healthcare costs. Comparisons of disease burden between countries are complicated by heterogeneity in diagnostic testing and surveillance practices. AIMS: To quantify CDI-related hospitalisations in Ireland between 2009 and 2022 and to examine temporal trends in patient demographics, length of stay (LOS), admission type, and in-hospital mortality. METHODS: We conducted a retrospective analysis of the national Hospital Inpatient Enquiry (HIPE) database, including all discharges from Irish public hospitals coded with CDI (ICD-10-AM A04.7) between 2009 and 2022. Temporal trends were examined, and multivariable logistic regression was conducted using SPSS (v30) to identify factors independently associated with in-hospital mortality. RESULTS: Between 2009 and 2022, 20,956 CDI-related hospitalisations were recorded, accounting for approximately 0.2% of all hospitalisations in Ireland. Annual CDI-related hospitalisations increased by 66%, from 1,301 in 2009 to 1,962 in 2022. Over the same period, in-hospital mortality declined from 21.0% to 11.8%, and mean LOS decreased from 44.0 to 31.5 days. Logistic regression adjusting for age, sex, LOS, admission type, and year of hospitalisation, found the odds of in-hospital mortality were approximately 45% lower in 2022 versus 2009. Increasing age was the strongest independent predictor of mortality; patients aged ≥ 85 years had 72-fold higher odds of mortality compared with the youngest age group. CDI was recorded as the primary diagnosis in 28% of hospitalisations and was associated with lower mortality (adjusted OR 0.36, p < 0.001). Male sex (adjusted OR 1.26, p < 0.001) and elective admission (adjusted OR 1.31, p < 0.001) were independently associated with higher mortality. CONCLUSIONS: CDI-related hospitalisations in Ireland increased substantially between 2009 and 2022, while in-hospital mortality rates and LOS declined. Despite these improvements, CDI is still associated with significant mortality among the elderly. Further research should examine the impact of acute hospital bed availability, faecal microbial transplant (FMT) access, and recurrent infections on CDI case rates.}, }
@article {pmid42343035, year = {2026}, author = {Lan, M and Ding, H and Cao, Y and Liu, J and Tu, L and Fu, S and Guo, W}, title = {Gut microbiota and aging: current understanding and future perspectives.}, journal = {Molecular biomedicine}, volume = {7}, number = {1}, pages = {}, pmid = {42343035}, issn = {2662-8651}, support = {202503AP140024//Yunnan International Joint Laboratory for Exploration and Utilization of Aromatic Chinese Medicinal Materials in Agriculture/ ; 32272955//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 32372961//National Natural Science Foundation of China/ ; 32472984//National Natural Science Foundation of China/ ; 32372959//National Natural Science Foundation of China/ ; 45124031D101//Jilin University Outstanding (Excellent) Young Talent Development Program/ ; }, mesh = {Humans ; *Aging/physiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis/microbiology ; Probiotics ; }, abstract = {Aging is a complex biological process characterized by progressive functional decline at molecular, cellular, and systemic levels, accompanied by increased susceptibility to chronic diseases. Accumulating evidence indicates that the gut microbiota plays a critical role in shaping aging trajectories and age-related health outcomes. This review systematically summarizes current research progress on the relationship between gut microbiota and aging. We first describe the characteristic alterations of the gut microbiota during aging, including reduced microbial diversity, shifts in core bacterial taxa, and profound changes in microbial metabolite profiles such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. We then discuss the mechanistic links between gut microbiota dysbiosis and age-related functional decline, focusing on immunosenescence and inflammaging, gut barrier dysfunction, metabolic disorders and oxidative stress, as well as endocrine and neuroendocrine regulation through gut-organ axes. In addition, major internal and external factors influencing gut microbiota composition in the elderly, including diet, medication use, lifestyle, host immunity, and living environment, are reviewed. Finally, we summarize current and emerging gut microbiota-targeted anti-aging intervention strategies, such as dietary modulation, probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and natural product-based approaches, and discuss future research directions and clinical translation challenges. Overall, this review highlights the gut microbiota as a key modifiable factor in aging biology and underscores its potential as a promising target for promoting healthy aging.}, }
@article {pmid42343158, year = {2026}, author = {Aryal, S and Mell, B and Tummala, R and Manandhar, I and Kumariya, S and Kondapalli, N and Yeoh, BS and Ahlidja, W and Mautin Akinola, O and Pachhain, S and Bardhan, P and Saha, P and Zeydabadinejad, S and Osman, I and Thodeti, C and Yang, T and Vijay-Kumar, M and Reddivari, L and Joe, B}, title = {Gut microbiome drives glycodeoxycholic acid-mediated attenuation of hypertension.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2691346}, doi = {10.1080/19490976.2026.2691346}, pmid = {42343158}, issn = {1949-0984}, mesh = {Animals ; *Hypertension/microbiology/metabolism/physiopathology/drug therapy ; Receptors, G-Protein-Coupled/genetics/metabolism ; *Gastrointestinal Microbiome ; Rats, Inbred Dahl ; Blood Pressure/drug effects ; Rats ; Male ; *Glycodeoxycholic Acid/metabolism ; Bile Acids and Salts/metabolism ; Cecum/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota and bile acids are increasingly recognized to regulate blood pressure, but the mechanisms remain unclear. Takeda G-protein coupled receptor 5 (TGR5) is a major receptor for secondary bile acids. We hypothesized that loss of TGR5 function remodels gut microbiota and influences blood pressure. Using CRISPR/Cas9, TGR5 knockout (Tgr5KO) rats on the Dahl Salt-Sensitive (S) background were generated and characterized. Compared to the control S rats, Tgr5KO rats demonstrated significantly lower blood pressure, a distinct shift in gut microbiota composition, and an increase in the secondary bile acid, particularly, glycodeoxycholic acid. Supplementation of glycodeoxycholic acid to the control S rats produced a similar gut microbial shift and lowered blood pressure. Furthermore, cecal microbiota transplantation from Tgr5KO to control S rats lowered blood pressure in the recipient rats. This first loss-of-function study demonstrates that deletion of TGR5 remodels gut microbiota, increases glycodeoxycholic acid, and lowers blood pressure regardless of TGR5 signaling status, identifying a promising gut-liver axis target for lowering hypertension.}, }
@article {pmid42343653, year = {2026}, author = {Bruggeman, A and Vandenbroucke, RE and Santens, P}, title = {Rationale and current status of fecal microbiota transplantations for Parkinson's disease.}, journal = {Journal of Parkinson's disease}, volume = {}, number = {}, pages = {1877718X261455608}, doi = {10.1177/1877718X261455608}, pmid = {42343653}, issn = {1877-718X}, abstract = {Treating a neurological disorder through the gut may seem counterintuitive, yet multiple lines of evidence highlight the gut's important role in Parkinson's disease (PD). Prodromal gastrointestinal symptoms, the presence of aggregated α-synuclein in enteric neurons, increased intestinal inflammation, and impaired epithelial barrier integrity all point to gut-level involvement in PD pathophysiology. The gut microbiome, markedly altered in individuals with PD, may be a key driver of these changes. Fecal microbiota transplantation (FMT) is currently the most effective strategy for achieving broad and durable modifications of gut microbiota composition. However, FMT is a complex, multi-step procedure requiring stringent methodological control. Modulating gut bacteria has demonstrated therapeutic potential in preclinical models of PD, and recent clinical trials have begun evaluating FMT in patients, although outcomes have been variable. In this review, we examine potential explanations for these divergent results, with a particular focus on methodological differences across trials. We also outline future directions for optimizing FMT study design in PD and discuss how these insights may guide the development of next-generation microbiota-targeted therapies.}, }
@article {pmid42344668, year = {2026}, author = {Huang, F and Zhang, Z and Zhao, Y and Ye, S and Gan, M and Li, X and Zhang, Y and Chen, L and Zhang, Y and Chen, L and Wang, T and Huang, J and Zhang, X}, title = {Altitude-Associated Divergence of the Gut Microbiome in Endangered Forest Musk Deer: Evidence From Integrated Metagenomics, Metabolomics, and Culturomics.}, journal = {Evolutionary applications}, volume = {19}, number = {6}, pages = {e70285}, pmid = {42344668}, issn = {1752-4571}, abstract = {High-altitude environments expose mammals and their gut symbionts to multifaceted stressors-hypoxia, cold, and intense UV radiation. Whether gut microbial communities undergo compositional restructuring in response to these stressors, and whether such restructuring carries translational value for captive conservation, remain unresolved questions. Here, we integrated deep shotgun metagenomics (≥ 15 Gb per sample), untargeted fecal metabolomics, and culturomics in 75 captive forest musk deer (Moschus berezovskii Flerov, 1929) housed at high altitude (~3900 m) and low altitude (~1450 m) facilities under uniform husbandry. Neutral community modeling showed a greater contribution of deterministic processes at high altitude (only 34.3% of species conformed to neutral expectations vs. 89.3% at low altitude), consistent with stronger environmental filtering. At high altitude, we observed enrichment of a functionally coherent guild of short-chain fatty acid (SCFA)-producing bacteria-centered on Flavonifractor plautii, Intestinimonas butyriciproducens, and Enterococcus faecium-that formed antagonistic co-occurrence networks with opportunistic pathogens including Clostridioides difficile and Campylobacter species, mirroring SCFA enrichment in phylogenetically diverse high-altitude mammals. Fecal metabolomics revealed coordinated shifts in urolithin biosynthesis, branch-specific regulation of the tryptophan-kynurenine pathway, and energy metabolism remodeling, all robustly predicted by microbiome composition via neural network modeling. Culturomics yielded seven safety-validated isolates with confirmed gastrointestinal stress tolerance and broad-spectrum pathogen-antagonistic activity in vitro. These findings provide an actionable framework for altitude-informed facility siting, fecal microbiota transplantation (FMT) donor selection, host-derived probiotic development, and non-invasive health surveillance in captive endangered species, and are broadly transferable to other taxa facing microbiome-associated disease pressure in captivity.}, }
@article {pmid42344729, year = {2026}, author = {Qian, X and Wu, Y and Wang, W and Shao, H and Xu, Z}, title = {The selection of matching donors for patients in fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1859411}, pmid = {42344729}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy with potential applications in the treatment of various diseases, particularly those associated with gut microbiome dysbiosis. However, clinical trials have demonstrated considerable variability in FMT efficacy-even among patients with the same disease. The heterogeneity of gut microbiota from donors is considered a key factor influencing patient outcomes. Consequently, the development of donor-recipient matching models has emerged as an advanced approach to enhance the effectiveness of FMT. As a practical clinical intervention, the therapeutic impact of FMT on specific diseases requires further investigation. This article reviews the development of donors and the matching patterns between donors and recipients, and summarizes the key factors influencing the transfer of the microbiota. It provides new insights for exploring novel and effective donor-recipient matching patterns.}, }
@article {pmid42344797, year = {2026}, author = {Zhang, M and Lu, Y and Yuan, X}, title = {The tumor microenvironment: a dynamic ecosystem and therapeutic nexus in modern oncology.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1836055}, pmid = {42344797}, issn = {1663-9812}, abstract = {The tumor microenvironment (TME) has emerged as a central orchestrator of carcinogenesis, therapeutic resistance, and immune evasion, fundamentally reshaping the understanding of cancer as an ecosystem disease rather than a cell-autonomous genetic disorder. This review synthesizes contemporary advances in deconstructing the cellular and acellular architecture of the TME, encompassing cancer-associated fibroblasts, tumor-associated macrophages, aberrant vasculature, and a dynamically remodeled extracellular matrix. The molecular underpinnings of TME-mediated pathogenesis are critically evaluated, including metabolic reprogramming, epigenetic dysregulation, and systemic microbiome crosstalk, which collectively enforce immunosuppression and drive adaptive resistance. Building on this mechanistic framework, a new generation of therapeutic strategies designed to reprogram this malignant niche is highlighted: precision nanotechnologies for targeted and stimuli-responsive delivery; next-generation immunotherapies such as logic-gated CAR-T cells, bispecific engagers, and oncolytic viruses; metabolic and epigenetic modulators; stromal and vascular normalization approaches; and microbiome-based interventions, for instance fecal microbiota transplantation and defined bacterial consortia. Transformative tools, including patient-derived organoids, tumor-on-a-chip systems, 3D bioprinting, and artificial intelligence-powered multi-omics, are now enabling predictive modeling and personalized therapeutic forecasting. Despite persistent challenges posed by intratumoral heterogeneity, cellular plasticity, and the complexity of combination trial design, the convergence of these multidisciplinary approaches provides an unprecedented toolkit to durably reprogram the TME. Mastering this dynamic ecosystem is paramount to overcoming therapeutic roadblocks, and the strategic integration of these advances heralds a definitive paradigm shift toward TME-centric, adaptive, and personalized cancer therapy.}, }
@article {pmid42345020, year = {2026}, author = {Ismaiel, A and Almonajjed, MB and Wardeh, M and Abdelghafar, A and Popa, SL and Sabo, C and Dumitrascu, DL}, title = {From dysbiosis to malignancy: decoding gut-driven pathways to clinical management in hepatocellular carcinoma.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1852380}, pmid = {42345020}, issn = {2235-2988}, mesh = {Humans ; *Dysbiosis/complications ; *Liver Neoplasms/therapy/etiology/pathology/microbiology ; *Carcinoma, Hepatocellular/therapy/etiology/pathology/microbiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {Hepatocellular carcinoma (HCC) is undergoing a profound global epidemiological shift, transitioning from viral-driven etiologies to metabolic dysfunction-associated steatotic liver disease (MASLD). This transition challenges traditional cirrhosis-centric surveillance, as a significant proportion of MASLD-HCC develops in non-cirrhotic livers. Parallel to these metabolic shifts, the gut-liver axis has emerged as a central orchestrator of hepatocarcinogenesis. This review decodes the complex gut-driven pathways fueling HCC, highlighting the oncogenic consequences of structural and functional dysbiosis. Dietary patterns and etiology-specific microbial shifts compromise the intestinal and gut-vascular barriers, precipitating a structural "leaky gut". This disruption facilitates the robust translocation of pathogen-associated molecular patterns (PAMPs), particularly lipopolysaccharide (LPS), and toxic microbial metabolites like secondary bile acids, specifically deoxycholic acid, into the portal circulation. Consequently, hepatic innate immunity is chronically activated via Toll-like receptor 4 (TLR4) signaling on Kupffer and hepatic stellate cells, fostering metainflammation, cellular senescence, genomic instability, and a highly immunosuppressive, pro-tumorigenic microenvironment. Furthermore, the depletion of keystone commensals diminishes the protective reservoir of short-chain fatty acids (SCFAs), exacerbating oncogene activation. Translating these mechanistic insights into the clinic, we explore the utility of distinct microbial signatures and metabolomic profiles as non-invasive diagnostic biomarkers. Such tools are urgently needed to bridge the early-detection gap in the expanding MASLD demographic. Finally, we discuss the pivotal role of the microbiome in modulating responses to immune checkpoint inhibitors (ICIs), notably through immune-stimulating taxa like Akkermansia muciniphila, and outline emerging gut-targeted therapies, including next-generation probiotics and fecal microbiota transplantation, aimed at restoring host-microbiome homeostasis to prevent and manage HCC. By decoding these gut-driven pathways, this review provides a comprehensive framework for integrating the microbiome-onco axis into precision oncology, offering novel avenues to combat the rising global burden of hepatocellular carcinoma.}, }
@article {pmid42345401, year = {2026}, author = {Wang, R and Zheng, B and Guo, M and Xu, K and Wang, Z and Guo, X and Li, J and Wang, J and Li, Y and Sohail, A and Wang, D}, title = {Effects of Heat-Moisture Treatment on the Physicochemical Properties, Structural Characteristics, and Anti-Ulcerative Colitis Activity of Yam Starch.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.6c04224}, pmid = {42345401}, issn = {1520-5118}, abstract = {Yam starch (YS) alleviates ulcerative colitis (UC), but whether heat-moisture treatment (HMT) enhances this effect remains unclear. This study examined the impact of HMT on the structural features of yam starch and yam flour (YF) and their UC-mitigating capacity. The results showed that HMT increased the resistant starch (RS) content in YF by forming starch-lipid complexes and, in YS, it enhanced the RS content through recrystallization. Animal experiments demonstrated that YF, HMT-modified YF, YS, and HMT-modified YS all alleviate UC symptoms, with HMTYS being the most effective. Specifically, HMTYS corrected DSS-induced intestinal flora imbalances by promoting beneficial bacteria (Lachnospiraceae_NK4A136_group, bacteroides, and akkermansia). Short-chain fatty acids produced from RS fermentation by these bacteria repaired the intestinal barrier and inhibited inflammation, creating a cycle that alleviated the colitis. Fecal microbiota transplantation (FMT) experiments confirmed that HMTYS alleviates UC by modulating the gut microbiota and increasing the level of SCFA production.}, }
@article {pmid42346015, year = {2026}, author = {Habtemariam, S}, title = {The Gut Microbiome Dependency Continuum in Drug Discovery: A Unified Pharmacology Framework Linking Clinical Drugs, Natural Products, and Engineered Microbial Therapeutics.}, journal = {Biotech (Basel (Switzerland))}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biotech15020043}, pmid = {42346015}, issn = {2673-6284}, abstract = {Highlighting its pivotal role in modern pharmacology, the gut microbiome is emerging as a key determinant of drug efficacy, toxicity, and bioavailability. This review proposes the Gut Microbiome Dependency Continuum, a four-layer framework describing progressively deeper levels of microbiome involvement in drug discovery and therapeutic function. The first layer, intact functional microbiome-dependent therapeutics and includes interventions such as faecal microbiota transplantation and defined microbial consortia. The second layer, microbiome-modulated approved drugs include widely used therapeutics whose pharmacokinetics or pharmacodynamics are strongly influenced by microbial metabolism. Examples include metformin, irinotecan, levodopa, and digoxin, where gut microbial interactions influence efficacy, toxicity, and inter-individual variability in treatment outcomes. The third layer, microbiota-transformable natural products, encompasses dietary and plant-derived compounds such as polyphenols, ginsenosides, alkaloids, fibres, isoflavones, lignans, and glucosinolates. Their biological activity depends on microbial biotransformation into bioactive metabolites. The fourth layer, engineered microbiome therapeutics, includes synthetic biology approaches such as programmable microbial systems, engineered probiotics, CRISPR-based microbiome editing, and microbiome-responsive drug delivery systems. It also includes synthetic microbial consortia, enabling targeted sensing, therapeutic delivery, and ecological reprogramming of gut microbial communities. Altogether, these layers define a continuum in which the gut microbiome evolves from a passive modulator to an essential metabolic organ and ultimately a programmable therapeutic platform. The article provides an integrated framework for microbiome-informed drug discovery. It also supports the development of precision, ecology-aware, and engineered microbial therapeutics.}, }
@article {pmid42346347, year = {2026}, author = {He, J and Qin, L and Sun, X}, title = {Bile Acids and the Gut-X Axis: TCM-Mediated Systemic Protection and Therapeutic Opportunities for Multi-Organ Diseases.}, journal = {Metabolites}, volume = {16}, number = {6}, pages = {}, doi = {10.3390/metabo16060366}, pmid = {42346347}, issn = {2218-1989}, support = {82405310//National Natural Science Foundation of China/ ; 1020241792//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, abstract = {The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut-X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota-BA-host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut-heart, gut-kidney, gut-liver, gut-bone, and gut-endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM's benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota-BA-organ axis thus provides a potential framework for understanding TCM's systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM's ecological modulation strategies.}, }
@article {pmid42346411, year = {2026}, author = {Vankayala, USA and Sohail, A and George, B and Singh, M and Khayat, O and Kreidieh, M and Hasham, A and Quiel, L}, title = {The Gut Microbiome in Heart Failure: Pathways to Inflammation and Therapeutic Targets.}, journal = {Metabolites}, volume = {16}, number = {6}, pages = {}, doi = {10.3390/metabo16060431}, pmid = {42346411}, issn = {2218-1989}, abstract = {Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut-heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut-heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management.}, }
@article {pmid42346775, year = {2026}, author = {He, Z and Nie, Y and Li, C and Sun, G and Zheng, W and Liu, H and Geng, M and Tian, J and Zhang, Y}, title = {GV-971 Ameliorates Chronic Restraint Stress-Induced Depression-like Phenotypes Accompanied by Reshaping of the Microbiota-Gut-Brain Axis.}, journal = {Marine drugs}, volume = {24}, number = {6}, pages = {}, doi = {10.3390/md24060189}, pmid = {42346775}, issn = {1660-3397}, support = {2024CXPT029, 2025CXPT011//Key R&amp;D Program of Shandong Province, China/ ; ZR2024QH615//Shandong Provincial Natural Science Foundation/ ; SYS202205//Shandong Laboratory Program/ ; }, mesh = {Animals ; *Depression/drug therapy/etiology ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; *Stress, Psychological/drug therapy ; *Brain-Gut Axis/drug effects ; *Oligosaccharides/pharmacology ; Restraint, Physical ; Disease Models, Animal ; *Antidepressive Agents/pharmacology ; Mice, Inbred C57BL ; Brain/drug effects/metabolism ; Phenotype ; Hippocampus/drug effects/metabolism ; Intestinal Barrier Function ; }, abstract = {Depression is increasingly linked to microbiota-gut-brain axis dysfunction, yet current monoaminergic antidepressants show limited efficacy. This study investigated the therapeutic potential and underlying mechanisms of GV-971, a marine-derived oligosaccharide, in a chronic restraint stress (CRS) mouse model. We first established that 8 h of daily restraint for 4-8 weeks induces a stable depression-like phenotype characterized by behavioral despair and significant reduction in peripheral monoamine neurotransmitters (5-HT and norepinephrine). GV-971 treatment robustly attenuated CRS-induced depression- and anxiety-like behaviors, restored hippocampal serotonin levels, reduced elevated plasma corticosterone concentrations, and ameliorated CRS-induced adrenal cortical hyperplasia. Mechanistically, GV-971 significantly suppressed neuroinflammation by inhibiting microglial hyperactivation in the prefrontal cortex and hippocampus. Concurrently, it repaired intestinal barrier dysfunction, evidenced by reduced permeability, restored mucosal integrity, and recovered goblet cell numbers. Crucially, integrated shot-gun metagenomics and plasma metabolomics revealed that GV-971 not only reshaped microbial taxonomy but also functionally recalibrated the gut ecosystem. It enriched beneficial taxa (e.g., Bifidobacterium pseudolongum, Bacteroides uniformis) and specific metabolic pathways, leading to increased short-chain fatty acids (valeric and caproic acids) and a significant reduction in plasma levels of tryptophan-kynurenine pathway metabolites, specifically the neurotoxic compounds kynurenine and quinolinic acid. Fecal microbiota transplantation (FMT) from GV-971-treated donors partially recapitulated the antidepressant and gut-protective effects in CRS recipients, confirming a causal role for the remodeled microbiota. Collectively, GV-971 exerts antidepressant effects by coordinately remodeling the gut microbiota, normalizing tryptophan and SCFA metabolism, restoring gut barrier integrity, and dampening central neuroinflammation, supporting its potential as a novel gut-brain axis-targeted therapy for depression.}, }
@article {pmid42347926, year = {2026}, author = {Voigt, RM and Keshavarzian, A and Hall, DA}, title = {Fecal Microbiota Transplant in Parkinson's Disease: Insights into the Gut-Brain Axis and the Challenge of Sustained Response.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.78259}, pmid = {42347926}, issn = {1531-8249}, }
@article {pmid42350167, year = {2026}, author = {Yao, Y and Liu, Y and Li, Y and Lu, B and Lyu, D and Cui, X and Pan, X}, title = {Re: Fecal Microbiota Transplantation plus Immunotherapy in Metastatic Renal Cell Carcinoma: The Phase 1 PERFORM Trial.}, journal = {European urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eururo.2026.05.015}, pmid = {42350167}, issn = {1873-7560}, }
@article {pmid42337290, year = {2026}, author = {Roubalová, R and Luthar, J and Procházková, P and Zadáková, K and Coufalová, K and Kreisinger, J and Semerád, J and Nehasilová, A and Mácha, H and Luptáková, D and Tlaskalová-Hogenová, H and Holanová, P and Lambertová, A and Papežová, H}, title = {Gut microbiota contributions to anorexia nervosa pathogenesis: insights from the activity-based anorexia model.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01055-y}, pmid = {42337290}, issn = {2055-5008}, support = {NU23-04-00381//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; NU22-04-00010//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; Talking microbes - understanding microbial interactions within One Health framework (CZ.02.01.01/00/22_008/0004597)//Ministry of Education, Youth, and Sports of the Czech Republic/ ; Cooperatio Program 207038//Univerzita Karlova v Praze/ ; }, abstract = {Anorexia nervosa (AN) is a severe eating disorder that profoundly affects quality of life. Despite increasing understanding of the neurobiological basis of the disease, many patients develop a chronic course of illness accompanied by a variety of physical and psychiatric comorbidities. To investigate the contribution of the gut microbiome to disease progression, we employed the activity-based anorexia (ABA) mouse model of AN. We performed fecal microbiota transplantation using samples from three donor groups: healthy controls, patients with acute AN, and patients with severe and enduring AN (SEAN). We continuously assessed changes in the gut microbiota and fecal metabolites (e.g., short-chain fatty acids, serotonin, and GABA) throughout the experiment, along with behavioral traits across the three groups of mice. Mice colonized with microbiota from acute AN patients exhibited reduced hunger signaling (via NPY, AgRP, MCH, and orexin), accompanied by decreased food intake. In contrast, mice transplanted with microbiota from SEAN patients showed appetite signaling and food consumption comparable to those colonized with microbiota from healthy controls but displayed significantly higher running activity relative to the other groups. However, the distinct microbiota did not affect the development of the ABA phenotype. Overall, our findings suggest that changes in the gut microbiome during disease development contribute to disease progression. Our results also indicate that restoration of a healthy gut microbiome is essential for complete recovery.}, }
@article {pmid42337655, year = {2026}, author = {Scott, JS and Munir, S and Lynn, MA and Duggan, JA and Castro, J and Harrington, AM and Brierley, SM and Schober, G and Cash, K and Gutschmidt, B and Hutchinson, MR and Yong, A and Costello, SP and Sikdar, S and Tangseefa, P and Hewett, DR and Cross, CB and Park, SB and Ryan, FJ and Zannettino, ACW and Lynn, DJ and Vandyke, K and Wardill, HR and Mrozik, KM}, title = {Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03909-w}, pmid = {42337655}, issn = {1742-2094}, support = {1163245//Priority-driven Collaborative Cancer Research Scheme and co-funded by Cancer Australia, Cure Cancer, and Leukaemia Foundation of Australia/ ; }, abstract = {BACKGROUND: Peripheral neuropathy and gastrointestinal dysfunction are frequent, debilitating side effects of the neurotoxic myeloma drug bortezomib that reduce quality of life and adherence to optimal therapy. Therapeutic strategies to manage these complications are limited. Here, we have developed a mouse model of bortezomib side effects to investigate the role of the gut microbiota in their development.<br><br>METHODS: C57BL/6 specific pathogen-free (SPF), germ-free (GF) and ex-GF mice (colonised with healthy gut microbiota via faecal microbiota transplantation [FMT]) were treated with bortezomib (1&#xa0;mg/kg) twice-weekly for two weeks. Neurotoxicity and neuroimmune signalling were assessed by serum neurofilament light chain (NfL) quantitation and real-time qPCR analysis of inflammatory markers in sensory and autonomic nerve ganglia, respectively. Faecal microbiota composition was characterised using 16S rRNA gene sequencing. Bortezomib side effects were assessed using behavioural phenotyping, von Frey mechanical sensitivity and rotarod testing, and FITC-dextran gut permeability and Evans Blue dye transit assays.<br><br>RESULTS: Bortezomib-treated SPF mice displayed altered spontaneous behaviour and developed acute gastric retention, altered gastrointestinal motility and increased intestinal permeability, in the absence of intestinal micro-architecture changes. Concurrently, bortezomib induced sensory loss in, and increased grooming of, paws, and reduced motor performance, indicative of peripheral neuropathy. Bortezomib neurotoxicity was evidenced by elevated serum NfL levels and neuroimmune signalling in sciatic nerve dorsal root and vagal nerve nodose ganglia. In SPF mice, bortezomib altered gut microbiota composition with an acute decrease in microbial diversity and expansion of Lactobacillus gasseri. Notably, GF mice developed a milder symptom profile following bortezomib treatment compared with SPF mice, while FMT mice did not develop overt bortezomib side effects despite displaying evidence of nerve damage.<br><br>CONCLUSIONS: This is the first study to model gastrointestinal side effects of bortezomib in rodents, implicating neuroimmune dysregulation of the vagus nerve. Our data show that the gut microbiota is not a primary driver of bortezomib side effects. However, the absence of a symptom profile in FMT mice suggests that, in GF mice, the gut microbiota beneficially modulates the host to protect against bortezomib side effects. Further studies are required to determine whether this can be harnessed to mitigate clinical complications of bortezomib.}, }
@article {pmid42338488, year = {2026}, author = {Chen, B and Chen, J and Feng, Z and Lv, H and Lin, Q and Jiang, G}, title = {Gut microbiota reconstruction after liver transplantation and its association with early postoperative infections in patients with liver failure.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1845273}, pmid = {42338488}, issn = {2235-2988}, mesh = {Humans ; *Liver Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Retrospective Studies ; *Postoperative Complications/microbiology ; Dysbiosis/microbiology ; Male ; *Liver Failure/surgery/complications ; Probiotics/administration &amp; dosage/therapeutic use ; Middle Aged ; Metagenomics ; Feces/microbiology ; Adult ; *Bacterial Infections/microbiology/epidemiology ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND: Postoperative infection remains a major cause of morbidity after liver transplantation (LT) in patients with liver failure. Increasing evidence suggests that gut microbiota dysbiosis may contribute to infection risk, but its dynamic changes after LT are not fully understood.<br><br>METHODS: This retrospective study included 60 patients with liver failure who underwent LT and developed postoperative infection-related risk. Patients were divided into a probiotic group and a non-probiotic group. Fecal samples were collected before transplantation and on postoperative days 7, 14, 21, and 28. Metagenomic sequencing was performed to analyze gut microbial composition, diversity, and antibiotic resistance genes.<br><br>RESULTS: The probiotic group showed a significantly lower rate of postoperative bacterial infection, especially intra-abdominal infection. After LT, gut microbiota gradually recovered in both groups, but restoration was faster in the probiotic group. The non-probiotic group showed persistent dysbiosis, characterized by enrichment of opportunistic pathogens such as Enterococcus and Klebsiella, whereas beneficial genera including Bifidobacterium and Lactobacillus were more abundant in the probiotic group. Antibiotic resistance genes were also more enriched in the non-probiotic group.<br><br>CONCLUSION: Early postoperative gut microbiota reconstruction is closely associated with infectious complications after LT, and modulation of gut microbiota may help improve postoperative outcomes.}, }
@article {pmid42338743, year = {2026}, author = {Zhao, H and Ao, L and Hao, L and Wei, Y and Yin, HZ and Lee, XQ and Guo, C and Wang, Z and Yang, J and Yang, R and Zhou, GL}, title = {Integrative mechanisms and intervention targets of the microbiota-gut-brain axis in depressive disorders: advances across immune, endocrine, and central nervous system pathways.}, journal = {Frontiers in psychiatry}, volume = {17}, number = {}, pages = {1848918}, pmid = {42338743}, issn = {1664-0640}, abstract = {Depressive disorders are highly heterogeneous syndromes characterized not only by depressed mood but also by cognitive impairment, sleep-circadian rhythm disturbances, altered appetite, somatic discomfort, and metabolic or gastrointestinal comorbidities. In recent years, the microbiota-gut-brain axis (MGBA) has been increasingly recognized as an integrative biological framework linking abnormalities in mood regulation, immune responses, endocrine function, metabolism, and neuroplasticity. This review provides a systematic synthesis of gut microbial ecology and host phenotypic features associated with depressive disorders, with particular emphasis on the depletion of short-chain fatty acid-producing commensals, the enrichment of potentially pro-inflammatory taxa, and the functional remodeling of key metabolic pathways, including the tryptophan-kynurenine pathway, short-chain fatty acids, bile acids, and trimethylamine N-oxide. We further discuss how bidirectional gut-to-brain and brain-to-gut communication may contribute to the onset and progression of depressive disorders through intestinal barrier disruption, low-grade systemic inflammation, hypothalamic-pituitary-adrenal axis activation, vagal signaling, and dysregulation of neurotransmitter and neurotrophic pathways. Current interventional evidence suggests that dietary and lifestyle modification, psychobiotics, and fecal microbiota transplantation may exert antidepressant potential in selected populations; however, the overall effect sizes remain limited and between-study heterogeneity is substantial. Patients with prominent gastrointestinal symptoms, metabolic abnormalities, or low-grade inflammatory states may represent priority candidates for MGBA-targeted interventions; nevertheless, a putative microbiota-responsive phenotype should not be simply equated with high stress exposure alone, and its definition requires prospective validation integrating stress burden, host responses, and microbial/metabolic readouts. Overall, MGBA research is gradually moving beyond descriptive profiling of microbial composition toward functional integration and clinical translation; however, causal inference, multi-omics standardization, and the identification of stratification biomarkers remain major challenges. Future studies should incorporate phenotype-based stratification, strengthened functional readouts, and precision intervention designs to determine which patients are most likely to benefit from microbiota-targeted therapies.}, }
@article {pmid42340049, year = {2026}, author = {Mao, H and Wang, X and Pang, Y and Lu, Y and Wang, H and Li, H and Ni, Y and Jia, W}, title = {The Gut Microbiome-Endocrine Axis in Obesity: Mechanisms and Therapeutics.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.70511}, pmid = {42340049}, issn = {1440-1746}, support = {C2406002//Shenzhen Medical Research Fund/ ; 92357305//Major Research Plan of National Natural Science Fund of China (NSFC)/ ; 24HAA01325//Excellent Young Scientists Fund of the National Natural Science Foundation of China (Overseas)/ ; }, abstract = {Obesity, a major global health challenge and a key risk factor for metabolic diseases, represents a state of dysregulated energy homeostasis. The gut microbiome has emerged as a critical mediator of obesity pathogenesis, yet the precise endocrine mechanisms linking microbial signals to metabolic dysfunction remain incompletely understood. Therefore, at the perspectives of gut microbiome-endocrine axis encompassing gut-brain, gut-adipose, and gut-pancreas axes, this review elucidates how gut microbiota and their metabolites influence systemic endocrine homeostasis through energy intake, fat storage, and hormonal secretion. Mechanistic studies highlight the roles of short-chain fatty acids, bile acids, and microbial peptides in modulating obesity control and related metabolic health. We further summarize the current therapeutics targeting gut microbiome in the gut-endocrine axis, including prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, and lifestyle approaches and highlight their mechanistic and translational relevance. The major challenges of gut microbiome studies are discussed, including obscure phenotyping, insufficient cross-organ integration, and limited causal inference. Overcoming these limitations by precise obesity measurement, integrated cross-organ models, and AI-driven causal modeling could advance the pathophysiological insight and management of obesity.}, }
@article {pmid42341529, year = {2026}, author = {Wu, C and Zheng, T and Huang, S and Meng, C and Wang, W and Li, M and Cheng, H and Ju, Z and Wang, Y and Mao, W and Zhou, X}, title = {Lithospermic acid-induced gut microbiota remodeling alleviates intraplaque inflammation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158462}, doi = {10.1016/j.phymed.2026.158462}, pmid = {42341529}, issn = {1618-095X}, abstract = {BACKGROUND: Atherosclerosis is a leading cause of mortality worldwide. The gut microbiota (GM) plays a significant role in the initiation and progression of atherosclerosis, making its modulation a promising therapeutic strategy for atherosclerotic cardiovascular disease. Salvia miltiorrhiza, a traditional Chinese medicine renowned for its therapeutic effects in treating cardiovascular diseases, contains lithospermic acid (LA) as one of its key active constituents.<br><br>PURPOSE: To elucidate whether LA can alleviate atherosclerosis and its mechanism.<br><br>STUDY DESIGN AND METHODS: Atherosclerosis was induced in Apolipoprotein E knockout mice through a Western diet, followed by a 12-week treatment with LA. In a separate model, low-density lipoprotein receptor knockout mice were fed a Western diet for 8 weeks prior to receiving LA for an additional 12 weeks. The role of GM in LA-mediated alleviation of atherosclerosis was assessed using fecal microbiota transplantation (FMT) models coupled with 16S rRNA gene sequencing. Furthermore, serum metabolomics was employed to elucidate the mechanism by which LA modulates serum metabolites via GM to attenuate atherosclerosis.<br><br>RESULTS: LA administration significantly attenuated the development of atherosclerosis in both models. FMT experiments further indicated that the GM contributes to the anti-atherosclerotic effects of LA. 16S rRNA gene sequencing revealed that LA modified the composition of the GM. Metabolomic analysis demonstrated that LA reduced serum levels of lysophosphatidylcholine (LysoPC), a metabolite critical for macrophage function.<br><br>CONCLUSION: Collectively, these findings highlight the therapeutic potential of LA in the treatment of atherosclerosis.}, }
@article {pmid42342152, year = {2026}, author = {Gray, SM and Wood, MC and Mulkeen, SC and Ahmed, S and Thaker, SD and Chen, B and Sander, WR and Bibeva, V and Zhang, X and Yang, J and Herzog, JW and Moss, AD and Zhang, S and Dogan, B and Simpson, KW and Sartor, RB and Montrose, DC}, title = {Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101825}, doi = {10.1016/j.jcmgh.2026.101825}, pmid = {42342152}, issn = {2352-345X}, abstract = {BACKGROUND AND AIMS: Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the components and mechanisms underlying the differential effects of these diets remain poorly understood. This study investigated the differential impact of dietary protein source on experimental colitis and related mechanisms.<br><br>METHODS: Isocaloric synthetic diets containing protein isolates from beef (BP), egg whites (EP), casein (CP), soy (SP) or pea (PP) were tested in acute (dextran sodium sulfate-induced) and chronic (Il10-deficient) murine colitis models. Gut resident microbes were quantified with 16S-sequencing and their role evaluated by antibiotic depletion, germ-free, selectively colonized gnotobiotic, and fecal microbiota transplant mouse studies.<br><br>RESULTS: Mice fed a BP diet exhibited the most severe colitis, while mice fed PP developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila, which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios.<br><br>CONCLUSIONS: These data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.}, }
@article {pmid42342194, year = {2026}, author = {He, H and Liu, LZ and Duan, HF and Fan, LL and Feng, YC and Liang, XJ and Peng, ZW}, title = {Gut Microbiota from GAD patients with divergent early pharmacological responses transmits anxiety-like behaviors and distinct metabolic profiles in recipient mice.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {}, number = {}, pages = {111803}, doi = {10.1016/j.pnpbp.2026.111803}, pmid = {42342194}, issn = {1878-4216}, abstract = {The gut microbiota is implicated in the pathogenesis of generalized anxiety disorder (GAD), but whether microbial differences between GAD patients with remission (R-GAD) and those with poor early treatment response (P-GAD) causally contribute to variable therapeutic outcomes remains unclear. Here, we transplanted feces from R-GAD and P-GAD patients into antibiotic-pretreated male C57BL/6 mice. P-GAD recipients showed heightened anxiety-like behaviors (reduced central zone time in open field test and shorter open-arm duration in elevated plus-maze), lower gut microbial α-diversity, and distinct β-diversity. Linear discriminant analysis effect size (LEfSe) detected 155 differentially abundant taxa. Genera enriched in R-GAD mice included Blautia, Roseburia, and Lachnospiraceae_NK4A136_group, whereas P-GAD mice were characterized by higher abundances of Bacteroides, Ileibacterium, and Allobaculum. Metabolomic analysis revealed that P-GAD mice had higher levels of neurotoxic tryptophan metabolite indoxyl-β-D-glucuronide (Indoxyl-GlcA) and lower levels of neuroprotective metabolites (indole-3-lactic acid, ILA; L-kynurenine, L-Kyn). Among 34 fatty acids, only C22:5 N3 (docosapentaenoic acid, DPA) was significantly lower in P-GAD mice. Correlation analyses further revealed that genera enriched in P-GAD mice were positively associated with pro-anxiety behaviors and neurotoxic metabolites, whereas those enriched in R-GAD mice showed the opposite trends. These findings suggest that gut microbiota from GAD patients with poor early treatment response may transmit anxiety-like phenotypes and metabolic disturbances in mice, providing a rationale for microbiota-targeted interventions in GAD.}, }
@article {pmid42332289, year = {2026}, author = {Porcari, S and Ferrari, M and Melekhova, A and Severino, A and Fusco, W and Carlà, AS and De Maio, F and Tilg, H and Gasbarrini, A and Elinav, E and Ianiro, G}, title = {Klebsiella genus as driver of human disease: from infections to non-communicable disorders.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {42332289}, issn = {1740-1534}, abstract = {Klebsiella spp. are pathobionts associated with acute infections, including pneumonia and infections in the urinary tract and bloodstream, often acquired in health-care settings. They represent a global threat owing to the prevalence of multidrug-resistant strains. Moreover, Klebsiella spp., similarly to other members of the human gut microbiota, can contribute to the pathogenesis of non-communicable disorders. In this Review, we describe the taxonomical and molecular characteristics of the Klebsiella genus, as well as its epidemiology and impact as an infectious agent. We also review current evidence that associates Klebsiella spp. with different non-communicable disorders, including chronic inflammatory and metabolic disorders and cancer. We discuss different approaches to target Klebsiella spp., including tailored antibiotics, faecal microbiota transplantation, live biotherapeutic products and bacteriophages. Finally, we discuss the importance of preventative measures, such as epidemiological surveillance, infection control practices and lifestyle interventions, to reduce the spread of Klebsiella spp. in health-care settings and the broader community.}, }
@article {pmid42334201, year = {2026}, author = {Moutsoglou, D and Staley, C and Kabage, AJ and Khoruts, A and Vaughn, BP}, title = {Colonoscopic and oral microbiota transplant therapy yield similar stool and neoterminal ileal engraftment profiles in a single-blind pilot randomized trial.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izag096}, pmid = {42334201}, issn = {1536-4844}, support = {T32 HL144472//National Institutes of Health/ ; //Achieving Cures Together (a nonprofit)/ ; //Crohn's and Colitis Litwin Pioneer Award/ ; }, abstract = {BACKGROUND: The intestinal microbiota play a key role in Crohn's disease (CD) and postoperative recurrence following ileocecal resection. Microbiota transplant therapy (MTT) could impact postoperative CD recurrence. This study aimed to compare donor engraftment kinetics in the stool and neoterminal ileum in CD participants with a history of ileocecal resection given either liquid MTT administered via colonoscopy or encapsulated, lyophilized, oral MTT.<br><br>METHODS: We performed a single-blind (participant), pilot, randomized trial evaluating ileal and stool engraftment kinetics in participants given MTT either via colonoscopy or oral capsules. Participants with a history of ileocecal resection underwent baseline colonoscopy and were randomized (1:1) to a single administration of liquid MTT at the time of colonoscopy or 5 days of MTT capsules. All underwent ileocolonoscopy with biopsies at week 8. Clinical assessments were obtained over 16&#x2009;weeks.<br><br>RESULTS: Alpha and beta diversity were significantly different between baseline neoterminal ileum and stool samples. Stool and mucosal-adherent ileal engraftment levels were not significantly different from each other based on the delivery method at week 8, and stool and ileal engraftments were significantly correlated to each other. Following MTT, there was a significant reduction in CD symptoms measured by the Harvey-Bradshaw Index; however, no differences were noted by the MTT administration route. Donor engraftment did not correlate to clinical outcomes.<br><br>CONCLUSIONS: In this pilot study of MTT in postoperative CD, oral and colonoscopy administration had similar donor engraftment. Oral MTT was well tolerated, supporting further evaluation of oral administration earlier in the postoperative disease course.NCT05248191, FMT for Postop Crohn's Disease, https://clinicaltrials.gov/study/NCT05248191.}, }
@article {pmid42335639, year = {2026}, author = {Yu, D and Jia, B and Zu, F and Zhang, W and Guo, D}, title = {Ciwujianoside B alleviates cholestatic liver injury by regulating TMAO synthesis via remodeling of the gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158426}, doi = {10.1016/j.phymed.2026.158426}, pmid = {42335639}, issn = {1618-095X}, abstract = {BACKGROUND: Cholestatic liver injury (CLI) is mainly driven by intrahepatic cholestasis, a pathological condition characterized by systemic and intrahepatic accumulation of bile acids. Ciwujianoside B (CWB), the active constituent of Eleutherococcus senticosus, has demonstrated protective effects in various hepatic pathologies, but its functional role in CLI has not yet been investigated.<br><br>PURPOSE: This study aims to evaluate the therapeutic potential of CWB against CLI and investigate its mechanism.<br><br>METHODS: CLI was induced via bile duct ligation, and the protective effects of CWB were assessed through H&amp;E, Sirius red, and immunohistochemical staining. Inflammatory cytokines in serum were measured by ELISA. Integrated analysis of 16S rDNA sequencing, serum metabolomics, and fecal microbiota transplantation was performed to investigate the interactions between gut microbiota and host metabolism. Trimethylamine oxide (TMAO) was supplemented to evaluate its impact on the hepatoprotective effects of CWB. In AML-12 cells, flavin-containing monooxygenase 3 (FMO3) was knockdown or overexpressed to assess TMAO levels, apoptosis, reactive oxygen species (ROS) content, and endoplasmic reticulum (ER) stress. The interaction between CWB and FMO3 was evaluated with molecular docking and molecular dynamics simulations.<br><br>RESULTS: CWB alleviated hepatocellular damage and apoptosis, which was accompanied by reduced serum levels of ALT, AST, ALP, and inflammatory cytokines. Mechanistic analyses revealed that CWB remodeled the gut microbiota, suppressed Cut C and Cut D levels in feces, thereby reducing systemic TMAO accumulation. Exogenous TMAO supplementation reversed the protective effect of CWB. Antibiotic treatment partially abrogated the hepatic protective effects of CWB. CWB significantly suppressed FMO3 expression. Knockdown of FMO3 in AML-12 cells led to a reduction in intracellular TMAO levels, apoptosis rate, ROS content and ER stress activation. Molecular docking revealed a stable binding interaction between CWB and FMO3.<br><br>CONCLUSIONS: Our results suggest that CWB alleviates CLI by suppressing TMAO biosynthesis, primarily through reducing trimethylamine-producing bacteria and directly inhibiting hepatic FMO3 expression.}, }
@article {pmid42335643, year = {2026}, author = {Kong, Y and Feng, J and Xu, H and Chen, X and Huo, W and Pan, S and Wang, Q and Chen, J and Liu, Y and Li, J and Lu, Y}, title = {Psoralen ameliorates sepsis-induced acute lung injury by regulating microbiota-dependent tryptophan metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158396}, doi = {10.1016/j.phymed.2026.158396}, pmid = {42335643}, issn = {1618-095X}, abstract = {BACKGROUND: Sepsis frequently leads to acute lung injury (ALI). Despite the documented anti-inflammatory effects of Psoralen (PSO), the exact mechanism by which it confers protection against septic ALI remains poorly understood.<br><br>PURPOSE: This research explored the protective efficacy and mechanistic aspects of PSO in sepsis-induced ALI.<br><br>METHODS: Lipopolysaccharide (LPS) was employed to create a murine ALI model. Pathological and inflammatory responses were evaluated. The dependency on gut microbiota was assessed through intestinal flora ablation and fecal microbiota transplantation. The aryl hydrocarbon receptor (AhR) engagement was demonstrated by its agonist FICZ and antagonist CH-223191.<br><br>RESULTS: In a septic ALI model, PSO ameliorated the histopathological damage and attenuated the inflammatory response. Evidence for this included a lower lung neutrophil percentage and decreased amounts of the proinflammatory mediators tumor necrosis factor-&#x3b1;, interleukin-6, interleukin-1&#x3b2;, as well as MPO-DNA complexes. Additionally, PSO downregulated the abundance of key markers in pulmonary tissue, including peptidylarginine deiminase 4, colony-stimulating factor 2, citrullinated histone H3, and MPO, thereby suppressing neutrophil extracellular trap formation. Furthermore, PSO altered gut microbial diversity, an effect that relied on tryptophan metabolism originating from the gut microbiota. The treatment raised the relative abundance of indole-3-propionic acid (IPA) in serum, which subsequently triggered the AhR/CYP1A1 pathway and thereby alleviated ALI. Moreover, PSO enhanced intestinal tight junction protein expression. Nonetheless, these protective effects were abolished by the AhR inhibitor CH-223191.}, }
@article {pmid42336338, year = {2026}, author = {Su, Z and Huang, Z and Huang, Y and Guo, J and Wang, Q and Xu, S and Kang, Y and Wang, Z and Shi, Y and Jia, B}, title = {Context-Dependent Short-Chain Fatty Acids in Inflammatory Skin Diseases: Immunometabolic Mechanisms, Evidence Boundaries, and Translational Perspectives.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {108318}, doi = {10.1016/j.phrs.2026.108318}, pmid = {42336338}, issn = {1096-1186}, abstract = {Inflammatory skin diseases(ISDs) arise from dynamic interactions among epithelial barrier dysfunction, immune dysregulation, microbial imbalance and metabolic cues. Within gut-skin and skin-microbiome axes, short-chain fatty acids (SCFAs) have attracted attention as microbial metabolites with anti-inflammatory and barrier-regulatory potential. However, treating SCFAs as uniformly beneficial obscures major biological and translational uncertainties. This narrative review synthesizes evidence from mechanistic, preclinical and clinical studies to define how acetate, propionate and butyrate regulate cutaneous immunity and barrier function. SCFAs act through free fatty acid receptors(FFARs), hydroxycarboxylic acid receptor 2(HCAR2), histone deacetylase inhibition(HDAC) and metabolic-substrate effects, but their outcomes depend on species, source, dose, tissue bioavailability, pH, receptor expression, target-cell identity and disease stage. Gut-derived SCFAs are more likely to support systemic immunometabolic regulation and barrier maturation, whereas locally produced cutaneous SCFAs can either maintain microbial and lipid homeostasis or amplify Toll-like receptor-driven inflammation in pilosebaceous niches. We discuss these mechanisms across immune cells, keratinocytes, sebocytes, fibroblasts, adipocytes and endothelial cells, and interpret their relevance to atopic dermatitis, psoriasis, acne vulgaris, rosacea, hidradenitis suppurativa, chronic spontaneous urticaria and contact dermatitis. We further evaluate dietary, prebiotic/probiotic, topical, fecal microbiota transplantation, engineered probiotic, prodrug and delivery-based strategies, distinguishing SCFA-specific causality from broader microbiome remodeling. A context-resolved framework is needed to translate SCFA biology into rational immunometabolic interventions for ISDs.}, }
@article {pmid42326403, year = {2026}, author = {Ryazanov, V and Vershinina, I and Inchagova, K and Bukareva, E and Kolpakov, V and Ruchay, A and Kosyan, D and Marinchev, M and Zdorov, A}, title = {Fecal microbiota and microbial community transplantation: a review of current research.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1814047}, pmid = {42326403}, issn = {1664-302X}, abstract = {Homeostasis across diverse ecosystems, ranging from human hosts to environmental matrices, is profoundly governed by microbial communities. Dysbiosis, the disruption of this microbial equilibrium, leads to significant adverse outcomes in medicine, agriculture, aquaculture, and environmental health. This review synthesizes current knowledge on microbial transfusions, defined as the deliberate transfer of microbial communities or their components to restore, reconstitute, or enhance functional capacities across these systems. We explore the historical context and cutting-edge applications, including Fecal Microbiota Transplantation (FMT) for Clostridioides difficile infection, metabolic and neurological disorders, alongside advancements in vaginal microbiota transplantation. In agriculture, we summarize the engineering of soil microbiomes for enhanced plant health, stress adaptation, and bioremediation, as well as transplantation practices in livestock and wild species. Furthermore, we discuss the role of microbiota transplantation in aquaculture for improving fish health and disease resistance, highlighting both natural and synthetic consortia. The application of microbial communities in bioremediation and ecological restoration is explored, addressing challenges such as stability, cost, and ecological impacts. Ultimately, this review integrates these diverse applications within a "One Health" framework, emphasizing the systemic links among human, animal, and environmental microbiomes. We underscore the potential of microbiota transplantation as a sustainable strategy for restoring ecological balance while identifying critical research gaps and future directions regarding standardized methodologies and the long-term functionality of transplanted microbiomes.}, }
@article {pmid42326424, year = {2026}, author = {Liang, L and Min, L and Liu, J and Liu, Y and Cheng, W}, title = {Gut microbiota dysbiosis in endometriosis: mechanistic insights and gut microbiota-targeted therapeutic strategies.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1776574}, pmid = {42326424}, issn = {1664-302X}, abstract = {Endometriosis (EMs) is a prevalent, estrogen-dependent gynecological disorder characterized by the ectopic implantation and proliferation of endometrial-like tissue outside the uterine cavity, affecting approximately 10% of reproductive-aged women globally. Despite its high incidence, the exact pathogenesis of EMs remains incompletely elucidated, and current clinical treatments are often limited by suboptimal efficacy and adverse effects. Accumulating evidence over the past decade has revealed a strong observational association between gut microbiota dysbiosis and EMs development, suggesting that the gut microbiota may serve as a novel potential target for understanding and managing this disease. This review systematically summarizes the potential mechanistic links underlying the interplay between gut microbiota dysbiosis and EMs progression, focusing on three core pathways: intestinal barrier dysfunction and microbial translocation, immune dysregulation and ectopic lesion immune escape, and estrogen metabolism disorder mediated by microbial enzymes and metabolites. In addition, this review stratifies gut microbiome profiles by EMs clinical subtypes (peritoneal, ovarian, deep infiltrating), clarifies anatomical correlations of the gut-lesion axis, and discusses confounding factors and causal inference methodologies. Beyond mechanistic insights, this review also discusses emerging gut microbiota-targeted therapeutic strategies for EMs, including probiotic supplementation, prebiotic intervention, fecal microbiota transplantation (FMT), and dietary modulation, with supplementary ethical considerations for FMT. Collectively, this review provides a comprehensive overview of the gut microbiota-EMs axis, highlighting current evidence levels and offering perspectives for the development of innovative, effective, and safe therapeutic approaches for EMs patients.}, }
@article {pmid42326427, year = {2026}, author = {Chen, L and Wu, W and Kong, Q}, title = {Gut microbiota alters cardiac metabolism and immune system composition in viral myocarditis mice.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1828423}, pmid = {42326427}, issn = {1664-302X}, abstract = {BACKGROUND: The effects of the gut microbiota on the regulation of host physiology have recently garnered considerable attention, particularly in metabolism and the immune system. However, the role of the gut microbiota in viral myocarditis (VMC) remains to be fully elucidated.<br><br>METHODS: Balb/c mice were injected with CVB3 to induce VMC. VMC mice were treated with fecal microbiota transplantation (FMT) or antibiotics (ABX) to evaluate the therapeutic effects of these interventions. Echocardiography, HE, and Masson's staining of the heart were used to assess cardiac function and pathological changes. 16S rDNA sequencing was conducted to explore alterations in gut microbial composition. UPLC-MS/MS-based metabolomics was used to detect disturbances of cardiac metabolic profiles. Flow cytometry was applied to analyze the dynamics of immune cell subsets, including M1, M2, Th1, Th2, Th17, and Treg cells. RT-PCR was performed to quantify cytokine expression levels in the heart.<br><br>RESULTS: FMT reduced cardiac inflammation and fibrosis, enhanced heart function, remodeled the structure of gut microbiota in VMC, and increased bacterial diversity, with an enrichment of p-Proteobacteria, the reduction of g-Pseudomonas, g-Streptococcus, and g-Ralstonia. Meanwhile, FMT induced alterations in cardiac metabolites in VMC, with enrichment of the steroid hormone biosynthesis pathway. A significant negative correlation was found between desoxycortone, corticosterone, 21-deoxycortisol, and cortodoxone with p_Spirochaetota and p_Kapabacteria. Furthermore, FMT reduced the proportions of M1 macrophages, Th1, and Th17 cells, as well as the cytokines TNF-a, IL-6, and IL-1&#x3b2;, and increased M2 macrophages and Treg cells. Regarding the role of antibiotics in VMC, our findings indicated that antibiotics altered the gut microbiota, myocardial metabolism, and immune response. Compared with antibiotics, FMT exerted a better effect on the alleviation of cardiac inflammation and fibrosis.<br><br>CONCLUSION: In VMC mice, the gut microbiota, which mediates disturbances in cardiac metabolites and the host immune response, may contribute significantly to the development of cardiac inflammation and fibrosis. Furthermore, FMT may represent a promising therapeutic approach for VMC.}, }
@article {pmid42327212, year = {2026}, author = {Damiani, F and Ashtiani, KC and Tognozzi, A and Abdelkarim, S and Cornuti, S and Caldarelli, M and Baldi, P and Tognini, P}, title = {The Critical Period Microbiota Shape Brain Plasticity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.06.08.730811}, pmid = {42327212}, issn = {2692-8205}, abstract = {The gut microbiota is increasingly recognized as a regulator of brain function, yet its role in experience-dependent plasticity during postnatal development remains largely unknown. Here, we show that disrupting the gut microbiota with antibiotics during critical periods of visual cortex development impairs ocular dominance plasticity (ODP) in juvenile mice. Antibiotic treatment induces marked changes in microbial community composition and is accompanied by extensive transcriptional remodeling of the visual cortex, including pathways involved in extracellular matrix organization, blood-brain barrier function, and myelination. Remarkably, fecal transplantation of the juvenile microbiota into adult recipients restores ODP. These findings identify the gut microbiota as a previously unrecognized regulator of neurodevelopmental plasticity and support the existence of microbiota-dependent critical periods of brain development. More broadly, our results suggest that early-life microbial perturbations may have lasting consequences for lifelong brain function and reveal that juvenile microbiota-derived signals could be exploited to promote plasticity in the adult brain.}, }
@article {pmid42327683, year = {2026}, author = {Knudsen, MJS and Rubin, IMC and Mirsepasi-Lauridsen, HC and Tomiak, J and Halkjær, SI and Petersen, AM and Helms, M}, title = {Decolonisation of a multi-drug-resistant Escherichia coli and a vancomycin-resistant Enterococcus faecium after intervention with faecal microbiota transplantation.}, journal = {Infection prevention in practice}, volume = {8}, number = {3}, pages = {100554}, pmid = {42327683}, issn = {2590-0889}, abstract = {In this study, we report a case of decolonisation of a multi-drug-resistant extended spectrum beta-lactamase-producing Escherichia coli, and a vancomycin-resistant Enterococcus faecium after intervention with capsulated faecal microbiota transplantation (FMT). Following eradication, our patient acquired an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, which was subsequently eliminated after a second round of FMT capsules. Additionally, we report the detection of six distinct carbapenemase-producing organisms in this patient, who was evacuated from the war in Ukraine.}, }
@article {pmid42328867, year = {2026}, author = {Wang, Y and Sheng, P and Wang, S and Zhong, X and Cao, H and Li, D and Yan, J and Yang, J and Wang, Y and Peng, J and Sun, F and Wang, S and Feng, Y and Sun, J and Zhang, F}, title = {Gut microbiota translocation contributes to early islet apoptosis in streptozotocin-induced diabetes.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0017226}, doi = {10.1128/msystems.00172-26}, pmid = {42328867}, issn = {2379-5077}, abstract = {Dysbiosis of the gut microbiota and impaired intestinal barrier are associated with diabetes development. The translocation of gut microbiota induced by streptozotocin (STZ) has been confirmed to damage pancreatic islets. However, it remains uncertain whether dysregulated gut microbiota plays an essential role in the translocation leading to pancreatic injury. In specific pathogen-free (SPF) and germ-free (GF) mice treated with STZ, we measured glucose metabolism levels, pancreatic islet damage, intestinal barrier integrity, and bacterial content in the pancreas to investigate the role of gut microbiota translocation in diabetes development. Shotgun metagenomic sequencing was used to analyze the impact of STZ on gut microbiota structure and function. Fecal microbiota transplantation was performed to explore if gut microbiota translocation depends on STZ-induced structural dysregulation. STZ induced intestinal damage in SPF mice, resulting in gut microbiota translocation to the pancreas, pancreatic apoptosis, and dysregulated glucose metabolism. Despite inherent intestinal barrier damage, absence of pancreatic apoptosis in GF mice further indicates that gut microbiota translocation is an essential prerequisite for STZ-induced pancreatic islet apoptosis. STZ significantly altered mouse gut microbiota composition and function. Transplantation of fecal microbiota from STZ-treated or saline-treated mice into STZ-induced GF mice also resulted in microbial translocation and pancreas apoptosis. Apoptosis of β cells in STZ-treated mice results from gut microbiota translocating to the pancreas through impaired intestinal barrier caused by STZ treatment independent of alterations in the gut microbial community.IMPORTANCEIn our study, the apoptosis of β cells in STZ-treated mice is the result of the translocation of gut microbiota to the pancreas through the impaired intestinal barrier induced by STZ, independent of alterations in the gut microbiota. These findings proposed the potential role of compounds in impairing the intestinal barrier integrity, promoting microbiota migration and finally damaging pancreatic islets.}, }
@article {pmid42332220, year = {2026}, author = {Piñero-Pérez, C and Velasco-Guardado, A and Pérez-López, E and Cortés-Rodríguez, M and Cabrero-Calvo, M and Martín-López, AA and Sánchez-Guijo, F and López-Corral, L}, title = {Fecal calprotectin as a biomarker for the diagnosis of gastrointestinal graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {42332220}, issn = {1476-5365}, abstract = {Gastrointestinal graft-versus-host disease (GI-GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), often requiring invasive endoscopy for diagnosis. Fecal calprotectin (FC) offers a non-invasive marker of intestinal inflammation, but its utility in GI-GVHD needs clarification. In this prospective observational study of 165 adult allo-HSCT recipients, FC was measured on days +7, +14, and +21 post-transplant, at GI-GVHD onset, and 7 days post-treatment, alongside clinical, endoscopic, and histological data. GI-GVHD developed in 52.7% of patients, with histological confirmation in 90.3% of cases. FC lacked predictive value on day +7 (AUC = 0.50) but showed moderate-to-high accuracy on days +14 (AUC = 0.69) and +21 (AUC = 0.77), with an optimal day +21 cutoff of 52.5 µg/g (sensitivity 75%, specificity 87%). At diagnosis, median FC was 120 µg/g, correlating with endoscopic severity (r = 0.31; p = 0.02) but not clinical or histological grades. FC declined significantly post-treatment (120 to 51.5 µg/g; p = 0.04), though concurrent infections elevated levels without compromising discriminative ability. FC serves as a dynamic biomarker for predicting, diagnosing, and monitoring GI-GVHD, but requires integrated clinical interpretation due to limited specificity amid other inflammations.}, }
@article {pmid41612728, year = {2026}, author = {Li, S and Che, C and Zhou, Y and Fan, D and Bai, X and Lu, Y and Zhao, X}, title = {Gut microecology empowers cancer immunotherapy: commensal microbiota-mediated mechanisms and translational prospects of PD-1/PD-L1 therapy.}, journal = {Cancer biology &amp; medicine}, volume = {23}, number = {1}, pages = {60-77}, pmid = {41612728}, issn = {2095-3941}, support = {82222058//National Natural Science Foundation of China/ ; 82425046//National Natural Science Foundation of China/ ; 82273142//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/drug therapy/microbiology ; *Immunotherapy/methods ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Animals ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *B7-H1 Antigen/antagonists &amp; inhibitors ; Fecal Microbiota Transplantation ; Tumor Microenvironment/immunology ; }, abstract = {Anti-programmed cell death protein 1 (PD-1) or its ligand (PD-L1) are immune checkpoint inhibitors (ICIs) that have revolutionized cancer therapy. However, the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability. In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy. Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms, including the production of metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, and extracellular polysaccharides that remodel the tumor microenvironment, as well as the activation of immune pathways involving dendritic cells, CD8[+] T cells, and M1 macrophages to increase antitumor immunity. Moreover, clinical studies have shown that fecal microbiota transplantation (FMT) and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy, while reducing the risk of immune-related adverse events (irAEs). This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies. The integration of multiomics technologies, synthetic biology, and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.}, }
@article {pmid41613006, year = {2025}, author = {Wang, ZQ and Zheng, HD and Li, LJ and Cao, LL and Shen, L and Qiao, Y and Chen, YY and Wu, LY and Li, GN and Wu, HG}, title = {Electroacupuncture alleviates Parkinson's disease by targeting HDAC/SIRT-mediated deacetylation of 14-3-3.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1719326}, pmid = {41613006}, issn = {1663-4365}, abstract = {INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of pathological α-synuclein. Although current treatments can alleviate symptoms, they do not modify disease progression. Growing evidence implicates gut microbiota dysbiosis and aberrant protein acetylation in PD pathogenesis. Electroacupuncture (EA) has shown therapeutic potential in PD; however, its effects on protein acetylation remain unclear.<br><br>METHODS: A PD mouse model was established through MPTP induction and fecal microbiota transplantation (FMT) from PD patients. Mice received EA stimulation at Baihui (GV20) and Yanglingquan (GB34) acupoints for 14&#x202f;days. Behavioral tests, immunohistochemistry, Western blot, qPCR, and 4D label-free acetyl proteomics were employed to assess motor function, neuronal integrity, protein expression, and acetylation profiles.<br><br>RESULTS: EA significantly improved motor coordination, enhanced sensorimotor function in the adhesive removal test, and increased open-field activity in PD mice. It attenuated the loss of tyrosine hydroxylase-positive neurons and decreased &#x3b1;-synuclein accumulation in the substantia nigra. Proteomic analysis revealed hyperacetylation of Ywhaq (14-3-3) in PD mice, which was reversed by EA. Mechanistically, EA upregulated the expression of deacetylases HDAC1/2/3 and SIRT1/2 at both protein and mRNA levels, restoring acetylation homeostasis.<br><br>CONCLUSION: Electroacupuncture ameliorates behavioral and neuropathological phenotypes in a PD mouse model by restoring deacetylase expression and normalizing protein acetylation, particularly of 14-3-3. Our results underscore the therapeutic potential of EA and highlight acetylation modulation as a promising strategy for PD treatment.}, }
@article {pmid41613143, year = {2025}, author = {Liu, L and Zhang, X and Wang, C and Zhou, K and Bao, J and Cheng, Z and Sun, H and Zhu, C and Yu, G and Xiao, W and Wan, R}, title = {Dysregulation of the microbiota-gut-brain axis induced by chronic pancreatitis mediates anxiety- and depression-like behaviors in mice.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1753424}, pmid = {41613143}, issn = {1664-3224}, mesh = {Animals ; *Depression/etiology/microbiology ; *Anxiety/etiology/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Pancreatitis, Chronic/psychology/microbiology/complications/chemically induced ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Behavior, Animal ; *Brain-Gut Axis ; Dysbiosis ; Fecal Microbiota Transplantation ; *Brain/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Anxiety and depression are common psychological complications in patients with chronic pancreatitis (CP). This study aims to investigate the dysregulation of microbiota-gut-brain axis induced by CP in driving anxiety- and depression-like behaviors in mice.<br><br>METHODS: C57BL/6J mice injected with caerulein (Cae) were used to establish an experimental CP model. Behavioral tests were performed to assess anxiety- and depression-like behaviors. The gut microbiota composition and serum metabolites were analyzed via 16S rRNA sequencing and liquid chromatography-mass spectrometry, respectively. Antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) models were employed to validate the direct role of the gut microbiota, while mixed probiotic gavage was used for intervention evaluation.<br><br>RESULTS: Cae-injected mice presented typical CP symptoms and significant anxiety- and depression-like behaviors. 16S rRNA sequencing revealed altered gut microbiota composition in CP mice, with a reduced abundance of Lactobacillus and enrichment of Helicobacter. ABX and FMT experiments confirmed that the CP-derived gut microbiota can independently induce anxiety/depression-like behaviors. In CP mice, Serum corticosterone and its metabolite levels were significantly increased in CP mice. CP-induced microbiota dysbiosis can induce the downregulation of intestinal barrier and blood-brain barrier functions, increase inflammatory levels, and extensively dysregulate neurotransmitter transmission in the brain. Treatment with mixed probiotics improved anxiety- and depression-like behaviors in CP mice.<br><br>CONCLUSIONS: CP promotes anxiety- and depression-like behaviors in mice by inducing gut microbiota dysbiosis. This study provides experimental evidence for the use of microbiota-targeted interventions for treating the psychological complications of CP.}, }
@article {pmid41613791, year = {2026}, author = {Mozga, K and Synowiecka, O and Rydzyk, I and Marek, A and Wieczorek, E and Petniak, A and Gil-Kulik, P}, title = {The Frontier of Melanoma Treatment: Defeating Immunotherapy Resistance-A Systematic Review.}, journal = {Oncology research}, volume = {34}, number = {2}, pages = {4}, pmid = {41613791}, issn = {1555-3906}, mesh = {Humans ; *Melanoma/immunology/therapy/drug therapy ; *Immunotherapy/methods ; *Drug Resistance, Neoplasm/immunology ; Animals ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; }, abstract = {OBJECTIVES: Immunotherapy based on immune checkpoint blockade (ICB) has become a key treatment for melanoma. However, the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance. This study aims to collect the most recent information on melanoma immunotherapy, discuss potential strategies to overcome resistance to immunotherapy, and identify areas that require further analysis.<br><br>METHODS: To achieve this goal, scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed. The databases were searched using the following terms: "melanoma", "immunotherapy", "Immune Checkpoint Blockade", and "immunoresistance".<br><br>RESULTS: The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1 (TBK-1), fecal microbiota transplant (FMT), Toll-like Receptor 9 (TLR9), lipid nanoparticles (LNPs) containing a stimulator of an interferon gene agonist (STING), BRAF inhibitors, Lymphocyte Activation Gene (LAG-3), T-Cell Immunoglobulin and ITIM Domain (TIGIT), and oncolytic viruses (OVs) as potential methods to enhance melanoma sensitivity to ICB.<br><br>DISCUSSION: To optimize immunotherapy, further research is needed to determine the detailed mechanisms of action, safety profiles, tolerability, and precise patient selection criteria for methods capable of overcoming melanoma's immunoresistance.}, }
@article {pmid41614677, year = {2026}, author = {Pettersson, M and La Sala, G and Gunnarsson, A and Vildhede, A and Sparklin, B and Holm, B and Petrović, D and Lasky, G and Turick, S and Szydlowska, M and Gopalakrishnan, V and Bake, T and Petersen, J and Brånalt, J and Westerlund, K and Taillefer, M and Henricsson, M and Ek, M and Warrener, P and Roth, R and Cohen, T and Sjögren, T and Fahlander, U and Jurva, U and Morias, Y and Liddle, J}, title = {Discovery of a Highly Potent and Selective Small-Molecule Inhibitor of In Vivo Anaerobic Choline Metabolism by Human Gut Bacteria.}, journal = {Journal of medicinal chemistry}, volume = {69}, number = {3}, pages = {2115-2129}, doi = {10.1021/acs.jmedchem.5c01451}, pmid = {41614677}, issn = {1520-4804}, mesh = {Humans ; Animals ; Methylamines/metabolism ; Rats ; *Choline/metabolism ; Mice ; *Enzyme Inhibitors/pharmacology/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Small Molecule Libraries/pharmacology/chemistry ; Anaerobiosis ; *Drug Discovery ; Structure-Activity Relationship ; *Lyases/antagonists &amp; inhibitors/metabolism ; Male ; }, abstract = {Trimethylamine (TMA) Lyase is an enzyme expressed in human gut bacteria that plays a pivotal role in the formation of trimethylamine oxide (TMAO), a metabolite implicated in the development of heart failure. Here, we describe a strategy to design covalent inhibitors targeting the active site thiyl radical involved in the catalytic cycle of the enzyme under anaerobic conditions. This strategy led to the discovery of 7, a previously unreported highly potent and selective inhibitor of TMA Lyase. When dosed orally to rats, 7 shows a significant reduction of circulating TMAO levels and, importantly, demonstrates inhibition of TMAO generated from a human microbiome when profiled in a human fecal mouse transplant model.}, }
@article {pmid41614846, year = {2025}, author = {Montoya Montoya, J and Gómez, EC and Tabares Guevara, JH and Arango Rincón, JC and Naranjo Preciado, TW}, title = {Effect of Gut Microbiota Alteration on Colorectal Cancer Progression in an In Vivo Model: Histopathological and Immunological Evaluation.}, journal = {Current issues in molecular biology}, volume = {48}, number = {1}, pages = {}, pmid = {41614846}, issn = {1467-3045}, support = {646-2021//Ministerio de Ciencia, Tecnolog&#xed;a e Innovaci&#xf3;n/ ; }, abstract = {Background/Objectives: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with its development influenced by diet, obesity, and gut microbiota (GM) alterations. This study aimed to evaluate the impact of human fecal microbiota transplantation (FMT) on the progression of CRC in a murine model. Methods: CRC was chemically induced in BALB/c mice using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice were transferred with GM via FMT and divided into two experimental groups according to the microbiota source (healthy donors or CRC patients). A positive control group (AOM/DSS without FMT) and a negative control group (no CRC induction or FMT) were included. Clinical parameters, histopathological analyses, and cytokine profiling were performed. Results: Mice receiving FMT, particularly from CRC patients, exhibited increased mitotic activity, dysplasia, neoplastic proliferation, structural alterations in the colon, and more pronounced GALT hyperplasia. At the immunological level, both FMT groups (healthy and CRC-derived) showed modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, and TNF-α compared to the positive control. Conclusions: Human GM transplantation modulated the colonic microenvironment through histopathological and immunological changes, influencing CRC progression in this murine model. These findings highlight the role of GM in shaping CRC development and suggest that human-derived microbiota may significantly impact tumor dynamics.}, }
@article {pmid41614917, year = {2026}, author = {Zhan, M and Chen, H and Fu, X and Tang, S and Song, X and Li, H and Zhu, L and Wang, B}, title = {TUDCA Ameliorates Cognitive Impairment in APP/PS1 Mice by Modulating the Microbiota-Gut-Brain Axis.}, journal = {Current issues in molecular biology}, volume = {48}, number = {1}, pages = {}, pmid = {41614917}, issn = {1467-3045}, support = {2020ZY013802//Chongqing Municipal Health Commission and Chongqing Science and Technology Bureau/ ; }, abstract = {Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer's disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, assessments of amyloid-β (Aβ) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4/NF-κB/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced Aβ accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4/NF-κB/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota-gut-brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD.}, }
@article {pmid41615004, year = {2026}, author = {Tremblay, C and Edger-Lacoursière, Z and Schneider, G and Jean, S and Calva, V and Nedelec, B}, title = {Rehabilitation Evaluation and Treatment for Skin Graft Complications of the Genitalia.}, journal = {Journal of burn care &amp; research : official publication of the American Burn Association}, volume = {47}, number = {3}, pages = {868-878}, pmid = {41615004}, issn = {1559-0488}, mesh = {Humans ; Male ; *Fournier Gangrene/surgery/rehabilitation ; *Fasciitis, Necrotizing/surgery ; Adult ; *Skin Transplantation/adverse effects ; Aged ; Perineum/surgery ; *Burns/surgery/complications ; Treatment Outcome ; }, abstract = {Skin graft complications may include pain, contractures, hypertrophic scars (HSc), hypersensitivity, and recurrent wounds. Complications involving grafts to the genitalia, perineum, and/or buttocks can be particularly challenging, directly affecting walking, sitting, voiding, bowel elimination, sexual function, and intimacy, ultimately diminishing quality of life. Perineal and pelvic floor rehabilitation (PPFR) is commonly used to treat various pelvic floor disorders; however, its application following burn injury or necrotizing fasciitis has not been previously described. This manuscript presents the evaluation and treatment outcomes of patients with necrotizing fasciitis or Fournier's gangrene. Initial evaluation was conducted approximately 4 months postadmission by a certified pelvic floor physiotherapist and occupational therapist. Treatment included pelvic floor rehabilitation, patient education, sensory re-education, bladder and bowel training, use of adapted pressure garments, gel application, cutaneous and myofascial stretching, and manual therapy. This report details the outcomes of 2 male patients (37 and 69 years old) who underwent skin grafting and reconstructive surgery following necrotizing fasciitis and Fournier's gangrene. Both presented with complex wounds that closed approximately 4 months postadmission, accompanied by contractures, HSc, altered sensory perception, incontinence, and sexual intimacy dysfunction. Following PPFR treatment, improvements were observed in pruritus, urinary and fecal retention capacity, sexuality-related fear avoidance, penile deviation, lower extremity range of motion, satisfaction with sexual function, and sensory perception. This is the first description of a standardized PPFR protocol in this context, demonstrating that specialized interdisciplinary rehabilitation can enhance sexual function, body-image satisfaction, and overall quality of life in patients with genital, perineal, and/or buttock grafts.}, }
@article {pmid41616125, year = {2026}, author = {Zhu, S and Bian, S and Lu, J and Wang, Y and Iqbal, M and Kiani, FA and Dong, H and Zhang, X and Yuan, Z and Liu, F and Li, A}, title = {Pathogenesis of Bovine Mastitis and Influence of the Gut Microbiota: A Review.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {5}, pages = {4222-4234}, doi = {10.1021/acs.jafc.5c13667}, pmid = {41616125}, issn = {1520-5118}, mesh = {Animals ; Cattle ; Female ; *Mastitis, Bovine/microbiology/immunology/therapy/metabolism ; *Gastrointestinal Microbiome ; Bacteria/genetics/isolation &amp; purification/classification ; Intestinal Barrier Function ; Toll-Like Receptors/genetics/immunology ; }, abstract = {Bovine mastitis (BM) is a highly prevalent bacterial infection that causes significant economic losses in the dairy industry. Its pathogenesis involves the recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs, primarily TLR2 and TLR4) and the subsequent activation of the NF-κB signaling pathway. Emerging evidence highlights the critical role of the gut microbiota in regulating BM through the "gut-mammary axis." Gut dysbiosis reduces microbial diversity, impairs the intestinal barrier, and promotes endotoxemia or translocation of metabolites, such as LPS (lipopolysaccharide) and short-chain fatty acids (SCFAs), which modulate mammary inflammation. Traditional antibiotic therapy is increasingly limited by resistance and residues, necessitating alternative approaches: targeting the gut microbiota through probiotics, fecal microbiota transplantation (FMT), or plant-derived active components offers promising strategies to restore microbial balance, enhance intestinal barrier function, and suppress excessive inflammation, thereby providing novel avenues for the prevention and treatment of BM.}, }
@article {pmid41617211, year = {2026}, author = {Sang, X and Zheng, Q and Qin, M and Chen, M and Wan, X and Hao, M and Yang, Q and Cao, G}, title = {Pentagalloylglucose, a limited oral bioavailability polyphenol, improves allergic asthma through regulating gut microbiota and modulating enteritis.}, journal = {British journal of pharmacology}, volume = {183}, number = {10}, pages = {2556-2577}, doi = {10.1111/bph.70345}, pmid = {41617211}, issn = {1476-5381}, support = {82274101//National Natural Science Foundation of China/ ; 82374123//National Natural Science Foundation of China/ ; LY24H280002//Natural Science Foundation of Zhejiang Province/ ; LQ23H280004//Natural Science Foundation of Zhejiang Province/ ; 2025JKZKTS23//Research Project of Zhejiang Chinese Medical University/ ; 2024R410A033//Students Science and Technology Innovation Activity Plan of Zhejiang Province/ ; }, mesh = {Animals ; *Asthma/drug therapy/microbiology/immunology ; *Hydrolyzable Tannins/pharmacology/administration &amp; dosage/pharmacokinetics/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Mice ; Biological Availability ; Administration, Oral ; Fecal Microbiota Transplantation ; Mice, Inbred BALB C ; Female ; *Anti-Asthmatic Agents/pharmacology/pharmacokinetics/administration &amp; dosage ; Male ; *Polyphenols/administration &amp; dosage/pharmacology/pharmacokinetics ; Colitis/drug therapy/microbiology ; }, abstract = {BACKGROUND AND PURPOSE: Pentagalloylglucose (PGG), a natural hydrolysable gall tannin, has limited bioavailability, and its biological activities are concentrated in the digestive system. However, our study discovered that this nonabsorbable compound can improve allergic asthma. This study focuses on elucidating the mechanisms underlying PGG's anti-allergic asthma effects.<br><br>METHODS: PGG serum metabolites were analyzed by UPLC/Q-TOF MS. To further explore its mechanisms, 16S rRNA sequencing, qPCR, and UPLC/Q-TOF MS were used to assess gut microbiota and metabolites. Fecal microbiota transplantation from PGG-treated mice into antibiotic-treated asthmatic mice evaluated its microbiota-dependent effects. Flow cytometry analyzed PGG's modulation of pulmonary ILC2s in a murine asthma&#x2011;colitis comorbid model.<br><br>KEY RESULTS: PGG's serum metabolites were below the quantification limit. PGG administration improved colonic injury and modulated L. reuteri; notably, exogenous L. reuteri alleviated asthma via increasing I3A from Trp metabolism. However, fecal microbiota transplantation from PGG-treated mice did not alleviate asthma, and PGG remained effective in microbiota-depleted mice, suggesting its action is microbiota-independent. Furthermore, PGG alleviated intestinal inflammation in both normal and antibiotic-treated asthmatic mice. In a comorbid colitis-asthma model, PGG counteracted colitis-aggravated asthma symptoms by modulating lung ILC2s.<br><br>CONCLUSION AND IMPLICATIONS: Although PGG modulates the gut microbiota and related metabolites, its anti-asthmatic effect is not primarily dependent on this pathway. Notably, it can ameliorate lung ILC2 dysregulation by alleviating enteritis.}, }
@article {pmid41617714, year = {2026}, author = {Du, Q and Li, Q and Ullah, H and Wei, Y and Liao, G and Xiao, X and Yao, J and Li, K}, title = {Harnessing gut microbiota for brain health: protective role of Hungatella hathewayi for post-mTBI cognitive impairment.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41617714}, issn = {2055-5008}, support = {2024NSFSC0592//Sichuan Province Science and Technology Support Program/ ; U22A20334//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats ; Male ; *Cognitive Dysfunction/etiology/prevention &amp; control/microbiology/therapy ; Humans ; *Brain ; *Eubacteriales/physiology ; Microglia ; Fecal Microbiota Transplantation ; Butyrates/metabolism ; Fatty Acids, Volatile/metabolism ; *Brain Concussion/complications/microbiology ; Disease Models, Animal ; Feces/microbiology/chemistry ; }, abstract = {Cognitive impairment (CI) following mild traumatic brain injury (mTBI) poses a clinical challenge, with emerging evidence implicating gut microbiota. This study found that mTBI patients who developed CI exhibited decreased Hungatella hathewayi, while those without CI showed an increase. Microbiota transplantation in mTBI rats revealed that higher Hungatella hathewayi levels enriched beneficial, short-chain fatty acid (SCFA) -producing bacteria and reduced harmful ones. Elevated Hungatella hathewayi improved performance in the Morris water maze and novel object recognition tests, indicating enhanced spatial learning and memory. It also reduced gut and brain inflammation, shown by lower TNF-α and IL-6 mRNA expression, and promoted M2 microglia polarization in the peri-lesional cortex. Metabolomics identified increased fecal and serum butyrate, a SCFA with anti-neuroinflammatory properties. Thus, Hungatella hathewayi may mitigate Post-mTBI CI by boosting butyrate production, which alleviates intestinal inflammation, shifts microglia toward the protective M2 phenotype, reduces neuroinflammation, and supports neuroprotection, ultimately lowering CI risk after mTBI. This study was registered with the Chinese Clinical Trial Registry (ChiCTR) on May 31, 2023 (Registration number: ChiCTR2300072000, URL: https://www.chictr.org.cn/showproj.html?proj=197867).}, }
@article {pmid41618079, year = {2026}, author = {Cheng, C and Li, Y and Lv, W and Zhao, J and Zhang, Y and Lu, H}, title = {A dual pathway intervention of tES and FMT enhances emotion regulation in stressed military personnel.}, journal = {Discover mental health}, volume = {6}, number = {1}, pages = {}, pmid = {41618079}, issn = {2731-4383}, support = {LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; }, abstract = {This review explores novel strategies for enhancing emotion regulation in military personal under stress, based on the interaction mechanisms of the microbiota-brain-gut axis. Military stress often triggers emotional fluctuations, cognitive decline, and physiological dysregulation, significantly impairing both mental health and combat performance. Existing research has primarily focused on psychological remediation, with insufficient attention paid to physiological mechanisms-particularly brain-gut interactions in emotion regulation. This paper proposes a dual-mode intervention strategy combining "top-down" and "bottom-up" approaches. On one hand, non-invasive neuromodulation techniques such as transcranial electrical stimulation (tES) are used to precisely regulate emotion-related brain regions, enabling immediate mitigation of negative emotions. On the other hand, fecal microbiota transplantation (FMT) is employed to restore gut microbial balance, thereby modulating neurotransmitter production and central nervous function via the gut-brain axis to enhance long-term emotional stability. Ultimately, we propose an integrated intervention combining tES and FMT, which addresses both acute emotional control and sustained regulation. This approach offers a promising theoretical and practical framework for enhancing emotion regulation, safeguarding psychological health, and maintaining combat effectiveness in high-stress military environments.}, }
@article {pmid41618133, year = {2026}, author = {Wang, S and Fan, X and Zheng, Z and Gu, Q and Xu, S and Zhu, Y and Zhang, F and Diao, M and Hu, W}, title = {Multi-omics characterized the effects of Akkermansia muciniphila and fecal microbiota transplant on the microglial activation after traumatic brain injury.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {117}, pmid = {41618133}, issn = {1471-2180}, support = {2024ZL718//Science and Technology Program of Traditional Chinese Medicine in Zhejiang Province/ ; 2025KY1055//The medical and healthresearch project of Zhejiang province/ ; 2025KY1091//The medical and healthresearch project of Zhejiang province/ ; A20250077//Hangzhou Health Science and Technology Program/ ; 20220919Y006//Hangzhou Science and Technology guide project/ ; 2025HZZD04//The Construction Fund of Key Medical Disciplines of Hangzhou/ ; }, abstract = {BACKGROUND: The microbiota-gut-brain axis plays a pivotal role in numerous neurological disorders, including traumatic brain injury (TBI). TBI induces neuroinflammation accompanied by alterations in the gut microbiota. However, the contribution of gut microbiota dysbiosis to post-TBI neuroinflammation and its underlying mechanisms remain poorly understood.<br><br>RESULTS: Here, we found that TBI mice treated with Akkermansia(Akk) exhibited increased Akkermansia abundance at 28 days post-TBI, whereas those receiving fecal microbiota transplantation (FMT) showed elevated levels of Bifidobacteriaceae and Bifidobacterium. Both Akk and FMT alleviated persistent microglial activation in the hippocampus of TBI mice at 28 days. FMT prevented the reduction of 5-hydroxyindole in TBI mice, and prolonged FMT suppressed the sphingolipid signaling pathway in these animals. Furthermore, two macrophage activation-associated genes, ACx3cr1 and Cd68, were upregulated after TBI, but their expression was inhibited by FMT at 28 days. Sphingolipid metabolism was elevated in TBI mice at 7 and 28 days post-injury, and Akk treatment (p&#x2009;=&#x2009;0.027) effectively blocked this increase at 28 days.<br><br>CONCLUSION: This study suggests that prolonged Akkermansia supplementation may mitigate post-TBI microglial activation by modulating the sphingolipid metabolic pathway. Both FMT and Akk represent potential therapeutic targets for developing novel strategies to address persistent microglial activation and chronic neuroinflammation following TBI, though their precise mechanisms require further validation.}, }
@article {pmid41618858, year = {2026}, author = {Yang, T and Gao, Z and Huang, H and Zhang, C and Tang, Y and Qu, Q and Li, H and Ke, J and Chen, Z and Feng, M and Zhou, H and Shu, Y and Yuan, W}, title = {Gut-Metabolome-Proteome Interactions in Age-Related Hearing Loss: Insights from Fecal Microbiota Transplantation and Multi-Omics Analyses.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {18}, pages = {e14269}, pmid = {41618858}, issn = {2198-3844}, support = {81873702//National Natural Science Foundation of China/ ; 81470694//National Natural Science Foundation of China/ ; 82225014//National Natural Science Foundation of China/ ; 82171114//National Natural Science Foundation of China/ ; 2024NF008//National Clinical Research Center for Otolaryngologic Diseases/ ; CSTB2023TIAD-KPX0059//Chongqing Technology Innovation and Application Development Special Project/ ; 2022DBXM006//Major Programs of Chongqing Science and Health Union/ ; cstc2022ycjh-bgzxm0126//Chongqing Talent Project/ ; CSTB2022NSCQ-MSX0553//Chongqing Natural Science Foundation/ ; }, mesh = {Animals ; Mice ; Multiomics ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; *Metabolome/physiology/genetics ; *Proteome/metabolism ; *Aging ; Disease Models, Animal ; Proteomics/methods ; Male ; *Hearing Loss/metabolism ; Metabolomics ; *Presbycusis/metabolism ; }, abstract = {Age-related hearing loss (ARHL) is a prevalent sensory disorder lacking disease-modifying interventions. The biological drivers, particularly the contribution of the gut microbiota and gut-inner ear crosstalk, remain poorly defined. Here, we utilize germ-free (GF) mice and fecal microbiota transplantation (FMT) to isolate microbiota-dependent effects on ARHL progression. Through integrated metagenomic, metabolomic, and proteomic profiling, we map molecular signatures of auditory aging and uncover functional gut-inner ear network, prioritizing 5-hydroxytryptophan (5-HTP) as a key intermediate metabolite within this network. Furthermore, in an aging-like House Ear Institute-Organ of Corti 1 (HEI-OC1) model, 5-HTP exhibits protective effects, potentially mediated through the PI3K/Akt-antioxidant signaling axis. Collectively, this study provides a valuable multi-omics resource and highlights microbiota-derived metabolic regulation as a promising avenue for biomarker discovery and therapeutic development in ARHL.}, }
@article {pmid41620444, year = {2026}, author = {Zhou, X and Liu, X and Peng, B and Yang, Y and Lu, H and Li, D and Deng, Y and Jiang, Z and Wu, C and Fang, W and You, Y and Kwan, HY and Zhao, X and Liu, Y}, title = {Simiao Decoction alleviates hyperuricemia-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41620444}, issn = {2055-5008}, support = {2023A1515110757//National Natural Science Foundation of China-Guangdong Joint Fund/ ; 20231800913372//Science and Technology Program of Dongguan, China/ ; U22A20365//Joint Funds of National Natural Science Foundation of China/ ; T2341019//National Natural Science Foundation of China/ ; 81830117//the Key Project of National Natural Science Foundation of China/ ; 2024B03J1343//Guangzhou Science and Technology Plan Project/ ; 20252D003//The Major scientific and technological project of Guangzhou Municipal Health Commission/ ; }, mesh = {Animals ; *Hyperuricemia/complications/drug therapy ; Rats ; *Dysbiosis/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Uremic Toxins/metabolism ; Disease Models, Animal ; Male ; Fecal Microbiota Transplantation ; Kidney/drug effects/injuries ; Indican/metabolism ; Tryptophan/metabolism ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects ; Cresols/metabolism ; Tyrosine/metabolism ; Bacteria/classification/drug effects/metabolism ; }, abstract = {Renal injury is a common complication of hyperuricemia (HUA), which has been recognized as an independent risk factor for chronic kidney disease (CKD). The gut-kidney axis theory suggests that targeting the gut microbiota may be a potential treatment option for kidney disease. In this study, we utilized a spontaneous HUA rat model to demonstrate that Simiao decoction (SMD), a traditional Chinese medicine formula, can effectively alleviate HUA-induced renal injury by modulating gut microbiota and bacterial metabolism of tryptophan and tyrosine, thereby reducing gut-derived uremic toxins such as indoxyl sulfate (IS) and p-Cresol (PC). Fecal microbiota transplantation (FMT) further confirmed that the therapeutic effect of SMD was mediated by gut microbiota. Finally, in vitro studies revealed that IS promotes epithelial-mesenchymal transition (EMT) while PC induces cellular senescence in tubular cells. Collectively, our findings suggest that SMD can effectively alleviate HUA-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins. This study sheds light on a novel mechanism by which SMD exerts its effects on HUA-induced renal injury.}, }
@article {pmid41620567, year = {2026}, author = {Yang, S and Song, J and Wang, Z and Peng, G and Tong, L and Li, X and Yang, K and Chen, Y and Zhang, H and Zhang, Q and Chen, R}, title = {eIF6 deficiency alleviates colorectal cancer by modulating the gut microbiota and related metabolites.}, journal = {Cell death and differentiation}, volume = {}, number = {}, pages = {}, pmid = {41620567}, issn = {1476-5403}, abstract = {eIF6 is overexpressed in multiple cancers. Previous work has showed that deficiency alters the gut microbiota. This study investigated the mechanism linking eIF6 deficiency, microbial dysbiosis, and colorectal cancer (CRC). eIF6 expression was assessed in human and mouse CRC samples. Functional assays were conducted in mice with AOM/DSS-induced CRC. Antibiotic treatment and faecal microbiota transplantation (FMT) were applied to evaluate microbiota-mediated effects. 16S rDNA sequencing and Dubosiella newyorkensis (D. newyorkensis) supplementation were used to identify key bacteria. Metabolites from the bacterial supernatant were analysed via targeted mass spectrometry. The effect of indole-3-carboxaldehyde (3-ICA) was tested in murine models. eIF6 expression was upregulated in CRC. Its deficiency reduced the tumour incidence and proliferation of tumours in mice and increased the abundance of beneficial bacteria such as Akkermansia and Dubosiella. FMT from eIF6 deficient mice and D. newyorkensis administration attenuated tumorigenesis and enhanced barrier function. 3-ICA, a metabolite of D. newyorkensis, also suppressed CRC progression. eIF6 deficiency exerts protective effects against CRC through the enrichment of D. newyorkensis and its metabolite 3-ICA, revealing a novel mechanism and potential therapeutic strategy for CRC.}, }
@article {pmid41621641, year = {2026}, author = {Chen, L and Yang, Y and Zhang, Y and Yang, X and Zhang, X and Chen, L and Li, W and Zhang, S and Xiong, R and Wang, J and Xu, Z and Zhang, ZY and Pan, C and Ji, M}, title = {Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {20}, number = {6}, pages = {101747}, pmid = {41621641}, issn = {2352-345X}, mesh = {Animals ; *Tuft Cells/metabolism/immunology ; Homeostasis ; Mice ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; *Alzheimer Disease/immunology/pathology ; Mice, Knockout ; Intestinal Mucosa/pathology ; *Cognitive Dysfunction ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND &amp; AIMS: Tuft cells, a type of epithelial cell in the gut, play a pivotal role in regulating type 2 immunity and maintaining the gut barrier. However, their role in cognitive impairments remains unclear.<br><br>METHODS: We compared behavioral performance between male tuft cell-absent mice (Pou2f3[-/-]) and their wild-type (WT) littermates. We analyzed gut microbiota using fecal 16S rRNA, measured gut permeability via FITC-dextran assay, and detected CD4[+]-T cells and type 2 innate lymphoid cells by flow cytometry in both genotypes. Co-housing and fecal microbiota transplantation experiments were conducted to explore the role of gut microbiota in cognitive diseases. Single-cell RNA sequencing and fluorescence imaging were used to examine tuft cell changes in the colon of WT and Alzheimer's disease (AD) model mice. Colonic organoids were used to assess the effect of &#x3b2;-amyloid on tuft cell differentiation. Succinic acid, a promoter of tuft cells, was administered, and tuft cell-deficient AD mice were generated to evaluate its impact on behavior and gut homeostasis.<br><br>RESULTS: Increased gut permeability, immune imbalance, neuroinflammation, and cognitive dysfunction occurred in 10-month-old mice lacking tuft cells. These alterations were mediated by gut microbiota, evidenced by shifts in microbiota composition and abundance, and supported by co-housing and fecal microbiota transplantation experiments. AD model mice had fewer tuft cells and impaired type 2 immunity in the gut, potentially because of &#x3b2;-amyloid inhibiting tuft cell differentiation. Succinic acid, a tuft cell activator, restored cognitive function and gut homeostasis in AD mice.<br><br>CONCLUSIONS: Tuft cells may be necessary for maintaining gut homeostasis in cognitive disorders.}, }
@article {pmid41622931, year = {2025}, author = {Hong, X and Deng, Y and Feng, J and Bao, C and Zhang, Y and Gao, N and Shen, H}, title = {[Fecal Microbiota Transplantation: A Promising Avenue for Lung Cancer Therapy].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {28}, number = {11}, pages = {841-848}, pmid = {41622931}, issn = {1999-6187}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Lung Neoplasms/therapy/immunology/microbiology ; Animals ; Gastrointestinal Microbiome ; }, abstract = {As lung cancer treatment continues to advance, mainstream approaches such as surgery, radiotherapy, chemotherapy, neoadjuvant therapy, targeted therapy and immunotherapy have become widely adopted in clinical practice. However, the efficacy of these methods is still limited and they are associated with significant side effects. In recent years, the pivotal role of the gut microbiota in tumor immune regulation has become increasingly recognized, with its potential impact on tumor immunotherapy emerging as a novel therapeutic focus in lung cancer management. Against this backdrop, fecal microbiota transplantation (FMT) has been proposed as a potential immunomodulatory strategy. It enhances host immune responses and improves the tumor immune microenvironment by regulating the gut microbiota. This paper provides a systematic review of the latest research advances in FMT for lung cancer treatment. Focusing on the relationship between gut microbiota and lung cancer, the therapeutic mechanisms of FMT and clinical application studies, it provides a comprehensive exploration of the challenges and prospects for the use of FMT in lung cancer therapy. .}, }
@article {pmid41622997, year = {2026}, author = {Li, Y and Wang, J and Wang, H and Ma, X and Ren, D and Wang, B}, title = {A novel exopolysaccharide from Lactiplantibacillus plantarum H6 improves cholesterol metabolism via Muribaculum-mediated activation of the enterohepatic FXR-FGF15 axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2623578}, pmid = {41622997}, issn = {1949-0984}, mesh = {Animals ; *Cholesterol/metabolism ; *Fibroblast Growth Factors/metabolism/genetics ; Mice ; *Polysaccharides, Bacterial/pharmacology/administration &amp; dosage/chemistry/isolation &amp; purification ; *Lactiplantibacillus plantarum/chemistry/metabolism ; Liver/metabolism/drug effects ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Receptor, Farnesoid X-Activated ; Male ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects ; *Hypercholesterolemia/metabolism/drug therapy ; Humans ; Cholesterol 7-alpha-Hydroxylase/metabolism/genetics ; }, abstract = {Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease; however, current therapeutic options such as statins are limited by issues including hepatotoxicity and patient intolerance. Probiotics and their metabolites show promise in modulating cholesterol metabolism through the gut‒liver axis, yet the specific commensal bacteria and molecular mechanisms underlying these effects remain poorly understood. In this study, we isolated and characterized EPS-D1, a novel exopolysaccharide (15.003 kDa) derived from Lactiplantibacillus plantarum H6, which is composed primarily of mannose (46.10%) and glucose (33.98%) and features a highly branched structure (branching degree of 29.5%). The administration of EPS-D1 significantly reduced the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) by 40.31%, 37.55%, and 43.15%, respectively, in high-cholesterol diet (HCD) mice. Additionally, it improved hepatic steatosis and reduced markers of liver injury. Through 16S rRNA sequencing and fecal microbiota transplantation (FMT), we identified Muribaculum as the key commensal bacterium enriched by EPS-D1. Direct administration of Muribaculum (Muribaculum intestinale) replicated the cholesterol-lowering effects, decreasing ileal and fecal cholesterol levels by 74.79% and 53.16%, respectively. Mechanistically, both EPS-D1 and M. intestinale activated the enterohepatic FXR‒FGF15 axis, which resulted in the upregulation of hepatic cholesterol 7α-hydroxylase (CYP7A1) expression and the downregulation of ileal ASBT and NPC1L1, thereby promoting bile acid synthesis and inhibiting cholesterol absorption. Furthermore, M. intestinale increased intestinal short-chain fatty acids (SCFAs), particularly acetic acid and caproic acid, by 37.88% while also modulating the composition of the bile acid pool. These findings establish M. intestinale as a precise microbial target for cholesterol management and demonstrate that EPS-D1 from L. plantarum H6 enhances cholesterol metabolism through microbiota-mediated activation of the enterohepatic FXR‒FGF15 axis, providing a novel therapeutic strategy for managing hypercholesterolemia.}, }
@article {pmid41623601, year = {2026}, author = {Koda, K and Mimura, T and Yamana, T and Ishizuka, M and Takahashi, T and Takano, S and Abe, T and Nishizawa, Y and Katsuno, H and Sato, M and Nishimura, K and Yoshida, M and Maeda, K}, title = {The Japan Society of Coloproctology Practice Guidelines for Fecal Incontinence 2024 (Revised Second Edition).}, journal = {Journal of the anus, rectum and colon}, volume = {10}, number = {1}, pages = {64-134}, pmid = {41623601}, issn = {2432-3853}, abstract = {In 2024, the second edition of the Japan Society of Coloproctology (JSCP) Practice Guidelines for Fecal Incontinence was published in Japan, followed by the release of this English version. This marks the first major revision in 7 years since the publication of the first edition. The second edition was completed over a span of 3 years, and its overview and key features are summarized below. This guideline begins with a clinical flowchart outlining the general diagnostic and therapeutic approach. A notable update is the inclusion of insertable anal and vaginal continence devices, which are now considered a form of conservative therapy under clinical research frameworks. In Chapter I-B (Epidemiology), the prevalence of anal incontinence was newly reported: among a Japanese population with an average age of 35 years, 15.5% of men and 42.7% of women were affected. In Chapter II (Diagnosis), the utility of a bowel diary for patient assessment is discussed for the first time. The guideline also provides a detailed description of the evaluation method for digital rectal examination. Additionally, a new section was added addressing incontinence-associated dermatitis (IAD), including its risks and methods of assessment. In Chapter III (Diagnostic Testing), the guideline expands upon previously established diagnostic tests by newly including detailed descriptions of ultrasound techniques-specifically, endoanal ultrasound, transperineal ultrasound, and transvaginal ultrasound. Chapter IV (Treatment) outlines conservative treatment strategies, including dietary guidance, bowel habit instruction, and care for fecal incontinence. Pharmacologic therapies are presented with itemized explanations by drug type. Pelvic floor muscle training, biofeedback therapy, and transanal irrigation are classified under "specialized conservative therapies" and discussed in detail. For surgical treatment, a new Clinical Question (CQ) addresses postpartum fecal incontinence. It recommends early referral to a specialized center when a sphincter injury is present to be repaired, whereas observation for one year may be appropriate when no injury is identified. Another new CQ discusses the mode of delivery in subsequent pregnancies following obstetric anal sphincter injuries (OASIS), emphasizing the need to evaluate fecal incontinence severity, anal sphincter function, and its integrity before making clinical decisions. Stoma creation is described in detail as one of the surgical treatment options, including its implications for improved postoperative quality of life. For the first time, regenerative therapy for the anal sphincter is introduced as a novel surgical option, reporting promising long-term outcomes from trials involving the transplantation of autologous cultured myoblasts into the external anal sphincter. Finally, Chapter V addresses special clinical scenarios in detail, including fecal incontinence associated with neurological and spinal disorders, dementia, frailty, and bedridden elderly patients.}, }
@article {pmid41623954, year = {2025}, author = {Abtahi Froushani, SM and Hasani, SJ and Ghaderi, M and Mahmoudzadeh, L}, title = {A review of inflammatory bowel diseases in humans and pets: treatment strategies.}, journal = {Veterinary research forum : an international quarterly journal}, volume = {16}, number = {11}, pages = {601-610}, pmid = {41623954}, issn = {2008-8140}, abstract = {Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory conditions that primarily impact the gastrointestinal system. While ulcerative colitis and Crohn's disease are the principal manifestations in humans, animals frequently exhibit lymphocytic-plasmacytic enteritis/colitis and eosinophilic enteritis/colitis. Growing evidence suggests a complex interplay among genetic predisposition, gut microbiota imbalance and abnormal immune responses to intestinal microbes in susceptible individuals. This intricate involvement results in remarkably similar clinical presentations across species. Patients often experience symptoms such as diarrhea, vomiting, weight loss and anemia. Extraintestinal manifestations including uveitis, skin rash and arthritis may also occur. Endoscopy and biopsy typically serve as the gold standard for confirming the diagnosis and differentiating it from other gastrointestinal disorders in humans and animals. The treatment approach generally focuses on managing disease activity through immunosuppressive medications such as glucocorticoids, administered at appropriate dosages. However, the precise cause of IBD remains a topic of ongoing research. With the emergence of additional treatment options like herbal compounds and fecal microbiota transplantation, which have demonstrated effectiveness in restoring gut health in IBD patients, there is optimism for novel therapeutic strategies. Ultimately, conclusion is that chronic gastrointestinal conditions like IBD are complex in both human and veterinary medicine. These diseases share numerous common pathophysiological features, yet, diagnostic and treatment challenges continue to exist.}, }
@article {pmid41625766, year = {2025}, author = {Zhao, H and Liu, Y and Su, L and Cui, P and Sai, J and Li, S and Wang, N and He, P}, title = {Gut-liver-muscle axis: linking gut microbiota dysbiosis to malnutrition and sarcopenia in liver disease.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1727270}, pmid = {41625766}, issn = {2296-858X}, abstract = {Nutritional disorders and muscle wasting associated with liver disease are key determinants of poor prognosis in patients with chronic liver disease. The formation of these conditions involves multiple factors, including impaired energy metabolism, enhanced protein degradation, and gut microbiota imbalance. In recent years, with the deepening of microbiome research, the concept of the "gut-liver-muscle axis" has gradually emerged to explain the more systematic interaction between gut microbiota, liver metabolism, and skeletal muscle homeostasis. Gut dysbiosis can promote liver inflammation and metabolic disorders through various pathways, further weakening muscle energy utilization and protein synthesis, ultimately leading to malnutrition and sarcopenia. This review systematically explores the crucial role of gut microbiota in liver disease-related malnutrition and muscle wasting, elucidates its potential mechanisms in influencing host metabolism and nutritional status through the "gut-liver-muscle axis," and discusses the prospects of microbiome interventions in improving nutritional outcomes in liver disease.}, }
@article {pmid41626654, year = {2026}, author = {Guo, YY and Xue, KJ and Wang, L and Wang, GG and Zhang, TT and Hou, SL}, title = {Alterations in Gut Microbiota and Metabolic Profiles in Relapsed or Refractory Lymphoma.}, journal = {MicrobiologyOpen}, volume = {15}, number = {1}, pages = {e70225}, pmid = {41626654}, issn = {2045-8827}, support = {20241201//Shanxi Province Applied Basic Research Program Project/ ; }, mesh = {Humans ; *Lymphoma/microbiology/metabolism ; *Metabolome ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; Metabolomics ; }, abstract = {To identify potential therapeutic strategies for relapsed or refractory lymphoma (R/RL) by examining differences in gut microbiota composition and metabolic profiles between patients with R/RL and those with primary, treatment-naïve lymphoma (PL), using fecal microbiota analysis and metabolomics. A total of 21 patients with lymphoma were enrolled at the Department of Lymphoma and Oncology, Shanxi Bethune Hospital, between November 2023 and December 2024. The cohort included 14 patients with R/RL and 7 with PL, who served as the control group. Pretreatment fecal samples and clinical data were collected from all participants. Gut microbiota profiling was conducted using 16S rDNA sequencing, including alpha diversity, beta diversity, species composition, and differential abundance. Untargeted metabolomics was employed to identify and analyze differentially expressed metabolites between the groups. Patients with R/RL exhibited increased relative abundances of Actinobacteriota and Alphaproteobacteria and decreased levels of Erysipelotrichales, Morganellaceae, Faecalibacterium, Clostridium, Klebsiella, and Ruminococcus. Seven metabolites were significantly upregulated in the R/RL group (p < 0.05): 3-amino-4-methylpentanoic acid (p = 0.028), 2-hydroxybutyric acid (p = 0.020), UDP-N-acetylglucosamine (UDP-N-AG) (p = 0.011), pantothenic acid (p = 0.037), isoleucine (p = 0.028), glycine (p = 0.044), and alanine (p = 0.025). Literature review and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated enhanced central carbon metabolism and amino acid metabolism in cancer. Alterations in gut microbiota and metabolic activity may contribute to the pathophysiology of R/RL. Therapeutic modulation of the gut microbiota, including the use of fecal microbiota transplantation, may improve the intestinal immune microenvironment in this patient population. The present work is hypothesis-generating and requires large-scale validation.}, }
@article {pmid41626790, year = {2026}, author = {Barati, S and Ghoflchi, S and Nakhaei, A and Yazdi, MP and Hosseinzadeh, P and Hosseini, H and Jalili-Nik, M}, title = {Gut Microbiome Strategies for Enhancing ICI Delivery Across the BBB in Glioblastoma.}, journal = {BioFactors (Oxford, England)}, volume = {52}, number = {1}, pages = {e70077}, doi = {10.1002/biof.70077}, pmid = {41626790}, issn = {1872-8081}, mesh = {Humans ; *Glioblastoma/drug therapy/immunology/microbiology/pathology ; *Blood-Brain Barrier/drug effects/metabolism/immunology ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use ; *Brain Neoplasms/drug therapy/immunology/microbiology/pathology ; Animals ; Tumor Microenvironment/drug effects/immunology ; Fecal Microbiota Transplantation ; CTLA-4 Antigen/antagonists &amp; inhibitors/immunology/genetics ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/genetics/immunology ; B7-H1 Antigen/antagonists &amp; inhibitors/immunology/genetics ; }, abstract = {Glioblastoma (GB) is highly malignant with a median survival of 14 months despite conventional treatments like surgery, radiotherapy, and temozolomide. Resistance to these therapies necessitates innovative approaches, such as immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1) to enhance T-cell-mediated tumor destruction. However, clinical trials have shown limited ICI efficacy in GB due to its immunosuppressive microenvironment and the blood-brain tumor barrier (BBTB), which impairs drug delivery. Emerging evidence highlights the gut microbiota as a pivotal modulator of ICI response, enhancing CD8[+] and CD4[+] T-cell function, antigen presentation, and immune modulation via the gut-brain axis in cancers. In addition, studies showed that gut-derived metabolites, including short-chain fatty acids, modulate immune responses and support blood-brain barrier integrity by regulating inflammatory signaling and tight junction proteins. Future GB research should prioritize clinical trials, mechanistic studies, and interventional strategies like fecal microbiota transplantation and probiotics to enhance ICI efficacy.}, }
@article {pmid41627354, year = {2026}, author = {Blonk, L and Straatman, J and Wierdsma, NJ and Gisbertz, SS and van der Peet, DL and Kazemier, G and van Berge Henegouwen, MI}, title = {Nutritional aspects and quality of life in gastroesophageal cancer patients that underwent colonic interposition.}, journal = {Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus}, volume = {39}, number = {1}, pages = {}, pmid = {41627354}, issn = {1442-2050}, mesh = {Humans ; *Quality of Life ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; *Colon/surgery/transplantation ; *Esophageal Neoplasms/surgery ; *Nutritional Status ; Intestinal Absorption ; Adult ; Surveys and Questionnaires ; *Esophagectomy/methods/adverse effects ; Energy Intake ; }, abstract = {The use of a colonic interposition after major esophageal surgery leads to substantial anatomical changes, but information regarding the effects of these changes on functional outcomes is limited. Objective of this study was to evaluate the presence of gastrointestinal symptoms, nutritional aspects, intestinal absorption capacity, and health-related quality of life (HR-QoL) in adult patients after colon interposition. This single-center study consisted of three parts. Part 1 involved a retrospective review of anthropometric data, dietary patterns, and gastrointestinal symptoms in all consecutive patients who underwent colonic interposition between 2010 and 2021 and in whom at least 6 months of follow-up were available. Patients from part 1 who were still alive in 2021 were invited for an in-depth evaluation of dietary intake and intestinal absorption capacity. This included measuring daily fecal losses of energy (kcal), fat (g), and protein (g) over a 72-hour period. The coefficients of fat and protein absorption (CFA and CNA) were calculated. Energy balance (kcal/day) was determined by subtracting fecal energy loss (kcal/day) and daily estimated total energy expenditure (eTEE) from the dietary energy intake (kcal/day). Part 3 assessed HR-QoL prospectively using the EORTC QLQ-C30 and OG-25 questionnaires. All consecutive patients presenting to the outpatient clinic between 2014 and 2021 were asked to complete these questionnaires. In part 1 of this study, 30 patients were included. Symptoms of steatorrhea/diarrhea (65%) and dysphagia (42%) were most frequently reported, and 31% could not cease enteral nutrition via jejunostomy or nasal tube due to weight loss or gastrointestinal symptoms. Ten patients were included in part 2 of this study. Intestinal malabsorption of fat and protein (CFA and CNA <85%) was found in 70% of patients, and 60% of patients had a negative energy balance. HR-QoL was measured in 20 patients. Median global QoL score (EORTC QLQ-C30) was 63 (IQR 50-83) and the OG-25 symptom score 19 (IQR 6.9-36). In conclusion a colonic interposition after esophagectomy is accompanied by gastrointestinal symptoms, intestinal malabsorption, and an impaired QoL. Adequate counseling of patients and follow-up with a multidisciplinary approach to treat gastrointestinal symptoms and correct for intestinal malabsorption is recommended.}, }
@article {pmid41628815, year = {2026}, author = {Nowicka, A and Gil, L}, title = {Fecal microbiota transplantation for carbapenem-resistant Pseudomonas spp. colonization in hematology patients: long-term real-world data.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {165}, number = {}, pages = {108447}, doi = {10.1016/j.ijid.2026.108447}, pmid = {41628815}, issn = {1878-3511}, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation/adverse effects/methods ; Retrospective Studies ; Male ; *Carbapenems/pharmacology/therapeutic use ; *Pseudomonas Infections/therapy/microbiology ; *Pseudomonas/drug effects ; Middle Aged ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Adult ; Aged ; Treatment Outcome ; Immunocompromised Host ; *Hematologic Neoplasms/complications/therapy ; }, abstract = {OBJECTIVES: Colonization with carbapenem-resistant Pseudomonas spp (CRP) contributes to infections and high mortality. Fecal microbiota transplantation (FMT) offers a strategy for eradicating multidrug-resistant organisms, but experience on CRP decolonization in immunocompromised patients is meagre.<br><br>DESIGNS AND METHODS: A single-center retrospective study of gastroscopic FMT in CRP-positive hematological patients. The primary objective was decolonization. Short and long-term post-FMT CRP-related infectious complications were evaluated.<br><br>RESULTS: By April 30, 2025, 14 patients (5 ALL, 5 AML, 2 MDS, 1 APL, 1 NHL) were enrolled; 8 had received allo-HCT. With a median follow-up of 16 months (1.45-26), decolonization was achieved in 10 in a median of 14 days (9-34) and was durable in 6. Eradication failure occurred in 4 due to persistence and 4 due to recurrence. Median time to recolonization was 83 (32-173). 9 patients experienced CRP-related infections following FMT: bloodstream infections (BSI) 67%, soft tissue 56%, gastrointestinal 56%, urinary tract 33%, pneumonia 22%, septic shock 22%. A total of 7 died; due to infections in 6, with CRP responsible in 5. No severe adverse events of FMT were reported.<br><br>CONCLUSIONS: FMT demonstrates safety and efficacy in early decolonization of CRP. In failure, CRP-related infections remain a leading cause of mortality.}, }
@article {pmid41628870, year = {2026}, author = {Zhang, A and Li, S and Qiao, J and Zhong, C and Zhang, Z and Ye, X and Jin, J and Shang, S and Wu, S and Zhang, Q and Yang, G}, title = {Isopsoralen alleviates osteoarthritis by modulating the MAPK/NF-κB signaling pathway and regulating the structure of gut microbiota.}, journal = {Journal of ethnopharmacology}, volume = {361}, number = {}, pages = {121257}, doi = {10.1016/j.jep.2026.121257}, pmid = {41628870}, issn = {1872-7573}, mesh = {Animals ; *Osteoarthritis/drug therapy/metabolism ; *NF-kappa B/metabolism ; *Furocoumarins/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; *MAP Kinase Signaling System/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; }, abstract = {The therapeutic effect of Psoralea corylifolia L. on knee joint pain was recorded as early as the Ming Dynasty in the Compendium of Materia Medica, which notes its actions of tonifying the kidney, strengthening tendons, and bones. Isopsoralen (ISO), derived from the Psoralea corylifolia L., has shown efficacy in improving osteoarthritis (OA) in both traditional use and our previous screening, demonstrating effects in alleviating joint inflammation and protecting cartilage.<br><br>AIM OF THE STUDY: OA is a common disabling disease. Its progression connects local joint pathology to systemic metabolic and inflammatory states, extending to gut microbiota and metabolites. This study examines the therapeutic mechanism of isopsoralen against OA using a DMM-induced model.<br><br>MATERIALS AND METHODS: ISO's targets were predicted by network pharmacology approaches. Therapeutic effects were evaluated through behavioral tests, micro-CT, histology, Western blot, and PCR, while safety was assessed via liver/kidney staining. 16S rDNA sequencing and targeted metabolomics were employed to analyze gut microbiota structure and short-chain fatty acids (SCFAs). Pseudo germ-free mice and fecal microbiota transplantation (FMT) were used to validate the role of gut microbiota.<br><br>RESULTS: Network pharmacology indicated ISO's multi-target action against OA. ISO downregulated the MAPK/NF-&#x3ba;B pathway, attenuated subchondral bone abnormalities, and alleviated joint degeneration in DMM mice. It also modulated gut microbiota composition and SCFA levels. FMT confirmed the essential role of gut microbiota in ISO's efficacy. Furthermore, no hepatorenal toxicity was observed.<br><br>CONCLUSION: ISO alleviates OA by modulating gut microbiota/SCFAs and inhibiting the MAPK/NF-&#x3ba;B pathway, thereby reducing inflammation and improving bone abnormalities, without hepatorenal toxicity.}, }
@article {pmid41629271, year = {2026}, author = {Yao, Y and Zhu, Y and Chen, K and Chen, J and Li, Y and Li, D and Wei, P}, title = {Microbiota in cancer: current understandings and future perspectives.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {39}, pmid = {41629271}, issn = {2059-3635}, support = {82273240, 82473078//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Neoplasms/microbiology/therapy/immunology/pathology ; *Microbiota/immunology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Immunotherapy ; }, abstract = {The intricate relationship between the microbiota and cancer has recently emerged as a pivotal area of research, highlighting their critical roles in carcinogenesis, progression, and prognosis. With the increasing recognition of the therapeutic potential of the microbiota in cancer, there is an urgent need to understand the diverse impacts of different microbiota on tumors and explore innovative strategies to harness their benefits. For the first time, this review traces the historical evolution of microbiota-cancer studies, from early observations of microbial presence in cancers to landmark discoveries linking specific microorganisms to carcinogenesis. Furthermore, this study delves into the molecular mechanisms underlying microbiota-mediated cancer progression to elucidate the modulatory roles of oncogenic pathways, immune responses, and tumor metabolism. We also discuss the dual roles of the microbiota in promoting and inhibiting cancer, highlighting its potential as both a facilitator of tumor growth and a target for therapeutic intervention. In addition, this review highlights the mechanism by which the microbiota mediates the response to anticancer immunotherapy, chemotherapy, and radiotherapy. Simultaneously, emerging anticancer strategies targeting microbiota (e.g., probiotics, antibiotics, and fecal microbiota transplantation) have been explored alongside U.S. Food and Drug Administration-approved drugs and ongoing clinical trials. Finally, this review outlines future directions in this field, emphasizing the need for personalized approaches to harness the anticancer potential of the microbiota. The interpretations in this review are expected to establish a stereoscopic, comprehensive framework for advancing research and clinical applications in microbiota-targeted oncology.}, }
@article {pmid41629813, year = {2026}, author = {Astudillo-Guerrero, C and Garrido, &#xc1; and Masferrer, D and Sepúlveda, C and Olavarría, L and Del Campo, R and Bravo-Sagua, R and Cubero, FJ and Salech, F and Thumala-Dockendorff, D and Urrutia, PJ and Quera, R and Bunout, D and Espinoza, R and Jorquera, G}, title = {Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study).}, journal = {BMC geriatrics}, volume = {26}, number = {1}, pages = {}, pmid = {41629813}, issn = {1471-2318}, abstract = {BACKGROUND: Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength in older adults, is a key determinant of frailty and functional decline. Affecting up to 15% of individuals aged 65–80 years and more than 50% of those over 80, sarcopenia not only compromises physical autonomy but also increases the risk of metabolic dysfunction and cognitive decline. Emerging evidence suggests that age-related gut microbiota dysbiosis contributes to these impairments by reducing microbial diversity and altering host metabolic signaling, leading to chronic inflammation and mitochondrial dysfunction. The present study aims to evaluate the safety, tolerability, and preliminary efficacy of oral fecal microbiota transplantation derived from young, physically active donors administered to older adults, focusing on outcomes related to functional autonomy, muscle performance, metabolism and cognition. METHODS: This is a double-blind, randomized, placebo-controlled clinical trial involving community-dwelling adults aged 65–84 years. Participants will be randomized 1:1 to receive either FMT capsules or placebo following a short course of oral rifaximin (or placebo). Assessments will be performed at baseline and at 4, 8, and 20 weeks post-intervention. The primary outcomes are safety and tolerability, as well as changes in the Global Index of Functional Autonomy (GDLAM battery) and muscle strength. Secondary outcomes include gait speed, body composition (DXA), metabolic biomarkers, gut microbiota composition (shotgun metagenomics), cognitive performance, and psychological well-being. EXPECTED IMPACT: By restoring microbial diversity and function, FMT from young, active donors may enhance muscle quality, cognitive resilience, and metabolic health in older adults. This study introduces a novel, non-invasive therapeutic approach based on lyophilized and encapsulated microbiota, offering a feasible and scalable strategy to promote healthy aging. TRIAL REGISTRATION: ClinicalTrials.gov NCT06649981. Date of registration October 21, 2024.}, }
@article {pmid41630697, year = {2026}, author = {Olasunkanmi, OI and Zheng, L and Zheng, P}, title = {Gut-brain axis in health and brain disease.}, journal = {Chinese medical journal}, volume = {139}, number = {6}, pages = {799-827}, pmid = {41630697}, issn = {2542-5641}, mesh = {Humans ; *Brain/metabolism ; *Brain Diseases/metabolism ; Gastrointestinal Microbiome/physiology ; Animals ; Probiotics/therapeutic use ; *Gastrointestinal Tract/metabolism ; }, abstract = {The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer's disease, and Parkinson's disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.}, }
@article {pmid41632030, year = {2026}, author = {Zhang, H and Li, Z and Xiao, Y and Bian, J and He, C and Liu, C and Gong, L and Han, L and Liu, Z and Wang, M}, title = {Gut Microbiota-Derived Anandamide Mediates the Therapeutic Effects of Urolithin A on Alcohol-Induced Cognitive and Social Dysfunction via CB1R-DRD2-RAP1 Signaling Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {20}, pages = {e08048}, pmid = {41632030}, issn = {2198-3844}, support = {CARS-07-E-2//financial support provided by the China Agriculture Research System/ ; 32001701//Natural Science Foundation of China/ ; }, mesh = {Animals ; *Endocannabinoids/metabolism/pharmacology ; Signal Transduction/drug effects ; *Gastrointestinal Microbiome/drug effects/physiology ; *Receptor, Cannabinoid, CB1/metabolism/genetics ; *Polyunsaturated Alkamides/metabolism/pharmacology ; *Arachidonic Acids/metabolism/pharmacology ; Mice ; *Receptors, Dopamine D2/metabolism/genetics ; Male ; Ethanol/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Chronic alcohol consumption disrupts the gut microbiome, exacerbating alcohol-induced cognitive and social dysfunction (AICSD), which constitutes a primary etiology of early-onset dementia. Urolithin A (UA) has been well-reported as an effective intervention for neurodegenerative diseases. However, the protective efficacy of UA against AICSD, and its underlying mechanisms remain largely elusive. First, our study demonstrates that UA significantly enhances work memory (60.43%), short-term memory (12-fold), long-term memory (50.32%), social ability (10-fold), and social novelty (12-fold), while concurrently reducing synaptic impairments and neuroinflammation. Moreover, UA restores AICSD by upregulating the dopamine D2 receptor (DRD2) via RAP1 signaling. Furthermore, antibiotic treatment and fecal microbiota transplantation experiments confirm the causality between the host microbiota and behavioral alterations. Treatment with UA-enriched Bacteroids sartorii and Parabacteroids distasonis, or their derived endocannabinoid-anandamide (AEA), also ameliorates AICSD. Finally, AEA inhibits the Rap1 signaling through cannabinoid receptor 1 (CB1R) and DRD2 interaction, eventually ameliorating AICSD. Collectively, our study elucidates that microbiota-derived AEA mediates the therapeutic effects of UA on AICSD through the CB1R-DRD2-RAP1 signaling axis, providing valuable insights for UA and microbiome-targeted endocannabinoid interventions against AICSD.}, }
@article {pmid41632104, year = {2026}, author = {Li, J and Song, L and Liang, X and Zhou, J and Luo, J and Sun, X and Jin, R and Zhang, Z}, title = {Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice.}, journal = {Food &amp; function}, volume = {17}, number = {4}, pages = {1952-1969}, doi = {10.1039/d5fo04423e}, pmid = {41632104}, issn = {2042-650X}, mesh = {Animals ; Male ; Mice ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; *Hyperuricemia/blood/microbiology/therapy ; *Lactiplantibacillus plantarum ; *Probiotics/therapeutic use ; Tryptophan/metabolism ; Disease Models, Animal ; Animals, Outbred Strains ; }, abstract = {Hyperuricemia (HUA) has become a worldwide metabolic disease, which can lead to acute gout attacks, renal dysfunction, uric acid (UA) urolithiasis, and cardiovascular damage. Probiotics, known for their cost-effectiveness, minimal toxic side effects, and high safety profile, have shown potential in alleviating HUA. In the present study, the beneficial function of Lactobacillus plantarum TY-S8 on HUA and related mechanisms were comprehensively investigated by constructing a mice model of hyperuricaemia, combined with the use of microbiomics and metabolomics. Our results demonstrated that L. plantarum TY-S8 markedly lowered serum UA (SUA) concentrations by 22.41%, suppressed xanthine oxidase (XOD) activity and modulated the level of key transporters, including GLUT9, ABCG2, and NTP1. Furthermore, the pathological damage in the liver, kidney and colon of hyperuricemic mice was alleviated by the probiotics. Meanwhile, the strain upregulated the levels of occludin, a key tight junction protein, and promoted the synthesis of short-chain fatty acids (SCFAs), with a notable increase in butyric acid. Microbiome sequencing and analysis revealed that L. plantarum TY-S8 significantly increased the proportions of Lactobacillus johnsonii and Limosilactobacillus reuteri. Additionally, metabolomic analysis of fecal and blood samples indicated that the differential metabolites among the three groups were primarily indole derivatives, such as indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-acetaldehyde (IAAld), which are involved in the tryptophan metabolism pathway. Notably, there is a clear correlation between the key bacterial strains and these differential metabolites. At last, fecal microbiota transplantation (FMT) was performed to confirm that the ameliorative effect of L. plantarum TY-S8 on the hyperuricemic mice is primarily mediated by the regulation of gut microbiota and tryptophan metabolites. In conclusion, L. plantarum TY-S8 exerts probiotic effects on hyperuricemic mice through multiple pathways. In particular, it alleviates intestinal inflammation by regulating tryptophan metabolism, thereby effectively promoting uric acid metabolism, which highlights its potential value in the intervention of HUA.}, }
@article {pmid41632629, year = {2026}, author = {Runaas, L and Fank, S and Palen, K and Szabo, A and Rein, LE and Ying, G and Salzman, N and Samanas, L and Abedin, S and Chhabra, S and Hamadani, M and Longo, W and Shah, NN and Haber, J and Gradissimo, A and Waters, N and Peled, JU and Johnson, B and Kearl, T and Drobyski, WR}, title = {Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.}, journal = {Blood advances}, volume = {10}, number = {8}, pages = {2698-2710}, pmid = {41632629}, issn = {2473-9537}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Graft vs Host Disease/prevention &amp; control/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Female ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology/administration &amp; dosage ; Adult ; Middle Aged ; Male ; Transplantation, Homologous/adverse effects ; Transplantation Conditioning ; Young Adult ; }, abstract = {We conducted a phase 1/2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tildrakizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. A total of 50 patients were enrolled between March 2020 and June 2023 with a median age of 56 years (range, 19-64). All patients received myeloablative busulfan-based conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts. Patients were treated with tildrakizumab on an extended subcutaneous administration schedule for 5 doses, which was well tolerated. The cumulative incidences of grades 2 to 4 and 3 to 4 acute GVHD were 14% (95% confidence interval [CI], 7-28) and 4% (95% CI, 1-16) at day 100, respectively. The incidence of chronic GVHD requiring systemic immune suppression was 52.7% (95% CI, 40.4-68.9) at 12 months. The 1-year probabilities of overall, disease-free, and GVHD-free relapse-free survival were 80% (95% CI, 70-92), 78% (95% CI, 67-90), and 19.3% (90% CI, 11.8-31.4), respectively. Pharmacokinetic analysis revealed the half-life of tildrakizumab at ∼28 days without formation of detectable anti-tildrakizumab-neutralizing antibodies. Comparative examination of fecal microbial composition in tildrakizumab and a similarly transplanted cohort treated with tocilizumab prophylaxis demonstrated that both cytokine blockade strategies had a low frequency of enterococcal dominance. We conclude that tildrakizumab resulted in a low incidence of acute GVHD and attenuation of microbiome dominance with potentially pathogenic organisms but did not mitigate the emergence of chronic GVHD as administered on this dosing schedule. This trial was registered at www.clinicaltrials.gov as #NCT04112810.}, }
@article {pmid41633775, year = {2026}, author = {Kang, KS and Choi, GH and Kim, YJ and Lee, WS and Lee, DE and Kim, MY and Yoon, H and Lee, DH}, title = {Analysis of gut microbiota in super donors for fecal microbiota transplantation and isolated gut commensal bacteria of inhibition against Clostridioides difficile.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2025.00179}, pmid = {41633775}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is increasingly recognized as an alternative to antibiotics for treating recurrent Clostridioides difficile infection. The success of FMT heavily depends on the appropriate selection of donors, encompassing factors such as diet patterns, lifestyle, environmental exposures, and intestinal microbiota diversity.<br><br>METHODS: A potential super donor was identified from 5 healthy adults and provided stool samples periodically over 2 years (2021-2022). The samples underwent 16S rRNA sequencing via the Illumina MiSeq platform, and microbial diversity was analyzed using QIIME 2 in comparison with 152 healthy individuals.<br><br>RESULTS: The stool microbiome composition of the potential super donor remained stable without significant changes over a 2-year period. Both alpha and beta diversity analyses revealed significant differences between the super donor and the 152 healthy individuals. The super donor exhibited significantly higher microbial diversity based on alpha diversity metrics (P< 0.0001) and distinct compositional profiles as shown by beta diversity. Linear discriminant analysis effect size (LEfSe) analysis indicated that Faecalibacterium and Prevotella strains comprised a significant proportion, with notable differences in relative abundance patterns (P< 0.05). Furthermore, 7 bacterial species were isolated from the super donor, all of which demonstrated inhibitory effects on the growth of C. difficile in vitro.<br><br>CONCLUSIONS: These findings suggest that selecting donors with specific microbiota profiles, particularly those exhibiting higher microbial diversity, may potentially contribute to the inhibition of C. difficile, and further clinical studies are warranted to validate these findings.}, }
@article {pmid41634704, year = {2026}, author = {Bao, L and Jin, L and Yang, Y and Zhao, Y and Wu, K and Shan, R and Liu, Y and Han, Y and Shang, S and Zhang, N and Hu, X and Fu, Y and Zhao, C and Jiang, H and Bian, W}, title = {Hexadecanamide alleviates experimental colitis in mice and modifies the gut microbiome.}, journal = {BMC biology}, volume = {24}, number = {1}, pages = {}, pmid = {41634704}, issn = {1741-7007}, mesh = {Animals ; *Colitis/drug therapy/chemically induced/microbiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; *Anti-Inflammatory Agents/pharmacology ; Disease Models, Animal ; }, abstract = {BACKGROUND: Hexadecanamide (HEX) has been recognized for its significant anti-inflammatory properties. However, its specific role and underlying mechanisms in the context of colitis remain poorly understood.<br><br>RESULTS: Herein, we first determined the effect of oral HEX on DSS-induced colitis in mice. Our results showed that HEX alleviated DSS-induced colitis in mice, which was related to the improvement of intestinal barrier integrity and the reduction of colonic inflammatory responses. Interestingly, HEX suppressed the initiation of DSS-induced ferroptosis. In detail, HEX inhibited autophagy and ferritinophagy, which subsequently blocked lipid peroxidation. 16S rRNA sequencing revealed that HEX intervention regulated the gut microbial composition, characterized by an increased relative abundance of Actinobacteriota and Patescibacteria and a decreased the relative abundance of Firmicutes. To validate these findings, fecal microbiota transplantation (FMT) was performed in DSS-treated mice. The microbiota derived from HEX-treated mice exhibited greater efficacy in alleviating colitis compared to that from control-treated mice, as evidenced by prominent anti-inflammatory effects and colonic barrier repair, and consistent alterations in the gut microbial community, which were further confirmed by FMT.<br><br>CONCLUSIONS: Overall, our findings suggest that HEX markedly ameliorates DSS-induced colitis by limiting inflammation, improving barrier integrity and regulating gut microbial composition. These results highlight the critical role of HEX in maintaining intestinal homeostasis and suggest its potential as a novel preventive and therapeutic strategy.}, }
@article {pmid41635847, year = {2025}, author = {Sun, Q and Gao, J and Zhao, X and Wang, T and Pan, W and Yu, J}, title = {The gut-lung axis in severe pneumonia-related lung injury: mechanisms and therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1700534}, pmid = {41635847}, issn = {1664-3224}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/immunology ; *Lung/immunology/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Pneumonia/therapy/immunology/microbiology ; Prebiotics/administration &amp; dosage ; *Lung Injury/therapy/microbiology/etiology/immunology ; Dysbiosis ; }, abstract = {Severe pneumonia-related lung injury is a life-threatening condition associated with high morbidity and mortality. Recent advances in research on the gut-lung axis have provided novel insights into its pathophysiology and revealed potential therapeutic targets. Within the conceptual framework of the microorganism-immunity-metabolism network, modulation of the gut microbiota has emerged as a promising strategy for intervention. Therapeutic approaches such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation aim to enhance microbial diversity and alter metabolite profiles, thereby optimizing immune responses and attenuating systemic and pulmonary inflammation. This review explores the mechanistic underpinnings of the gut-lung axis in the context of severe pneumonia-related lung injury, with a particular focus on microbiota-targeted interventions. Our goal is to provide a theoretical foundation for the clinical application of gut microbiota modulation in the prevention and treatment of severe pneumonia-related lung injury.}, }
@article {pmid41636306, year = {2026}, author = {Luan, M and Bao, S and Zhang, X and Huang, Y and Yuan, R and Zhong, P and Liu, M and Li, J and Liu, X and Chen, L and Huang, Q and Wu, R}, title = {Sinensetin Ameliorates Metabolic Syndrome via Regulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {6}, pages = {5256-5272}, doi = {10.1021/acs.jafc.5c12920}, pmid = {41636306}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Bile Acids and Salts/metabolism ; *Metabolic Syndrome/microbiology/metabolism/drug therapy ; Male ; Humans ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; *Flavonoids/administration &amp; dosage ; Diet, High-Fat/adverse effects ; Bacteria/isolation &amp; purification/classification/genetics/drug effects/metabolism ; }, abstract = {The exact mechanism through which dietary flavonoids alleviate metabolic syndrome (MetS) via the gut microbiota remains fully unclear. This study demonstrates that sinensetin markedly impeded the development of MetS and altered hepatic transcriptomic profiles by activating alternative bile acid biosynthesis signaling cascades both in vivo and in vitro. Importantly, sinensetin administration induced significant shifts in hepatic bile acid composition, notably increasing the relative abundance of non-12-hydroxy bile acids (non-12-OH BAs) in high-fat diet (HFD)-fed mice. Additionally, oral administration of sinensetin significantly relieved intestinal dysbiosis caused by HFD by altering the composition of gut microbiota in mice. The therapeutic efficacy of sinensetin against MetS was microbiota-dependent, as antibiotic-mediated depletion of gut microbiota abolished its beneficial effects, and fecal microbiota transplantation transmited this metabolic improvement. These findings suggest that sinensetin alleviated MetS by reshaping the gut microbiota to enhance non-12-OH BAs synthesis, offering novel mechanistic insights and promising avenues for therapeutic intervention.}, }
@article {pmid41639119, year = {2026}, author = {Xu, Q and Lv, Q and Yang, Z and Yang, Y and Li, Z and Zhang, Y and Chen, L and Zhan, S and Che, H and Wang, G and Wu, J and Han, J}, title = {Polygonatum cyrtonema Hua fructan ameliorates ulcerative colitis via gut microbiota modulation and follistatin targeting.}, journal = {NPJ science of food}, volume = {10}, number = {1}, pages = {}, pmid = {41639119}, issn = {2396-8370}, support = {2024AH051923//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 2024AH051934//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 2024AH040169//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 82270879//the National Natural Science Foundation of China/ ; 2508085QH341//the Natural Science Foundation of Anhui Province/ ; 2024CCCX260//the TCM Innovation and Inheritance Project of Anhui Province/ ; HKDCCM2024008//the Open Fund of the High-level Key Discipline of Chemistry of Chinese Medicine of the State Administration of Traditional Chinese Medicine, Anhui University of Chinese Medicine/ ; 2023yjsmsgzs037//he Anhui Provincial Postgraduate Education Quality Project (Han Jun Distinguished Mentor Studio)/ ; 2023yjsdstd053//the Anhui Provincial Pharmacy Graduate Supervisor Team/ ; 2023CXMMTCM011//the Research Funding for the Center of Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM/ ; 2023zc06//The "Chi Zhu Zhi Guang" Major Scientific and Technological Achievements Engineering Project of Wuhu City/ ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with persistent colonic inflammation and inadequate therapeutic options. The medicinal and edible plant Polygonatum cyrtonema Hua from Jiuhua Mountain contains polysaccharides with potent anti-inflammatory activities. In this study, a low-molecular-weight fructan (Mw = 2087 Da), designated PCP2, was isolated and purified from its rhizome. Biologically, PCP2 administration markedly alleviated disease severity in dextran sulfate sodium (DSS)-induced colitis mice, as shown by the improvement in multiple indicators of colon injury and inflammation. Fecal microbiota transplantation and antibiotic depletion experiments revealed that the protective effects of PCP2 are mediated through both modulation of the gut microbiota and additional microbiota-independent pathways. Importantly, through molecular dynamics simulations, microscale thermophoresis, and surface plasmon resonance assays, follistatin (Fst) is identified as a direct binding target of PCP2. Functional validation using siRNA-mediated Fst knockdown in Caco-2 cells, combined with adenovirus-mediated knockdown in the murine colon, confirmed that PCP2 exerts its therapeutic effect by directly interacting with Fst and suppressing the BMP4/Smad1/ID1 signaling axis. In summary, PCP2 ameliorates ulcerative colitis via dual mechanisms involving restoration of gut microbiota homeostasis and direct targeting of Fst. These findings establish a novel therapeutic strategy and support the clinical development of P. cyrtonema Hua from Jiuhua Mountain as a functional food for intestinal health.}, }
@article {pmid41639396, year = {2026}, author = {Weber, D and Tariq, M and Hazenberg, M and Poeck, H and Malard, F}, title = {Microbiome, GvHD, and immune reconstitution in allogeneic hematopoietic cell transplantation.}, journal = {Bone marrow transplantation}, volume = {61}, number = {4}, pages = {385-394}, pmid = {41639396}, issn = {1476-5365}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; *Graft vs Host Disease/microbiology/immunology/etiology ; Transplantation, Homologous/methods ; *Immune Reconstitution ; *Gastrointestinal Microbiome/immunology ; *Microbiota ; }, abstract = {The gut microbiota has emerged as a critical factor influencing outcomes following allogeneic hematopoietic cell transplantation (alloHCT). Notably, disruptions to the intestinal microbiome-referred to as dysbiosis-have been strongly linked to the development of acute graft-versus-host disease (aGVHD). The gut microbiome interacts closely with the host immune system, influencing both immune reconstitution and alloHCT complications. As a result, microbiome-targeted strategies are being investigated to improve outcomes and include antibiotic stewardship, prebiotic and diet intervention, probiotics including fecal microbiota transfer (FMT) and postbiotics. These approaches are being investigated not only as a therapeutic intervention in particular for aGVHD, but also as preventive strategies.}, }
@article {pmid41639673, year = {2026}, author = {Wu, H and Pang, MM and Li, YL and Huang, JJ and Geng, SZ and Hong, JH and Liu, PM and Yang, JJ}, title = {Flos sophorae immaturus exosome-like nanovesicles alleviate ulcerative colitis by attenuating intestinal oxidative stress and inflammation through activating Aryl hydrocarbon receptor via gut microbiota and tryptophan metabolism regulation.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {132}, pmid = {41639673}, issn = {1477-3155}, support = {82501460, U23A20421//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Oxidative Stress/drug effects ; *Colitis, Ulcerative/metabolism/drug therapy ; *Receptors, Aryl Hydrocarbon/metabolism ; *Tryptophan/metabolism ; Mice ; *Exosomes/chemistry/metabolism ; *Gastrointestinal Microbiome/drug effects ; Inflammation/metabolism/drug therapy ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Humans ; Indoleacetic Acids/metabolism ; *Sophora/chemistry ; Dextran Sulfate ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease that significantly impacts patients' quality of life. The pathogenesis of UC remains incompletely understood, with oxidative stress and inflammation emerging as novel research targets. This study first isolated Flos Sophorae immaturus exosome-like nanovesicles (FSIEVs), demonstrating high purity, uniform particle size, and excellent biocompatibility and biosafety, with potential for treating UC. In vivo, FSIEVs improve the overall condition of a dextran sodium sulfate-induced murine model of UC, reduce intestinal inflammation and oxidative stress, and repair intestinal barrier integrity. Moreover, FSIEVs exhibit anti-UC effects by modulating the gut microbiota (enhancing Lactobacillus species), promoting tryptophan metabolism, and increasing the production of indole-3-acetic acid (IAA). Findings from antibiotic treatment, fecal microbiota transplantation (FMT), and intestinal organoid models confirmed that IAA is a key metabolite mediating the anti-UC effects of FSIEVs, and all these approaches significantly activated the aryl hydrocarbon receptor (AhR). The role of AhR in the anti-UC effects of FSIEVs was further validated using AhR antagonists. Notably, FSIEVs alleviated UC symptoms involving the enrichment of beneficial anti-UC Lactobacillus species, L. paracasei by mono-colonization. In summary, FSIEVs improve UC by regulating the gut microbiota and tryptophan metabolites, enhancing IAA production, activating AhR, and suppressing NLRP3 inflammasome activation and ROS production.}, }
@article {pmid41640608, year = {2026}, author = {Velikova, T and Ali, H and Batselova, H and Chervenkov, L and Miteva, D and Peruhova, M and Gulinac, M and Tomov, L and Mitova-Mineva, Y and Velev, V}, title = {Interplay between viral infections and gut microbiota dysbiosis: Mechanisms and therapeutic potential.}, journal = {World journal of gastroenterology}, volume = {32}, number = {3}, pages = {112437}, pmid = {41640608}, issn = {2219-2840}, mesh = {Humans ; *Dysbiosis/therapy/immunology/microbiology/virology ; Fecal Microbiota Transplantation ; COVID-19/immunology ; Probiotics/therapeutic use ; SARS-CoV-2 ; *Gastrointestinal Microbiome/immunology ; Prebiotics/administration &amp; dosage ; *Virus Diseases/immunology/microbiology/therapy ; *Coronavirus Infections/immunology/therapy/microbiology ; Betacoronavirus/immunology ; Animals ; Pandemics ; *Pneumonia, Viral/immunology/therapy/microbiology ; Host-Pathogen Interactions ; }, abstract = {Viral infections, particularly those triggered by emerging pathogens like severe acute respiratory syndrome coronavirus 2, are increasingly recognized for their profound impact on the gut microbiota, causing dysbiosis, a condition characterized by an imbalance in microbial communities. Recent studies suggest that alterations in gut microbiota can influence disease progression, immune responses, and clinical outcomes. The bidirectional relationship between the gut microbiota and the host immune system is crucial in shaping responses to infection. Furthermore, dysbiosis has been linked to exacerbated inflammation, impaired mucosal barrier function, and altered drug metabolism, thereby complicating both disease pathogenesis and treatment efficacy. This review examines the interplay between viral infections and gut microbiota dysbiosis, with a focus on the underlying mechanisms and potential therapeutic strategies to modulate host immunity. We also evaluate the potential of microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, as therapeutic strategies for restoring microbial balance and mitigating the severity of infections. The paper underscores the need for further research to optimize microbiota-targeted therapies and integrate them into clinical practice, offering a comprehensive approach to managing dysbiosis in viral infectious diseases.}, }
@article {pmid41640872, year = {2026}, author = {Chen, YX and Sun, NQ and Mo, SJ}, title = {Rhapontin activating nuclear factor erythroid 2-related factor 2 to ameliorate Parkinson's disease-associated gastrointestinal dysfunction.}, journal = {World journal of gastroenterology}, volume = {32}, number = {4}, pages = {114468}, pmid = {41640872}, issn = {2219-2840}, mesh = {*NF-E2-Related Factor 2/metabolism ; *Parkinson Disease/complications/microbiology ; Animals ; Humans ; *Gastrointestinal Diseases/etiology/therapy/microbiology/drug therapy ; Gastrointestinal Microbiome/drug effects ; Mice ; Signal Transduction/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {This commentary provides a critical evaluation of the study by Wang et al, which focuses on rhapontin activating colonic nuclear factor erythroid 2-related factor 2 (NRF2) to explore its therapeutic potential for Parkinson's disease (PD)-associated gastrointestinal dysfunction. The commentary acknowledges the academic value of the study: It has not only validated intestinal NRF2 as a therapeutic target for PD but also provided experimental support for the "enteric pathology hypothesis". However, several key gaps remain unresolved in the study. At the gut microbiota level, the exploration of the causal relationship of the microbiota is insufficient, with no validation conducted via methods such as fecal microbiota transplantation; additionally, it fails to systematically integrate the gut-brain axis with PD and does not assess the impact of rhapontin on the composition or function of the gut microbiota. At the pathway mechanism level, it lacks an analysis of the crosstalk between NRF2 and other rhapontin-targeted pathways, including nuclear factor kappa-B, mitogen-activated protein kinase, adenosine monophosphate-activated protein kinase, and sirtuin 1. At the experimental method level, the behavioral testing methods for PD mouse models and the limitations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models need attention. Additionally, certain flaws exist in some experimental result figures. Furthermore, this commentary puts forward improvement suggestions for the study. Future research should prioritize multi-omics analysis, encompassing combined metabolomics and metagenomics detection, while conducting mechanistic validation of NRF2-interacting molecules (KEAP1 and p62). In addition, it is necessary to improve refined behavioral tests, focusing on incorporating cognitive function and anxiety-related assessment items.}, }
@article {pmid41641127, year = {2025}, author = {Rogalidou, M}, title = {Clostridioides difficile infection in pediatric inflammatory bowel disease: current understanding and clinical challenges.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1753289}, pmid = {41641127}, issn = {2296-2360}, abstract = {Clostridioides difficile infection (CDI) represents a significant and increasingly recognized complication in children with inflammatory bowel disease (IBD), contributing to prolonged hospitalization and risk of adverse outcomes. Children with IBD are particularly susceptible due to frequent antibiotic exposure, healthcare system contact, immunosuppressive therapy, and underlying gut dysbiosis, all of which promote colonization and toxin-mediated intestinal injury. Distinguishing CDI from an IBD flare is challenging, as gastrointestinal symptoms and systemic inflammation overlap, and asymptomatic toxigenic colonization is common. Management recommendations for pediatric IBD-associated CDI are largely extrapolated from adult studies, with prompt initiation of targeted antibiotics being critical. Immunosuppressive therapy is generally continued, with escalation considered if diarrhea persists despite CDI-directed therapy. Fecal microbiota transplantation (FMT) has emerged as a safe and promising option for recurrent CDI in children with IBD, although careful patient selection, donor choice, and timing remain crucial. Key challenges persist in differentiating true CDI from IBD flares, understanding the clinical impact of asymptomatic colonization, and optimizing microbiome-targeted interventions. Future research should prioritize biomarker-driven diagnosis, individualized therapeutic strategies, and longitudinal evaluation of microbiome-based treatments to improve outcomes in pediatric patients with concurrent CDI and IBD.}, }
@article {pmid41641369, year = {2026}, author = {Wang, N and Luo, L and Yang, X}, title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10876}, pmid = {41641369}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy/pathology ; *Dysbiosis/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Prebiotics ; *Eye/microbiology/pathology ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.}, }
@article {pmid41641458, year = {2025}, author = {Bai, H and Xu, Y and Qu, S and Li, B and Wang, X}, title = {The influence of the maternal microbiome on offspring neurodevelopment: a critical review of associations, controversies, and challenges.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1737795}, pmid = {41641458}, issn = {1662-4548}, abstract = {The role of the maternal microbiome in offspring neurodevelopment has become a prominent topic in neuroscience, yet its true causal status is under intense scrutiny. This critical review moves beyond conventional deconstructions of popular hypotheses in the field (e.g., "prenatal programming" "windows of opportunity") to challenge a more fundamental premise. We systematically argue that the currently observed associations along the "microbiota-gut-brain axis" may reflect complex confounding, with macroscopic social factors such as socioeconomic status (SES) being the true underlying drivers. The core thesis of this paper is that the maternal microbiome is, to a great extent, a "biological imprint" of the mother's living environment, diet, and stress levels-a highly sensitive "proxy" indicator acting as a biological mediator heavily shaped by the environment, rather than solely as an independent driver. By integrating evidence from social epidemiology, we contend that positioning the microbiome alongside factors like SES in a "flattened" network model is misleading. Instead, we propose a Hierarchical Causal Model where socioeconomic factors act as top-level "master regulators," systematically shaping all downstream biological processes, including the microbiome. Through a critical analysis of interventions such as Fecal Microbiota Transplantation (FMT) and vaginal seeding, this review further exposes the translational predicaments that arise from neglecting this hierarchical structure. Ultimately, this review advocates for a paradigm shift: from searching for a single "microbial panacea" to understanding the microbiome's true position within the socio-biological system, and proposes a conceptual framework for future research that is more aligned with real-world complexity and endowed with greater sociological imagination.}, }
@article {pmid41642353, year = {2026}, author = {Gholizadeh, P and Faghfuri, E}, title = {Reprogramming Gastric Cancer Therapy: A Microbiome-Guided Approach to Precision Oncology.}, journal = {Current microbiology}, volume = {83}, number = {3}, pages = {150}, pmid = {41642353}, issn = {1432-0991}, }
@article {pmid41642500, year = {2026}, author = {Wang, J and Xie, S and Li, Z and Jiang, S and Wang, Q and Qi, R}, title = {Dynamic changes in gut microbiota and identification of inflammation-associated biomarkers in high-fat diet-induced obese mice.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {3}, pages = {50}, pmid = {41642500}, issn = {1572-9699}, support = {U21A20245//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Gastrointestinal Microbiome ; Biomarkers ; *Obesity/microbiology/etiology ; *Inflammation/microbiology ; Male ; Mice, Obese ; Fecal Microbiota Transplantation ; Feces/microbiology ; Mice, Inbred C57BL ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {This study aimed to analyze the dynamic changes in gut microbiota during high-fat diet (HFD)-induced obesity in mice, investigate the transmissibility of obesity-associated inflammation via fecal microbiota transplantation (FMT), and identify key bacterial genera linked to inflammation. In experiment 1, 8 control group mice and 12 obese group mice were fed a normal diet (ND) and a HFD, respectively, and fecal samples were collected from six mice in each group at weeks 4, 8, and 12. The results showed that long-term HFD (12 weeks) significantly reduced the diversity and richness of the gut microbiota (p < 0.05). HFD significantly affected the composition of the gut microbiota during the experimental period, with an increase in the relative abundance of harmful bacteria genera such as Escherichia-Shigella and Proteus (p < 0.05). In experiment 2, the transmissibility of obesity-associated inflammation was validated through a fecal FMT experiment. The results indicated that the intestinal microbiota of obese mice increased the inflammation level of recipient mice (p < 0.05), and the composition of the intestinal microbiota in the obese recipient group was significantly affected by that in the obese donor group. Furthermore, correlation analysis revealed that the relative abundances of Proteus and Escherichia-Shigella were positively correlated with the levels of inflammatory factors in the serum and ileal tissue (p < 0.05), suggesting that these two bacterial genera may serve as potential pro-inflammatory biomarkers. This study revealed the dynamic changes in the gut microbiota during HFD-induced obesity, confirmed the critical role of the gut microbiota in the transmission of inflammation, and provided a new theoretical basis for the intervention of obesity-related diseases.}, }
@article {pmid41642539, year = {2026}, author = {Shenthilvel, RK and Umashankar, TA and Uvarajan, D and Mathuraj, M and Ravikumar, M}, title = {"Unfolding Parkinson's Disease Through the Microbiome-Gut-Brain Axis".}, journal = {Journal of molecular neuroscience : MN}, volume = {76}, number = {1}, pages = {25}, pmid = {41642539}, issn = {1559-1166}, mesh = {Humans ; *Parkinson Disease/microbiology/metabolism/therapy/pathology ; Animals ; *Gastrointestinal Microbiome ; *Brain/metabolism ; alpha-Synuclein/metabolism ; *Brain-Gut Axis ; }, abstract = {Parkinson's disease (PD) is a progressive and multifactorial neurodegenerative disorder primarily caused by the loss of dopaminergic neurons in the substantia nigra. This neuronal loss leads to characteristic motor symptoms such as tremors, rigidity, and slowness of movement. Although PD has long been regarded as a disorder originating in the brain, recent findings suggest that the gut-brain axis, the intricate communication network between the gastrointestinal tract and the central nervous system also plays an important role in the development and progression of PD. Interestingly, early non-motor symptoms such as constipation and other bowel irregularities often appear several years before the onset of motor symptoms, indicating that changes in gut function may precede and even contribute to neurodegeneration. The gut microbiota influences neuronal signaling, immune activity, and metabolic balance through neuroactive molecules such as neurotransmitters, short-chain fatty acids (SCFAs), and cytokines. In PD, microbial imbalance, intestinal barrier dysfunction, and chronic inflammation are closely linked to the misfolding and accumulation of α-synuclein (α-syn), which can spread from the gut to the brain through the vagus nerve in a prion-like manner. Current therapeutic approaches are increasingly exploring ways to restore gut microbial balance using probiotics, prebiotics, dietary interventions, fecal microbiota transplantation (FMT), and SCFA supplementation. These strategies not only aim to relieve symptoms but may also have the potential to slow disease progression. This review discusses the mechanisms through which the gut-brain axis contributes to PD, summarizes key clinical and preclinical findings, and highlights emerging gut-targeted therapeutic approaches.}, }
@article {pmid41643874, year = {2026}, author = {Liu, K and Ren, Y and Liu, Y and Zhang, Y}, title = {Scutellaria baicalensis Georgi and its active component scutellarin alleviate asthma in rats by modulating the gut microbiota-bile acid axis.}, journal = {Journal of ethnopharmacology}, volume = {362}, number = {}, pages = {121304}, doi = {10.1016/j.jep.2026.121304}, pmid = {41643874}, issn = {1872-7573}, mesh = {Animals ; *Glucuronates/pharmacology/therapeutic use/isolation &amp; purification ; *Asthma/drug therapy/microbiology/metabolism/physiopathology ; *Scutellaria baicalensis/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Apigenin/pharmacology/therapeutic use/isolation &amp; purification ; Male ; *Bile Acids and Salts/metabolism ; *Anti-Asthmatic Agents/pharmacology/isolation &amp; purification/therapeutic use ; Rats, Sprague-Dawley ; *Plant Extracts/pharmacology ; Rats ; Lung/drug effects ; Disease Models, Animal ; }, abstract = {The Complete Works of Jingyue recorded that Scutellaria baicalensis Georgi (SBG, Huangqin) cleared heat and relieved asthma from Ming Dynasty. SBG possesses a long history of medicinal use and has demonstrated efficacy in treating respiratory diseases. Building on these traditional applications, recent studies have reported its anti-asthmatic. Yet, it's unclear whether SBG improves asthma via gut microbiota modulation or which component is key.<br><br>AIM OF THE STUDY: This study established an asthma model and employed 16S rRNA sequencing and metabolomics approaches to investigate the active components and underlying mechanisms of SBG in the treatment of bronchial asthma through gut-lung axis.<br><br>MATERIALS AND METHODS: An innovative combined approach was employed, utilizing Ultra-high-performance liquid chromatography/Q/Q/Q Exactive HFX mass spectrometry (UHPLC-QE-MS), 16S rRNA sequencing, metabolomics, and molecular biology to analyze the effective components of SBG, the changes in gut microbiota, and the endogenous metabolic mechanisms involved in the improvement of bronchial asthma.<br><br>RESULTS: SBG and scutellarin reduced airway (Rrs) and elastic resistance (Ers) (P&#xa0;<&#xa0;0.05) in asthmatic rats, alleviated lung inflammation, and decreased serum IL-2 levels (P&#xa0;<&#xa0;0.05). They also mitigated mucosal damage and inflammatory infiltration, restoring colonic homeostasis and increasing beneficial gut bacteria. Multi-omics analysis suggested SBG acts through the bile acid pathway, modulating bile salt transformation, biosynthesis, and transport. Fecal microbiota transplantation (FMT) from treated rats to germ-free rats partially replicated the anti-asthma effects, indicating SBG and scutellarin inhibit asthma by up-regulating Bifidobacterium animalis. This bacterium produced cholic acid, especially when treated with SBG or scutellarin, showing anti-inflammatory and anti-allergic properties.<br><br>CONCLUSION: SBG and its core blood-absorbed component scutellarin augment Bifidobacterium animalis, stimulate cholic acid production, modulate the bile acid pathway, and alleviate pulmonary inflammation and allergic reactions, exerting anti-asthma effects.}, }
@article {pmid41644553, year = {2026}, author = {Wen, R and Xin, Y and Bao, S and Zhang, X and Wang, Q and Dang, Z and Zhou, Z and Wu, J and Song, D and Fu, L and Li, W and Niu, J and Wen, Y and Zhou, X and Han, M and Zhao, J}, title = {The gut microbiota mediates depression-like behaviors in mice with chronic Echinococcus multilocularis infection.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41644553}, issn = {2055-5008}, support = {NO. 32160181//National Natural Science Foundation of China/ ; 2022AAC02076//Ningxia Natural Science Found Project/ ; 2024BEG02028//Key research and development projects of the Ningxia Hui Autonomous Region/ ; }, mesh = {Animals ; *Echinococcus multilocularis/physiology ; *Depression/etiology/microbiology ; Mice ; Mice, Inbred BALB C ; *Echinococcosis/psychology/microbiology/complications ; Disease Models, Animal ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation ; Behavior, Animal ; Chronic Disease ; Metabolomics ; Metagenomics/methods ; Multiomics ; Chemokine CCL2 ; Interleukin-6 ; Male ; Hippocampus/pathology ; }, abstract = {Alveolar echinococcosis (AE), a chronic parasitic disease caused by Echinococcus multilocularis (E. multilocularis), remains poorly characterized with respect to central nervous system (CNS) involvement, and its long-term effects on mental health have not been systematically investigated. In this study, we established a BALB/c mouse model of chronic E. multilocularis infection and applied an integrative framework combining behavioral assessments, histomorphological analyses (hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy), cytometric bead array (CBA), and multi-omics approaches (16S rRNA sequencing, metagenomics, and untargeted metabolomics) to investigate infection-induced neuroimmune-gut microbiota interactions. Chronically infected mice exhibited pronounced depression-like behavioral phenotypes, accompanied by hippocampal neuronal nuclear membrane atrophy and disrupted microglial homeostasis. Both peripheral and central inflammatory profiling revealed elevated levels of pro-inflammatory mediators, particularly IL-6 and MCP-1, suggesting coordinated systemic immune activation and neuroimmune alterations. Notably, fecal microbiota transplantation (FMT) from infected donors was sufficient to induce depression-like behaviors in recipient mice, supporting a contributory role of infection-associated gut microbiota alterations in behavioral abnormalities. Integrated multi-omics analyses further revealed a marked reduction in Lactobacillus abundance in infected mice, which was positively correlated with decreased levels of key metabolites within the tryptophan/5-hydroxytryptamine (5-HT) metabolic pathway. Collectively, these findings suggest that chronic E. multilocularis infection may be associated with depression-like behaviors through gut microbiota dysbiosis and related metabolic perturbations. This study provides initial insights into the potential mechanisms underlying neuropsychiatric complications in AE and proposes a conceptual framework for future investigations into early intervention and microbiota-targeted therapeutic strategies.}, }
@article {pmid41644742, year = {2026}, author = {Ziogas, DC and Theocharopoulos, C and Martinos, A and Lyrarakis, G and Stefanou, D and Anastasopoulou, A and Gogas, H}, title = {Toward Microbiome-Informed Melanoma Care: The Gut Microbiota in Melanoma Evolution, Immunotherapy Response and Immune-Related Toxicity.}, journal = {Current oncology reports}, volume = {28}, number = {1}, pages = {10}, pmid = {41644742}, issn = {1534-6269}, mesh = {Humans ; *Melanoma/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immunotherapy/adverse effects/methods ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; Animals ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome (GM) has emerged as a pivotal modulator of melanoma pathogenesis and progression through its influence on systemic inflammation, immune surveillance, and antitumor immunity. Inter-individual variability in GM composition may underlie differences in immune checkpoint inhibitor (ICI) responsiveness and the development of immune-related adverse events (irAEs). This review aims to synthesize current knowledge on the complex interplay between the GM, host immunity, and melanoma, emphasizing its relevance to disease development, therapeutic response, and toxicity.<br><br>RECENT FINDINGS: Both preclinical and clinical evidence have demonstrated that alterations in microbial diversity and composition can affect melanoma outcomes. Depletion or imbalance of specific microbial taxa has been linked to an increased risk of melanoma development or, conversely, to reduced tumor burden. In patients treated with ICIs, distinct taxonomic GM signatures have been correlated with therapeutic efficacy and the likelihood of developing irAEs. Emerging studies have also explored strategies to modulate the GM-including diet, antibiotics, probiotics, and fecal microbiota transplantation-to restore gut "eubiosis" and enhance antitumor immune responses. The intricate crosstalk between the gut microbiome, host immunity, and melanoma significantly influences disease biology and treatment outcomes. A deeper understanding of these interactions will be critical to the development of microbiome-informed, personalized approaches to melanoma management and immunotherapy optimization.}, }
@article {pmid41644796, year = {2026}, author = {Krukowski, H and Valkenburg, S and Vich Vila, A and Maciel, LF and Vázquez-Castellanos, JF and Gryp, T and Joossens, M and Van Biesen, W and Verbeke, F and Derrien, M and Huys, GRB and Glorieux, G and Raes, J}, title = {Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function.}, journal = {Nature microbiology}, volume = {11}, number = {3}, pages = {664-677}, pmid = {41644796}, issn = {2058-5276}, support = {860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 101149152//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; }, mesh = {*Renal Insufficiency, Chronic/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Glomerular Filtration Rate ; Humans ; Feces/microbiology ; Dysbiosis/microbiology ; *Kidney/physiopathology ; Biomarkers ; Disease Progression ; Male ; Metagenomics ; Bacteria/classification/genetics/isolation &amp; purification ; Female ; }, abstract = {Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions.}, }
@article {pmid41645047, year = {2026}, author = {Thalib, HI and Fatima, N and Fakruddin, FH and Ali, HH and Khan, S and Zubair, MTM and Pereira, M and Sayed Hassan, FE}, title = {Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut-Brain Interactions and Immune Pathways: A Narrative Review.}, journal = {Brain and behavior}, volume = {16}, number = {2}, pages = {e71254}, pmid = {41645047}, issn = {2162-3279}, mesh = {Humans ; *Multiple Sclerosis/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology/physiology ; Animals ; *Dysbiosis/immunology ; *Brain-Gut Axis/immunology ; Probiotics ; Brain/metabolism/immunology ; }, abstract = {PURPOSE: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by progressive disability. Emerging evidence has implicated gut microbiome dysbiosis, characterized by decreased short-chain fatty acids (SCFAs)-producing taxa and increased pro-inflammatory species, in disturbed immune signaling, T-helper17/T-regulatory cells imbalance, disturbed tryptophan metabolism, and disrupted integrity of the blood-brain barrier. In this review, we summarize the mechanistic and therapeutic insights from studies that have explored the gut microbiome in MS.<br><br>METHOD: We performed a literature search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from database inception to January 2025; only English-language articles were included, comprising human MS cohorts and preclinical experimental autoimmune encephalomyelitis models. Of these, approximately 95 human and preclinical studies fulfilled the inclusion criteria. Evidence synthesis was narrative, without meta-analysis.<br><br>FINDING: There has been a consistent depletion of beneficial genera such as Faecalibacterium and Roseburia, expansion of Akkermansia muciniphila, and reduction in microbial metabolites such as butyrate, propionate, and neuroactive indole derivatives in MS patients across studies. These changes promote intestinal permeability, exaggerated pro-inflammatory cytokine responses, and microglial activation. The therapeutic approach of restoring microbial balance includes therapies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Early trials have shown modest improvements in relapse rates, fatigue, immune profiles, and microbiome composition. Results across randomized studies are heterogeneous, with no significant clinical benefit in several. Pilot trials report modest reductions in relapse rate (RR&#xa0;&#x2248;&#xa0;0.85) and fatigue (Cohen's&#xa0;d&#xa0;&#x2248;&#xa0;0.3), but several double&#x2011;blind RCTs showed no significant benefit (p&#xa0; >&#xa0; 0.05) in up to 40% of participants, highlighting variable effect sizes.<br><br>CONCLUSION: Interventions aimed at the microbiome are promising as adjunct approaches to the treatment of MS, acting principally through the restoration of SCFAs, immune modulation, and strengthening of the gut-brain axis. Larger, longer-term randomized trials are required to confirm clinical efficacy, define responder phenotypes, and inform personalized microbiome-based therapies.}, }
@article {pmid41645327, year = {2026}, author = {Zubair, A and Alkahtani, AM and Shahani, MY and Afghan, N}, title = {Gut microbiome-based strategies for HIV prevention and therapy, current challenges and future prospects.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {11}, pmid = {41645327}, issn = {1757-4749}, abstract = {The gut microbiome has become a primary controller of host immunity as well as the pathogenesis of human immunodeficiency virus (HIV) infection. Commensal microbes in healthy persons keep the intestinal and other body barriers intact and regulate mucosal and systemic immune responses and generate metabolites, including short-chain fatty acids and indole derivatives that suppress inflammation and stimulate epithelial healing. These functions are impaired by HIV infection via depletion of gut CD4 + T cells, damage caused to epithelium, microbial translocation, and microbiota disruption. In this review article, we summarize recent studies suggesting that a balanced microbiome can mitigate HIV susceptibility and progression by preserving mucosal defenses, limiting systemic immune activation, and generating antiviral compounds. Other interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), have been trialed with mixed outcomes in most cases, showing small but significant changes in the gut microbial composition and/or inflammatory markers. Current evidence highlights the potential of microbiome-targeted strategies to support HIV management; however, substantial gaps remain. Future research should focus on defining protective microbial signatures, developing next-generation live biotherapeutics, exploring metabolite-based therapies, and conducting large, mechanistically driven clinical trials. Harnessing the microbiome's protective functions could offer novel approaches to reducing HIV transmission, mitigating inflammation, and improving immune reconstitution in infected individuals.}, }
@article {pmid41646037, year = {2026}, author = {Syllaios, A and Papadakos, SP and Ioannou, A and Frountzas, M and Michelakis, D and Patsouras, D and Dritsas, S and Pramateftakis, MG and Schizas, D}, title = {Slow Transit Constipation: Pathophysiological Perspectives and Management Updates.}, journal = {Journal of digestive diseases}, volume = {27}, number = {1-2}, pages = {15-30}, pmid = {41646037}, issn = {1751-2980}, mesh = {Humans ; *Constipation/therapy/physiopathology/diagnosis/etiology ; *Gastrointestinal Transit/physiology ; Laxatives/therapeutic use ; Manometry ; Defecography ; }, abstract = {Slow transit constipation (STC) is a chronic colonic motility disorder characterized by markedly delayed transit, leading to reduced bowel movements, abdominal discomfort, and significant quality-of-life impairment. It predominantly affects women and is associated with abnormalities in enteric neuronal signaling, smooth muscle contractility, interstitial cells of Cajal, gut peptides, bile acid homeostasis, and autonomic regulation. Secondary causes of constipation and structural lesions must be excluded before the diagnosis of STC, with colonic transit studies serving as the gold standard. Complementary investigations such as anorectal manometry and defecography help detect coexisting outlet obstruction, which can alter management. The treatment of STC should follow a stepwise approach, beginning with dietary and lifestyle modification, osmotic and stimulant laxatives, and prokinetics such as prucalopride. Secretagogues and bile acid modulators may offer additional benefit. Biofeedback therapy is primarily indicated for overlapping dyssynergic defecation. For refractory STC, interventional therapies, such as fecal microbiota transplantation, acupuncture, sacral nerve stimulation, and transanal irrigation, are found to have equivocal outcomes. Antegrade continence enema procedures can be an alternative for patients unsuitable for colectomy. Surgical options, including subtotal colectomy with ileosigmoid or cecorectal anastomosis, and total colectomy with ileorectal anastomosis, are reserved for carefully selected patients with medically intractable symptoms, following thorough physiological evaluation. Although advances in understanding STC pathophysiology are guiding novel therapeutic development, robust randomized controlled trials remain scarce. Optimal care requires multidisciplinary collaboration between gastroenterologists, colorectal surgeons, and pelvic floor specialists to ensure accurate diagnosis, tailored treatment, and improved long-term outcomes.}, }
@article {pmid41646110, year = {2024}, author = {Kennedy, J and Iyer, K and Grinspan, A and Lai, J}, title = {Safe and successful fecal microbiota transplantation for recurrent Clostridioides difficile infection in a child with an intestinal transplant.}, journal = {Intestinal Failure (New York, N.Y.)}, volume = {4}, number = {}, pages = {100046}, pmid = {41646110}, issn = {2950-4562}, abstract = {Fecal microbiota transplantation (FMT) treats patients with recurrent Clostridioides difficile infections (CDI) by restoring the colonic flora with a balanced microbiome. There are currently no reports of safe and successful FMT in pediatric patients with history of intestinal transplant on immunosuppression. Our case report describes a 6-year-old boy with a multi-visceral transplant (including: stomach, small bowel, colon, liver, pancreas, and en-bloc bilateral kidneys) who had recurrent CDI episodes treated with antibiotics (including prolonged tapers). After multiple recurrences, he had a FMT via colonoscopy. The fecal preparation was inserted in the transplanted cecum without complication. The patient did well without any adverse events or need for hospitalization and the FMT was a success, as he had no recurrent symptoms in the 3 months following FMT.}, }
@article {pmid41647244, year = {2026}, author = {Zeng, L and Yang, Q and Luo, Y and Luo, Y and Sun, L}, title = {The Gut Microbiota: Emerging Evidence in Autoimmune and Inflammatory Diseases.}, journal = {Research (Washington, D.C.)}, volume = {9}, number = {}, pages = {1097}, pmid = {41647244}, issn = {2639-5274}, abstract = {Autoimmune diseases (AIDs) are a group of immune-related disorders primarily affecting joints and surrounding tissues, often marked by chronic inflammation and autoimmune activation. Common types include systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune cardiovascular diseases, and skin conditions. While their pathogenesis is unclear, recent studies suggest that abnormal gut microbiota may contribute. Previous research has shown that various patients with rheumatic disease exhibit altered gut microbiota, characterized by decreased microbial diversity, overall compositional changes, and microbiota-mediated functional alterations. Bacterial species closely associated with AIDs include Prevotella copri, Ruminococcus gnavus, and Ligilactobacillus salivarius. Dysregulated gut microbiota activates host immune responses through multiple mechanisms, including compromised intestinal barrier, systemic translocation, molecular mimicry of self-antigen epitopes, and changes in microbiota-derived metabolites, thereby substantially contributing to the development and progression of AIDs. Microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, are actively involved in driving disease progression. In addition, the therapeutic outcomes and adverse effects of immunotherapeutic agents can be modulated by gut microbiota through their impact on drug biotransformation processes. Clinically, analyzing gut microbiota characteristics can aid in disease diagnosis and prognosis prediction. Therapeutic strategies such as fecal microbiota transplantation, probiotics, prebiotics, and the Mediterranean diet may become effective measures for managing AIDs. This article reviews recent research progress, future directions, and the potential of microbiota-based interventions in treating AIDs.}, }
@article {pmid41648108, year = {2026}, author = {Martinez, NAP and Arnaldi, MR and Santiago-Rodriguez, TM and Rodriguez-Fernandez, IA}, title = {Microbiota-Based Interventions Differentially Rescue Gut and Social Behavior Phenotypes in a Drosophila Autism-like Model.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41648108}, issn = {2692-8205}, support = {P20 GM103642/GM/NIGMS NIH HHS/United States ; P30 GM149367/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a lifelong neurological and developmental disorder that has no cure and is often accompanied by gastrointestinal (GI) issues. The bidirectional communication system known as the gut microbiota-brain axis may help explain how GI dysfunction contributes to neurological symptoms. Loss-of-function mutations in the histone demethylases KDM5A, KDM5B or KDM5C are found in patients with intellectual disability and ASD. Previous studies using a Drosophila Kdm5 loss-of-function (Kdm5 [LOF]) ASD-like model revealed gut microbial dysbiosis, reduced abundance of Lactiplantibacillus plantarum, and impaired social behavior. While L. plantarum supplementation rescued intestinal abnormalities, it did not restore social behavior.<br><br>METHODS: Here, we evaluated multiple microbiota-based interventions, including probiotic supplementation with Lactiplantibacillus plantarum, Lactobacillus helveticus, their combination, and fecal microbiota transplantation (FMT), to determine their capacity to modulate gut microbial composition and behavior in Kdm5 [LOF] flies. Gut bacterial abundance was quantified using colony-forming unit (CFU) assays and full-length 16S rRNA gene sequencing. Social behavior was assessed using the social distance assay, while anxiety-like behavior and locomotion were evaluated using the open field test. Gut-specific Kdm5 knockdown was used to assess tissue-specific contributions to microbiota and behavioral phenotypes.<br><br>RESULTS: Kdm5 deficiency resulted in reduced abundance of culturable Lactobacillus, Acetobacter, and Enterobacter species, accompanied by impaired social behavior. L. plantarum supplementation restored gut microbial abundance in both whole-body Kdm5 [LOF] and gut-specific Kdm5 knockdown models but did not significantly rescue social behavior. In contrast, L. helveticus significantly improved social interaction in Kdm5 [LOF] flies despite minimal effects on gut bacterial abundance, revealing a dissociation between microbial restoration and behavioral outcomes. Gut-specific Kdm5 knockdown phenocopied both microbial and social defects observed in Kdm5 [LOF] mutants. Notably, FMT from healthy donors partially restored Lactobacillus abundance, reshaped gut microbial community structure, and partially improved social behavior in Kdm5 [LOF] recipient flies.<br><br>CONCLUSIONS: Together, these findings identify Kdm5 as a key regulator of gut microbial viability and social behavior and demonstrate that microbiota-based interventions exert strain- and phenotype-specific effects. Our results reveal that restoration of microbial abundance alone is insufficient to rescue social behavior and highlight the importance of functional host-microbe interactions in gut-brain communication. This work establishes Drosophila as a tractable platform for dissecting epigenetic regulation of microbiota-behavior relationships relevant to ASD and for evaluating targeted probiotic and microbiota-transfer strategies.}, }
@article {pmid41649412, year = {2026}, author = {Ishnaiwer, M and Dion, M and Montassier, E and Le Bastard, Q and Batard, E}, title = {Evaluation of Escherichia coli as a prophylactic treatment of intestinal colonization by extended-spectrum beta-lactamase-producing E. coli in a murine model of antibiotic-induced dysbiosis.}, journal = {Journal of applied microbiology}, volume = {137}, number = {3}, pages = {}, doi = {10.1093/jambio/lxag041}, pmid = {41649412}, issn = {1365-2672}, mesh = {Animals ; *Escherichia coli/enzymology/physiology/genetics ; *Dysbiosis/microbiology/chemically induced/prevention &amp; control ; Mice ; *beta-Lactamases/metabolism ; *Anti-Bacterial Agents/adverse effects ; Feces/microbiology ; *Intestines/microbiology ; Disease Models, Animal ; *Escherichia coli Infections/prevention &amp; control/microbiology ; Female ; }, abstract = {BACKGROUND: Intestinal colonization by multidrug-resistant Enterobacteriaceae represents a major public health concern as it can lead to difficult-to-treat infections, environmental contamination, and transmission. This study evaluated the efficacy of a prophylactic treatment using Escherichia coli strains isolated from murine feces [commensal E. coli (comEc)] to reduce intestinal colonization by extended-spectrum beta-lactamase (ESBL)-producing E. coli in a murine model of antibiotic-induced dysbiosis.<br><br>METHODS AND RESULTS: The comEc treatment was administered intragastrically 1 day prior to ESBL-producing E. coli challenge. Colonization levels were monitored daily using culture-based quantification. Fecal microbiota composition was analyzed before the ESBL-producing E. coli challenge to identify predictors of treatment efficacy. The comEc treatment significantly reduced mean ESBL-producing E. coli levels during the first four days. Notably, 14% of treated mice exhibited marked and sustained decolonization, whereas others had only a limited and transient effect.<br><br>CONCLUSION: In this proof-of-concept study, prophylactic treatment with murine-derived E. coli strains transiently reduced fecal ESBL-producing E. coli titers, although pronounced efficacy was observed in a small subset of animals.}, }
@article {pmid41651073, year = {2026}, author = {Liu, YZ and Cui, XF and Mao, SY}, title = {Effect of Gut Microbiota from Patients with Uremia on Body Weight and Microinflammation in Rats.}, journal = {The Journal of nutrition}, volume = {156}, number = {5}, pages = {101397}, doi = {10.1016/j.tjnut.2026.101397}, pmid = {41651073}, issn = {1541-6100}, mesh = {Animals ; *Uremia/microbiology ; Humans ; *Inflammation/microbiology ; *Gastrointestinal Microbiome ; Rats ; Male ; *Body Weight ; Fecal Microbiota Transplantation ; Dysbiosis ; Feces/microbiology ; Middle Aged ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic/microbiology ; Nutritional Status ; }, abstract = {BACKGROUND: Gut dysbiosis is associated with malnutrition and inflammation in chronic kidney disease (CKD); however, the causality remains unclear.<br><br>OBJECTIVES: This study aimed to determine whether fecal microbiota from patients with stage 5 CKD can directly induce nutritional impairment and inflammatory responses in recipient rats.<br><br>METHODS: Fecal microbiota from patients with stage 5 CKD and healthy controls were transplanted into rats treated with antibiotics. After 2 weeks, we assessed nutritional parameters, inflammatory markers, and microbial composition.<br><br>RESULTS: Compared with the healthy-fecal microbiota transplantation (FMT) group, rats receiving CKD-derived microbiota exhibited a significant reduction in body weight (466.70 &#xb1; 12.60 g compared with 433.90 &#xb1; 20.10 g) and serum albumin concentrations (22.87 &#xb1; 5.43 g/L compared with 20.36 &#xb1; 7.51 g/L). In contrast, serum inflammatory markers were significantly elevated in the CKD-FMT group, including C-reactive protein (12.10 &#xb1; 3.10 mg/L compared with 15.40 &#xb1; 5.00 mg/L) and interleukin-6 (14.30 &#xb1; 1.80 pg/L compared with 18.80 &#xb1; 2.10 pg/L) (all P < 0.05). Microbial analysis revealed enrichment of Enterobacteriaceae and depletion of beneficial genera such as Lactobacillus and Ruminococcaceae.<br><br>CONCLUSIONS: Our results provide direct evidence that gut microbiota from patients with uremia can impair nutritional status and aggravate systemic inflammation in recipient rats, underscoring a pathogenic role of dysbiosis in CKD complications.}, }
@article {pmid41651994, year = {2026}, author = {Huang, S and Yu, S and Zhang, W and Qi, D and Pei, X and Lu, D and Ba, M and Xuan, S and Huang, D and Yang, J and Li, Z}, title = {Sleep deprivation disrupts lacrimal gland homeostasis via hypothalamic-pituitary-adrenal axis and gut dysbiosis in mice.}, journal = {Communications biology}, volume = {9}, number = {1}, pages = {}, pmid = {41651994}, issn = {2399-3642}, support = {82101089//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Lacrimal Apparatus/metabolism/pathology/physiopathology ; *Hypothalamo-Hypophyseal System/metabolism ; Male ; *Homeostasis ; Mice ; *Pituitary-Adrenal System/metabolism ; *Sleep Deprivation/physiopathology/complications ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Interleukin-17/metabolism ; }, abstract = {Sleep deprivation (SD) disrupts systemic homeostasis, but how it drives ocular surface disease remains unclear. Using a male mouse SD model, we show that chronic SD activates the hypothalamic-pituitary-adrenal (HPA) axis, elevates corticosterone, alters gut microbiota, and depletes short-chain fatty acids (SCFAs). These alterations coincide with lacrimal gland atrophy, reduced tear secretion, and increased CD4[+]/CD8[+] T cell infiltration, accompanied by activation of IL-17-associated inflammatory pathways. Pharmacological inhibition of glucocorticoid synthesis with metyrapone preserves lacrimal gland structure and function while attenuating immune activation. Microbiome-directed interventions, including SCFA supplementation and fecal microbiota transplantation, rebalance gut communities, suppress pro-inflammatory T cell responses, and maintain lacrimal gland homeostasis. Transcriptomic and immunohistochemical analyses further reveal that all three interventions converge on the downregulation of IL-17 signaling. Collectively, these findings establish an HPA-gut microbiome-lacrimal gland axis that links neuroendocrine stress to microbial dysbiosis and ocular inflammation, and they suggest therapeutic strategies for SD-associated lacrimal gland dysfunction.}, }
@article {pmid41652876, year = {2026}, author = {Wang, Z and Guo, S and Sun, M and Zhu, Y and Gong, P and Yao, W}, title = {Chlorogenic Acid Ameliorates Lipid Metabolism Disorders via Gut Microbiota-Serum Metabolite-Liver Axis in High-Fat Diet-Induced Obesity.}, journal = {Phytotherapy research : PTR}, volume = {40}, number = {4}, pages = {2041-2060}, doi = {10.1002/ptr.70259}, pmid = {41652876}, issn = {1099-1573}, support = {//Fundamental Research Funds for the Central Universities/ ; 2024KF06//Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology/ ; 2024SF-GJHX-08//Key Projects of Shaanxi Provincial-Core Technology Breakthroughs-Social Development Field/ ; 2024NC2-GJHX-25//Key Projects of Shaanxi Provincial-Core Technology Breakthroughs-Agriculture and Rural Field/ ; }, mesh = {Animals ; *Obesity/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Liver/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice ; Male ; Mice, Inbred C57BL ; *Chlorogenic Acid/pharmacology ; *Lipid Metabolism/drug effects ; *Lipid Metabolism Disorders/drug therapy/metabolism ; Fecal Microbiota Transplantation ; Metabolomics ; }, abstract = {Obesity is a global metabolic disorder in which gut microbiota has emerged as a pivotal regulator. Chlorogenic acid (CGA) has been reported to improve lipid metabolism and mitigate obesity; however, its microbiota-mediated mechanisms remain unclear. Here, we established a diet-induced obesity (DIO) mouse model by high-fat diet feeding and integrated serum metabolomics, liver transcriptomics, and fecal microbiota transplantation (FMT) to elucidate the effects of CGA. CGA supplementation alleviated obesity-related phenotypes, reduced intestinal inflammation, and preserved mucosal barrier integrity, thereby restoring microbial homeostasis. Combined 16S rRNA sequencing and untargeted metabolomics revealed that CGA reshaped gut microbiota (suppressing Desulfovibrio and Allobaculum, enriching Oscillospira), accompanied by altered serum metabolites (elevated linoleic acid, reduced hexadecanoic and tetradecanoic acids). Transcriptomic analysis demonstrated that CGA downregulated genes related to hepatic lipid synthesis (FASN, ACACA, SCD1) and lipid uptake (FABP4, SCP2, CD36), which was further validated by qRT-PCR. Importantly, FMT from CGA-treated mice reproduced the metabolic improvements, confirming that the beneficial effects of CGA are closely associated with gut microbiota modulation. Collectively, these findings indicate that CGA ameliorates obesity through modulation of the gut microbiota-serum metabolite-liver axis.}, }
@article {pmid41653982, year = {2026}, author = {McCafferty, CE and Townsend, JO and Bacchi, SD and Jensen, SO}, title = {Protocols for decolonisation of carbapenem-resistant Enterobacterales and vancomycin-resistant enterococci: a systematic review and meta-analysis.}, journal = {The Journal of hospital infection}, volume = {170}, number = {}, pages = {184-196}, doi = {10.1016/j.jhin.2026.01.017}, pmid = {41653982}, issn = {1532-2939}, mesh = {Humans ; *Vancomycin-Resistant Enterococci/isolation &amp; purification ; *Carbapenem-Resistant Enterobacteriaceae ; *Gram-Positive Bacterial Infections/therapy/microbiology ; *Enterobacteriaceae Infections/therapy/microbiology ; Anti-Bacterial Agents ; *Carrier State/microbiology/therapy ; Carbapenems/pharmacology ; }, abstract = {BACKGROUND: Rises in the prevalence of multi-drug-resistant organisms threaten patient safety globally. Vancomycin-resistant enterococci (VREs) and carbapenem-resistant Enterobacterales (CRE) are linked with prolonged hospitalisation, treatment failure, and increased mortality. Decolonisation strategies could reduce transmission and improve outcomes, but their efficacy and safety remain uncertain. This study systematically evaluates decolonisation protocols for VRE and CRE through a meta-analysis.<br><br>METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review and meta-analysis were performed on studies using PubMed, ScienceDirect, Web of Science, and Scopus. Studies evaluating decolonisation protocols for VRE and CRE were included. Papers were assessed for risk of bias using the Risk of Bias 2 tool and Newcastle-Ottawa Scale. Meta-analyses were performed using RevMan, Cochrane, London, United Kingdom.<br><br>RESULTS: Sixteen studies with a total of 872 participants were included for meta-analysis. Faecal microbiota transplantation (FMT) significantly improved clearance of CRE (risk ratio [RR]: 2.01; 95% confidence interval [CI]: 1.27-3.18) and VRE (RR: 2.96, 95% CI: 1.60-5.47) compared with controls, with low to moderate heterogeneity. Selective digestive decontamination (SDD) significantly increased clearance of CRE (RR: 2.47, 95% CI: 1.32-4.63), but not VRE (RR: 1.52, 95% CI: 0.70-3.30). Adverse events were generally mild, but SDD was associated with increased antimicrobial resistance in several studies.<br><br>CONCLUSIONS: FMT and SDD are promising interventions for CRE decolonisation, with FMT also showing benefit in VRE. The durability of SDD effects appears limited, with significant risk of promoting resistance. Future studies should standardise endpoints, evaluate combination approaches, and explore bacteriophage therapy. We suggest implementing uniform terminology with 'provisional clearance' as a descriptor for eradication at 1 month post intervention and 'enduring clearance' following continuous eradication for 6 months.}, }
@article {pmid41654223, year = {2026}, author = {Fondevila, MF and Kreimeyer, H and Hsu, CL and Tamargo-Azpilicueta, J and Day, LZ and Gritsenko, M and Attah, K and Cabré, N and Harberts, A and Tonetti, FR and Yang, Y and Yamazaki, T and Schöler, D and Eguileor, A and Blasio, C and Meijnikman, AS and Zhang, X and Garcia-Carbonell, R and Hook, V and Zhou, E and Sun, Z and Jacobs, JM and Turner, JR and Llorente, C and AlcHepNet Investigators,  and Glass, CK and Stärkel, P and Reinheckel, T and Diaz-Moreno, I and Gonzalez, DJ and Schnabl, B}, title = {Macrophage-derived cathepsin B disrupts intestinal tight junctions through occludin degradation and promotes alcohol-associated liver disease.}, journal = {Journal of hepatology}, volume = {84}, number = {6}, pages = {1045-1061}, pmid = {41654223}, issn = {1600-0641}, support = {R21 GM144801/GM/NIGMS NIH HHS/United States ; R21 AA030654/AA/NIAAA NIH HHS/United States ; R01 DK061931/DK/NIDDK NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R00 AA031328/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; *Cathepsin B/metabolism/antagonists &amp; inhibitors ; *Occludin/metabolism ; Humans ; Mice ; *Tight Junctions/metabolism ; *Macrophages/metabolism ; Male ; Mice, Transgenic ; Intestinal Barrier Function ; Intestinal Mucosa/metabolism ; Feces/chemistry ; Female ; *Liver Diseases, Alcoholic/metabolism ; *Hepatitis, Alcoholic/metabolism ; Ethanol ; Proteomics ; }, abstract = {BACKGROUND &amp; AIMS: Disruption of the intestinal barrier facilitates microbial translocation to the liver and contributes to chronic liver disease. We aimed to study the role of the fecal proteome in disease progression in patients with alcohol-associated hepatitis.<br><br>METHODS: We used fecal proteomics data from a multicenter cohort of patients with alcohol-associated hepatitis (n = 80), alcohol use disorder (n = 20), and controls (n = 19) (InTeam), and a cathepsin B activity assay in an independent multicenter cohort of patients with alcohol-associated hepatitis (n = 80), alcohol use disorder (n = 20), and controls (n = 18) (AlcHepNet). Mice lacking cathepsin B in myeloid cells and transgenic mice overexpressing occludin in intestinal epithelial cells, were subjected to the chronic-plus-binge ethanol feeding model (NIAAA).<br><br>RESULTS: Fecal proteomics and activity analysis revealed that the protease cathepsin B progressively increased with alcohol use disorder and alcohol-associated hepatitis compared to controls, and is associated with higher short-term mortality in patients with alcohol-associated hepatitis. Cathepsin B is predominantly expressed in intestinal macrophages and is upregulated by ethanol. Cathepsin B deficiency in myeloid cells or oral treatment with the gut-restricted cathepsin B inhibitor CA074 stabilized the gut barrier by preserving the tight junction protein occludin, lowered serum lipopolysaccharide levels, and attenuated ethanol-induced steatohepatitis. Transgenic overexpression of occludin in intestinal epithelial cells sufficed to reduce steatohepatitis and blunted the effects of CA074 in ethanol-fed mice. Cathepsin B proteolytically cleaves occludin in enzymatic assays, and its inhibition prevented occludin degradation and barrier disruption in intestinal organoids and epithelial monolayers. Molecular modeling and peptide profiling reveal specific cathepsin B-induced cleavage sites in the extracellular region of occludin.<br><br>CONCLUSIONS: Intestinal cathepsin B is an essential mediator of gut barrier dysfunction and a potential therapeutic target in alcohol-associated liver disease.<br><br>IMPACT AND IMPLICATIONS: Intestinal barrier disruption facilitates microbial translocation to the liver, contributing to the progression of alcohol-associated liver disease; however, the molecular mechanisms driving barrier dysfunction remain incompletely understood. Our study identifies the protease cathepsin B as a key contributor to alcohol-associated liver disease progression by degrading the extracellular region of the tight junction protein occludin in the intestine, thereby leading to barrier disruption. This work advances the field by establishing causality, uncovering the molecular target, and proposing cathepsin B as a promising therapeutic target in alcohol-associated hepatitis - a condition for which liver transplantation remains the only effective treatment in a limited subset of patients.}, }
@article {pmid41655800, year = {2026}, author = {Zhu, J and Yang, L and Fang, Z and Chen, J and Fu, R and Liu, S and Chen, M}, title = {Xin-Jia-Tong-Xie-Yao-Fang restores the intestinal barrier to alleviate irritable bowel syndrome via microbial butyrate mediated PI3K/Akt pathway suppression.}, journal = {Microbial pathogenesis}, volume = {213}, number = {}, pages = {108344}, doi = {10.1016/j.micpath.2026.108344}, pmid = {41655800}, issn = {1096-1208}, mesh = {Humans ; Animals ; *Irritable Bowel Syndrome/drug therapy/microbiology ; Intestinal Barrier Function/drug effects ; *Signal Transduction/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/administration &amp; dosage/chemistry ; Caco-2 Cells ; *Butyrates/metabolism ; Mice ; Intestinal Mucosa/drug effects ; Tandem Mass Spectrometry ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Male ; Feces/chemistry/microbiology ; }, abstract = {BACKGROUND: Xin-Jia-Tong-Xie-Yao-Fang (XJTXYF) is a proven prescription for managing diarrhea-predominant irritable bowel syndrome (IBS-D), which is a prevalent functional gastrointestinal disorder. However, the underlying mechanism of XJTXYF remains unclear. This study aims to explore the material basis and potential mechanisms of XJTXYF against IBS-D.<br><br>METHODS: The constituents of XJTXYF were identified by UPLC-Q-TOF-MS/MS, and potential targets and pathways were screened by network pharmacology. Changes in the intestinal microbiome and fecal butyric acid levels after XJTXYF administration were analyzed through 16S rRNA sequencing and HPLC respectively. The abdominal withdrawal reflex score, serum levels of FITC-D and the expression of intestinal epithelial tight junction proteins, as well as the activity of the PI3K/Akt pathway were assessed. In-vitro experiments involved silencing GPR109A using small interfering RNA and inducing barrier damage with LPS pre-treatment in the Caco-2&#x202f;cell line. Barrier function was evaluated by FITC-D permeability and tight junction protein expressions. The activity of the PI3K/Akt pathway was determined through Western blotting analysis.<br><br>RESULTS: The major active compounds of XJTXYF identified by UPLC-Q-TOF-MS/MS include Saikosaponin C, Hesperetin, Neohesperidin, Albiflorin, Quercetin and so on. The PI3K/Akt signaling pathway was predicted by network pharmacology as a potential target of XJTXYF in treating IBS-D. Animal experiments demonstrated that XJTXYF could increase body weight, improve visceral hypersensitivity, rebalance gut flora dysbiosis and upregulate fecal butyric acid content in IBS mice. The XJTXYF also showed the abilities of intestinal barrier repairment and PI3K/Akt pathway suppression. Fecal microbiota transplantation and the positive controls (NaB and Clostridium Butyricum) verified that a causal relationship existed between gut microbiome changes and IBS-D improvement after XJTXYF treatment. In-vitro experiments revealed the role of butyrate in barrier protection via PI3K/Akt inhibition.<br><br>CONCLUSION: Overall, in this study, we revealed that XJTXYF could restore intestinal barrier function through microbial butyrate mediated PI3K/Akt inhibition and improve IBS-D symptoms.}, }
@article {pmid41657853, year = {2026}, author = {Ayivi-Tosuh, SM and Dofuor, AK and Yamoah, JAA and Gayi, BK and Aiduenu, AF and Akomea, A and Anovunga, SA and Ekloh, W and Basing, LA}, title = {Gut-Microbiome Interactions: Characterization, Therapeutic Implications and Machine Learning.}, journal = {Sage open pathology}, volume = {19}, number = {}, pages = {30502098251415109}, pmid = {41657853}, issn = {3050-2098}, abstract = {The gut microbiome is vital in maintaining overall health, yet its complexity and dynamic interactions are still not fully understood. This diverse microbial community comprises bacteria, viruses, fungi, and archaea, contributing to metabolism, immune regulation, and disease susceptibility. However, imbalances in the gut microbiome (dysbiosis), have been linked to various diseases, underscoring the importance of understanding microbial interactions within the gut ecosystem. This review explores these interactions, focusing on biochemical and molecular mechanisms that shape microbial behavior and function. Additionally, it examines the therapeutic potential of the gut microbiome, particularly its involvement in disease progression, prevention, and treatment. The role of medicinal plants in influencing gut microbial composition is also discussed, given their potential to support microbiome health. Lastly, it highlights the integration of machine learning in microbiome research, offering new insights into microbial interactions, predictive disease modeling, and personalized medicine. By addressing these key areas, this review aims to deepen our understanding of gut-microbiome dynamics and their implications for human health and disease management.}, }
@article {pmid41658610, year = {2026}, author = {Bautista, J and Bedón-Galarza, R and Martínez-Hidalgo, F and Masache-Cruz, M and Benítez-Núñez, M and Valencia-Arroyo, C and López-Cortés, A}, title = {Decoding the microbial blueprint of pancreatic cancer.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1737582}, pmid = {41658610}, issn = {2296-858X}, abstract = {Pancreatic cancer (PC) represents one of the most formidable challenges in oncology, characterized by its asymptomatic onset, delayed clinical detection, and dismal prognosis. Among pancreatic neoplasms, pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of cases and remains the most aggressive form, driven by late diagnosis, intrinsic chemoresistance, and a profoundly immunosuppressive tumor microenvironment. Recent advances have reframed the human microbiome not as a passive bystander but as an active architect of pancreatic tumor biology. This review delineates the mechanistic axes through which microbial ecosystems orchestrate PDAC progression across four key anatomical niches-gastrointestinal, oral, urogenital, and intrapancreatic. We elucidate how microbial dysbiosis fosters oncogenesis through immune evasion, metabolic reprogramming, and chronic inflammation, implicating specific taxa such as Fusobacterium nucleatum, Malassezia spp., and Porphyromonas gingivalis in immune suppression and chemoresistance. Microbial enzymatic inactivation of gemcitabine and modulation of cytokine networks further underscore the microbiome's pivotal role in therapeutic failure. Conversely, commensal and probiotic species may potentiate immunosurveillance and enhance treatment efficacy. This review also explores microbiota-derived biomarkers for early detection and the translational promise of microbiome-targeted interventions, including fecal microbiota transplantation, probiotics, and selective antibiotics. By decoding the microbial blueprint of PC, we propose a paradigm in which the microbiome emerges as both a biomarker and a therapeutic axis, offering novel avenues for precision oncology. Furthermore, this integrative synthesis emphasizes the multi-omic, immunometabolic, and therapeutic dimensions of the pancreatic cancer-microbiome interface, where metagenomic, transcriptomic, metabolomic, and immunomic layers converge to shape tumor evolution and therapeutic response, advancing the vision of microbiome-informed precision oncology.}, }
@article {pmid41659330, year = {2025}, author = {Wu, H and Wei, G and Huang, S and Wan, L and Xu, Q and Huang, C}, title = {The gut-brain axis mediates precocious puberty induced by environmentally relevant low-dose endocrine-disrupting chemical mixtures.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1728811}, pmid = {41659330}, issn = {1664-2392}, mesh = {*Endocrine Disruptors/toxicity/adverse effects ; *Puberty, Precocious/chemically induced/pathology ; Humans ; Animals ; *Brain-Gut Axis/drug effects ; *Gastrointestinal Microbiome/drug effects ; Female ; Dysbiosis/chemically induced ; *Environmental Exposure/adverse effects ; *Brain/drug effects ; }, abstract = {BACKGROUND: The global rise in precocious puberty (PP) is increasingly linked to exposure to endocrine-disrupting chemicals (EDCs). However, the mechanisms by which environmentally relevant, low-dose mixtures of EDCs influence PP remain inadequately explained by direct endocrine disruption.<br><br>OBJECTIVE: This systematic review evaluates a novel hypothesis: that disruption of the gut-brain axis (GBA) serves as a pivotal mechanism in EDC mixture-induced PP.<br><br>METHODS: We synthesized evidence from 87 studies (45 human, 32 animal, 10 in vitro) following PRISMA 2020 guidelines. An exploratory Random Forest analysis was employed to identify key mediators and estimate the relative contribution of the GBA pathway.<br><br>RESULTS: Perinatal exposure to low-dose EDC mixtures consistently induced gut dysbiosis, characterized by reduced microbial diversity (Shannon &#x394; = -1.8), a 40% decrease in Lactobacillus, and a 1.5-fold increase in Bacteroides. This dysbiosis was linked to impaired production of butyrate (&#x2193;50%) and secondary bile acids, increased intestinal permeability (FITC-dextran &#x2191;80%), and systemic inflammation (IL-6 &#x2191;1.8-fold). Fecal microbiota transplantation from PP donors into germ-free mice recapitulated early pubertal onset, supporting a causal role for gut microbiota. Exploratory modeling suggested that mediators within the GBA pathway could be associated with a large share (approximately 68%) of the model-internal variance explanation for PP risk at low experimental doses (&#x2264;1 &#x3bc;g/kg/day), indicating its potential prominence over direct endocrine disruption in this analysis. Significant synergistic effects (Synergy Index > 2.3) were observed under mixture exposures.<br><br>CONCLUSION: This review identifies the GBA as a critical and previously underappreciated mechanism for low-dose EDC mixture-induced precocious puberty in a dose-dependent manner. Our findings underscore the need for regulatory paradigms and future research to integrate this pathway when assessing the risks of complex, real-world chemical mixtures.}, }
@article {pmid41659429, year = {2026}, author = {Vallecillo-Zuniga, ML and Akeefe, A and Brown, DG and Wahlig, TA and Marchetti, M and Heiner, T and Davis, KL and Nieznanski, C and Flynn, A and Leung, DT}, title = {Longitudinal Changes in Nasal and Oral Microbiome and Antimicrobial Resistance Gene Profiles in Response to Human Fecal Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41659429}, issn = {2692-8205}, support = {UM1 TR004409/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; S10 OD034321/OD/NIH HHS/United States ; T32 HG008962/HG/NHGRI NIH HHS/United States ; S10 OD021644/OD/NIH HHS/United States ; T32 HL105321/HL/NHLBI NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; }, abstract = {The gut-lung axis describes interactions between intestinal and respiratory mucosal systems through microbial, metabolic, and immune pathways, but the systemic impact of gut-targeted therapies on upper respiratory tract (URT) communities remains underexplored. We conducted a longitudinal study in adult patients undergoing fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) alongside healthy controls. Fecal, nasal, and oral samples were collected at baseline (Day 0) and on Days 14 and 56 following FMT. Shotgun metagenomic sequencing was performed to quantify microbial diversity, taxonomic composition, and the abundance of antimicrobial resistance genes (ARGs). FMT was associated with increased gut diversity and decreased levels of key intestinal taxa commonly considered pathobionts, including Klebsiella spp., Escherichia spp., Shigella spp., and Klebsiella pneumoniae. At the phylum level, fecal Bacteroidota increased, while Mucoromycota decreased following treatment. Post-FMT nasal microbiome changes included reduced richness and diversity, expansion of Moraxella, and decreases in taxa linked with respiratory colonization, including Staphylococcus aureus and Streptococcus pneumoniae. By Day 56, nasal communities partially recovered toward healthy profiles. Baseline nasal ARG abundance decreased following FMT, particularly among β-lactam, aminoglycoside, and fluoroquinolone resistance genes, and remained comparable to healthy controls by Day 56. In contrast, the oral microbiome and oral resistome remained largely stable, with only minor fluctuations, and no consistent increases in respiratory pathobiont-associated taxa. In summary, FMT was associated with broader effects beyond the gut, including changes in the URT microbial ecology and antimicrobial resistance profiles. Together, these findings are consistent evidence of gut-lung microbial interactions, linking intestinal dynamics with respiratory microbial composition and antimicrobial resistance patterns.}, }
@article {pmid41660243, year = {2026}, author = {Ding, Y and Chen, X and Tao, Y and Dong, H and Zhang, Z and Xiao, X and Chen, G and Li, X and Xie, R}, title = {Gut-lung axis perturbation and Bifidobacterium potential after spinal cord injury in humans and mice.}, journal = {iScience}, volume = {29}, number = {2}, pages = {114655}, pmid = {41660243}, issn = {2589-0042}, abstract = {Spinal cord injury (SCI) predisposes patients to severe respiratory complications. Integrating clinical observations with a mouse model, we identified gut-lung axis perturbation as a key mechanism. SCI increased the similarity between gut and lung microbial communities, consistent with cross-compartment convergence driven by intestinal dysbiosis. Fecal microbiota transplantation from SCI donors reproduced this convergence in healthy recipients. Crucially, oral Bifidobacterium supplementation restored intestinal community structure, reduced gut-lung similarity, and attenuated pulmonary inflammation following an Escherichia coli challenge. These findings indicate that SCI disrupts gut-lung compartmentalization and that augmenting beneficial gut taxa mitigates downstream pulmonary consequences. Microbiota-targeted strategies therefore warrant evaluation as adjuncts to reduce post-SCI respiratory risk.}, }
@article {pmid41660969, year = {2026}, author = {Bautista, J and Bazantes-Rodríguez, E and Cedeño, H and Anrango-Flores, C and Carrera-Cruz, F and Cisneros-Nieto, Z and López-Cortés, A}, title = {Reprogramming human health through the microbiome and precision medicine.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/1040841X.2026.2629269}, pmid = {41660969}, issn = {1549-7828}, abstract = {The human microbiome, comprising trillions of microorganisms across multiple body sites, is increasingly recognized as a key contributor to host immunity, metabolism, and neurobiology, influencing development and disease susceptibility throughout life. Rather than acting in isolation, microbial communities operate within a complex host-environment system shaped by genetics, diet, lifestyle, and medical exposures. Conceptually, the microbiome can be understood as part of a host-microbe meta-organism and, from a translational perspective, as a dynamic and potentially modifiable organ system. While short-term perturbations such as antibiotics may transiently disrupt microbial ecosystems, persistent maladaptive configurations, commonly termed dysbiosis, are associated with metabolic disease, chronic inflammation, neurodevelopmental disorders, and cancer, although causality remains context dependent. This review synthesizes the functional roles of beneficial microbes and their metabolites, the mechanistic and clinical implications of dysbiosis, and immune pathways shaped by microbial signals. We further discuss emerging therapeutic strategies, including dietary modulation, probiotics, engineered microbial consortia, postbiotics, and fecal microbiota transplantation, enabled by multi-omics technologies, organoid models, and computational frameworks. Key challenges include defining context-specific microbial health, ensuring durable engraftment, and addressing regulatory and ethical considerations. Framing the microbiome as a dynamic component of host physiology provides a foundation for microbiome-guided precision and preventive medicine.}, }
@article {pmid41662314, year = {2026}, author = {van der Sligte, NE and Biedermann, L and Rogler, G and Scharl, M}, title = {Outcomes of Fecal Microbiota Transfer in Patients with Recurrent Clostridioides Difficile Infection: Real-World Data from a Single Center in Switzerland.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {44}, number = {2}, pages = {225-234}, pmid = {41662314}, issn = {1421-9875}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Female ; Aged ; Switzerland ; *Clostridium Infections/therapy/microbiology ; Recurrence ; Aged, 80 and over ; Middle Aged ; *Clostridioides difficile ; Male ; Adult ; Treatment Outcome ; Young Adult ; Retrospective Studies ; Feces/microbiology ; }, abstract = {UNLABELLED: <p>Introduction: Clostridioides difficile is the most frequently reported healthcare-associated infection with around 125'000 occurrences and 3'700 deaths annually in Europe. Recurrence rates are about 20% and risk factors include age >65 years and inflammatory bowel disease (IBD). Fecal microbiota transfer (FMT) has emerged as a highly effective treatment for recurrent C. difficile infection (rCDI), being successful in more than 90% of patients. This retrospective single-center study aimed to evaluate the effectiveness and safety of FMT in patients with rCDI at the University Hospital Zurich.<br><br>METHODS: Between 2012 and 2022, 84 patients underwent FMT for rCDI at our center, of which 83 were included in the final analysis. The median patient age was 71 years (22-97 years), and the majority of patients were female (67.5%). All patients had received multiple prior courses of antibiotic treatment for C. difficile infection.<br><br>RESULTS: The success rate following a single FMT was 92.8%, increasing to 97.6% with repeated procedures. Those rates were comparable in the IBD subgroup. FMT was well tolerated. Mild adverse events were reported in 14.5% of patients, most commonly reported adverse event being ongoing IBD activity (33.3%), and diarrhea (33.3%) followed by abdominal pain (25%). Serious adverse events occurred in 3.6% of patients mainly related to underlying conditions.<br><br>CONCLUSION: Our study confirms that FMT is a highly effective and well-tolerated treatment for rCDI, even in older patients with comorbidities. Importantly, FMT was successfully implemented without the use of a national stool bank, instead relying on locally processed related donor stool, highlighting its feasibility in resource-limited settings. </p>.}, }
@article {pmid41663002, year = {2026}, author = {Fang, J and Wu, M and Yu, J and Zhao, J and Liu, Y and Cui, Y and Chen, Y and Han, S and Chen, W and Peng, D and Yao, L}, title = {Mechanistic study of Dendrobium huoshanense polysaccharides improving ulcerative colitis by promoting Lachnoclostridium edouardi metabolism of short-chain fatty acids.}, journal = {Journal of ethnopharmacology}, volume = {362}, number = {}, pages = {121321}, doi = {10.1016/j.jep.2026.121321}, pmid = {41663002}, issn = {1872-7573}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology/pathology ; *Dendrobium/chemistry ; *Fatty Acids, Volatile/metabolism ; Male ; *Polysaccharides/pharmacology/therapeutic use/isolation &amp; purification ; PPAR gamma/metabolism ; Gastrointestinal Microbiome/drug effects ; Colon/drug effects/metabolism/pathology ; NF-kappa B/metabolism ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. Dendrobium huoshanense polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.<br><br>AIMS OF THIS STUDY: This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPAR&#x3b3; and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.<br><br>METHODS: This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPAR&#x3b3;/NF-&#x3ba;B pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, Lachnoclostridium edouardi was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through in vitro fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.<br><br>RESULTS: The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPAR&#x3b3; activation and inhibited NF-&#x3ba;B phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain Lachnoclostridium edouardi showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP in vitro and effectively suppressed inflammation in colonic epithelial cells.<br><br>CONCLUSIONS: This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPAR&#x3b3;/NF-&#x3ba;B pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the Lachnoclostridium edouardi strain in the gut microbiota, and its metabolites also showed therapeutic effects on UC. These findings provide a basis for the clinical application of DHP in UC.}, }
@article {pmid41664444, year = {2026}, author = {Xie, X and Li, X}, title = {Synergistic Modulation of the Tumor Microenvironment by Ultrasound-Assisted Fecal Microbiota Transplantation to Reverse Anti-PD-1 Resistance in Colorectal Cancer.}, journal = {Cancer biotherapy &amp; radiopharmaceuticals}, volume = {}, number = {}, pages = {10849785251414759}, doi = {10.1177/10849785251414759}, pmid = {41664444}, issn = {1557-8852}, abstract = {BACKGROUND: Colorectal cancer (CRC) development and therapy resistance are heavily controlled by the tumor microenvironment (TME). Although anti-PD-1 immunotherapy has significant therapeutic advantages, resistance remains a key challenge. Recent research has identified the gut microbiota as a key regulator of host immunity and checkpoint inhibitor effectiveness. Ultrasound (US) has emerged as a viable biophysical technique for improving medication and microbial delivery and controlling immune activation within tumors.<br><br>OBJECTIVES: The purpose of this work was to assess the synergistic effects of US-assisted fecal microbiota transplantation (US-FMT) on TME remodeling and anti-PD-1 resistance in a CRC cell line-derived xenograft mouse model.<br><br>MATERIALS AND METHODS: Tumor-bearing mice were randomized into four treatment groups: vehicle control, anti-PD-1 alone, fecal microbiota transplantation (FMT) alone, and US-FMT plus anti-PD-1 therapy. Low-intensity focused US was utilized to promote microbial engraftment and intestinal permeability. Flow cytometry, ELISA, and transcriptome profiling were used to investigate tumor growth kinetics, immune cell infiltration, cytokine profiles, and TME-related gene expression.<br><br>RESULTS: In comparison with the other groups, US-FMT reduced tumor development and restored sensitivity to anti-PD-1 treatment. US facilitated beneficial microbial colonization, boosted CD8 T cell infiltration, and decreased immunosuppressive cell populations. Furthermore, US-FMT modified cytokine release and reduced pro-tumorigenic inflammatory mediators, reprogramming the TME to be immune-active.<br><br>CONCLUSIONS: US-assisted microbiota manipulation is a unique and synergistic biotherapeutic method for reversing immunological resistance in CRC. The combination of US and FMT has translational promise for enhancing immunotherapy response and developing noninvasive cancer treatment techniques.}, }
@article {pmid41667242, year = {2026}, author = {Chen, X and Zuo, Z and Xiao, B and Zhao, F}, title = {Modulating the gut-reproductive tract axis: microbial influence on gynaecological cancer pathogenesis and treatment.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-337778}, pmid = {41667242}, issn = {1468-3288}, abstract = {The gut microbiota plays a crucial role in regulating host immunity, metabolism and inflammation, with accumulating evidence linking its composition and function to the development and progression of cancers in the reproductive tract. Patients with ovarian, endometrial and cervical cancers exhibit distinct alterations in their gut microbiota, characterised by reduced microbial diversity and shifts towards taxa associated with dysbiosis and chronic inflammation. Mechanistically, gut-derived metabolites and microbial translocation appear to influence systemic immune responses and oestrogen metabolism, thereby fostering a tumour microenvironment conducive to cancer growth. Beyond its role in tumourigenesis, the gut microbiota also affects treatment outcomes. Dysbiosis can reduce sensitivity to chemotherapy and alter immunotherapy responses, while antibiotic use during cancer treatment has been linked to poorer prognosis. Clinically, these insights highlight emerging applications of microbiome modulation as biomarkers for patient stratification and as adjuvant approaches to enhance therapeutic efficacy in gynaecological oncology, underscoring the therapeutic potential of targeting the microbiota-through dietary interventions, probiotics or faecal microbiota transplantation-to improve cancer treatment outcomes. However, most of these applications remain investigational, and current evidence is limited by heterogeneity across study designs, patient cohorts and cancer subtypes. This review summarises current understanding of gut microbiota profiles in reproductive tract cancers, examines potential mechanisms by which the microbiota influences malignancy, discusses its impact on therapy response and explores its emerging role in precision oncology.}, }
@article {pmid41667440, year = {2026}, author = {Jia, J and Liu, Y and Wang, D and Pan, Z and Zheng, Q and Lu, J and Liang, C and Li, D}, title = {Ulcerative colitis: signaling pathways, therapeutic targets and interventional strategies.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {51}, pmid = {41667440}, issn = {2059-3635}, support = {82073313//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Colitis, Ulcerative/genetics/therapy/pathology/immunology ; *Signal Transduction/genetics ; MicroRNAs/genetics ; Animals ; }, abstract = {Ulcerative colitis (UC) is the most common chronic inflammatory disease of the intestinal tract in clinical practice, and long-term chronic inflammation leads to repeated damage to and repair of the colonic mucosa, which may progress to malignancy through atypical hyperplasia. However, there are currently no fully targeted drugs for the treatment of UC. In this review, we discuss several cellular processes, such as autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, macrophage polarization, ferroptosis and the Th/Treg cell balance, which are associated with the occurrence and development of UC. Many molecular targets and signaling pathways, such as nuclear factor kappa-B (NF-κB), phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), Wnt/β-catenin, adenosine 5'-monophosphate-activated protein kinase (AMPK), toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK/STAT), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs), play crucial roles in the progression of UC. We also summarize the common treatment strategies for UC, including lifestyle interventions, aminosalicylic acid preparations, corticosteroid drugs, biologics, fecal microbiota transplantation, and other drugs for symptomatic treatment. This review provides a detailed theoretical basis for the pathology and treatment of UC. Future research could focus on optimizing the treatment plan and achieving more precise and personalized treatment with multiple targets in multiple aspects.}, }
@article {pmid41669929, year = {2025}, author = {Qiu, J and Wu, C and Li, S and Yang, X}, title = {Fecal Microbiota Transplantation Attenuated Inflammation Through TGF-β1/Smad Signaling Pathway in Caco-2 and RAW264.7 Cells.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {37}, number = {2}, pages = {161-169}, pmid = {41669929}, issn = {2148-5607}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Transforming Growth Factor beta1/metabolism ; Caco-2 Cells ; *Signal Transduction ; Animals ; Mice ; *Smad3 Protein/metabolism ; Smad2 Protein/metabolism ; RAW 264.7 Cells ; Smad7 Protein/metabolism ; *Colitis, Ulcerative/therapy/microbiology ; Inflammation/therapy ; *Smad Proteins/metabolism ; }, abstract = {BACKGROUND/AIMS: Ulcerative colitis (UC) represents a persistent inflammatory condition that influences millions of people worldwide, with rising prevalence and limited treatment options. Current therapies, such as corticosteroids and immunosuppressants, offer symp tom relief but are associated with significant adverse effects. Fecal microbiota transplantation (FMT) is being increasingly viewed as an effective alternative, but the molecular basis for its benefits in UC is still not fully understood. This study aimed to explore the function of the transforming growth factor-beta 1 (TGF-β1)/Smad signaling cascade in FMT-induced remission of UC.<br><br>MATERIALS AND METHODS: Stable Smad3-knockdown and Smad3-overexpression Caco2 cell lines were established via lentivirus-medi ated transduction. These modified Caco-2 cells were co-incubated with RAW264.7 macrophages to mimic intestinal inflammation in vitro. Following FMT treatment, the expression of major components of the TGF &#x3b2;1/Smadsignaling cascade was assessed.<br><br>RESULTS: The results demonstrated that FMT markedly downregulated TGF-&#x3b2;1, Smad2, and Smad3 expression, while enhancing Smad7 expression in both Smad3-knockdown and overexpression cell lines. In addition, FMT treatment attenuated the phosphorylation of Smad2 and Smad3, indicating a decrease in the activation of the TGF-&#x3b2;1/Smad signaling pathway.<br><br>CONCLUSION: These findings suggest that optimizing FMT protocols targeting this pathway could improve therapeutic outcomes for UC patients. &#xa0; Cite this article as:Qiu J, Wu C, Li S, Yang X. Fecal microbiota transplantation attenuated inflammation through TGF-&#x3b2;1/Smad signaling pathway in Caco-2 and RAW264.7 cells. Turk J Gastroenterol. 2026;37(2):161-169.}, }
@article {pmid41669940, year = {2026}, author = {Zhong, J and Tang, J and Han, L and Wang, W and Zhang, X and Zhang, S}, title = {Compound probiotics alleviate Escherichia coli-induced diarrhea in calves by modulating tryptophan and bile acid metabolism of the fecal microbiota.}, journal = {Virulence}, volume = {17}, number = {1}, pages = {2629106}, pmid = {41669940}, issn = {2150-5608}, mesh = {Animals ; *Probiotics/administration &amp; dosage/pharmacology ; *Tryptophan/metabolism ; *Diarrhea/veterinary/microbiology/therapy ; *Bile Acids and Salts/metabolism ; Cattle ; *Escherichia coli Infections/veterinary/microbiology ; *Feces/microbiology ; Escherichia coli ; *Gastrointestinal Microbiome/drug effects ; *Cattle Diseases/microbiology/therapy ; Mice ; Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Calf diarrhea, particularly that caused by diarrheagenic Escherichia coli, has become a major issue affecting the sustainable development of the calf farming industry. Although the use of traditional antimicrobial agents can alleviate symptoms, challenges such as antibiotic resistance, drug residues, and intestinal microbiota dysbiosis urgently need to be addressed. Therefore, this study investigates the mechanism by which compound probiotics alleviate diarrheagenic Escherichia coli-induced diarrhea in calves. Compound probiotics were administered to calves with diarrheagenic Escherichia coli-induced diarrhea, and their effects on growth performance, intestinal microbiota structure, and metabolic profiles were evaluated. The results showed that compound probiotic intervention significantly improved calf growth performance and weight gain. Integrated 16S rRNA sequencing and metabolomics analyses revealed that compound probiotic intervention markedly modulated the intestinal microbiota, particularly by increasing the abundance of the genus Blautia, while also improving tryptophan and bile acid metabolic pathways. Furthermore, fecal microbiota transplantation experiments conducted in both calves and antibiotic-induced microbiota depletion mouse models confirmed the regulatory effects of compound probiotics on the intestinal microbiota, especially with respect to tryptophan and bile acid metabolism. Compound probiotic intervention regulated key metabolites, including kynurenic acid, taurodeoxycholic acid, and ursodeoxycholic acid, which were positively correlated with Blautia, and significantly reduced inflammation by downregulating pro-inflammatory factors and upregulating anti-inflammatory factors, thereby alleviating diarrheagenic Escherichia coli-induced diarrhea in calves. Overall, this study provides new insights into the application of probiotics in intestinal health management and highlights the significant potential of compound probiotics as an alternative to antibiotics for the treatment of calf diarrhea.}, }
@article {pmid41670365, year = {2026}, author = {Ling, MTM and Krishnan, I and Govindaraju, K and Lokanathan, Y and Hoe, TC and Yusof, MRM and Subramani, B and Ibrahim, B}, title = {Metabolomic Analysis of Metabolic Syndrome and Effects of Wharton's Jelly Mesenchymal Stem Cell Small Extracellular Vesicles Therapy in Rat Models Using Nuclear Magnetic Resonance Spectroscopy.}, journal = {Cell biochemistry and function}, volume = {44}, number = {2}, pages = {e70180}, doi = {10.1002/cbf.70180}, pmid = {41670365}, issn = {1099-0844}, support = {FF-2022-065/1//Universiti Kebangsaan Malaysia/ ; DPK-2023-004//Universiti Kebangsaan Malaysia/ ; FF-2022-065//Medixcell Sdn. Bhd/ ; }, mesh = {Animals ; *Metabolic Syndrome/therapy/metabolism ; *Mesenchymal Stem Cells/metabolism/cytology ; Rats, Sprague-Dawley ; Rats ; *Metabolomics ; Magnetic Resonance Spectroscopy ; *Extracellular Vesicles/metabolism/transplantation ; *Wharton Jelly/cytology/metabolism ; Disease Models, Animal ; Male ; *Mesenchymal Stem Cell Transplantation ; }, abstract = {Long-term management of metabolic syndrome (MetS) often involves polypharmacy, which may lead to undesirable outcomes. Regenerative approaches such as mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have gained attention due to their paracrine effects, lower immunogenicity, and safer profile compared to whole-cell therapies. Previous studies suggest that MSC-sEVs improve insulin sensitivity, reduce inflammation, and support cardiovascular health, yet their precise mechanisms remain unclear. This study aimed to compare fecal and serum metabolic profiles of healthy, MetS, and MSC-sEVs-treated MetS rats using NMR-based metabolomics and to identify metabolic pathways underlying the therapeutic effects of Wharton's jelly MSC-sEVs (WJMSC-sEVs). 18 Sprague Dawley rats were divided into three groups: healthy controls, MetS + saline, and MetS + WJMSC-sEVs. After 16 weeks of MetS induction, rats received intravenous saline or WJMSC-sEVs every 3 weeks for 12 weeks. Multivariate analysis revealed clear separations between groups. MetS was associated with reduced serum isoleucine, acetate, and propionic acid, and elevated lactate, threonine, and glucose; fecal samples showed increased valine, alanine, leucine, glutamate, and fructose but reduced threonine and SCFAs. Pathway analysis highlighted disturbances in starch and sucrose metabolism, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. WJMSC-sEVs partially restored these imbalances, suggesting their therapeutic potential by targeting key metabolic pathways in MetS.}, }
@article {pmid41672393, year = {2026}, author = {Lan, Y and You, T and Feng, X and Guo, J and Xu, H}, title = {Combined Enterohepatic Toxicity of Polystyrene Microplastics and Di(2-ethylhexyl) Phthalate in Mice: Gut Microbiota-Dependent Synergistic Effects.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {395}, number = {}, pages = {127792}, doi = {10.1016/j.envpol.2026.127792}, pmid = {41672393}, issn = {1873-6424}, mesh = {Animals ; *Microplastics/toxicity ; *Diethylhexyl Phthalate/toxicity ; Mice ; *Polystyrenes/toxicity ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice, Inbred C57BL ; Plasticizers/toxicity ; Liver/drug effects ; Oxidative Stress ; }, abstract = {With growing toxicological research on microplastics (MPs), scientific attention has shifted from their single toxicity to their combined toxicity with other pollutants. Di(2-ethylhexyl) phthalate (DEHP), a common synthetic plasticizer, may co-occur with MPs through intrinsic association during production or through exogenous environmental pathways, posing the significant risk of co-exposure to organism. Oral exposure represents the primary route for MPs and DEHP, which traverse the gastrointestinal tract and target the enterohepatic system through direct intestinal interaction and systemic circulation. However, their combined toxicity, especially enterohepatic, remains poorly studied in the mammals. In this study, adult C57/BL6J mice were employed and exposed to polystyrene MPs (PS-MPs), DEHP or both for eight weeks. It was revealed that co-exposure to PS-MPs and DEHP induced more significant enterohepatic toxicity than the single exposures, involving enhanced enterohepatic inflammatory response and oxidative stress, as well as intestinal microbial disturbance. Furthermore, after fecal microbiota transplantation, the recipient mice developed similar trends of enterohepatic toxicity to those observed in the corresponding donor mice, revealing the key function played by intestinal microbiota. This study highlighted the crucial link of the gut-liver axis in the combined effects of PS-MPs and DEHP-induced enterohepatic toxicity in mammals and provided a mechanism insight of co-exposure to MPs and other environmental pollutants.}, }
@article {pmid41672583, year = {2026}, author = {Fornero, L and Wille-Bille, A and Fabio, MC and Peñalver, P and Marengo, L and Ezquer, F and Pautassi, RM}, title = {Modeling microbiota-mediated risk for alcohol use disorder: a preclinical study of fecal transplantation from ethanol-exposed mice.}, journal = {The American journal of drug and alcohol abuse}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/00952990.2025.2609229}, pmid = {41672583}, issn = {1097-9891}, abstract = {Background: Alcohol use during adolescence and early adulthood promotes the development of alcohol use disorder (AUD). Emerging evidence suggests that ethanol-induced gut microbiota alterations may contribute to AUD vulnerability; however, it remains unclear whether microbiota imbalances are a causal risk factor or a consequence of alcohol exposure.Objectives: This preclinical study assessed if fecal microbiota transplantation (FMT) from donors exposed to ethanol during adolescence/early adulthood would alter ethanol drinking and other behaviors, in unrelated naïve mice.Methods: Forty-two (31 males and 11 females) C57BL/6J mice were exposed to a repeated 2-days-on, 2-days-off ethanol access protocol from postnatal day 43 to 80. Fecal microbiota from ethanol-exposed (or control) donors was transplanted into antibiotic-pretreated naïve male (n = 26) and female (n = 16) recipients. These were assessed for ethanol intake, including compulsive-like drinking (i.e. after quinine adulteration). Anxiety and repetitive behavior were measured in the light-dark box, elevated plus maze and marble-burying tests.Results: Female, but not male, recipients of FMT from ethanol-exposed donors showed significantly increased ethanol consumption (n[2]p = .32) and preference (n[2]p = .36) compared to controls (p < .05). This included sustained intake despite quinine adulteration (p < .05), suggestive of compulsive-like drinking. Ethanol-exposed male mice showed a significant increase in marble-burying (p < .05), consistent with compulsive-like tendencies. Additionally, both male (n[2]p = .30) and female (n[2]p = .28) donor mice exhibited behavioral disinhibition (p < .05).Conclusions: These findings provide preclinical evidence that microbiota alterations after ethanol exposure at late adolescence can transmit vulnerability to alcohol intake, with sex-specific effects. The results highlight the potential of microbiota-targeted interventions in prevention and treatment strategies for AUD.}, }
@article {pmid41672982, year = {2026}, author = {D'Onofrio, AM and Gomez-Nguyen, A and Camardese, G and Scaldaferri, F and Burberry, A and Cominelli, F}, title = {Fecal microbiota transplantation from psychiatric patients to mice - systematic review of methodologies and a call for standardization.}, journal = {Translational psychiatry}, volume = {16}, number = {1}, pages = {}, pmid = {41672982}, issn = {2158-3188}, support = {NIDDK097948//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; R01AG085316//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, mesh = {*Fecal Microbiota Transplantation/standards/methods ; Animals ; Humans ; Mice ; *Mental Disorders/therapy/microbiology ; *Gastrointestinal Microbiome ; Disease Models, Animal ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a key tool to explore the role of the microbiome-gut-brain axis in psychiatric disorders. However, the field is hindered by significant methodological inconsistencies.<br><br>METHODS: A comprehensive literature search identified 31 studies performing FMT from human patients with psychiatric conditions into rodent models.<br><br>RESULTS: None of the 31 studies followed an identical FMT protocol. Significant heterogeneity was observed across studies in rodent model selection, including germ-free, antibiotic-pretreated, or specific pathogen-free approaches, in antibiotic regimens, timing and microbiota depletion verification, as well as in FMT donor strategy, dosage, frequency, engraftment assessment, and behavioral testing schedules.<br><br>CONCLUSIONS: This review highlights the necessity for standardized methodologies in microbiome research. Evidence-based recommendations are provided to promote reproducibility in future work. Investigators are encouraged to publish transparent and rigorous protocols, to enhance the translational potential of microbiome-gut-brain axis research.}, }
@article {pmid41673679, year = {2026}, author = {Liao, J and Mou, H and Luo, S and Shen, L and Jiao, B}, title = {Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.}, journal = {Translational neurodegeneration}, volume = {15}, number = {1}, pages = {3}, pmid = {41673679}, issn = {2047-9158}, support = {82371434//National Natural Science Foundation of China/ ; 2024JJ2097//Outstanding Youth Fund of Hunan Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Alzheimer Disease/microbiology/therapy/metabolism ; *Microbiota/physiology ; *Dysbiosis/microbiology ; Animals ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation/methods ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by multifactorial mechanisms. Increasing evidence suggests that dysbiosis, a term denoting an imbalance in the composition of the microbiota, may play a pivotal role in the pathogenesis of AD across multiple bodily sites, including the gut, oral cavity, nasal passages, lungs, and skin. Microbial imbalances may promote neuroinflammation, immune dysfunction, and metabolic disturbances through complex host-microbiota networks. This review synthesizes current advances in the understanding of microbiota-driven modulation of AD, introduces the "Multi-Axis Co-Regulation" concept, and evaluates microbial biomarkers for early diagnosis. Finally, the translational potential of microbiota-targeting interventions, including probiotics, dietary modulation, fecal microbiota transplantation, and oral microbiome-based therapies, are discussed, which represent novel strategies for precision prevention and treatment of AD.}, }
@article {pmid41674471, year = {2026}, author = {Figura, M and Milanowski, &#x141; and Nowak, JM and Antoniak, A and Kopczyński, M and Zając, W and Sadowski, K and Hołubiuk, &#x141; and Walęcik-Kot, W and Szlufik, S and Friedman, A and Kaczmarczyk, B and Biliński, J and Koziorowski, D}, title = {Safety and Efficacy of Fecal Microbiota Transplantation in Alleviating Symptoms of Parkinson's Disease: A Randomized, Placebo-Controlled, Double-Blinded Study.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.78153}, pmid = {41674471}, issn = {1531-8249}, support = {2021//Biocodex Microbiota Foundation National Grant/ ; NZP/1/Z/GW/N/21//Medical University of Warsaw/ ; 09/M/MBS/N/21//Medical University of Warsaw/ ; 1/Z/MG/24//Medical University of Warsaw/ ; NZP/1/Z/MG/N/23//Medical University of Warsaw/ ; M/MG/77/22//Medical University of Warsaw/ ; }, abstract = {OBJECTIVES: Changes in the gut microbiome may be involved in the pathogenesis and progression of Parkinson's disease (PD). This randomized, placebo-controlled, double-blinded study aimed to assess the effects of fecal microbiota transplantation (FMT) on the manifestation of the motor symptoms of PD (The Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III [MDS-UPDRS III]) over a 12 month long observation and non-motor symptoms as secondary objectives: the Movement Disorders Society-Non-Motor Rating Scale; EuroQol-5 Dimension; PD Quality-of-Life Questionnaire; Montreal Cognitive Assessment (MoCA); UPDRS I, II, and IV; Gastrointestinal Dysfunction Scale for PD; modified Constipation Assessment Scale; and levodopa equivalent dose.<br><br>METHODS: The patients were randomly assigned to receive either fecal microbiota (Mbiotix, Human Biome Institute) or placebo (auto-fecal microbiota, prepared from the patient's stool) in a 1:1 ratio. The fecal microbiota transplantation was performed via colonoscopy. Assessments were performed before and after 12&#x2009;months for the MoCA and at 1, 3, 6, and 12&#x2009;months for the other scales. Intention-to-treat analysis was performed using a multivariable mixed regression model.<br><br>RESULTS: Of the 59 patients included, 28 were randomly assigned to the Mbiotix group (median age&#x2009;=&#x2009;65&#x2009;years; 15 male patients) and 31 to the placebo group (median age&#x2009;=&#x2009;63&#x2009;years; 14 male patients). No significant differences were observed in the MDS-UPDRS III "OFF" state score at 12&#x2009;months between groups (1.50 points, 95% confidence interval [CI]&#x2009;=&#x2009;-4.28 to 7.28, p&#x2009;=&#x2009;1.00), however, some non-motor symptoms improved in different study timepoints.<br><br>INTERPRETATION: A single FMT does not influence motor symptoms manifestation in patients with PD but could improve non-motor functioning via gut-brain axis. Trial registration information: Clinical Trial ID NCT05204641 was submitted on November 29, 2021. The first patient was enrolled on January 4, 2022. ANN NEUROL 2026.}, }
@article {pmid41674575, year = {2025}, author = {Zhang, Z and Xu, Y and Pang, K and Wu, C and Zhao, C and Lei, T and Zhang, J and Hai, T and Zhao, F and Zhao, Y}, title = {Microbiota humanization drives human-like metabolic and immune transcriptomic shifts in pigs.}, journal = {iMetaOmics}, volume = {2}, number = {3}, pages = {e70034}, pmid = {41674575}, issn = {2996-9514}, abstract = {Pigs are increasingly recognized as promising candidates for clinical xenotransplantation and as large-animal models for biomedical research; however, interspecies differences in gut microbiota, immune function, and metabolism remain major barriers. To address this, we established gut microbiota-humanized (GMH) pigs by transplanting human fecal microbiota into antibiotic-treated pigs. We systemically evaluated alterations in microbiota composition, serum metabolites, and immune cell profiles using integrated metagenomic, quasi-targeted metabolomic and single-cell transcriptomic (scRNA-seq) analyses. Metagenomic profiling revealed a shift in the intestinal microbiota of GMH pigs toward a human-like composition, characterized by enrichment of Bacteroidia and depletion of Bacilli. Metabolomic analysis showed that GMH pigs exhibited serum metabolite profiles more closely resembling those of humans. Among 423 detected serum metabolites, 136 that were lower in control pigs than in humans were upregulated in GMH pigs, whereas 79 that were elevated in control pigs decreased post-transplantation. Notably, pathways related to tryptophan metabolism, bile acid biosynthesis, and fatty acid metabolism were enhanced in GMT pigs, while carbon-related and glycolytic pathways were attenuated, indicating partial convergence toward human metabolic phenotype. Integration of microbial and metabolite data identified 20 and 33 metabolites associated with Bacteroidia and Bacilli, respectively. scRNA-seq profiling of peripheral blood mononuclear cells demonstrated transcriptional and compositional remodeling of T cells, monocytes, and B cell subsets in GMH pigs. These findings demonstrated that human fecal microbiota can reshape both systemic metabolic and immune artitecture in pigs, offering a robust large-animal platform for studying host-microbiota interactions and advancing translational application in xenotransplantation and microbiome-based therapeutics.}, }
@article {pmid41675162, year = {2025}, author = {Lyu, Y and Shen, J and Che, Y and Dai, L}, title = {Skin microbiome engineering: Challenges and opportunities in skin diseases treatment.}, journal = {iMetaOmics}, volume = {2}, number = {2}, pages = {e70012}, pmid = {41675162}, issn = {2996-9514}, abstract = {The skin microbiome, consisting of a vast array of microorganisms, is essential for human skin health, aiding in barrier protection, immune regulation, wound repair, and defense against pathogens. Disruptions in this microbial balance are closely linked to the onset and worsening of various skin disorders. This review evaluates the potential of skin microbiome engineering as a therapeutic strategy for treating skin diseases. We discuss nontargeted approaches like probiotics and fecal microbiota transplantation that aim to reshape the microbial community, as well as targeted methods such as phage therapy, phage lysins, and engineered bacteria, which specifically modulate microbial populations or influence the skin environment. These approaches open new avenues for personalized dermatological treatments. Despite significant progress, challenges remain in the clinical translation of microbiome-based therapies. Safety, standardization, regulatory approval, and long-term ecological stability must be addressed to ensure efficacy and reproducibility in clinical settings, underscoring the critical need for further research in their dermatological applications.}, }
@article {pmid41675345, year = {2026}, author = {Mylavarapu, M and Tiwari, A and Kaur, H and Vempati, R and Kumar, H and Kodali, LSM and Khan, KG and Dadana, S and Garcia, I and Cabrera, FEP and Singh, A and Kyasa, SL and Purewal, VS}, title = {The Gut-Heart Axis: A Comprehensive Review of Microbiota's Role in Cardiovascular Health and Disease and Emerging Therapeutic Strategies.}, journal = {Cardiology research and practice}, volume = {2026}, number = {}, pages = {9920016}, pmid = {41675345}, issn = {2090-8016}, abstract = {This review examines the bidirectional relationship between the gut microbiota and cardiovascular diseases (CVDs), aiming to understand how microbial dysbiosis contributes to CVDs, including atherosclerosis, hypertension, and heart failure. Recent research emphasizes the gut microbiota's role in modulating immunity via SCFAs and tryptophan metabolites, maintaining intestinal barrier integrity, and producing metabolites such as SCFAs (acetate, propionate, butyrate) and pro-atherogenic TMAO. Dietary patterns, particularly the Mediterranean versus Western diet, significantly influence gut microbiota composition and CVD risk. Polyphenols and exercise have shown positive effects on gut microbiota and cardiovascular outcomes. A significant interplay exists between gut microbiota and cardiovascular health. Dysbiosis and metabolites like TMAO and LPS are implicated in CVD, while SCFAs and a balanced microbiota offer protection. Future research should focus on precision medicine, next-gen probiotics, optimized FMT, and multiomics approaches to identify personalized CVD therapies.}, }
@article {pmid41675494, year = {2025}, author = {Wu, Z and Wang, X and Guan, Z and Han, M and Ma, W and Li, J and Man, S and Wang, Z and Wu, Q}, title = {Deciphering the immunocellular regulatory network in inflammatory bowel disease: from susceptibility genes to cellular effectors and toward precision therapies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1719366}, pmid = {41675494}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/immunology/genetics/etiology ; *Genetic Predisposition to Disease ; *Precision Medicine/methods ; Animals ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, more than 30% of patients either fail to respond initially or lose response over time, underscoring the need for a deeper mechanistic understanding of immunogenetic pathways and the development of individualized therapeutic strategies. We first discuss how newly identified susceptibility genes (e.g., IL23R, NOD2, BDNF, SLC) and their polymorphisms influence immune cell function and epithelial barrier integrity. Single-cell technologies have further revealed novel cell subsets and interactions underlying disease heterogeneity. We then explore the clinical efficacy of classical and emerging targeted therapies, including cytokine-specific biologics, JAK inhibitors, and novel strategies aimed at restoring regulatory T-cell function or blocking integrin-mediated lymphocyte trafficking. Additionally, we highlight promising therapeutic approaches such as fecal microbiota transplantation, microbial metabolite-based interventions, and nanotherapeutics. We further discuss how genetic insights and immune biomarkers can facilitate treatment personalization and improve prognostic stratification. Ultimately, this review emphasizes the transition from broad immunosuppression to precision medicine and proposes integrated approaches-combining multiomics profiling, immune monitoring, and novel therapeutics-to achieve sustained remission and improve long-term outcomes in IBD patients.}, }
@article {pmid41675700, year = {2025}, author = {Zhong, P and Li, Q and Zhang, Y and Guo, C and Abdelsattar, MM and Bi, Y}, title = {Precision microbial regulation: Strategies for modulating GIT microbiota for host health.}, journal = {iMetaOmics}, volume = {2}, number = {1}, pages = {e54}, pmid = {41675700}, issn = {2996-9514}, abstract = {Recent advancements in analytical techniques have unveiled the spatiotemporal diversity of the gastrointestinal tract (GIT) microbiota and their associations with host well-being. Despite these insights, the precise regulation of GIT microbiota remains a significant challenge. Currently, microbial regulatory strategies, including fecal microbiota transplantation (FMT), synthetic microbial communities (SynComs), genetically engineered microorganisms (GEMs), phages, and nanomaterials, are increasingly utilized for their precise influence on GIT microbiota. This review emphasizes the necessity for developing targeted regulatory strategies in GIT and provides a comprehensive summary and comparison of these approaches to explore their regulatory potential. We discuss recent advancements in these strategies, focusing on their mechanisms, efficacy, safety considerations, clinical trials, and optimization at the application level. Finally, we highlight support methods for optimizing modulation strategies, including the timing of microbial regulation, the selection of microbial targets, and the importance of monitoring the gastrointestinal environment to guide effective microbial interventions.}, }
@article {pmid41675715, year = {2025}, author = {Ren, H and Cao, B and Xu, Q and Zhao, R and Li, H and Wei, B}, title = {Role of microbiota in pain: From bench to bedside.}, journal = {iMetaOmics}, volume = {2}, number = {1}, pages = {e58}, pmid = {41675715}, issn = {2996-9514}, abstract = {Interactions between the microbiota and host have been proven to be critical regulators of homeostasis, and pain perception is no exception. Emerging evidence has identified the mechanisms by which microbiota dysbiosis contributes to hyperalgesia and revealed the potential value of microbiota-associated therapies in pain management. Herein, the authors introduce the basic knowledge of pain and microbiota for readers who are not simultaneously majoring in these two fields. The clarified mechanisms underlying the regulation of pain by the microbiota are outlined in terms of three ways. This review summarizes the current advancements in pain management and microbiology research for clinicians who wish to focus on this area. Probiotics, fecal microbiota transplantation, and other methods of microbiota modulation for pain management have entered clinical translation. The authors further propose the present limitations and prospects for high-quality development of preclinical and clinical investigations. Importantly, despite the large amount of attention given to gut bacteria, this review also puts forward great expectations on the role of nongut and nonbacterial microbiota in pain sensation. Efforts to decipher the mechanisms of microbiota functions will help to promote achievements in pain management from bench to bedside.}, }
@article {pmid41676058, year = {2026}, author = {Sivamaruthi, BS and Kesika, P and Chaiyasut, C and Ragu Varman, D}, title = {Gut dysbiosis in neurodevelopmental disorders: linking microbiota signatures to cognitive rigidity in autism spectrum disorder.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1760635}, pmid = {41676058}, issn = {1664-302X}, abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterised not only by social-communication difficulties but also by restricted interests, stereotyped behaviours, and marked cognitive rigidity. Over the past decade, converging lines of evidence have implicated gut dysbiosis, an imbalance in intestinal microbial composition and function, as a potentially important modulator of these behavioural phenotypes via the microbiota-gut-brain axis. In this narrative review, we integrate preclinical and clinical data to examine how specific microbial signatures, metabolic pathways, and immune and synaptic mechanisms may contribute to inflexible cognition in ASD. The manuscript outlines the organisation of the microbiota gut-brain axis in neurodevelopment and summarises reproducible microbial alterations reported in ASD cohorts. We then discuss how microbial metabolites, including short-chain fatty acids and tryptophan-derived neuroactive molecules, as well as immune mediators and neurotransmitter precursors, converge on pathways regulating excitatory-inhibitory balance, synaptic plasticity, and corticostriatal circuit function. Evidence from germ-free, genetic, and environmental rodent models provides causal support for microbiota-dependent modulation of repetitive and rigid behaviours, whilst clinical studies reveal associations between dysbiosis, metabolomic profiles, gastrointestinal symptoms, and ASD severity. Finally, we consider the translational landscape of microbiota-targeted interventions, probiotics, prebiotics, dietary strategies, and faecal microbiota transplantation and highlight key methodological and ethical challenges for moving toward precision microbiome-based therapies. Taken together, current data support gut dysbiosis as both a mechanistic contributor and a tractable therapeutic target for cognitive rigidity in ASD.}, }
@article {pmid41676136, year = {2026}, author = {Ni, FX and Wang, HX and Hu, J and Chen, PS and Xu, P and Chen, HH and Jiang, ZB and Huang, DH}, title = {The gut-lung axis in COPD: immunomodulatory roles of gut microbiota and novel therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1733726}, pmid = {41676136}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Pulmonary Disease, Chronic Obstructive/immunology/therapy/microbiology/metabolism ; Animals ; *Lung/immunology/microbiology/metabolism ; Dysbiosis/immunology ; *Immunomodulation ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and systemic inflammation, with accumulating evidence implicating gut microbiota dysbiosis as a key modulator of disease pathogenesis via the gut-lung axis. This review synthesizes current knowledge on the bidirectional communication between the gut and lungs, highlighting how microbial metabolites-particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and bile acids-regulate pulmonary immunity through G-protein-coupled receptors, histone deacetylase inhibition, and aryl hydrocarbon receptor signaling. Dysbiosis-driven disruptions in these pathways exacerbate neutrophilic inflammation, impair regulatory T-cell function, and sustain TLR4/NF-κB activation, amplifying lung tissue damage and remodeling. Therapeutic strategies targeting the gut-lung axis show promise in restoring microbial homeostasis and mitigating COPD progression. Probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., inulin), and dietary interventions (e.g., high-fiber diets) enhance SCFA production, strengthen epithelial barriers, and suppress pro-inflammatory cytokines. Advanced approaches, including fecal microbiota transplantation, nanotechnology-enabled metabolite delivery (e.g., dendrimer-complexed indole-3-acetic acid), and traditional Chinese medicine (TCM) formulations (e.g., the postbiotic formulation Qipian), demonstrate efficacy in preclinical and clinical studies by synchronizing gut-lung microbiota and inhibiting inflammatory pathways. Despite these advances, challenges remain in translating findings to clinical practice, including methodological heterogeneity, antibiotic and corticosteroid confounding, and inter-individual microbiota variability. Future research must integrate multi-omics technologies, validate biomarkers (e.g., Bacteroidales/Lactobacillus ratio, SCFA levels), and develop personalized interventions to bridge the bench-to-bedside gap. Harnessing the gut-lung axis offers transformative potential for COPD management, shifting the paradigm from symptomatic treatment to disease-modifying strategies rooted in microbiome immunology.}, }
@article {pmid41676450, year = {2025}, author = {Zhang, L and Liu, Y and Wang, S and Ching, JY and Tam, WH and Leung, TF and Leung, TY and Chan, PKS and Mak, JWY and Cheung, CP and Tun, HM and Chang, EB and DeLeon, O and Huang, Q and Chen, X and Huo, H and Miao, Y and Cheong, PK and Ip, KL and Yeung, YL and Chang, MK and Lyu, C and Yang, H and Li, B and Fan, Y and Sun, Y and Jiang, S and Ng, SC and Chan, FKL}, title = {MOMMY study profile: An integrative early-life multi-omics cohort in China.}, journal = {iMetaOmics}, volume = {2}, number = {4}, pages = {e70068}, pmid = {41676450}, issn = {2996-9514}, abstract = {Large-scale, prospective birth cohorts capturing the complex interplay between the gut microbiome, host biology, and environmental exposures are crucial to understanding early-life health but remain scarce, particularly within Asian populations. To address this gap, we established the MOMMY cohort (The MOther-infant Microbiota transmission and its link to long terM health of babY), a large, prospective birth cohort uniquely designed to investigate maternal-paternal-infant microbiota transmission and its impact on child health within the understudied Chinese population. MOMMY aims to recruit 20,000 families from three geographically and economically diverse regions across China. This cohort prospectively follows pregnant mothers, fathers, and their infants, with children up to 7 years of age. Since September 2019, we have systematically collected a comprehensive repository of longitudinal biospecimens-including maternal and infant stool, breast milk, cord blood, and parental blood-stored in an accredited biobank. This is complemented by extensive data on environmental exposures, diet, and health outcomes gathered through validated questionnaires and physician assessments. The MOMMY cohort's unique value lies in its unprecedented scale, geographic diversity, and its integrative multi-omics design, which will combine metagenomic, metabolomic, immunologic, and epigenetic data. By creating this unique resource, MOMMY will elucidate how early-life microbial and molecular trajectories, shaped by genetic and environmental factors, influence child development and disease risk, thereby filling a critical gap in global microbiome research.}, }
@article {pmid41677424, year = {2026}, author = {Zhang, Z and Yang, J and Chen, X and Shi, J and Li, B and Wang, L and Geng, Z and Li, J and Zhang, X and Wang, Y and Song, X and Li, Y and Hu, J and Zuo, L}, title = {Aucubin Restores Intestinal Mucosal Immunity and Barrier Integrity in Experimental Colitis via the Microbiota-SCFAs-GPR41/GPR43 Axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {4}, pages = {e71569}, doi = {10.1096/fj.202502948R}, pmid = {41677424}, issn = {1530-6860}, support = {82370534//National Natural Science Foundation of China/ ; 2019byyfyjq01//Research Project of Bengbu Medical University/ ; BYYFY2022TD002//Research Project of Bengbu Medical University/ ; 2021byfy001//Research Project of Bengbu Medical University/ ; gxyqZD2022066//Anhui Provincial Research Project/ ; 2024Aa40007//Anhui Provincial Research Project/ ; 2024Aa10051//Anhui Provincial Research Project/ ; 202427b10020093//Anhui Provincial Research Project/ ; 202427b10020088//Anhui Provincial Research Project/ ; 202427b10020099//Anhui Provincial Research Project/ ; 2022AH020085//Anhui Provincial Research Project/ ; 2023AH010067//Anhui Provincial Research Project/ ; }, mesh = {*Intestinal Mucosa/drug effects/immunology/microbiology ; Immunity, Mucosal/drug effects ; *Fatty Acids, Volatile/metabolism ; *Receptors, G-Protein-Coupled/antagonists &amp; inhibitors/metabolism ; *Iridoid Glucosides/pharmacology/therapeutic use ; *Inflammatory Bowel Diseases/chemically induced/drug therapy/immunology ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; T-Lymphocytes, Regulatory/drug effects/immunology ; Th17 Cells/drug effects/immunology ; Disease Models, Animal ; Animals ; Mice ; Mice, Inbred C57BL ; Dextran Sulfate/pharmacology ; }, abstract = {BackgroundInflammatory bowel disease (IBD) pathogenesis involves immune dysfunction and gut microbiota dysbiosis. Aucubin (AU), a naturally occurring iridoid glycoside known for its ability to alleviate inflammation and modulate intestinal flora, has not yet been investigated in the context of colitis MethodsThe effects of AU on DSS-induced colitis in mice were evaluated, including disease severity, the balance of regulatory T cells (Tregs) and Th17 cells, intestinal barrier, inflammatory markers, fecal short-chain fatty acids (SCFAs), and safety. The gut microbiota was assessed using 16S rRNA sequencing. GPR41/43 involvement was tested using receptor antagonists. The antibiotic-treated mice and fecal transplantation were used to validate the microbiota-dependent effects. ResultsAU treatment broadly ameliorated the DSS-induced colitis and restored immune homeostasis by rebalancing Treg/Th17 cell populations. Meanwhile, intestinal barrier function was reinforced through upregulation of MUC2 and enhanced tight junction protein levels. Importantly, AU modulated gut microbiota composition, particularly enriching taxa associated with SCFA production, which indeed led to elevated fecal SCFA levels. Interestingly, the therapeutic effects of AU were absent in microbiota-depleted mice but could be conferred to DSS-induced recipients via fecal microbiota transplantation from AU-treated donors. Furthermore, the protective benefits of AU were partially attenuated upon pharmacological inhibition of the SCFA receptors GPR41/GPR43. No treatment-related toxicity was observed. ConclusionsAU safely alleviates colitis in mice by rebalancing the gut microbiota, activating SCFAs-GPR41/GPR43 axis to support mucosal immune regulation and barrier repair.}, }
@article {pmid41677988, year = {2026}, author = {Feng, R and Yang, Z and Zhou, Y and Zhao, H}, title = {The Gut-Brain-Immune Axis in Glioma: Emerging Mechanisms and Therapeutic Opportunities.}, journal = {Cellular and molecular neurobiology}, volume = {46}, number = {1}, pages = {}, pmid = {41677988}, issn = {1573-6830}, support = {ZR2022QH372//Science and Technology Development Plan of Shandong Province/ ; }, abstract = {Gliomas, particularly glioblastomas, represent some of the most treatment-resistant cancers due to their profoundly immunosuppressive tumor microenvironment (TME) and the restrictive nature of the blood–brain barrier. While recent advances in immunotherapy have transformed the treatment landscape for peripheral tumors, success in gliomas remains limited. Emerging evidence suggests that the gut microbiota—through the gut-brain-immune axis—may play a significant role in shaping systemic and central immune responses. Gut-derived microbial metabolites, immune cell modulation, and neuro-immune signaling pathways have been shown to influence microglial activation, T cell infiltration, and even response to immune checkpoint inhibitors (ICIs) such as PD-1 and emerging targets like TIM-3, LAG-3, and TIGIT. Furthermore, the efficacy and persistence of CAR-T and CAR-NK therapies may also be impacted by microbial composition, offering a novel avenue for therapeutic optimization. This review explores the biological underpinnings of the gut-brain-immune axis in glioma, summarizes key preclinical and clinical findings, and highlights the potential of gut microbiota modulation—via probiotics, engineered microbes, or fecal microbiota transplantation (FMT)—as an adjunct to immunotherapy. We also discuss technical and translational challenges, including interindividual variability and mechanistic uncertainty. Understanding the dynamic crosstalk between the gut and the glioma immune microenvironment may unlock new therapeutic strategies and improve outcomes in this highly lethal disease.}, }
@article {pmid41680132, year = {2026}, author = {Raschdorf, A and de Almeida, LN and Solbach, P and Kirstein, MM and Marquardt, JU and Schmelter, F and Günther, UL and Schlichting, H and Hicken, M and Christiansen, L and Wiestler, M and Tews, HC and Bettenworth, D and ,  and Peipp, M and Valerius, T and Ragab, M and Sauer, T and Gemoll, T and Ehlers, M and Rosenstiel, P and Manz, RA and Künstner, A and Busch, H and Sina, C and Derer, S}, title = {Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {1590}, pmid = {41680132}, issn = {2041-1723}, mesh = {Animals ; *Crohn Disease/immunology/metabolism/pathology/genetics ; *Plasma Cells/metabolism/immunology/pathology ; Humans ; Mice ; *Mitochondria/metabolism/pathology ; Proteomics/methods ; *Colon/metabolism/immunology/pathology ; Disease Models, Animal ; *Immunoglobulin A, Secretory/metabolism/immunology ; Cell Differentiation ; Single-Cell Analysis ; Male ; B-Lymphocytes/immunology/metabolism ; Intestinal Mucosa/immunology/metabolism/pathology ; Female ; Immunoglobulin A/metabolism ; Oxidative Phosphorylation ; Mice, Inbred C57BL ; }, abstract = {Secretory IgA (SIgA) is critical for maintaining the intestinal barrier. A dysregulated B-cell compartment and altered Ig secretion have been well documented in Crohn's disease (CD) patients, although their origin is unknown. To unravel the role of mucosal humoral immunity in CD pathogenesis, we in-depth phenotype colonic plasma cell (PC) differentiation in CD at the single-cell level, linked to ex vivo functional characterization and experimental mouse models with a congenital mitochondrial defect or under glucose-free high-protein dietary intervention. Here, we demonstrate that despite expanded colonic B cells, CD patients in remission present significantly diminished mucosal dimeric IgA and fecal SIgA. Colonic plasmablasts and immature CD19[+]CD45[+] PCs are increased at the expense of the mature CD19[-]CD45[-] phenotype. Accordingly, CD-derived ex vivo differentiated PCs display impaired maturation into dimeric IgA-secreting PCs. In this study, patient-derived data from colonic RNA-seq, spatial single-cell proteomics, and plasma metabolomics are combined with data from both mouse models and highlight the crucial role of mitochondrial oxidative phosphorylation in colonic IgA[+]-PC differentiation, suggesting promising directions for future therapeutic strategies.}, }
@article {pmid41683324, year = {2026}, author = {Zhao, Z and Zhao, S and Li, W and Lai, Z and Zhou, Y and Guan, F and Liang, X and Zhang, J and Wang, L}, title = {Gut Microbiota and Exercise-Induced Fatigue: A Narrative Review of Mechanisms, Nutritional Interventions, and Future Directions.}, journal = {Nutrients}, volume = {18}, number = {3}, pages = {}, pmid = {41683324}, issn = {2072-6643}, support = {2022AH040100//The Scientific Research Project of Higher Education Institutions in Anhui Province/ ; }, mesh = {Humans ; *Fatigue/microbiology/etiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Animals ; *Exercise/physiology ; Probiotics ; Prebiotics/administration &amp; dosage ; Post-Exercise Recovery ; }, abstract = {Background: Exercise-induced fatigue (EIF) impairs performance and recovery and may contribute to overreaching/overtraining and adverse health outcomes. Beyond classical explanations (substrate depletion, metabolite accumulation, oxidative stress), accumulating evidence indicates that the gut microbiota modulates fatigue-related physiology through metabolic, immune, barrier, and neurobehavioral pathways. Methods: We conducted a structured narrative review of PubMed and Web of Science covering 1 January 2015 to 30 November 2025 using predefined keywords related to EIF, gut microbiota, recovery, and nutritional interventions. Human studies, animal experiments, and mechanistic preclinical work (in vivo/in vitro) were included when they linked exercise load, microbial features (taxa/functions/metabolites), and fatigue-relevant outcomes. Results: Across models, high-intensity or prolonged exercise is consistently associated with disrupted gut homeostasis, including altered community structure, reduced abundance of beneficial taxa, increased intestinal permeability, and shifts in microbial metabolites (e.g., short-chain fatty acids). Evidence converges on four interconnected microbiota-mediated pathways relevant to EIF: (1) energy availability and metabolic by-product clearance; (2) redox balance and inflammation; (3) intestinal barrier integrity and endotoxemia risk; and (4) central fatigue and exercise motivation via microbiota-gut-brain signaling. Nutritional strategies-particularly targeted probiotics, prebiotics/plant polysaccharides, and selected bioactive compounds-show potential to improve fatigue biomarkers and endurance-related outcomes, although effects appear context-dependent (exercise modality, baseline fitness, diet, and baseline microbiota). Conclusions: Current evidence supports a mechanistic role of the gut microbiota in EIF and highlights microbiota-targeted nutrition as a promising adjunct for recovery optimization. Future work should prioritize causal validation (e.g., fecal microbiota transplantation and metabolite supplementation), athlete-focused randomized trials with standardized fatigue endpoints, and precision approaches that stratify individuals by baseline microbiome features and training load.}, }
@article {pmid41683353, year = {2026}, author = {Gong, B and Shi, Z and Qi, J and Wang, F and Chen, G and Su, H}, title = {GLP-1RA Liraglutide Attenuates Sepsis by Modulating Gut Microbiota and Associated Metabolites.}, journal = {Nutrients}, volume = {18}, number = {3}, pages = {}, pmid = {41683353}, issn = {2072-6643}, support = {Yunnan Province Medical High-level Talents Program, L2024012//Guobing Chen/ ; }, mesh = {*Liraglutide/pharmacology/therapeutic use ; Animals ; *Sepsis/drug therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis ; *Glucagon-Like Peptide-1 Receptor Agonists ; Metabolome/drug effects ; Fecal Microbiota Transplantation ; Feces/microbiology ; Cytokines/metabolism ; Cecum ; }, abstract = {BACKGROUND: Sepsis-induced organ dysfunction poses a significant clinical challenge with limited therapeutic options. This study investigated the therapeutic potential of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide in sepsis and its underlying mechanisms, focusing on modulation of the gut microbiota-derived metabolome.<br><br>METHODS: Public transcriptomic data analysis identified overlapping targets between liraglutide and sepsis-related genes. In a murine cecal ligation and puncture (CLP) model, liraglutide treatment was evaluated for its effects on survival, systemic inflammation, and organ injury. The gut microbiota composition and fecal metabolome were assessed via 16S rRNA sequencing and UPLC-MS. We also measured plasma GLP-1 in sepsis patients and examined the microbiota-dependency of liraglutide's effects using antibiotic-depleted mice and fecal microbiota transplantation (FMT) from liraglutide-treated mice. Additionally, citrulline, a key identified metabolite, was functionally validated both in vitro and in a clinical cohort.<br><br>RESULTS: Liraglutide significantly improved survival, reduced pro-inflammatory cytokines, and alleviated lung, liver, and colon damage in septic mice. It partially restored sepsis-induced gut dysbiosis and modulating associated metabolites, including increasing citrulline. The survival benefit of liraglutide was abolished in microbiota-depleted mice, while FMT from liraglutide-treated mice conferred protection against sepsis, confirming the gut microbiota as a critical mediator. Furthermore, citrulline exhibited direct anti-inflammatory properties in cellular assays, and its plasma levels were negatively correlated with sepsis biomarkers (PCT and CRP) in patients.<br><br>CONCLUSIONS: Taken together, our findings indicate that liraglutide mitigates sepsis by modulating the gut microbiota and regulating associated metabolic pathways. Citrulline may represent a potential microbial mediator or exploratory biomarker within this axis, warranting further mechanistic investigation.}, }
@article {pmid41683859, year = {2026}, author = {Unrug-Bielawska, K and Sandowska-Markiewicz, Z and Kaniuga, E and Cybulska-Lubak, M and Borowa-Chmielak, M and Czarnowski, P and Piątkowska, M and Bałabas, A and Goryca, K and Zeber-Lubecka, N and Kulecka, M and Dąbrowska, M and Surynt, P and Statkiewicz, M and Rumieńczyk, I and Mikula, M and Ostrowski, J}, title = {Human Fecal Transplantation Modifies the Gut Microbiota but Not Metabolites in Colon Cancer Patient-Derived Xenografts.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683859}, issn = {1422-0067}, support = {2017/27/B/NZ5/01504//National Science Centre/ ; }, mesh = {Humans ; Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Gastrointestinal Microbiome ; Fluorouracil/pharmacology/therapeutic use ; Xenograft Model Antitumor Assays ; *Colonic Neoplasms/therapy/microbiology/metabolism ; Leucovorin/pharmacology/therapeutic use ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Organoplatinum Compounds/pharmacology ; Fatty Acids, Volatile/metabolism ; }, abstract = {Gut microbiota influences colorectal cancer (CRC) development, tumor progression, and response to therapy. Fecal microbiota transplantation (FMT) has been proposed as a strategy to restore microbial balance and modulate treatment outcomes. We evaluated the effects of human fecal transplantation on gut microbiota composition, metabolites, tumor growth, and the efficacy of folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy in four CRC patient-derived xenograft (CRC PDX) models in NSG mice. Gut microbiota was profiled by 16S rRNA sequencing; short-chain fatty acids (SCFAs) and amino acids (AAs) were analyzed by mass spectrometry. Prolonged FMT significantly altered gut microbiota structure, increasing α-diversity and modifying β-diversity, and induced distinct changes in bacterial genera. FMT alone did not affect tumor growth. FOLFOX inhibited tumor progression in all CRC PDXs, with FMT enhancing therapeutic efficacy in two models. Despite substantial microbiota shifts, FMT exerted minimal or no effect on fecal SCFAs and AAs. FMT induced robust microbiota remodeling but did not modify selected stool metabolites or intrinsic tumor growth. However, FMT enhanced FOLFOX responsiveness in selected CRC PDXs, supporting a microbiota-mediated modulation of chemotherapy outcomes.}, }
@article {pmid41683874, year = {2026}, author = {Kim, KJ and Zhong, H and Tai, D and Shah, P and Park, D and Goes, V and Li, J and Jung, C and Kim, L and Guzman, S and Brar, G and Castillo, D}, title = {Microbiome Signatures in Advanced Gastric Cancer: Emerging Biomarkers for Risk Stratification, Therapy Guidance, and Prognostic Insight.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683874}, issn = {1422-0067}, mesh = {Humans ; *Stomach Neoplasms/microbiology/therapy/pathology/diagnosis ; Prognosis ; *Gastrointestinal Microbiome ; *Biomarkers, Tumor ; Dysbiosis/microbiology ; Helicobacter Infections/microbiology ; Animals ; Immunotherapy/methods ; Risk Assessment ; }, abstract = {Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa-including Fusobacterium nucleatum (F. nucleatum)-have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management.}, }
@article {pmid41684898, year = {2025}, author = {Huang, J and Yin, X and Zhang, Y and Zheng, W and Li, G}, title = {Fecal microbiota transplantation from gestational diabetes mellitus patients induces glucose intolerance and subclinical inflammation in mice.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1723816}, pmid = {41684898}, issn = {1664-302X}, abstract = {BACKGROUND: The pathogenesis of gestational diabetes mellitus (GDM) is not fully understood, with gut microbiota dysbiosis emerging as a potential contributing factor. Existing animal models primarily mimic type 1 or type 2 diabetes, inadequately representing GDM. This study aimed to investigate whether fecal microbiota transplantation (FMT) from GDM patients is associated with the development of GDM-like phenotypes in mice, comparing this approach to traditional modeling methods.<br><br>METHODS: Fecal microbiota from GDM patients and healthy controls were transplanted into antibiotic-treated pregnant mice, creating trimester-specific FMT models. Control groups included mice on a high-fat diet (HFD) and HFD combined with streptozotocin (STZ). Metabolic phenotypes were assessed via glucose and insulin tolerance tests, fasting blood glucose, and insulin measurements. Serum inflammatory markers were analyzed, and gut inflammation was evaluated. 16S rRNA sequencing was performed on key model groups.<br><br>RESULTS: Mice receiving FMT from mid-late trimester GDM donors or traditional treatments developed significant glucose intolerance, insulin resistance, and gestational weight gain. Serum levels of inflammatory factors (e.g., IL-1&#x3b2;, MMP-9) were elevated. 16S rRNA sequencing revealed markedly reduced gut microbiota diversity and increased Firmicutes/Bacteroidota ratio in both GDM-FMT and traditional model groups, with similar microbial community structures and alterations in metabolic and inflammation-related pathways.<br><br>CONCLUSION: Gut microbiota from GDM patients may disrupt glucose homeostasis and contribute to a pro-inflammatory state during pregnancy. The GDM-FMT model effectively recapitulates key metabolic, inflammatory, and microbial dysbiosis features of GDM, providing a novel and reliable experimental tool for mechanistic studies.}, }
@article {pmid41684902, year = {2025}, author = {Li, X and Li, G and Cui, K and Yin, X and Yang, W and Li, W and Xu, S}, title = {Electroacupuncture improves depression with constipation by balancing gut microbiota in WKY rats.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1680596}, pmid = {41684902}, issn = {1664-302X}, abstract = {Accumulating evidence underscores the pivotal role of the gut microbiota in the pathogenesis of depression. In this study, we employed the Wistar-Kyoto (WKY) rat, a well-established animal model of depression comorbid with constipation. Using 16S rRNA gene sequencing, we characterized the gut microbial community structure and investigated the impact of microbiota modulation on depressive-like behaviors and gastrointestinal dysfunction. Comparative analyses revealed that WKY rats exhibited significantly increased relative abundances of Proteobacteria, Bacteroidetes, and Desulfobacterota, accompanied by a marked reduction in Firmicutes compared to control Wistar rats. Fecal microbiota transplantation (FMT) demonstrated that colonization of WKY rats with microbiota from Wistar rats restored microbial composition, improved depressive-like behaviors, and normalized gut motility. In contrast, Wistar rats receiving microbiota from WKY donors developed depression-like phenotypes and impaired intestinal function. Moreover, electroacupuncture (EA) treatment not only alleviated depressive-like behaviors in WKY rats but also promoted recovery of colonic epithelial ultrastructure and rebalanced gut microbial composition. Collectively, these findings demonstrate that both FMT and EA effectively ameliorate depressive behaviors and constipation in WKY rats, with EA likely exerting its therapeutic effects through modulation of the gut microbiota.}, }
@article {pmid41684914, year = {2026}, author = {Yang, G and Zhu, J and Wang, M and She, S and Dai, K}, title = {Research advances on gut microbiota dysbiosis and chronic liver diseases: a review.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1765047}, pmid = {41684914}, issn = {2296-858X}, abstract = {The gut microbiota is fundamental to human health, maintaining intricate symbiotic interactions with the host. Accumulating evidence highlights a critical association between gut microbiota dysbiosis and the initiation and progression of chronic liver diseases (CLDs). Particularly hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, alcoholic liver disease (ALD), metabolic-associated steatotic liver disease (MASLD), and cirrhosis. This microbial imbalance may contribute to the progression of CLDs primarily via the "gut-liver axis," the mechanisms involve gut barrier dysfunction, abnormal immune regulation, and metabolic alterations. This review synthesizes cutting-edge research on the interplay between gut dysregulation and CLDs, elaborating molecular mechanistic pathways including the TLR4/NF-κB signaling pathway, AMPK pathway, and farnesoid X receptor (FXR)-mediated bile acid signaling. Additionally, it discusses clinically oriented therapeutic strategies targeting microbiota modulation, including probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions, offering innovative insights for the prevention and management of chronic liver diseases.}, }
@article {pmid41685140, year = {2026}, author = {Ma, H and Wu, Y and Li, D and Sun, H and Xie, Y and Zhao, S and Guo, W and Wang, M and Cui, R and Huang, Y and Zhang, X and Wan, JY and Yao, H and Yuan, CS}, title = {Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.}, journal = {Acta pharmaceutica Sinica. B}, volume = {16}, number = {2}, pages = {836-853}, pmid = {41685140}, issn = {2211-3835}, abstract = {Obesity-prone (OP) individuals exhibit an intrinsic predisposition to obesity and associated metabolic disorders, and early intervention in this population holds significant clinical value; however, the underlying mechanisms driving this susceptibility remain largely obscure. This study enrolled 46 OP subjects without diagnosed metabolic diseases and 35 healthy controls. Our findings revealed that, despite not reaching obesity diagnoses, OP subjects exhibited significant metabolic disturbances strongly associated with gut microbiota dysbiosis. They also displayed disturbed bile acid (BA) profiles, with depleted glycodeoxycholic acid (GDCA) identified as the most potent discriminator between the OP and healthy controls. Fecal microbiota transplantation (FMT) recapitulated metabolic dysfunction and BA pool remodeling, mediated by dysregulated hepatic expression of BA synthesis genes of Cyp8a1, Cyp7a1, and Cyp7b1. Notably, FMT-OP mice also phenocopied the diminished GDCA levels observed in OP subjects. GDCA supplementation in obese mice markedly improved body weight, hepatic steatosis, and metabolic dysfunction. Mechanistically, GDCA exerted anti-obesity effects by activating the TGR5 signaling, which enhanced brown adipose tissue (BAT) thermogenesis and stimulated ileal glucagon-like peptide-1 (GLP-1) secretion, thereby ameliorating obesity and associated metabolic dysregulation. Thus, these findings indicate that gut microbiota-driven dysregulation of BA signaling, particularly impaired TGR5 activation due to diminished GDCA, underlies glycolipid metabolic dysfunction in OP individuals.}, }
@article {pmid41687425, year = {2026}, author = {Xie, QX and Zeng, XN and Wang, YH and Tan, LX and Yang, M and Du, YX and Chen, XP}, title = {Gut microbiota influence pharmacokinetics variability in aging mice: Effects vary from drug to drug.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {54}, number = {3}, pages = {100241}, doi = {10.1016/j.dmd.2026.100241}, pmid = {41687425}, issn = {1521-009X}, mesh = {Animals ; *Aging/metabolism ; Mice ; Male ; *Gastrointestinal Microbiome/physiology ; Midazolam/pharmacokinetics/administration &amp; dosage ; Dextromethorphan/pharmacokinetics/administration &amp; dosage ; Phenacetin/pharmacokinetics/administration &amp; dosage ; Chlorzoxazone/pharmacokinetics/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; Age Factors ; }, abstract = {Pharmacokinetics (PKs) changes in the aging state are relatively common in clinical practice, but their underlying mechanisms remain unclear. This study aims to explore the potential effects of gut microbiota on PK of P450 probe drugs in old and young mice. A cocktail of probe drugs including phenacetin (PHE), midazolam (MID), dextromethorphan tartrate (DEX), and chlorzoxazone was gavage administered to control and pseudo-sterile old and young mice, and the PK parameters were compared. Subsequently, fecal microbiota transplantation (FMT) from young to old mice was performed to assess the impact of FMT on PK of the probe drugs. We observed that gut microbiota significantly affected the systemic exposure of PHE and MID, whereas age-related increase in DEX exposure in the old mice could be reversed by clearance of microbiota. No changes in PK parameters of the probe drugs were observed in old mice with FMT from young mice, suggesting that the alterations in PHE, MID, and DEX metabolism in the old mice could not be explained by unique microbiota from young mice. Our findings provide valuable guidance on how to improve the individualized medication for the elderly population. SIGNIFICANCE STATEMENT: This article offers new insights into the role of gut microbiota in the pharmacokinetic changes with aging, which is conducive to individualized medication for elderly patients and provides new insight for the research and development of drugs for elderly population.}, }
@article {pmid41687433, year = {2026}, author = {Libriani, S and Facchinetti, G and Marti, F and Tolentino Diaz, MY and Sandri, E}, title = {The association between gut microbiota and cognitive decline: A systematic review of the literature.}, journal = {Nutrition research (New York, N.Y.)}, volume = {147}, number = {}, pages = {16-31}, doi = {10.1016/j.nutres.2026.01.003}, pmid = {41687433}, issn = {1879-0739}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/microbiology ; Probiotics ; Fecal Microbiota Transplantation ; Cognition ; Diet, Ketogenic ; Dementia/microbiology ; }, abstract = {The gut-brain axis has emerged as a key pathway in the pathogenesis of neurodegenerative disorders, with age-related shifts in gut microbiota potentially contributing to cognitive decline and dementia progression. This systematic review evaluated the effects of microbiota-targeted interventions on cognitive outcomes in adults aged >45 years with cognitive impairment or at risk of dementia. Randomized controlled trials and quasi-experimental studies published up to June 2025 were identified through PubMed, COCHRANE, CINAHL, Web of Science, and EMBASE. Methodological quality, assessed using the Joanna Briggs Institute Critical Appraisal Checklist, ranged from moderate to high.Fifteen studies involving 4,275 participants across Europe, Asia, North America, and the Middle East met inclusion criteria. Interventions included probiotic supplementation, fecal microbiota transplantation, and dietary strategies such as Mediterranean and ketogenic diets. Cognitive outcomes were measured using validated tools, including the Mini-Mental State Examination, Montreal Cognitive Assessment, and Repeatable Battery for the Assessment of Neuropsychological Status. Narrative synthesis indicated that microbiota modulation was associated with improvements in memory, executive function, and global cognition, particularly in individuals with prodromal or mild cognitive impairment. Reported benefits correlated with increased microbial diversity, enhanced short-chain fatty acid production, and reduced neuroinflammatory markers. In contrast, effects were limited in advanced Alzheimer's disease.Overall, gut microbiota modulation represents a promising nonpharmacological strategy to support cognitive health, with early intervention appearing crucial for optimal benefit. Nevertheless, heterogeneity in study design and intervention protocols highlights the need for large-scale, longitudinal randomized controlled trials to confirm efficacy and clarify underlying biological mechanisms.}, }
@article {pmid41687676, year = {2026}, author = {Thiele, M and Bhadoria, AS and Mellinger, J and Zelber-Sagi, S and Manousou, P and Shawcross, DL and Bhala, N}, title = {Global gains, metabolic pains: unmasking the hidden burden on liver health.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {11}, number = {5}, pages = {351-353}, doi = {10.1016/S2468-1253(26)00006-3}, pmid = {41687676}, issn = {2468-1253}, }
@article {pmid41688126, year = {2026}, author = {Edvinsson, M and Thelander, A and Dimopoulos, N and Pauksens, K}, title = {Chronic norovirus infection in a patient with Good's syndrome resolved after fecal microbiota transplantion and improved nutrional status.}, journal = {Infectious diseases (London, England)}, volume = {58}, number = {4}, pages = {453-458}, doi = {10.1080/23744235.2026.2631113}, pmid = {41688126}, issn = {2374-4243}, mesh = {Humans ; *Caliciviridae Infections/therapy/virology ; *Fecal Microbiota Transplantation ; *Norovirus/isolation &amp; purification ; Male ; *Agammaglobulinemia/therapy/complications ; *Nutritional Status ; Feces/virology/microbiology ; Treatment Outcome ; Female ; Chronic Disease ; Immunocompromised Host ; Diarrhea/therapy ; }, abstract = {Norovirus may cause chronic infection in immunocompromised patients. Both B-cell and T-cell responses are important for viral clearance. Currently, there is no established treatment but various substances have been evaluated, yielding mixedresults. This report presents a patient diagnosed with Good's syndrome, which includes hypogammaglobulinemia, who suffered from a chronic norovirus infection for several years. Nitazoxanide treatment was administered for 4 weeks due to ongoing diarrhoea and declining nutritional status; however, symptoms did not improve. Subsequently, fecal microbiota transplantation (FMT) was assessed using a single dose of cultured human microbiota. This procedure improved symptoms but did not eliminate the infection. The patient's symptoms returned after 6 months, at which time two FMT doses were administered, resulting in symptom amelioration. Three months later, a more pronounced relapse led to severe nutritional decline, most notably manifesting as overt vitamin A deficiency accompanied by visual impairment. Again, the patient underwent two administrations of FMT; however, relapse occurred shortly thereafter. Parenteral nutrition was then initiated after consultation with the hospital's clinical nutrition team. Symptoms promptly improved, with a decrease in diarrhoea and an increase in weight. A stool sample collected 2.5 months following the final FMT combined with parental nutrition demonstrated no detectable norovirus, and the patient has remained in stable health for 3 years. We believe that the patient's chronic norovirus infection was resolved through the combination of enhanced nutritional status and FMT.}, }
@article {pmid41689915, year = {2026}, author = {Li, M and Yuan, F and Li, G and Fu, Y and Wei, X}, title = {Clinical analysis of fecal microbiota transplantation for refractory acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a five-year retrospective study.}, journal = {Cytotherapy}, volume = {28}, number = {4}, pages = {102043}, doi = {10.1016/j.jcyt.2025.102043}, pmid = {41689915}, issn = {1477-2566}, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Female ; Retrospective Studies ; Male ; Adult ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; Transplantation, Homologous/adverse effects ; *Gastrointestinal Diseases/therapy/etiology ; Adolescent ; Acute Disease ; Young Adult ; Treatment Outcome ; }, abstract = {BACKGROUND AIMS: Refractory acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is associated with significantly increased mortality. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic strategy for this condition, and its efficacy and safety have garnered substantial attention in clinical research.<br><br>OBJECTIVE: To explore the clinical efficacy and safety of FMT for refractory acute GI-aGVHD after allo-HSCT.<br><br>METHODS: Data from 22 patients with refractory GI-aGVHD who received FMT and 20 patients who did not undergo FMT, all diagnosed with refractory GI-aGVHD after allo-HSCT and treated at Henan Cancer Hospital between December 2017 and March 2023, were retrospectively analyzed to evaluate short-term efficacy, safety, and long-term survival outcomes.<br><br>RESULTS: FMT significantly reduced the median diarrhea volume (1300 versus 450 mL, P = 0.017) and frequency (10 versus 5.5 times/d, P = 0.049) in the FMT group, whereas the control group showed no significant improvement in either parameter (diarrhea volume: 1350 versus 900 mL, P > 0.05; frequency: 10 versus 9 times/d, P > 0.05). The FMT group exhibited significantly higher complete response (CR) (31.8% versus 5%, P = 0.047) and overall response rate (ORR) (59.1% versus 25%, P = 0.033) compared with the control group. Subgroup analyses showed that patients with isolated intestinal involvement (ORR = 100%) and those without bloody stool before FMT (ORR = 78.6%) had superior responses to FMT. The FMT group achieved a median progression-free survival (PFS) of 30 (10-2113) days and a median overall survival (OS) of 150 (51-2130) days, with the 100-day, 1-year and 3-year PFS rates of 40.9%, 28.1%, and 28.1%, respectively, and the 100-day, 1-year and 3-year OS rates of 59.1%, 50.0% and 34.3%. In contrast, the control group had notably poorer survival outcomes: median PFS was 23 (7-1820) days, median OS was 80 (20-1901) days, while the 100-day, 1-year, and 3-year PFS rates remained 5% across all time points, and the 100-day, 1-year, and 3-year OS rates were 20.0%, 10.0%, and 10%.<br><br>CONCLUSION: FMT is effective and safe as a clinical treatment for refractory GI-aGVHD after allo-HSCT, and the effectiveness of FMT can be used as a prognostic indicator for long-term survival in refractory GI-aGVHD.}, }
@article {pmid41690650, year = {2026}, author = {Ma, C and Zou, Z and Zhao, W and Rao, Y and Liu, B and Sun, M and Chen, D}, title = {The gut microbiota in Salmonella Typhi infection and translocation: Mechanisms of colonization resistance, pathogen subversion, and prospects for microecological intervention.}, journal = {Microbial pathogenesis}, volume = {213}, number = {}, pages = {108381}, doi = {10.1016/j.micpath.2026.108381}, pmid = {41690650}, issn = {1096-1208}, mesh = {Humans ; *Salmonella typhi/pathogenicity/immunology ; Animals ; *Typhoid Fever/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology/physiology ; Host-Pathogen Interactions/immunology ; Fecal Microbiota Transplantation ; Probiotics ; Mice ; *Bacterial Translocation ; Dysbiosis ; }, abstract = {The systemic establishment of the strictly human-adapted pathogen Salmonella Typhi critically depends on functional interplay between its virulence effectors and the host gut microbiome. Organized within a "colonization-toxicity-immunity- microecological intervention" framework, this review synthesizes recent molecular and multi-omics evidence to delineate key host-pathogen-microbiota dynamics. During colonization, a healthy gut microbiota exerts multi-layered colonization resistance through nutrient and niche competition, as well as via microbial metabolites such as short-chain fatty acids and secondary bile acids. Current evidence more consistently supports DDR-associated cellular senescence and type I IFN signaling as major outcomes of typhoid toxin activity; pyroptosis, if observed, appears context-dependent and should not be presented as a universal endpoint. Concurrently, the Vi capsule and type III secretion system (T3SS) effector proteins (e.g., SteD) act in concert to disrupt innate and adaptive immunity, reprogram the mucosal immunometabolic landscape, and exacerbate microbial dysbiosis. We also evaluate the strength of evidence and applicability of microbiota-targeted interventions, including probiotics, prebiotics, synthetic microbial consortia, and fecal microbiota transplantation (FMT), and address the limitations of extrapolating from Salmonella Typhimurium mouse models to human Salmonella Typhi, typhoid toxin infection. Furthermore, we emphasize the need for cross-validation using human intestinal organoids, humanized immune mice, and population-level data, integrated with metabolomic and immune profiling, to establish a definitive "metabolism-immunity-toxicity" causal chain. Confronting the persistent evolution of H58 and other drug-resistant lineages, we propose a paradigm shift through the convergence of genomic epidemiology, microbiota-informed risk stratification, and vaccine-microbiota synergism; these elements collectively chart an implementable roadmap for precision medicine in disease control.}, }
@article {pmid41691535, year = {2026}, author = {Blaney, H and Asgharpour, A}, title = {The alcohol-associated hepatitis treatment landscape.}, journal = {Current opinion in gastroenterology}, volume = {42}, number = {3}, pages = {107-113}, doi = {10.1097/MOG.0000000000001158}, pmid = {41691535}, issn = {1531-7056}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Liver Transplantation/methods ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: Alcohol-associated hepatitis is a severe form of alcohol-associated liver disease and is associated with a high mortality. Treatment of alcohol-associated hepatitis has historically been limited, with few therapies demonstrating survival benefit. However, multiple promising new therapies are on the horizon, with this review highlighting recent advances in alcohol-associated hepatitis treatment.<br><br>RECENT FINDINGS: Multiple new pharmacological agents targeting different mechanisms are under study for alcohol-associated hepatitis, including larsucosterol, F-652, and INT-787. Manipulation of the gut-brain axis has also been leveraged for alcohol-associated hepatitis, with use of fecal microbiota transplant and other modalities. Early liver transplantation, while not universally available, has offered improved survival with similar outcomes compared to other etiologies of liver disease. Living donor liver transplantation has also been investigated in alcohol-associated hepatitis, with promising results. While steroids still remain the mainstay of therapy, recent studies have offered nuances to their use, including use of a taper to reduce risk of infection without changing efficacy.<br><br>SUMMARY: Medical management of alcohol-associated hepatitis has remained largely unchanged since the 1970&#x200a;s. However, promising therapies targeting multiple aspects of pathophysiology are on the horizon, including a planned phase 3 trial for larsucosterol, an active phase 2a study with INT-787 and a planned trial using F-652.}, }
@article {pmid41691676, year = {2026}, author = {Chen, Z and Chen, A and Chen, Y and Chen, X and Lin, H and Tu, H}, title = {Pathogenic Mechanisms and Therapeutic Approaches of Intestinal Flora in the Immune Microenvironment of Hepatocellular Carcinoma.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673423753251229070800}, pmid = {41691676}, issn = {1875-533X}, abstract = {This paper initially presents an overview of the fundamental aspects of Hepatocellular carcinoma (HCC), intestinal microbiota, and the immune microenvironment. The paper discusses how metabolites from intestinal microbiota, such as lipopolysaccharides (LPS), bile acids, short-chain fatty acids (SCFA), branched-chain amino acids (BCAA), tryptophan, choline, and inosine, influence immune cell activation and the immune microenvironment, thereby contributing to HCC development. Current laboratory methods focus on using immune checkpoint inhibitors, acetic acid, fecal microbiota transplantation, probiotics, antibiotics, and other strategies to alter intestinal microbiota composition or suppress metabolitemediated immune responses to treat HCC. This study offers suggestions for potential avenues of future investigation. A systematic analysis of the interrelationship between intestinal microbiota, HCC, and the immune microenvironment facilitates the provision of refined and personalized therapeutic options in clinical settings, enhances patient survival rates.}, }
@article {pmid41694125, year = {2025}, author = {Fu, J and Zhang, Y and Gao, J and Lan, M and Zhang, Z and Liang, R and Zhou, H and Liu, S and Zhou, Z and Zhao, J and Yu, X and Liu, Y and Han, P and Chen, X and Lin, C and Guo, Q}, title = {Efficacy effects of fecal microbiota transplantation on depressive symptoms: a meta-analysis based on randomized controlled trials.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1629290}, pmid = {41694125}, issn = {1664-0640}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in the bidirectional communication between the gut and the brain. Although there has been much discussion in recent years on the link between depression and fecal microbiota transplantation (FMT), its effectiveness in treating depression remains debatable. The purpose of this study was to examine if FMT alleviates depression or its symptoms and to examine the possible impacts of various demographic subgroups and supplementation techniques.<br><br>METHODS: A systematic search of articles in the database (PubMed, EMBASE, Web of Science, and Cochrane libraries) before March 2025. The Revman 5.3 software was used to incorporate standardized mean difference (SMD) and assess quality of evidence using recommended grading assessment, development and evaluation tools to investigate whether FMT efficacy on depressive symptoms or depression.<br><br>RESULTS: This meta-analysis included seven studies involving 235 subjects, and the results did not support a significant treatment effect of FMT on depression [SMD: -0.10; 95%CI: (-0.60,0.41); p = 0.71]. Subgroup analysis showed the correlation between the intervention effect of FMT and confirmed depression at baseline, intervention dose, donor source, repeated route of drug administration, and dietary habits of subjects.<br><br>CONCLUSIONS: There is insufficient evidence to support a significant efficacy of FMT on depressive symptoms, but subgroup analyses suggest that FMT may have a better antidepressant effect in the population with confirmed depression, and therefore more randomized controlled trials are necessary to validate the association between FMT and depressive symptoms.}, }
@article {pmid41695569, year = {2025}, author = {Yang, J and Dai, Y and Li, J}, title = {Gut microbiota-immunity cascade in hepatocellular carcinoma: mechanisms and therapeutic opportunities.}, journal = {Oncology reviews}, volume = {19}, number = {}, pages = {1687901}, pmid = {41695569}, issn = {1970-5565}, abstract = {Hepatocellular carcinoma (HCC) constitutes a major global health burden, with limited responsiveness to current immunotherapeutic regimens. Accumulating evidence underscores the gut microbiota as a crucial regulator of the gut-liver axis, modulating tumor initiation, immune evasion, and the outcomes of immunotherapeutic interventions-and notably, it concurrently exhibits both potential diagnostic biomarker value and actionable therapeutic target properties. In the present review, we synthesize the characteristic features of gut dysbiosis in HCC, delineate the mechanisms by which microbial metabolites-including short-chain fatty acids (SCFAs), bile acids, and indoles-modulate the tumor immune microenvironment (TME), and elaborate on their dual roles in promoting anti-tumor immunity while concomitantly mediating immune suppression. We further examine the clinical correlations between specific microbial taxa and the efficacy of immune checkpoint inhibitors (ICIs)-findings that support the utility of gut microbiota signatures as predictive or diagnostic biomarkers-and explore emerging microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), probiotic supplementation, phage therapy, and dietary modulation, which validate the gut microbiota as a viable therapeutic target.}, }
@article {pmid41695578, year = {2026}, author = {Ni, S and Fu, W and Zhang, L and Zhang, Z and Li, X}, title = {Circadian rhythms regulate osteoclast recycling through gut microbiota-dependent Th17 cell expansion.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100561}, pmid = {41695578}, issn = {2666-5174}, abstract = {The circadian clock coordinates diverse biological processes to maintain physiological function and homeostasis in mammals under the day-night light cycle. Disruption of circadian rhythms impairs immune and metabolic functions and increases susceptibility to various diseases. Here, we demonstrate that long-term rest-phase time-restricted feeding (TRF), which disrupts circadian rhythmicity, induces bone loss and gut microbiota dysbiosis in male mice. Fecal microbiota transplantation (FMT) from circadian-misaligned feeding donors to germ-free recipients increased Th17 cell populations, thereby promoting the fusion of osteomorphs-a recently identified osteoclast precursor-into mature osteoclasts through the RANKL-RANK-OPG signaling pathway. Collectively, our findings identify a gut microbiota-Th17-osteomorph axis as a critical mediator of circadian disruption-induced bone loss, uncovering a previously unrecognized mechanism by which circadian rhythms regulate skeletal homeostasis.}, }
@article {pmid41695956, year = {2026}, author = {Ali, A and AlHussaini, KI}, title = {Diagnostic challenges and treatment approaches for Clostridioides difficile infection in IBD patients.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1740387}, pmid = {41695956}, issn = {1664-302X}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) poses a major clinical challenge in patients with inflammatory bowel disease (IBD) due to overlapping symptoms, diagnostic complexities, and distinct therapeutic considerations. The interaction between CDI and IBD involves disrupted gut microbiota, immune dysregulation, and disease-specific risk factors.<br><br>METHODS: This review critically examines the current evidence on the diagnosis and management of CDI in patients with IBD. Literature sources discussing diagnostic methodologies, therapeutic strategies, and preventive interventions were analyzed, with a focus on recent advances and their clinical applicability.<br><br>RESULTS: Diagnosing CDI in IBD remains difficult due to similar clinical presentations between infectious colitis and IBD flares, alongside limitations of stool assays, molecular tests, and endoscopic evaluations. Emerging diagnostic tools may enhance the accuracy and timeliness of detection. Standard therapies, antibiotics, and fecal microbiota transplantation (FMT) remain essential; however, their application requires individualization, taking into account immunosuppressive therapy, drug interactions, and the risk of recurrence. Treatment outcomes are further influenced by disease severity and patterns of antimicrobial resistance. Preventive strategies, including antimicrobial stewardship, probiotics, and vaccination, may help reduce the incidence of CDI among patients with IBD.<br><br>CONCLUSION: CDI in IBD necessitates a personalized management approach that incorporates accurate diagnostics, targeted therapy, and preventive measures. Despite therapeutic advances, significant knowledge gaps persist regarding host microbiome interactions and the optimization of individualized treatment. Future research should focus on improving diagnostic precision and developing personalized medicine strategies to enhance outcomes for IBD patients affected by CDI.}, }
@article {pmid41697021, year = {2025}, author = {Han, B and Wen, H and Li, Y and Wang, Y and Lv, X and Kang, M and Huang, W and Lan, Y and Tong, S and Zhang, M and Chen, D and Zhu, C and Jiang, Y and Tang, D}, title = {Gut microbial production of lithocholic acid reprograms pro-resolutive macrophages to enhance vedolizumab responsiveness via the TGR5/FXR-NF-κB axis.}, journal = {The ISME journal}, volume = {20}, number = {1}, pages = {}, pmid = {41697021}, issn = {1751-7370}, support = {LHGJ20250299//Henan Provincial Medical Science and Technology Research Joint Venture Project/ ; 2025M772035//China Postdoctoral Science Foundation/ ; 82460108//National Natural Science Foundation of China/ ; 2023GXNSFAA026135//Guangxi Natural Science Foundation/ ; 2025GXNSFDA069030//Key Project of Guangxi Natural Science Foundation/ ; }, mesh = {Animals ; *Lithocholic Acid/metabolism ; *Gastrointestinal Microbiome ; *Macrophages/metabolism/immunology/drug effects ; *NF-kappa B/metabolism ; Mice ; Humans ; Disease Models, Animal ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Receptor, Farnesoid X-Activated ; *Crohn Disease/drug therapy ; Colitis/chemically induced/drug therapy ; Signal Transduction ; Metabolomics ; *Gastrointestinal Agents/pharmacology ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; }, abstract = {Crohn's disease (CD) is a complex chronic transmural inflammatory bowel disease. Although vedolizumab (VDZ) markedly improves clinical outcomes in CD, treatment non-response remains a significant limitation, constraining its broader utility. Elucidating the mechanisms underlying VDZ responsiveness is thus critically needed. In this research, we employed a humanized mouse model of 2,4,6-trinitrobenzene sulfonic acid-induced colitis to investigate VDZ treatment response in CD. Our findings indicate that VDZ significantly alleviated disease phenotypes in a portion of CD mice. Integrated metagenomic and metabolomic profiling identified baseline gut microbiota-derived secondary bile acids as potential predictors of VDZ efficacy. Subsequent fecal microbiota transplantation from clinical donors into pseudo-germ-free mice confirmed that gut microbial composition critically influences VDZ responsiveness. Targeted metabolomics further pinpointed lithocholic acid (LCA) as a key microbially derived metabolite correlated with therapeutic remission. Single-cell RNA sequencing also revealed that intestinal macrophages serve as pivotal mediators of LCA-driven modulation of treatment outcomes. Furthermore, transcriptomic analyses demonstrated that LCA polarizes macrophages toward an M2-resolutive phenotype via concurrent engagement of the TGR5/FXR and their downstream nuclear factor kappa-B (NF-κB) pathways. Ultimately, using a conditioned medium co-culture system, we established that the regulatory effects of pro-resolutive macrophage niche on treatment response in a manner dependent on the TGR5/FXR-NF-κB axis. Taken together, our study elucidates a microbiota-immune circuit in which gut microbial metabolite LCA augments VDZ responsiveness in CD by reprogramming macrophages toward a pro-resolutive phenotype via the TGR5/FXR-NF-κB signaling network. These insights provide a mechanistic foundation for biomarker development and personalized therapeutic strategies in inflammatory bowel disease.}, }
@article {pmid41698880, year = {2026}, author = {Huang, T and Yang, H and Zhang, L and Wang, X and Chen, Y and Dai, H and Hashimoto, K and Luo, Y and Pu, Y and Liu, Y}, title = {HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2630561}, pmid = {41698880}, issn = {1949-0984}, mesh = {*HLA-B27 Antigen/genetics/immunology/metabolism ; Humans ; *Spondylitis, Ankylosing/microbiology/immunology/metabolism ; *Gastrointestinal Microbiome ; *Amino Acids/metabolism ; Animals ; *Macrophage Activation ; Female ; Adult ; *Macrophages/immunology ; Male ; Mice ; Fecal Microbiota Transplantation ; Feces/microbiology ; Middle Aged ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Metabolomics ; }, abstract = {Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen B27 (HLA-B27), yet how this genetic risk factor interacts with the gut microbiome remains unclear. We integrated fecal gut microbiota analysis, untargeted metabolomics, and clinical phenotyping in 88 participants, including HLA-B27-positive patients with AS (n = 28), HLA-B27-positive healthy controls (n = 30), and HLA-B27-negative healthy controls (n = 30). HLA-B27 positivity, particularly in AS, was associated with marked alterations in gut microbial composition and metabolic profiles, with forty bacterial species showing progressive disease-related shifts across cohorts. Integrated pathway and metabolomic analyses identified three amino acid-related pathways consistently disrupted in AS: tryptophan metabolism, cysteine metabolism, and pyruvate-centered biosynthesis of branched-chain amino acids, ornithine, and lysine. Correlation network analyses linking differential taxa, metabolites, and clinical indices revealed previously unrecognized microbial and metabolic signatures that robustly distinguished AS from both control groups. To explore causality, fecal microbiota transplantation (FMT) from clinical donors into antibiotic-treated mice recapitulated key disease-relevant features, including impaired intestinal barrier function, systemic inflammation, trabecular bone loss, and polarization of macrophages toward a proinflammatory M1 phenotype. Mechanistic validation identified cinnabarinic acid as a critical microbial-derived metabolite that suppresses M1 macrophage polarization via activation of the aryl hydrocarbon receptor (AhR) pathway and confers protection in the FMT model. Together, these findings support a model in which HLA-B27-associated gut dysbiosis and metabolic reprogramming promote AS pathogenesis through macrophage-mediated inflammation and osteocatabolic signaling, highlighting microbial-metabolic pathways as potential therapeutic targets.}, }
@article {pmid41698951, year = {2026}, author = {Guo, L and Pei, X and Tan, J and Sun, H and Jiang, S and Wei, H and Peng, J}, title = {From association to intervention: Muribaculaceae driven SCFAs production enhances boar semen quality via inflammation alleviation.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41698951}, issn = {2055-5008}, support = {CARS-35//Agriculture Research System of China/ ; 32430099//Key Program of the National Natural Science Foundation of China/ ; 2662023DKPY002//the Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Male ; Swine ; *Fatty Acids, Volatile/metabolism ; *Semen Analysis ; *Semen ; Mice ; *Inflammation ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fermentation ; }, abstract = {The gut microbiota plays a vital role in host reproduction, yet its contribution to semen quality in boars remains unclear. In this study, we analyzed 556 boars from three commercial breeds and identified Muribaculaceae as a key microbial taxon positively associated with sperm quality, with the effect mediated by short-chain fatty acids (SCFAs). This association was validated in Yorkshire boars with extreme semen phenotypes. Fecal microbiota transplantation in mice confirmed that enrichment of Muribaculaceae improved semen quality, likely through enhanced SCFA production and reduced inflammation in the gut and reproductive tract. Furthermore, in vitro fermentation and mouse experiments demonstrated that a designed functional fiber selectively promoted Muribaculaceae, increased SCFA levels, and improved sperm quality. These findings suggest a functionally supported and potentially translational association between gut microbiota and boar fertility, suggesting that targeted dietary modulation of Muribaculaceae may represent a novel strategy to enhance reproductive performance in livestock.}, }
@article {pmid41699270, year = {2026}, author = {Bashiardes, S and Heinemann, M and Adlung, L and Valdés-Mas, R and Mahdi, JA and Nobs, SP and Tuganbaev, T and Yamada, T and Horn, M and Mor, U and Cohen, Y and Israel, S and Korem, M and Oster, Y and Olshtain-Pops, K and Orenbuch-Harroch, E and Arslan, MD and Molina, S and Zur, M and Eliyahu-Miller, S and Bukimer, A and Federici, S and Dori-Bachash, M and Amar, N and Elbirt, D and Cohen-Poradosu, R and Turner, D and Hershcovici, T and Vainer, E and Stettner, N and Harmelin, A and Gebremeskel, H and Kebede, Y and Schmidt, S and Zmora, N and Dhamodaran, A and Puschhof, J and Bentwich, Z and Shapiro, H and Amit, I and Elinav, H and Elinav, E}, title = {Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection.}, journal = {Nature microbiology}, volume = {11}, number = {3}, pages = {690-703}, pmid = {41699270}, issn = {2058-5276}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology/microbiology ; Mice ; Fecal Microbiota Transplantation ; *HIV Infections/immunology/microbiology/complications/virology ; Feces/microbiology ; *Opportunistic Infections/immunology/microbiology ; Ethiopia ; Female ; CD4-Positive T-Lymphocytes/immunology ; Male ; Disease Susceptibility ; Metagenomics ; Bacteria/classification/genetics/isolation &amp; purification ; Cryptosporidiosis/immunology ; CD4 Lymphocyte Count ; Cohort Studies ; }, abstract = {The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4[+] T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4[+] T cell counts induced colonic epithelium-associated CD4[+] T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity.}, }
@article {pmid41699414, year = {2026}, author = {Karlović, D and Kršul, D and Fučkar Čupić, D and Zelić, M}, title = {Autologous skin graft intersphincteric implantation in anal fistula treatment (ASGIIFT) - A novel surgical technique in the treatment of complex transsphincteric anal fistulas.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {28}, number = {2}, pages = {e70407}, pmid = {41699414}, issn = {1463-1318}, mesh = {Humans ; *Rectal Fistula/surgery ; Male ; Female ; Adult ; Prospective Studies ; Treatment Outcome ; Middle Aged ; *Skin Transplantation/methods ; Postoperative Complications/etiology/epidemiology ; *Anal Canal/surgery ; Wound Healing ; Colorectal Surgical Procedures ; Transplantation, Autologous/methods ; Fecal Incontinence/etiology ; }, abstract = {AIM: This study aimed to evaluate whether implantation of an autologous skin graft in the intersphincteric space, as part of the ASGIIFT procedure, improves the primary healing of complex transsphincteric cryptoglandular anal fistulas.<br><br>METHODS: A prospective observational IDEAL stage 2a study was conducted at a tertiary referral centre for minimally invasive colorectal surgery and proctology in Croatia between September 2021 and January 2023, with an 18-month follow-up. Preoperative pelvic MRI was performed in all cases, and 40 adult patients who met the inclusion criteria were included in the study. The primary outcome was the postoperative primary healing rate which was defined clinically. Secondary outcomes included postoperative continence disturbance, postoperative pain, time of healing and other postoperative complications (Wexner score and VAS - Visual Analogue Scale were used). The ASGIIFT procedure includes all standard steps of the LIFT technique (ligation of the intersphincteric fistula tract), with the addition of a pre-prepared autologous dermal graft placed into the intersphincteric space. The study was approved by the institutional ethics committee.<br><br>RESULTS: Primary clinical healing was achieved in 35 patients (87.5%) within a median of 4&#x2009;weeks postoperatively (range 3-6&#x2009;weeks). Five initially unhealed patients showed conversion from transsphincteric to intersphincteric fistula during the follow-up period and were subsequently treated by fistulotomy without complications. No patient experienced worsening continence, and no serious postoperative complications occurred.<br><br>CONCLUSION: ASGIIFT appears to be a safe and feasible technique for treating transsphincteric anal fistulas, showing promising early results in this single-centre IDEAL 2a study. Further prospective comparative studies are warranted to validate these initial findings.}, }
@article {pmid41702649, year = {2026}, author = {Qi, X and Yang, M and Liu, X and Ma, L and Kaifi, JT and Ericsson, AC and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {Modulating Bacteroides to boost anti-PD-1 immunotherapy in HCC.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {2}, pages = {}, pmid = {41702649}, issn = {2051-1426}, support = {R01 CA208396/CA/NCI NIH HHS/United States ; R01 CA250536/CA/NCI NIH HHS/United States ; R01 CA274959/CA/NCI NIH HHS/United States ; R01 DK130340/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Carcinoma, Hepatocellular/drug therapy/immunology/microbiology ; *Liver Neoplasms/drug therapy/immunology/microbiology ; Mice ; Humans ; *Bacteroides ; *Immunotherapy/methods ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Female ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: The gut microbiota is increasingly recognized as a critical external regulator along the gut-liver axis, influencing hepatocarcinogenesis and modulating responses to immunotherapy. However, the specific microbial determinants, underlying mechanisms, and potential clinical applications remain incompletely elucidated.<br><br>METHODS: Building on the observed association between gut microbiota and anti-programmed cell death protein-1 (PD-1) immunotherapeutic efficacy in patients with hepatocellular carcinoma (HCC), we leveraged a suite of clinically relevant murine HCC models to comprehensively characterize tumor-associated microbial signatures using 16S ribosomal RNA gene sequencing. By precisely manipulating microbial composition through a non-hepatotoxic antibiotic cocktail 3 (ABX-3), targeted microbial supplementation, human fecal microbiota transplant (FMT), and controlled Bacteroides thetaiotaomicron (B.th) repopulation following gut sterilization with ABX-5, we demonstrated a direct causal relationship between microbiota modulation and intrahepatic immune activation. Single-cell RNA sequencing of hepatic non-parenchymal cells, together with functional validation experiments, was performed to elucidate the underlying immune mechanisms.<br><br>RESULTS: Bacteroides-enriched gut microbiota derived from anti-PD-1-responsive patients with HCC significantly suppressed tumor growth in murine HCC models. In parallel, within our murine HCC system, ABX-3 administration, implemented as both a preventive and therapeutic intervention, attenuated tumor initiation and progression by selectively enriching Bacteroides within the gut microbial community. Functionally, ABX-3 enhanced the capacity of tumor antigen-specific T-cell receptor-I T cells to mount robust immune responses, culminating in targeted tumor regression following antigen-specific immunization. Among the Bacteroides species, B.th emerged as a critical mediator that potentiated &#x3b1;PD-1 immunotherapy in HCC by relieving Kr&#xfc;ppel-like factor 2 (KLF2)-dependent suppression in dendritic cells (DCs). Mechanistically, the KLF2-toll-like receptor 9 (TLR9) signaling axis in DCs governed the activation of antigen-specific CD8[+] T cells, thereby amplifying antitumor immunity within the HCC microenvironment.<br><br>CONCLUSIONS: B.th is identified as a key immunomodulatory species that enhances anti-PD-1 efficacy by reprogramming DCs through the KLF2/TLR9 signaling pathway. These findings reveal a novel microbiota-informed strategy to improve immunotherapeutic outcomes in HCC.}, }
@article {pmid41704316, year = {2026}, author = {Wang, Y and Yang, Z and Liu, C and Liu, Y and Bai, Z and Miao, W and Zhang, T and Wang, Y and Li, X and Lai, Z and Xu, J}, title = {Gut microbial signatures of advanced hepatocellular carcinoma and their potential diagnostic value.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1760859}, pmid = {41704316}, issn = {1664-302X}, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy worldwide. Gut microbiota play crucial roles in liver disease progression and may offer noninvasive diagnostic value, yet microbial signatures specific to advanced HCC remain unclear.<br><br>METHODS: Seventy-six participants, including early-stage HCC (HCC12), advanced HCC (HCC34), liver cirrhosis (LC), and healthy controls (CG), were prospectively enrolled. Fecal samples underwent 16S rRNA sequencing to characterize microbial diversity and community composition. Differential taxa were identified using Kruskal-Wallis tests, linear discriminant analysis effect size (LEfSe), and zero-inflated negative binomial regression (ZINB). Machine learning models were constructed using clinical features, representative microbiota, and their combination. External validation was performed using 74 published HCC cases.<br><br>RESULTS: Advanced HCC exhibited reduced microbial richness and diversity, accompanied by substantial community structure alterations. Enterococcus, Enterococcaceae, Enterobacteriaceae, and Escherichia-Shigella were enriched in HCC34, whereas Ruminococcus and Blautia were depleted. These taxa correlated strongly with liver injury markers and HCC-specific biomarkers. The extreme gradient boosting model showed high diagnostic potential when using either clinical or microbial features alone, while the combined model achieved improved accuracy (AUC&#x202f;=&#x202f;1.0 in the primary test set). External validation supported the good generalizability of the model (AUC&#x202f;=&#x202f;1.0 in the external cohort). Feature importance analysis identified Enterococcus as the most influential discriminator of advanced HCC.<br><br>CONCLUSION: This study reveals distinct gut microbial signatures associated with advanced HCC and suggests that Enterococcus may serve as a potentially important microbial marker linked to disease severity. Integrating gut microbiota profiling with clinical features may offer a promising noninvasive strategy for the accurate identification of advanced HCC and provides hypothesis-generating insights for microbiome-based therapeutic interventions.}, }
@article {pmid41704851, year = {2025}, author = {Soriano, S and Marshall, A and Holcomb, M and Flinn, H and Burke, M and Kara, G and Scalzo, P and Villapol, S}, title = {Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's disease pathology in mice.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1703708}, pmid = {41704851}, issn = {1664-302X}, support = {R56 AG080920/AG/NIA NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.<br><br>OBJECTIVE: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.<br><br>METHODS: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24&#x202f;h later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1-, and 3-days post-injury (dpi) included Thioflavin-S and 6E10 immunostaining for A&#x3b2;, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.<br><br>RESULTS: TBI increased cortical and dentate gyrus A&#x3b2; burden, with females showing greater vulnerability. FMT reduced A&#x3b2; deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume at 3 dpi. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.<br><br>CONCLUSION: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.}, }
@article {pmid41705053, year = {2026}, author = {Chen, L and Xinxin, Z and Yue, Z and Qianlei, X and Huijun, G and Xuewei, L}, title = {Intestinal microecology: a crucial factor influencing incomplete immune reconstitution after antiretroviral therapy in people living with HIV-1.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1729968}, pmid = {41705053}, issn = {2296-2565}, mesh = {Humans ; *HIV Infections/drug therapy/immunology ; *HIV-1 ; *Immune Reconstitution ; *Gastrointestinal Microbiome/immunology ; Quality of Life ; Fecal Microbiota Transplantation ; *Anti-Retroviral Agents/therapeutic use ; CD4 Lymphocyte Count ; Probiotics/therapeutic use ; }, abstract = {Some people living with HIV-1 (PLWH) experience insufficient increases in CD4 + T cell counts after antiretroviral therapy (ART), a clinical manifestation referred to as incomplete immune reconstitution (INR). INR significantly increases in the incidence of AIDS and non-AIDS events and profoundly affects the life expectancy and quality of life of PLWH. Recent studies have indicated that intestinal microecology plays a crucial role in immune reconstitution through multiple pathways. This review summarizes several mechanisms through which intestinal microecology contributes to impaired immune reconstitution in PLWH, including changes in microbiota composition, variations in intestinal metabolic products, and damage to the intestinal mucosal barrier. Additionally, intervention strategies such as fecal microbiota transplantation, probiotics, and traditional Chinese medicine are proposed. These innovative therapeutic approaches hold promise for overcoming the limitations of conventional treatments, providing clinicians with a scientific basis for personalized therapeutic strategies and researchers with theoretical guidance for exploring novel mechanisms and research methods. Ultimately, these efforts aim to improve the prognosis and quality of life for PLWH and reduce the global public health burden posed by HIV-1 infection.}, }
@article {pmid41705405, year = {2026}, author = {Wetthasinghe, L and Ng, HF and Chew, KS and Ranai, NM and Ngeow, YF and Lee, WS}, title = {Paediatric Crohn's Disease Management: A Mini Review Exploring Conventional and Innovative Therapies With Promising Potential.}, journal = {Journal of gastroenterology and hepatology}, volume = {41}, number = {4}, pages = {1204-1212}, doi = {10.1111/jgh.70307}, pmid = {41705405}, issn = {1440-1746}, support = {//UTAR Research Scholarship Scheme/ ; 6274/0016//UTAR Research Fund/ ; 6555/1L02//UTAR Research Fund/ ; 4417/0004//Toray Science Foundation Japan/ ; }, mesh = {Humans ; *Crohn Disease/therapy/epidemiology/etiology/immunology ; Fecal Microbiota Transplantation ; Child ; Therapy with Helminths ; Biological Products/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Immunologic Factors/therapeutic use ; Gastrointestinal Microbiome ; Dysbiosis ; Quality of Life ; Immunomodulating Agents/therapeutic use ; Enteral Nutrition ; Treatment Outcome ; }, abstract = {Pediatric Crohn's disease (pCD) is a chronic, relapsing inflammatory bowel disease with increasing incidence worldwide, including in Asia where it was once rare. Affected children often experience gastrointestinal symptoms, growth failure, malnutrition, and psychosocial impacts that significantly impair quality of life. This review summarizes current knowledge on the epidemiology and pathogenesis of pCD, highlighting the role of dysbiosis, environmental triggers, and immune dysregulation. Conventional management strategies, including aminosalicylates, corticosteroids, immunomodulators, biologics, surgery, and nutritional interventions such as exclusive enteral nutrition, are discussed, alongside their limitations in efficacy, tolerability, or long-term safety. The paper further explores emerging therapeutic approaches, including helminthic therapy, fecal microbiota transplantation, and synthetic biotics, which aim to modulate the gut microbiome or immune response more precisely. Although early data from clinical trials are promising, these novel modalities require further investigation, particularly in pediatric populations, to establish optimal protocols, safety profiles, and long-term outcomes. The integration of established and innovative strategies, informed by ongoing research, offers the potential for more personalized and effective care in managing pCD.}, }
@article {pmid41707754, year = {2026}, author = {Zhang, N and Shi, J and Zhang, H and Zhou, Z and Liu, M and Liang, X and Zhou, Y and Zhang, K and Cui, Z and Xue, M and Liang, H}, title = {Folic acid mitigation of alcohol-induced sarcopenia via gut-muscle axis modulation.}, journal = {Metabolism: clinical and experimental}, volume = {178}, number = {}, pages = {156567}, doi = {10.1016/j.metabol.2026.156567}, pmid = {41707754}, issn = {1532-8600}, mesh = {Animals ; Male ; Mice ; *Sarcopenia/chemically induced/prevention &amp; control/metabolism/drug therapy ; Mice, Inbred C57BL ; *Ethanol/adverse effects ; *Folic Acid/pharmacology/therapeutic use ; *Muscle, Skeletal/drug effects/metabolism ; Gastrointestinal Microbiome/drug effects ; Myostatin/metabolism ; Fecal Microbiota Transplantation ; Oxidative Stress/drug effects ; Myoblasts/drug effects ; }, abstract = {BACKGROUND: Alcohol-related muscle dysfunction is highly prevalent and substantially impairs the quality of life in individuals with alcohol use disorders. Chronic alcohol consumption-induced folic acid (FA) deficiency, potentially worsening alcohol-related diseases, and has been reported to FA exert protective effects on muscle health. However, the precise mechanisms by which FA may protect skeletal muscle via the gut-muscle axis in alcohol-induced sarcopenia remain insufficiently elucidated. This study aims to investigate whether FA can prevent alcohol-induced sarcopenia and to elucidate the underlying mechanisms of the gut-muscle axis.<br><br>METHODS: In vivo, eight-week-old male C57BL/6&#xa0;J mice were given a Lieber-DeCarli alcohol diet for 12&#xa0;weeks and administered either FA (2.5 or 5&#xa0;mg/kg) or idebenone (2.5&#xa0;mg/kg). To further elucidate the role of the gut-muscle axis, we conducted in vivo myostatin (MSTN) manipulation and fecal microbiota transplantation (FMT) experiments. Evaluations included muscle mass and strength, histology, mitochondrial function, markers of oxidative stress and inflammation, gut microbiota, and serum metabolomics. In vitro, C2C12 myoblasts were treated with ethanol or indoxyl sulfate (IS) and then supplemented with FA to assess the mechanism of their action.<br><br>RESULTS: FA intervention effectively restored muscle mass and strength, reduced homocysteine levels, and improved mitochondrial function (P&#xa0;<&#xa0;0.05). Mechanistically, FA downregulated MSTN signaling, resulting in decreased protein degradation and increased protein synthesis (P&#xa0;<&#xa0;0.05). In vivo gain- and loss-of-function experiments, confirming MSTN's critical mediation of FA's protective effects. Concurrently, integrated multi-omic analysis identified that FA rebalanced the gut microbiota-metabolite network, with IS identified as a key gut-derived mediator. FMT from high-dose FA-treated donors replicated the muscle-protective effects, confirming the critical causal role of gut microbiota in FA's therapeutic efficacy. In vitro, FA (40&#xa0;&#x3bc;M) improved mitochondrial membrane potential and increased the myotube fusion index while suppressing MSTN pathway activation (P&#xa0;<&#xa0;0.05).<br><br>CONCLUSIONS: FA significantly attenuated alcoholic sarcopenia by modulating the gut-muscle axis. Specifically, FA corrected the dysregulation of the alcohol-Hcy axis, and enhanced mitochondrial function. Additionally, FA rebalanced to the intestinal microbiota-metabolite network and inhibited MSTN-mediated excessive protein degradation, collectively restoring muscle protein homeostasis.}, }
@article {pmid41707756, year = {2026}, author = {Lou, S and Li, W and Wang, G and Qian, H and Zhou, J}, title = {Microbiome-gut-liver axis in chronic inflammation and cancer immunotherapy: Multi-omics Insights and a translational roadmap toward personalized medicine.}, journal = {Critical reviews in oncology/hematology}, volume = {221}, number = {}, pages = {105217}, doi = {10.1016/j.critrevonc.2026.105217}, pmid = {41707756}, issn = {1879-0461}, mesh = {Humans ; *Precision Medicine/methods ; Multiomics ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Inflammation/microbiology/therapy/immunology ; Animals ; *Neoplasms/therapy/immunology/microbiology ; *Liver/metabolism/immunology/pathology ; *Liver Neoplasms/therapy/immunology ; Dysbiosis ; Chronic Disease ; }, abstract = {Gut-liver axis is critical to integrate microbial, metabolic, and immune signaling networks to control hepatic homeostasis and carcinogenesis. Gut microbial balance disruption (dysbiosis) stimulates chronic inflammation, metabolic disorders, and transition from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Latest evidence points to the gut and intratumoral microbiota's roles in shaping immune regulation and responsiveness to immunotherapy against cancer. This review encapsulates the latest evidence on the microbiome-gut-liver axis in chronic liver disease and cancer, highlighting multi-omics evidence, mechanisms of immune modulation, and translational avenues to microbiome-informed precision medicine in HCC. Comprehensive literature search on PubMed, Scopus, Web of Science, and Embase (until September 2025) focused on the gut-liver axis, microbiome, immune checkpoint inhibitors (ICIs), and multi-omics integration. Only mechanistically and translationally relevant peer-reviewed studies were included. Dysbiosis disrupts the permeability of the intestines and metabolism of bile acids and affects immune signaling to induce hepatic inflammation and fibrogenesis. Multi-omic studies identify key microbial metabolites, short-chain fatty acids, secondary bile acids, and tryptophan derivatives to govern the function of T-cell and responsiveness to checkpoint. Clinical research demonstrates that increased abundance of taxa like Akkermansia muciniphila, Bifidobacterium longum, and Faecalibacterium prausnitzii improves ICI efficacy but antibiotic exposure decreases therapeutic efficacy. Tumor-residing microbiomes further determine immune infiltration and risk of recurrence. Multi-omic and computational integration of gut and tumor microbiome data provides mechanistic insight to microbial-informed immunotherapy. Standardization, regulatory convergence, and ethical guidelines are critical to translate microbiome therapeutics, namely fecal microbiota transplantation, engineered probiotics, and metabolite-directed interventions to safe and individualized strategies to treat liver cancer.}, }
@article {pmid41707880, year = {2026}, author = {Sun, H and Yu, Z and Piao, C and Gu, J and Geng, F and Ai, H and Jiang, S and Ren, Y and Gao, J and Wang, Z and Liu, J and Zhang, N and Xu, H}, title = {A multi-omics investigation of Zuojin Wan in alleviating ulcerative colitis: Involvement of gut microbiota, SCFAs, and serum metabolites.}, journal = {Fitoterapia}, volume = {190}, number = {}, pages = {107135}, doi = {10.1016/j.fitote.2026.107135}, pmid = {41707880}, issn = {1873-6971}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Fatty Acids, Volatile/metabolism ; Male ; Multiomics ; *Drugs, Chinese Herbal/pharmacology ; Cytokines/blood ; Disease Models, Animal ; Dysbiosis/drug therapy ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Metabolomics ; Dextran Sulfate ; Colon/pathology/drug effects ; }, abstract = {OBJECTIVE: Ulcerative colitis (UC) involves barrier disruption, dysbiosis, and altered host-microbe metabolism. Zuojin Wan (ZJW) benefits gastrointestinal disorders, but its systems-level mechanisms in UC are unclear.<br><br>METHODS: In DSS-induced UC mice, ZJW chemistry was profiled by HPLC-MS, and efficacy was assessed by DAI, colon length, histology, and serum cytokines. Mechanistic assays included 16S sequencing, GC-MS SCFA quantification, serum metabolomics, tight-junction immunohistochemistry, and FMT from ZJW-treated donors.<br><br>RESULTS: ZJW reduced DAI, protected colon structure, improved mucosal injury, and decreased IL-6, TNF-&#x3b1;, IL-1&#x3b2;, and IL-18. It corrected dysbiosis with increased beneficial taxa (e.g., Akkermansia), elevated SCFAs-especially propionic and n-pentanoic acids-and remodeled metabolites in glycerophospholipid and aromatic amino-acid pathways. SCFAs correlated with key serum metabolites. ZJW restored Claudin-5 and Occludin localization, and FMT transferred protection to depleted recipients.<br><br>CONCLUSIONS: ZJW ameliorates colitis via a microbiota-SCFA-metabolic axis that suppresses inflammation and strengthens tight junctions, supporting its multi-target utility in UC.}, }
@article {pmid41708187, year = {2026}, author = {Fang, M and He, J and Zhou, S and Hong, P and Ke, L and Wu, H and Shu, Y}, title = {Pleurotus ostreatus polysaccharides improve microcystin-LR-induced intestinal damage in tadpoles by regulating the interaction between microbiota and intestine.}, journal = {Harmful algae}, volume = {153}, number = {}, pages = {103056}, doi = {10.1016/j.hal.2026.103056}, pmid = {41708187}, issn = {1878-1470}, mesh = {Animals ; *Microcystins/toxicity ; *Pleurotus/chemistry ; *Polysaccharides/pharmacology ; Marine Toxins ; *Intestines/drug effects ; Larva/drug effects ; *Ranidae ; *Gastrointestinal Microbiome/drug effects ; Oxidative Stress/drug effects ; }, abstract = {Exposure to microcystins (MCs) can cause severe intestinal damage. This study aimed to assess the efficacy of Pleurotus ostreatus polysaccharide in alleviating intestinal damage induced by microcystin-leucine-arginine (MC-LR) in tadpoles. Over a 30-day period, tadpoles (Pelophylax nigromaculatus) received daily exposures to MC-LR and were provided with diets either supplemented with or devoid of P. ostreatus polysaccharide. Results revealed that feeding P. ostreatus polysaccharide conferred protection against MC-LR-induced intestinal damage by mitigating barrier damage, lowering intestinal permeability, and reducing the tissue burden of MC-LR. The LPS/TLR4 pathway response was attenuated, reducing inflammation, and oxidative stress-mediated apoptosis response was also diminished. Gram-negative bacteria (e.g., Bacteroides) in the intestine show a positive correlation with LPS content and the transcription of key genes in the LPS/TLR4 pathway. Metagenomic and metabolite analysis of intestinal contents revealed increased abundance of the alanine-glyoxylate aminotransferase gene (agxt)-the key enzyme converting glyoxylic acid to glycine-and elevated glycine content in the MC-LR-exposed group fed polysaccharide. Results from the corresponding fecal microbiota transplantation experiment aligned with the trends observed in the exposure experiment. Therefore, polysaccharide alleviates MC-LR-induced intestinal damage by enhancing intestinal microbiota-mediated glycine synthesis, supplying raw materials for intestinal GSH production, reducing oxidative stress levels, and simultaneously dampening the LPS/TLR4 pathway response. Moreover, feeding polysaccharides might also regulate the intestine's defense against pathogens after MC-LR exposure by enhancing lysozyme activity. There is no evidence of intestinal damage in the P. ostreatus exopolysaccharide group. This study highlights for the first time the role of P. ostreatus polysaccharides in mitigating MC-LR-induced intestinal tissue damage, potentially offering novel insights for their application in aquaculture.}, }
@article {pmid41708473, year = {2026}, author = {Liss, MA and White, JR and Doris, M and Lai, Z and Johnson-Pais, TL and Leach, RJ and Goros, M and Gelfond, J and Wickes, B}, title = {Gut Microbiome as a Lifestyle Risk Factor Associated with Prostate Cancer.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2026.01.001}, pmid = {41708473}, issn = {2405-4569}, abstract = {BACKGROUND AND OBJECTIVE: Most prostate cancer prevention strategies suggest lifestyle modifications, which lack personalization. Gut microbiome is increasingly recognized as an influencing factor in nongastrointestinal cancers, including prostate cancer. The use of gut microbiome as a lifestyle biomarker could help identify individuals with lifestyle more prone to prostate cancer and allow for modification. We aimed to develop a gut microbiome-based biomarker derived from patients undergoing prostate cancer screening.<br><br>METHODS: We assessed whether the future cancer risk can be evaluated based on a microbiome risk analysis. After extracting DNA, sequencing, and performing a bioinformatics analysis, we identified 39 unique microbial genera of importance. We utilized an artificial intelligence model to calculate their presence, abundance, and weighted significance, generating a microbiome score (Prostate Cancer Risk Insight using Microbiome UnderStanding [PRIMUS]) that ranges from 0 to 1.<br><br>KEY FINDINGS AND LIMITATIONS: Men with an increasing PRIMUS signature showed a sequential increase in prostate cancer risk. The prostate cancer risk persisted after a median follow-up of 4.5&#xa0;yr. As a risk-assessment tool, the microbiome score compared favorably with prostate cancer risk calculators. Study limitations include the use of two patient groups to diversify the population for both a screening and a prebiopsy scenario; however, the cohorts used different collection methods, including stool, rectal swabs, and glove tip samples, but the same DNA isolation and sequencing. We relied on the longitudinal approach to help reduce these initial differences.<br><br>The gut microbiome may serve as a lifestyle risk factor for prostate cancer, but it is not intended to guide biopsy decisions. The implications of this study hinge on the potential for modifiability of the microbiome that could be tested in future clinical trials on prostate cancer risk reduction.}, }
@article {pmid41708595, year = {2026}, author = {Moses, AB and Yeh, AC}, title = {The gut microbiome in graft-versus-host disease: mechanisms of immune modulation and therapeutic approaches.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2631224}, pmid = {41708595}, issn = {1949-0984}, support = {K08 HL167161/HL/NHLBI NIH HHS/United States ; }, mesh = {*Graft vs Host Disease/immunology/microbiology/therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Animals ; Gastrointestinal Tract/microbiology/immunology ; Immunity, Innate ; Adaptive Immunity ; Host-Directed Therapy ; T-Lymphocytes/immunology ; }, abstract = {Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation and occurs when T cells from the donor graft target recipient-derived antigen on host tissue. The involvement of the gastrointestinal (GI) tract drives morbidity and mortality-not coincidentally, the GI tract also harbors the most complex and abundant human microbial reservoir. In this review, we first revisit how the microbiota initiates, propagates, and protects against GvHD in the context of both innate and adaptive immunity. Historically, the impact of the microbiota on GvHD has been ascribed primarily to the activation of innate immunity, setting the stage for donor alloreactivity. Although established models of GvHD focus on donor-host genetic disparity as the principal driver of donor T-cell activation, commensal microbes in the GI tract, whose collective gene content exceeds that of the human genome by more than two orders of magnitude, constitutes an immense and poorly understood source of potential T-cell antigens. We next discuss the evolution of therapeutic approaches aimed at modifying the microbiota to improve GvHD outcomes, incorporating over 40 clinical studies spanning the last 40 years, from broad decontamination strategies to pre/probiotic approaches and targeted ecosystem replacement, including fecal microbiota transplantation.}, }
@article {pmid41709304, year = {2026}, author = {Zhang, Q and Zhu, Q and Xiao, Y and Liao, S and Liu, S and Shi, S}, title = {Microbiota-derived propionate suppresses Salmonella virulence gene expression via LuxS quorum sensing.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {70}, pmid = {41709304}, issn = {2049-2618}, support = {32573258//National Natural Science Foundation of China/ ; YZ2024242//Yangzhou Science and Technology Program/ ; CARS-41-G01//Agriculture Research System of China/ ; }, mesh = {Animals ; *Quorum Sensing/drug effects ; Chickens/microbiology ; *Propionates/metabolism/pharmacology ; *Bacterial Proteins/genetics/metabolism ; *Carbon-Sulfur Lyases/genetics/metabolism ; Virulence/genetics ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Bacterial/drug effects ; *Salmonella Infections, Animal/microbiology ; Cecum/microbiology ; Biofilms/drug effects/growth &amp; development ; RNA, Ribosomal, 16S/genetics ; Homoserine/analogs &amp; derivatives/metabolism ; *Salmonella/pathogenicity/genetics/drug effects ; Virulence Factors/genetics ; Lactones/metabolism ; Feces/microbiology ; Fatty Acids, Volatile/metabolism ; Poultry Diseases/microbiology ; }, abstract = {BACKGROUND: Despite mounting evidence that commensal microbes enhance host defenses, whether and how they directly suppress pathogen virulence remains elusive. Here, we investigate metabolites from the gut microbiota of infection‑resistant Tibetan chickens for their ability to reduce Salmonella virulence gene expression and elucidate the molecular mechanism by which these compounds inhibit the LuxS/AI‑2 quorum‑sensing system.<br><br>RESULTS: Initially, we compared the expression of the quorum&#x2011;sensing gene luxS and biofilm-associated virulence genes in Tibetan chickens and broiler chickens post-Salmonella infection. Notably, Tibetan chickens exhibited significantly lower virulence gene expression than broiler chickens. Subsequently, fecal microbiota transplantation (FMT) from Tibetan chickens to broiler chickens reduced virulence gene expression in infected recipients. Further, 16S rRNA gene sequencing of cecal contents revealed that FMT enhanced microbial diversity and altered composition in infected broiler chickens, specifically enriching short-chain fatty acids (SCFA)-producing beneficial bacteria (e.g., Bacteroides, Rikenellaceae_RC9_gut_group, Phascolarctobacterium, Desulfovibrio). Critically, using Transwell chambers to separate microbes and metabolites, we identified metabolites as mediators of this effect. Subsequent liquid chromatography-mass spectrometry (LC-MS) quantification demonstrated significantly elevated propionate concentrations in both uninfected and infected Tibetan chickens, and FMT-recipient broiler chickens. Propionate levels correlated negatively with key virulence factor expression. Moreover, in vitro experiments showed that propionate inhibited Salmonella biofilm formation, reduced autoinducer-2 (AI-2) activity, and downregulated the expression of virulence genes. In vivo, we further confirmed that propionate decreased the expression of Salmonella virulence genes. Taken together, these results support that propionate suppresses Salmonella virulence gene expression by targeting the LuxS/AI-2 quorum-sensing pathway. To validate this mechanism, we generated a luxS knockout strain by homologous recombination; strikingly, propionate failed to attenuate virulence gene expression in this mutant, thereby establishing the essential role of LuxS/AI-2. Finally, molecular docking identified propionate-LuxS binding sites (Ile53), and site-directed mutagenesis validated critical functional residues, highlighting structural determinants for virulence gene expression regulation.<br><br>CONCLUSION: These findings underscore the role of the gut-derived metabolite propionate in directly modulating pathogen virulence gene expression by targeting the LuxS/AI-2 quorum&#x2011;sensing system, offering novel insights into microbiota-based strategies for infectious disease management.}, }
@article {pmid41710924, year = {2026}, author = {Liu, X and Chen, Z and Lu, Y and Wu, Y and Huang, Y and Zhang, Y and Li, M and Feng, N}, title = {Fecal microbiota transplantation: a novel strategy and challenges in the adjuvant treatment of bladder Cancer.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1756107}, pmid = {41710924}, issn = {1664-302X}, abstract = {The clinical management of bladder cancer faces major challenges due to treatment resistance and recurrence, which require the development of new adjuvant strategies. The role of the gut microbiome in influencing bladder cancer progression and treatment response through the "gut-bladder axis" is gaining recognition. This understanding provides a theoretical rationale for exploring microbiota-targeting interventions, such as fecal microbiota transplantation (FMT). As a method capable of thoroughly reshaping the gut microbiota, FMT may have broad clinical potential. This review systematically explores the possible role of FMT in treating bladder cancer. It begins by summarizing the observational and causal evidence linking gut microbiota dysbiosis to bladder cancer, which forms the rationale for considering FMT as an intervention. Then, it discusses how FMT might improve therapeutic effectiveness, including regulation of microbial metabolites (such as short-chain fatty acids, tryptophan, and bile acids), repair of the intestinal barrier, induction of epigenetic reprogramming and modulation of the urinary microbiota. The review also considers potential scenarios for combining FMT with existing adjuvant therapies, including immunotherapy, chemotherapy, and radiotherapy. Finally, it objectively evaluates the key challenges in translating FMT into clinical practice, including effectiveness, safety, standardization, and regulatory or ethical issues, and outlines future directions. By synthesizing current evidence, this review highlights FMT as a potentially promising and innovative adjuvant strategy worthy of further investigation, which, if validated, could contribute to overcoming current therapeutic challenges in bladder cancer.}, }
@article {pmid41711677, year = {2026}, author = {Rinderknecht, S and Bertolo, A and Valido, E and Stojic, S and Wong, S and Farkas, GJ and Iyer, P and Jaric, I and Stoyanov, J and Glisic, M}, title = {The role of short-chain fatty acids in spinal cord injury: A systematic review of human and animal evidence.}, journal = {The journal of spinal cord medicine}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10790268.2025.2607831}, pmid = {41711677}, issn = {2045-7723}, abstract = {CONTEXT: Spinal cord injury (SCI) disrupts gut microbiota composition, resulting in dysbiosis that can worsen neuroinflammation and impede post-injury recovery. Short-chain fatty acids (SCFA), metabolites produced by the gut microbiome with anti-inflammatory properties, offer a promising avenue for improving recovery and rehabilitation outcomes.<br><br>OBJECTIVE: We aimed to compile a summary of the human and animal evidence on the potential benefits of SCFA or SCFA &#xa0;- producing bacteria in individuals with SCI.<br><br>METHODS: Three databases (EMBASE, Medline (Ovid) and Web of Science) were searched from inception until 19 October 2023. No language restrictions were applied. Title and abstract screening, data extraction and risk of bias assessments were done independently by two reviewers.<br><br>RESULTS: A total of 2492 studies were retrieved, 69 full-text studies were reviewed, and 13 studies were included (11 animal and 2 human). Human studies, which involved participants with chronic SCI, linked gut dysbiosis (a proxy for low SCFA production) and human metabolic profiles, suggesting a potential role for microbiome-targeted interventions even in later stages of injury. Evidence from animal studies, predominantly in acute and sub-acute models of SCI, consistently associated SCFA interventions with improved motor function, reduced tissue damage and favorable changes in inflammatory and oxidative stress markers. Fecal microbiota transplantation and probiotics improved motor function and reduced lesion size in animal models. Gut microbiome modulations through treatments such as melatonin, moxibustion, and intermittent fasting was correlated with improved motor outcomes and increased abundance of SCFA-producing bacteria.<br><br>CONCLUSIONS: This review highlights the potential of targeting the gut microbiota and SCFAs as therapeutic strategies for SCI recovery. However, despite promising results in animal models, human evidence remains limited.}, }
@article {pmid41713032, year = {2026}, author = {Park, J and Choi, Y and Lee, W and Kang, A and Seo, E and Kim, MG and Jang, KB and Song, M and Oh, S and Kim, Y}, title = {Heat-killed Bacteroides fragilis SLAM_BAF01 alleviates weaning-induced stress responses and cognitive impairments by modulating the gut-brain-microbiome axis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {196}, number = {}, pages = {119121}, doi = {10.1016/j.biopha.2026.119121}, pmid = {41713032}, issn = {1950-6007}, mesh = {Animals ; *Bacteroides fragilis ; *Weaning ; *Brain/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; *Stress, Psychological/microbiology ; Swine ; *Probiotics/pharmacology ; Fecal Microbiota Transplantation ; Hot Temperature ; Mice ; Male ; Mice, Inbred C57BL ; Female ; *Cognition ; Stress, Physiological ; }, abstract = {Weaning transition in porcine industry is marked by nutritional, microbial, and psychological stresses that can impair growth and development. Accumulating evidence indicates that weaning-related stress not only disrupts gut microbial homeostasis but impairs gut-brain axis signaling through activation of stress-related neuroendocrine pathways. However, current interventions have largely focused on improving growth performance or enteric symptoms, while integrated strategies targeting the gut-brain-microbiome axis remain limited. Next-generation probiotics (NGPs) such as Bacteroides fragilis have been reported to exert beneficial effects on both intestinal health and brain function, positioning them as promising candidates for alleviating weaning stress. However, their practical application remains challenging due to the strict anaerobic nature. In this study, we investigated that a porcine-derived heat-killed B. fragilis SLAM_BAF01 exerts beneficial effects under weaning stress through gut-brain-microbiome modulation, thereby enabling a more stable and scalable application. First, to investigate the relationship within the gut-brain-microbiome axis under weaning stress conditions, we employed a fecal microbiota transplantation (FMT)-based mouse model and a physiologically relevant weaning pig model. Multi-omics analyses were conducted to characterize microbial and host responses. B. fragilis SLAM_BAF01 exhibited acid and bile tolerance, preserved structural integrity, and lacked enterotoxicity. In the mouse FMT model, heat-killed SLAM_BAF01 positively modulated gut microbial composition, reinforced intestinal barrier function, and attenuated stress-related responses. Especially, brain γ-aminobutyric acid (GABA) levels increased by 150 %, while serum corticosterone levels were reduced by 17 % compared with the control. In the weaning pig model, heat-killed SLAM_BAF01 improved growth performance by 7 % and significantly reduced inflammation and stress markers. These findings demonstrate that heat-killed postbiotic B. fragilis SLAM_BAF01 as a promising candidate capable of mitigating weaning-associated stress through enhancing gut-brain-microbiome axis function in porcine industry.}, }
@article {pmid41713730, year = {2026}, author = {Li, Y and Zhang, Y and Liu, T and Tuo, Y and Zhang, Y and You, H and Peng, S and Wu, T and Cai, T and Lin, Z and Feng, Z and Liu, Z and Wu, J and Liu, X and Ding, L}, title = {Alleviation of high-fat diet-induced lipid metabolism disorders: role of quinoa peptides in reducing high-activity BSH-producing gut microbiota abundance and modulating BA-FXR/TGR5 signaling.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.02.040}, pmid = {41713730}, issn = {2090-1224}, abstract = {INTRODUCTION: Lipid metabolism disorders contribute significantly to various metabolic diseases and are closely related to gut microbiota dysbiosis. Quinoa intake has been increasingly linked to improved metabolic regulation and body weight control. In our earlier work, oral administration of quinoa-derived peptides (QPep) modulated gut microbiota composition and mitigated hepatic lipid dysregulation in high-fat diet (HFD)-induced obese mice. Nevertheless, the specific mechanisms responsible for these effects remain incompletely understood.<br><br>OBJECTIVES: This study aimed to elucidate the mechanisms by which QPep alleviates lipid metabolic disorders in HFD-induced obese mice.<br><br>METHODS: Mice were fed a HFD with or without oral QPep intervention. Both antibiotic treatment and fecal microbiota transplantation were employed to assess the microbiota-dependent effects of QPep. Comprehensive multi-omics and molecular analyses were conducted to characterize metabolic phenotypes alongside gut microbial composition, bile acids (BAs) metabolism, and host signaling pathways in the liver, ileum, and adipose tissues.<br><br>RESULTS: QPep administration alleviated HFD-induced metabolic disorders, leading to reductions in body weight and adiposity, improvements in serum lipid profiles and hepatic steatosis, and restoration of glucose homeostasis. Microbiota depletion and transplantation experiments suggested a microbiota-dependent contribution to the observed effects. Mechanistically, QPep selectively reduced high-activity bile salt hydrolase (BSH)-producing bacteria abundance, reduced intestinal BSH activity, and preserved conjugated BAs, thereby suppressing ileal FXR-FGF15 signaling, enhancing hepatic BAs synthesis, and activating TGR5 in adipose and ileum tissues to restore systemic lipid metabolism.<br><br>CONCLUSION: These findings demonstrate that QPep modulate gut microbiota-BAs signaling to restore lipid homeostasis, highlighting their potential as a dietary intervention for the prevention and management of obesity-related metabolic disorders.}, }
@article {pmid41713731, year = {2026}, author = {Xu, J and Hu, R and Zheng, J and Ju, Q and Liu, Y and Chen, S and Liu, Z and Lei, Y and Yang, J and Zhang, D and Shen, W}, title = {Modulation of the intestinal microbiome and reversal of the immunosuppressive microenvironment by nanoparticles for chemoimmunotherapy in prostate cancer.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.02.027}, pmid = {41713731}, issn = {2090-1224}, abstract = {INTRODUCTION: Prostate cancer (PCa), a "cold" tumor with an immunosuppressive microenvironment, exhibits poor sensitivity to immunotherapies, limiting treatment efficacy. Chemotherapeutics often cause intestinal injury and disrupt gut microbiota, further impairing chemoimmunotherapy outcomes. Modulating gut microbiota to reverse immunosuppression represents a potential strategy to enhance PCa treatment.<br><br>OBJECTIVES: To develop a novel therapeutic strategy using nanomedicine to regulate intestinal flora, thereby reversing the immunosuppressive microenvironment and improving chemoimmunotherapy efficacy in PCa.<br><br>METHODS: Cabazitaxel (CBZ)-loaded, folic acid (FA)-modified pH/ROS dual-responsive nanoparticles (CBZ/FA-CA-OCD NPs) were fabricated. In vitro and in vivo experiments evaluated NPs accumulation, cellular internalization (via FA-mediated endocytosis), drug release, intestinal mucosal injury, and tumor growth inhibition. Gut microbiota modulation (e.g., Lachnospiraceae, Firmicutes, Muribaculaceae, Bacteroidota) and CD4[+]/CD8[+] T-cell infiltration were assessed. Fecal microbiota transplantation (FMT) validated microbiota-mediated immune effects.<br><br>RESULTS: The CBZ/FA-CA-OCD NPs accumulated in PCa tissues were internalized by PC-3/LNCaP cells and released CBZ in acid/ROS microenvironments to inhibit tumor growth. Compared to free CBZ, NPs attenuated intestinal injury, modulated microbiota (increased Lachnospiraceae/Firmicutes, decreased Muribaculaceae/Bacteroidota), and enhanced anti-PD-1 efficacy by increasing CD4[+]/CD8[+] T-cell infiltration. FMT confirmed that microbiota from NP-treated mice promoted T-cell infiltration in tumors.<br><br>CONCLUSION: CBZ/FA-CA-OCD NPs improve PCa chemoimmunotherapy by regulating gut microbiota, reversing immunosuppression, and enhancing T-cell infiltration. This nanomedicine-based strategy provides a promising approach to boost PCa treatment outcomes.}, }
@article {pmid41713817, year = {2026}, author = {Zhao, Q and Cao, Y and Zhang, Z and Yang, Y and Wang, L and Xu, M and Mao, Y and Zhang, X and Zeng, M and Yang, P and Chen, Q and Yan, H and Yang, G}, title = {Xiao-Chaihu-Tang preserves intestinal barrier and ameliorates irinotecan-evoked delayed diarrhea by anchoring endogenous tryptophol to modulate inflammation and oxidation dependent on AhR-UGT1A1-microbiota axis.}, journal = {Journal of ethnopharmacology}, volume = {363}, number = {}, pages = {121380}, doi = {10.1016/j.jep.2026.121380}, pmid = {41713817}, issn = {1872-7573}, mesh = {Animals ; *Irinotecan/toxicity ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Diarrhea/chemically induced/drug therapy/metabolism/prevention &amp; control ; Male ; Rats, Sprague-Dawley ; UGT1A1 Enzyme ; Glucuronosyltransferase/metabolism ; *Gastrointestinal Microbiome/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; Rats ; Intestinal Barrier Function/drug effects ; Humans ; Inflammation/drug therapy/metabolism ; Oxidation-Reduction/drug effects ; *Indoles/metabolism ; }, abstract = {Xiao-Chaihu-Tang (XCHT), a well-known traditional formula, is commonly used to treat various types of diarrhea. It also exhibits promising efficacy against chemotherapy irinotecan (CPT-11)-induced delayed diarrhea (DD). However, its underlying mechanisms, specifically concerning endogenous metabolites, key pathways, and functional gut bacteria at the species level, remain unclear, severely restricting its clinical application.<br><br>AIM OF THE STUDY: This study aimed to elucidate the biomarkers, pathways, and functional bacteria involved in XCHT's alleviating CPT-11-evoked DD using multi-omics approaches, antagonists, and fecal microbiota transplantation (FMT).<br><br>MATERIALS AND METHODS: First, the ingredients of XCHT and absorbed compounds in rat plasma were identified using liquid chromatography-mass spectrometry (LC-MS). Next, the therapeutic effects of XCHT were assessed by monitoring perianal status, body weight, disease activity index, food and water intake, and histopathological changes in the colon (hematoxylin and eosin, alcian blue-periodic acid-schiff staining). The underlying mechanisms were studied using metabolomics and network pharmacology, which highlighted the role of endogenous biomarkers and associated pathways. Tryptophol was identified as a key correlate, and its efficacy was further validated in rat and Caco-2 models using antagonists of potential targets (AhR and UGT1A1). The levels of inflammatory cytokines, and oxidative stress markers, intestinal barrier proteins, and mucins were detected by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunofluorescence. Furthermore, functional gut bacteria were identified using metagenomic sequencing and validated using FMT, while gut leakage was detected using fluorescence in situ hybridization (FISH). Finally, the interactions between tryptophol with targets of AhR and UGT1A1 were examined using molecular docking, molecular dynamics, and surface plasmon resonance.<br><br>RESULTS: LC-MS analysis identified 43 phytochemicals in XCHT and 17 compounds absorbed in plasma. XCHT, similar to tryptophol, attenuated DD by improving perianal status, disease activity index, and colon pathology, while increasing body weight, food intake, and water intake. Metabolomics analysis revealed 33 potential endogenous biomarkers, including PGB3, LysoPA, and so on. Integrated with network pharmacology, the results indicated that the therapeutic effect of XCHT involved the regulation of tryptophan metabolism, arachidonic acid metabolism, inflammation, and oxidative stress. Tryptophol, which exhibited a strong correlation with efficacy indices, reduced inflammation and oxidation in vivo/vitro, and enhanced intestinal barrier protein and mucin expression in an AhR-UGT1A1-dependent manner. Furthermore, metagenomic sequencing and FISH demonstrated that both XCHT and tryptophol normalized the abundance of 10 gut bacterial species (for example, Lactobacillaceae bacterium, Massiliimalia timonensis, and Limosilactobacillus reuteri) and inhibited bacterial invasion. Molecular interaction studies confirmed the strong binding between tryptophol with AhR and UGT1A1.<br><br>CONCLUSION: This study demonstrates that XCHT preserves intestinal barrier integrity in rats and alleviates CPT-11-induced DD. This protective effect is mediated by modulating inflammation and oxidative stress via the tryptophol- AhR-UGT1A1-microbiota axis, providing a novel paradigm for mechanistic studies on toxicity reduction in clinical chemotherapy drugs.}, }
@article {pmid41713826, year = {2026}, author = {Yerushalmy-Feler, A and Spencer, EA and Dubinsky, MC and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Sladek, M and Yeh, PJ and Tzivinikos, C and Henderson, P and Wlazlo, M and Hackl, L and Shouval, DS and Mouratidou, N and Bramuzzo, M and Urlep, D and Olbjørn, C and Mancuso, G and Schneider, AM and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Romano, C and Martinelli, M and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Rimon, RM and Granot, M and Scarallo, L and Trindade, E and Rodríguez-Belvís, MV and Turner, D and Cohen, S}, title = {Upadacitinib Maintenance Therapy in Pediatric Ulcerative Colitis: 52-Week Multicenter Study From the Porto Group of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2026.02.012}, pmid = {41713826}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a maintenance therapy in pediatric UC.<br><br>METHODS: Children treated with upadacitinib for maintenance of remission of active UC or IBD-U from 35 centers affiliated with the Porto group of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were enrolled in this retrospective study. Data on demographic, clinical, laboratory, endoscopic, imaging, and adverse events (AEs) were recorded over 52 weeks of follow-up.<br><br>RESULTS: A total of 105 children were included (95 with UC and 10 with IBD-U; mean age, 14.6 &#xb1; 3.3 years). Prior to upadacitinib, 103 of 105 children (98%) were treated with biologic therapies and 79 (75%) with &#x2265;2 biologics. Clinical remission and corticosteroid-free clinical remission (CFR) were observed after 8 weeks in 61 (58%) and 53 (51%) children, respectively. By week 52, 75 children (71%) achieved clinical remission and 73 (70%) achieved CFR. Sustained CFR was recorded in 63 children (60%). CFR with normal C-reactive protein was observed in 56% of children, and CFR with fecal calprotectin levels <150 mcg/g was observed in 38%, by week 52. Fifty-two children (50%) experienced AEs, 2 of which were serious (an appendiceal neuroendocrine tumor and cytomegalovirus colitis). The most frequent AEs were hyperlipidemia (n = 20), infections (n = 18), and acne (n = 14).<br><br>CONCLUSIONS: Upadacitinib is an effective induction and maintenance therapy for refractory pediatric UC and IBD-U. Effectiveness should be weighed against the potential risks of AEs.}, }
@article {pmid41714075, year = {2026}, author = {Konar, D}, title = {Clinical applications of live biotherapeutics: Current trends and future prospects.}, journal = {Progress in molecular biology and translational science}, volume = {220}, number = {}, pages = {103-138}, doi = {10.1016/bs.pmbts.2026.01.003}, pmid = {41714075}, issn = {1878-0814}, mesh = {Humans ; Animals ; *Biological Therapy/trends ; *Biological Products/therapeutic use ; }, abstract = {Live biotherapeutic (LBP) is defined by the FDA as a biological product that: (1) contains live organisms, such as bacteria; (2) applies to the prevention, treatment, or cure of a disease or condition of human beings; and (3) is not a vaccine. Progress in microbiome science and the limitations of antibiotics have necessitated the use of LBPs to complement or replace conventional therapies across multiple medical disciplines. The most important advancement is in the infectious disease domain, where fecal microbiota transplantation validated ecological restoration for recurrent Clostridioides difficile infection and paved the way for the first approved LBPs (REBYOTA® and VOWST™/SER-109). Constructing rational microbial consortia and strain-level strategies aim to induce commensal resilience and prevent the establishment of multidrug-resistant organisms. In oncology, gut microbial composition modulates response to immune checkpoint inhibitors. So, defined microbial consortia and engineered E. coli Nissle are being developed to enhance antitumor immunity and localize payloads. Early studies in animals and humans also support the application of this approach in metabolic disease, allergy, and oral health. Translation from benchside to bedside, however, is fraught with hurdles-variable patient response, manufacturing consistency, safety standards, cost, and ethics-exacerbated by heterogeneous global regulations, underscoring the need for harmonization. Precision microbial consortia, programmable "living medicines," and biohybrid formulations could extend LBPs into broader indications and global health, shifting practice toward an ecological model of therapeutics.}, }
@article {pmid41714079, year = {2026}, author = {Bhowmick, J and Bagchi, A}, title = {Fecal microbiota transplantation in liver diseases: Therapeutic potential and associated risks.}, journal = {Progress in molecular biology and translational science}, volume = {220}, number = {}, pages = {229-246}, doi = {10.1016/bs.pmbts.2026.01.001}, pmid = {41714079}, issn = {1878-0814}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Liver Diseases/therapy/microbiology ; Risk Factors ; Animals ; }, abstract = {Fecal microbiota transplantation (FMT) is a biologically coherent strategy to modulate the gut-liver axis by restoring ecosystem structure and function. This chapter synthesizes current evidence and practice of FMT in various liver disease conditions. In cirrhosis with recurrent hepatic encephalopathy (HE), randomized trials demonstrate adjunctive benefits of FMT, reducing recurrence and hospitalizations as well as improving cognition, with route flexibility (lower-GI infusions or oral capsules) and emerging microbiome predictors of response. In severe alcohol-associated hepatitis and ACLF, early single-center trials suggest fewer infections and short-term survival gains, warranting confirmation in multicenter, blinded studies for further outcomes. For MASLD/MASH, FMT consistently shifts intestinal permeability, bile-acid signatures, and hepatic transcriptomics, although it has not reliably improved MRI-PDFF or insulin resistance in unselected cohorts; future success likely requires phenotype enrichment and function-matched donors or defined consortia. Data in chronic hepatitis B remain exploratory, positioning FMT, if at all, as an adjunct to antivirals. Methods are standardized around rigorous donor screening, controlled manufacturing, indication-specific endpoints, and strain-resolved engraftment analytics linking mechanism to outcome. Refractory Clostridium difficile is the only FDA-approved indication of FMT. Use of FMT in hepatology use should remain protocolled and regulated. Priorities include precision donor matching, next-generation consortia, platform trials, and long-term safety registries.}, }
@article {pmid41714082, year = {2026}, author = {Mahajan, S and Nk, A and Banerjee, SK}, title = {Recent advances of microbial medicine to prevent and treat cardiovascular disease.}, journal = {Progress in molecular biology and translational science}, volume = {220}, number = {}, pages = {305-337}, doi = {10.1016/bs.pmbts.2026.01.028}, pmid = {41714082}, issn = {1878-0814}, mesh = {Humans ; *Cardiovascular Diseases/prevention &amp; control/therapy/microbiology ; Animals ; Gastrointestinal Microbiome ; }, abstract = {Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with standard pharmacological interventions often failing to fully address their complex pathophysiology. Recent advances in microbial medicine highlight the human gut microbiome as a critical regulator of cardiovascular health. Gut microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and indole derivatives play pivotal roles in modulating inflammation, lipid metabolism, immune function, and vascular homeostasis. Dysbiosis, or microbial imbalance, has been strongly associated with atherosclerosis, hypertension, and heart failure. Consequently, therapies targeting the gut microbiota including probiotics, prebiotics, synbiotics, and postbiotics have emerged as promising adjuncts in CVD prevention and treatment. Moreover, fecal microbiota transplantation (FMT) and synthetic biology approaches using engineered microbes offer novel strategies to restore microbial balance and deliver therapeutic molecules. Dietary interventions, particularly Mediterranean and fiber-rich diets, further support cardiovascular health through microbiota modulation. While preclinical and clinical studies underscore the potential of microbiome-based interventions, challenges related to strain specificity, delivery systems, and regulatory frameworks remain. Nonetheless, integrating microbial medicine into cardiovascular care represents a transformative shift toward precision, holistic, and personalized treatment paradigms. This chapter explores these cutting-edge therapeutic interventions and their implications for reshaping the future landscape of cardiovascular disease management.}, }
@article {pmid41715264, year = {2026}, author = {Kumar, R and Elangovan, S and Asrani, SK}, title = {Emerging therapeutic regimens as alternatives to glucocorticoids for severe alcohol-associated hepatitis: a comprehensive review.}, journal = {Clinical and molecular hepatology}, volume = {32}, number = {2}, pages = {599-619}, pmid = {41715264}, issn = {2287-285X}, mesh = {Humans ; *Glucocorticoids/therapeutic use ; *Hepatitis, Alcoholic/drug therapy/pathology/diagnosis ; Oxidative Stress ; }, abstract = {Severe alcohol-associated hepatitis (SAH) is the most aggressive form of alcohol-associated liver disease and is associated with very high short-term mortality. It is characterized by the acute onset of jaundice in the context of ongoing alcohol use, most commonly defined by a Maddrey's discriminant function ≥32 or a model for end-stage liver disease score ≥20. Despite its increasing global burden and substantial healthcare costs, therapeutic options remain limited, and outcomes are poor. The severity of liver failure, systemic inflammation, infectious complications, and extrahepatic organ dysfunction determines the prognosis in SAH. The pathophysiology of SAH is multifactorial, involving direct hepatotoxicity from alcohol metabolites, oxidative stress, dysregulated immune activation, gut dysbiosis with increased intestinal permeability, impaired hepatic regeneration, and genetic susceptibility. These interrelated mechanisms culminate in an exaggerated inflammatory response driven by macrophage activation and cytokine release, resulting in hepatocellular injury and multi-organ failure. Glucocorticoids remain the guideline-recommended standard of care for selected patients; however, their benefit is limited to modest short-term survival gains, with high rates of non-response and infection. Numerous investigational therapies targeting inflammation, oxidative stress, liver regeneration, bile acid signalling, epigenetic regulation, and the gut-liver axis have been evaluated, with largely disappointing results. Emerging approaches, including interleukin-22 agonists and epigenetic modulators such as larsucosterol, show promise but require validation in well-designed trials. This review synthesizes current evidence on the definition, prognostic assessment, and pathophysiology of SAH, critically appraises existing and emerging therapies, and highlights the need for combination strategies, improved patient stratification, and personalized treatment approaches.}, }
@article {pmid41716272, year = {2026}, author = {Li, M and Xiao, S and Wang, Y and Li, T and Hu, Q and Dong, L and Guo, Y and Shi, Z and Yang, Q and Cai, W and Li, Q and Peng, B and Li, P and Weng, X and Wang, Y and Li, Y and Dong, Y and Zhu, X and Gong, Z and Chen, Y}, title = {Wuji Pill and Akkermansia muciniphila alleviates intestinal dysfunction and depression-like behavior in irritable bowel syndrome through the microbiota-gut-brain axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1739408}, pmid = {41716272}, issn = {1664-302X}, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a typical disorder of gut-brain interaction (DGBI). The microbiota-gut-brain (MGB) axis is pivotal in preventing and treating IBS. Wuji Pill is a traditional Chinese medicine commonly used to treat IBS. This study aimed to investigate the mechanism by which Wuji Pill improves IBS via the MGB axis.<br><br>METHODS: The visceral sensitivity and colonic motor function were evaluated using the abdominal wall withdrawal reflex test and the colonic motility curve. Depression-like behavior were evaluated using sucrose preference test, open field test, novelty-suppressed feeding test, and forced swimming tests. The intestinal mucus secretion and the activation status of microglia was detected using AB-PAS staining and immunofluorescence staining, respectively. The species composition and abundance of gut microbiota were detected through 16S rRNA sequencing and RT-qPCR. Targeted metabonomics and RT-qPCR were used for metabolites and metabolic enzymes analysis.<br><br>RESULTS: In this study, Wuji Pill improved the symptoms of IBS rats and increased the relative abundance of Akkermansia muciniphila in feces. Additionally, antibiotics affected the repair of intestinal mucus secretion and significantly reduced the level of short-chain fatty acids. Subsequently, fecal microbiota transplantation and A. muciniphila transplantation can improve the symptoms of IBS rat by increasing intestinal mucus secretion, elevating the levels of acetic acid and butyric acid in feces. Additionally, the microglia in the cortex were suppressed, and the tryptophan-kynurenine pathway in the hippocampus was inhibited, leading to the conversion of tryptophan into 5-HT.<br><br>DISCUSSION: This study highlights the Wuji Pill may alleviate IBS symptoms by modulating A. muciniphila and regulating the tryptophan metabolism pathway through MGB axis.}, }
@article {pmid41716280, year = {2026}, author = {Jiang, HB and Zhang, JQ and Liang, H and Sun, LY and Deng, CQ and Yang, SF}, title = {Exploring osteosarcopenia from the gut microbiota perspective: mechanistic insights and therapeutic potentials based on the gut-muscle-bone Axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1729870}, pmid = {41716280}, issn = {1664-302X}, abstract = {The aging society presents a growing challenge in the form of osteosarcopenia (OS). This syndrome is marked by the concomitant deterioration of bone (osteoporosis) and muscle (sarcopenia), and significantly elevates the risks of fractures, disability, and mortality. Despite its clinical relevance, the shared pathophysiology and effective interventions for OS remain elusive. Emerging evidence highlights the gut microbiota (GM) as a critical modulator of musculoskeletal health. This review integrates current evidence to delineate "gut-muscle-bone Axis" framework, summarizing current evidence on how GM dysbiosis may be involved in OS through multifaceted mechanisms, including intestinal barrier disruption, chronic inflammation, endocrine dysregulation, impaired nutrient absorption, and disrupted muscle-bone crosstalk. GM-derived metabolites, such as short-chain fatty acids (SCFAs), interact with immune, metabolic, and hormonal pathways to influence osteoblast/osteoclast activity and muscle protein synthesis. Furthermore, systemic inflammation triggered by GM imbalance exacerbates bone resorption and muscle atrophy. The axis also highlights bidirectional feedback between muscle and bone, mediated by myokines (e.g., irisin) and osteokines (e.g., osteocalcin), which synergistically regulate musculoskeletal homeostasis. Therapeutic strategies targeting GM modulation-such as dietary optimization (plant-based proteins, high-fiber diets), probiotics/prebiotics, exercise, and fecal microbiota transplantation (FMT)-suggest a potential capacity to modulate gut-muscle-bone interactions, which may be relevant to osteosarcopenia-related pathophysiological processes. This review proposes an integrative conceptual framework for understanding the pathogenesis of OS, synthesizing evidence primarily derived from osteoporosis and sarcopenia research, as well as animal and mechanistic studies. While direct clinical evidence in OS remains limited, emerging findings suggest that microbiota-centered strategies may hold potential for future preventive and therapeutic exploration.}, }
@article {pmid41716434, year = {2026}, author = {Mohiuddin, M}, title = {Chronic Antibiotic Use, Gut Microbiota Dysbiosis, and Increased Risk of Colorectal Cancer: An Emerging Threat.}, journal = {Health science reports}, volume = {9}, number = {2}, pages = {e71866}, pmid = {41716434}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: The gut microbiota plays a vital role in host health by regulating metabolic processes, immune function, and epithelial barrier functions. Chronic use of antibiotics can alter this environment and introduce gut dysbiosis, which is defined as an alteration of microbial communities characterized by a loss of beneficial microbes and overgrowth of pathogenic microbes. Gut dysbiosis is increasingly associated with the development and progression of colorectal cancer (CRC). We explored the relationship between long-term antibiotic exposure, gut microbiota dysbiosis, and CRC risk, as well as strategies for preventing and restoring gut microbiomes.<br><br>METHODS: Relevant information was extracted from published articles available in PubMed, Scopus, and Google Scholar. The keywords "Gut," "Dysbiosis," "Antibiotic," "Colorectal," and "Microbiota" were used to search for relevant information.<br><br>RESULTS: Studies have demonstrated that chronic antibiotic exposure significantly reduces microbial diversity, particularly by decreasing beneficial species (e.g., Lactobacillus, Bifidobacterium, and Faecalibacterium), while favoring pathogenic species (e.g., Klebsiella pneumoniae and Enterococcus faecium). Antibiotic-induced dysbiosis reduces the production of microbial metabolites, including short-chain fatty acids, which are essential for supporting epithelial integrity and immune homeostasis. Prior antibiotic use is associated with a 13% increased risk of CRC, with antibiotic-induced microbiota alterations lasting for months to years. Several factors, including diet, pollution, and over-the-counter access to antibiotics in low-and middle-income countries, may contribute to an increased risk of dysbiosis and CRC. Additionally, interventions such as dietary fiber, probiotic supplementation, fecal microbiota transplantation, next-generation probiotics, and phage therapy may be potential strategies to restore the microbiome and achieve gut health.<br><br>CONCLUSION: Substantial use of antibiotics may alter the gut microbiota and increase the risk of CRC. To mitigate this risk, it is essential to practice prudent antibiotic use and adopt dietary, probiotic, and microbiome-restoring practices to support the health of the gut microbiome.}, }
@article {pmid41716460, year = {2026}, author = {Guo, Y and Wang, X and Wu, Y and Li, Y and Wei, X}, title = {The role of the microbial-immune-bone axis in bone tumor development: mechanistic integration, systems modeling, and intervention prospects.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1762046}, pmid = {41716460}, issn = {2235-2988}, mesh = {Humans ; Animals ; *Bone Neoplasms/immunology/pathology ; *Gastrointestinal Microbiome/immunology ; *Bone and Bones/immunology/pathology ; Tumor Microenvironment/immunology ; Bone Remodeling ; }, abstract = {The emergence and development of bone tumors stem from a combination of intrinsic genetic alterations in tumor cells, remodeling of the bone marrow microenvironment, and shifts in the host's systemic immune-metabolic state. In recent years, gut microorganisms have been shown not only to influence bone mass regulation and conditions involving disrupted bone homeostasis, such as osteoporosis, but also to substantially affect the formation of primary bone tumors and metastatic lesions by modulating immune cell differentiation, inflammatory activity, and the coupling of bone remodeling. Focusing on the "Microbiota-Immune-Bone axis" (MIB), a growing body of fundamental and translational research indicates that alterations in gut microbial composition and function can reshape metabolite profiles-including short-chain fatty acids, bile acids, indole derivatives-and pathogen-associated molecular patterns (PAMPs). These signals act on the intestinal barrier and bone marrow immunity through G-protein-coupled receptors, nuclear receptors, and pattern-recognition receptors, thereby shifting the balance between bone resorption and formation and modifying the immune characteristics of the bone microenvironment, ultimately facilitating bone tumor cell colonization, proliferation, and immune escape. This review takes the MIB axis as its central framework to integrate the major pathways through which gut microbes and their metabolites regulate intestinal and myeloid immunity, bone remodeling, and bone tumor biology, to construct a systems-level model of tumor initiation and progression, to identify druggable signaling nodes, and to assess the potential and challenges of microbiota-modulating approaches-including antibiotics, probiotics, dietary strategies, and fecal microbiota transplantation-in preventing and treating bone tumors, thereby offering a theoretical foundation for developing integrated interventions targeting the gut microbiota and the MIB axis.}, }
@article {pmid41716676, year = {2026}, author = {Wang, R and Tong, A and Jin, K and Yu, R and Lin, D and Yang, D and Liu, X and Cui, J and Niu, J and Cui, Y and Zhu, H and Zhou, M}, title = {Harnessing the gut-immune-joint axis: Oral microalgae-based thermoresponsive microspheres enhance intra-articular therapy for rheumatoid arthritis.}, journal = {Bioactive materials}, volume = {61}, number = {}, pages = {72-91}, pmid = {41716676}, issn = {2452-199X}, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily caused by an aberrant immune response that erroneously attacks the synovial joints, leading to inflammation and joint damage. Emerging evidence suggests that impaired intestinal barrier integrity and imbalanced gut microbiota play crucial roles in driving RA development, promoting systemic inflammation, and exacerbating joint pathology. Here we propose a synergistic therapeutic strategy that concurrently addresses both the systemic gut-immune axis and local joint inflammation. This approach integrates intra-articular injection of triamcinolone acetonide (TAA) with oral administration of thermoresponsive microspheres encapsulating Chlorella vulgaris (CV) and ginseng polysaccharides (GPS), designated as CG@GelMA. The microspheres undergo temperature-induced gelation at body temperature, thereby facilitating gastric transit and enabling prolonged drug release in the intestinal tract. Oral administration of CG@GelMA restored intestinal barrier function by enhancing tight junction protein expression and exerting anti-inflammatory effects, while intra-articular TAA synergistically alleviated synovial inflammation, improved locomotor function, and preserved bone and cartilage integrity. Moreover, the combination therapy elicited superior immune modulation, characterized by increased regulatory T cells, reduced Th17 cells, and a systemic cytokine shift toward elevated interleukin-10 and reduced interleukin-17. Notably, this systemic immunomodulation was driven by CG@GelMA-mediated remodeling of the gut ecosystem, which enriched beneficial taxa (e.g., Lactobacillus), reduced potentially pathogenic genera (e.g., Escherichia-Shigella), and, importantly, led to a significant increase in the intestinal levels of immunomodulatory metabolites, including several short-chain fatty acids (SCFAs). Fecal microbiota transplantation (FMT) and depletion studies definitively established the gut microbiota as the central mediator of these therapeutic effects. Together, these findings highlight a synergistic combinatorial strategy that couples microbiota-driven systemic immunomodulation with potent local anti-inflammatory effects, offering a promising avenue for the treatment of RA and other systemic inflammatory disorders.}, }
@article {pmid41716824, year = {2026}, author = {Ge, C and Zou, C and Lv, Y and Huang, W and Luo, X and Wu, L and Hu, Z and Zhan, S and Shen, X and Lin, G and Yu, D and Liu, B}, title = {Trace mineral sources affect oxidized oil induced intestinal damage in chickens by modulation of gut microbiota and short-chain fatty acid metabolism.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {24}, number = {}, pages = {522-533}, pmid = {41716824}, issn = {2405-6383}, abstract = {This study investigated in vivo interactions between oil quality and trace mineral sources (organic vs. inorganic) on oxidative stress and intestinal damage in chickens. A total of 360 one-day-old male Lingnan yellow-feathered chickens with similar initial body weight (40 ± 2 g) were randomly assigned to four treatments in a 2 × 2 factorial design, with two oil qualities (fresh or oxidized) and two trace mineral sources (inorganic or organic). The experiment lasted for 21 days, with 6 replicates per treatment and 15 birds per replicate. Results showed that oxidized soybean oil (OSO) impaired jejunal barrier function (damaged morphology, downregulated tight junction genes), associated with reduced antioxidant capacity, elevated proinflammatory cytokines, and altered gut microbiota/short-chain fatty acid (SCFA) metabolism. Significant interactions were observed between oil quality and trace mineral sources (P < 0.05): only in the OSO group, organic trace minerals (OTM) outperformed inorganic ones (ITM) in enhancing total antioxidant capacity (P = 0.005) and glutathione peroxidase activity (P = 0.001), suppressing proinflammatory cytokines (e.g., interleukin-1β, P = 0.019; interleukin-2, P = 0.019; interleukin-6, P = 0.014; tumor necrosis factor-α, P = 0.001), increasing SCFA-producing bacteria (e.g., Lactobacillus and Butyricicoccus) while reducing pathogens (e.g., Helicobacter), and elevating SCFAs (P = 0.030). Furthermore, targeted metabolomic analysis revealed that OTM significantly increased the production of SCFAs, especially butyric acid (P = 0.001), which were positively correlated with the OTM-enriched microbiota. Mantel-test analysis revealed that the altered microbiota and metabolites showed strong correlations with specific parameters of intestinal health. The fecal microbiota transplantation experiment further confirmed that the intestinal protective effect is likely mediated by OTM-altered gut microbiota and their metabolites. In summary, the replacement of ITM by OTM in chicken diets can minimize the negative impact on OSO induced intestinal damage by improving intestinal barrier function and alleviating inflammatory responses mediated by gut microbiota modulation and SCFA metabolism.}, }
@article {pmid41718442, year = {2026}, author = {Stafford, WH and McArthur, J and Ghafoor, S}, title = {Critical Intestinal Perforations in Pediatric Immunocompromised Patients: A Case-Based Review.}, journal = {Pediatric reports}, volume = {18}, number = {1}, pages = {}, pmid = {41718442}, issn = {2036-749X}, abstract = {As survival rates for children with cancer and immune disorders have improved, clinical focus has shifted toward managing serious treatment-related complications. Intestinal perforation remains life-threatening and is typically diagnosed by signs of peritonitis and inflammation. This report presents three high-risk pediatric patients who developed severe intestinal perforation without the usual clinical symptoms. Each patient was receiving high-dose corticosteroids and/or targeted biologic immunomodulators (ruxolitinib, anakinra, tocilizumab, eculizumab). Classic indicators such as fever, leukocytosis, hemodynamic instability, and abdominal pain were absent, despite surgical findings of fecal contamination and bowel necrosis. All three patients survived to hospital discharge. These cases demonstrate that potent immunomodulatory therapies can mask the physiological response to perforation. Relying solely on traditional clinical signs may delay diagnosis. In this population, subtle findings such as persistent gastrointestinal bleeding, feeding intolerance, or minor imaging abnormalities should prompt consideration of perforation. Early imaging and multidisciplinary review are essential for timely intervention and improved outcomes.}, }
@article {pmid41718556, year = {2026}, author = {Johnson, KM and Grady, J and Kellermayer, R and Winter, HS and Tabibian, JH and Buness, CW and Fischer, R and Shah, A and Dulai, PS and Rangnekar, AS and Alrabadi, L and Shah, SB and Holtmann, G and Räisänen, L and Lewindon, P and Ali, AH}, title = {Oral vancomycin for primary sclerosing cholangitis and associated inflammatory bowel disease - paving a path forward.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {20}, number = {3}, pages = {233-246}, doi = {10.1080/17474124.2026.2635420}, pmid = {41718556}, issn = {1747-4132}, mesh = {Humans ; *Cholangitis, Sclerosing/drug therapy/complications ; *Vancomycin/administration &amp; dosage/therapeutic use/adverse effects ; Administration, Oral ; *Inflammatory Bowel Diseases/drug therapy/complications ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use/adverse effects ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is a fibro-inflammatory cholangiopathy strongly associated with inflammatory bowel disease (PSC-IBD). With no approved PSC therapy, clinicians face uncertainty about oral vancomycin (OV) as a therapeutic option. This review synthesizes clinical effectiveness evidence alongside mechanistic data.<br><br>AREAS COVERED: We searched PubMed/Google Scholar for studies of vancomycin in PSC from 1998 through November, 2025. OV shows consistent IBD benefits and variable liver responses. In PSC-IBD, clinical and endoscopic remission occurred in 60% at 6&#x2009;months and in 71% at 12&#x2009;months in a pediatric cohort; in an adult single-arm study (n&#x2009;=&#x2009;15), 80% achieved endoscopic remission at 4&#x2009;weeks with universal mucosal healing, reductions in fecal calprotectin and Mayo scores, and relapse after withdrawal. For liver disease, a pediatric open-label cohort (n&#x2009;=&#x2009;45) reported &#x2265;50% declines in gamma-glutamyl transferase in 82%; in an adult pilot randomized controlled trial, alkaline phosphatase fell 46% at 12&#x2009;weeks. Imaging/histology improved as evidenced by MRCP in 26/34 large-duct PSC and reduced portal/periportal inflammation in 11/12 small-duct PSC. No vancomycin-resistant enterococci development has been reported.<br><br>EXPERT OPINION: OV appears effective for colitis control in PSC-IBD. Differences in observed liver outcomes across studies likely reflect variation in treatment duration, dose, and endpoint selection. Liver responses may depend on higher doses. Cross-specialty guidance and pragmatic, integrated trials are needed.}, }
@article {pmid41718784, year = {2026}, author = {Peltz, Z and Wiblin, R and Kattunga, VM and Pai, CG and Andersen, JK and Chinta, SJ}, title = {The role of gut dysbiosis in Parkinson's disease: pathophysiology, epidemiology, and emerging therapeutic strategies.}, journal = {Metabolic brain disease}, volume = {41}, number = {1}, pages = {}, pmid = {41718784}, issn = {1573-7365}, abstract = {Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor and non-motor symptoms. While the underlying pathobiology remains incompletely understood, emerging evidence suggests a pivotal role for neuroinflammation, microglial activation, and misfolded α-synuclein aggregates. Recent research has highlighted gut dysbiosis as a contributing factor in PD pathology, with potential implications for disease onset and progression. Recent studies suggest that gut dysbiosis may influence PD onset and progression, highlighting the gut-brain axis as a critical mechanistic link. This review explores epidemiology, molecular etiology, genetic predispositions, and risk factors associated with PD, with particular emphasis on the role of gut microbiota. Furthermore, we discuss emerging gut-targeted therapeutic strategies, including probiotics, dietary interventions, and fecal microbiota transplantation (FMT), and their potential in mitigating PD pathology. Addressing gut dysbiosis may offer novel therapeutic avenues for early intervention and disease modification in PD.}, }
@article {pmid41719127, year = {2026}, author = {Wang, S and Su, LY and Lan, D and Pan, H and Xiong, M and Yao, M and Deng, Y and Fan, Z and Cao, Y and Zhou, H}, title = {Adenosine signaling driven by the gut microbiota underlies chronic alcohol-induced anesthetic resistance.}, journal = {Cell reports}, volume = {45}, number = {3}, pages = {117015}, doi = {10.1016/j.celrep.2026.117015}, pmid = {41719127}, issn = {2211-1247}, mesh = {Animals ; *Adenosine/metabolism ; *Signal Transduction/drug effects ; *Ethanol ; Humans ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; Mice, Inbred C57BL ; *Anesthetics/pharmacology ; Fecal Microbiota Transplantation ; Receptors, GABA/metabolism ; }, abstract = {Chronic alcohol consumption increases anesthetic tolerance, yet the underlying in vivo mechanisms remain unclear. Here, we demonstrate that long-term alcohol exposure reduces anesthetic efficacy in both humans and mice, prolonging induction and shortening maintenance. Fecal microbiota transplantation from alcohol-exposed donors recapitulated this phenotype in naive mice, indicating a causal role of gut microbiome alterations. Metagenomic and metabolomic analyses identified elevated adenosine as a key microbiota-derived metabolite. Adenosine supplementation decreased anesthetic sensitivity, likely via downregulation of gamma-aminobutyric acid (GABA) receptors. Our findings reveal a gut microbiota-adenosine pathway mediating alcohol-induced anesthetic resistance.}, }
@article {pmid41720783, year = {2026}, author = {Lee, JM and Kim, MJ and Lee, H and Hyun, Y and Nam, SW and Jeon, DG and Shin, JH and Kim, ES}, title = {Maternal gut microbial legacy shapes intestinal health and susceptibility of offspring to colitis.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41720783}, issn = {2055-5008}, support = {RS-2021-NR060094//National Research Foundation of Korea/ ; 2023R1A2C2005817//National Research Foundation of Korea/ ; 2021R1A6C101A416//Ministry of Education/ ; }, mesh = {Animals ; *Colitis/microbiology/etiology ; Female ; *Dysbiosis/microbiology ; Pregnancy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice ; Disease Susceptibility ; Lactobacillus ; Disease Models, Animal ; Intestines/microbiology ; Inflammatory Bowel Diseases ; }, abstract = {Maternal gut dysbiosis caused by inflammatory bowel disease during pregnancy can affect the gut health of the offspring by altering the composition of the gut microbiota, as well as immune function; however, the underlying mechanisms and potential for therapeutic intervention remain unclear. This study investigated the impact of maternal colitis on the gut health of offspring, and assessed the therapeutic potential of microbial manipulation. Offspring born to mothers with colitis exhibited gut microbial dysbiosis characterized by Lactobacillus spp. depletion, impaired barrier function, low-grade intestinal inflammation, compromised Wnt signaling, reduced crypt cell proliferation and diminished organoid-forming capacity, all of which increased their susceptibility to colitis in adulthood. Notably, early-life interventions such as fecal microbiota transplantation (FMT), targeted supplementation with Lactobacillus and cross-fostering during the postnatal period effectively reshaped the gut microbiota and reduced the risk of developing colitis later in life. These findings underscore the critical impact of the prenatal maternal gut microbial community on programming offspring intestinal barrier function and immune homeostasis, thereby influencing lifelong disease susceptibility. Moreover, the early-postnatal period represents a crucial therapeutic window in which microbial interventions like FMT can effectively mitigate gut dysbiosis and confer long-term protection against colitis.}, }
@article {pmid41721978, year = {2026}, author = {Mokhtari, H and Hoseini, MHM and Hashemi, SM and Tahvildari, S and Yeganeh, F}, title = {Intrarectal delivery of chitosan hydrogel-encapsulated mesenchymal stem cell-conditioned media attenuates disease severity in experimental ulcerative colitis.}, journal = {Inflammopharmacology}, volume = {34}, number = {3}, pages = {1683-1699}, pmid = {41721978}, issn = {1568-5608}, support = {43002260//Deputy of Research, Faculty of Medicine, Shahid Beheshti University of Medical Sciences/ ; }, mesh = {Animals ; *Chitosan/administration &amp; dosage/chemistry ; *Colitis, Ulcerative/drug therapy/pathology ; *Mesenchymal Stem Cells/metabolism ; Mice ; Culture Media, Conditioned/pharmacology ; *Hydrogels/administration &amp; dosage/chemistry ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL ; Administration, Rectal ; Dextran Sulfate ; Cytokines/metabolism ; Mesenchymal Stem Cell Transplantation/methods ; Severity of Illness Index ; Colon ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by mucosal immune dysregulation and epithelial injury. While mesenchymal stem cells (MSCs) hold regenerative and immunomodulatory promise, their use entails safety and logistical challenges. MSC-derived conditioned medium (MSC-CM) may offer a safer, cell-free alternative. Here, we present a novel intrarectal delivery strategy that pairs MSC-CM with a mucoadhesive chitosan hydrogel (Cs-Hyd), aiming for localized mucosal therapy in colitis.<br><br>METHODS: Experimental colitis was induced in mice via DSS exposure. Human MSCs were cultured under standardized conditions to generate CM enriched in immunoregulatory factors. This CM was loaded into a chitosan hydrogel, validated for mucoadhesion and release kinetics, and administered intrarectally. Clinical metrics (weight loss, stool consistency, fecal blood), colon length, histopathology, cytokine profiles, and myeloperoxidase (MPO) activity were assessed. Data were analyzed via ANOVA with post hoc Tukey correction; significance was set at p&#x2009;<&#x2009;0.05.<br><br>RESULTS: In the DSS model, 60% mortality was observed by day 10, whereas the Cs-Hyd containing MSC-CM (Cs-Hyd-CM) group achieved 100% survival (n&#x2009;=&#x2009;4-6, log-rank p&#x2009;=&#x2009;0.034). Cs-Hyd-CM-treated mice exhibited substantially less weight loss (-&#x2009;5.2&#x2009;&#xb1;&#x2009;1.3% vs.&#x2009;-&#x2009;15.1&#x2009;&#xb1;&#x2009;2.2%; repeated-measures ANOVA, p&#x2009;=&#x2009;0.008), lower Disease Activity Index (DAI: 2.1&#x2009;&#xb1;&#x2009;0.6 vs. 8.0&#x2009;&#xb1;&#x2009;0.9; p&#x2009;=&#x2009;3.2&#x2009;&#xd7;&#x2009;10[-4]), and preserved colon length (7.5&#x2009;&#xb1;&#x2009;0.4&#xa0;cm vs. 6.0&#x2009;&#xb1;&#x2009;0.3&#xa0;cm; p&#x2009;=&#x2009;6.2&#x2009;&#xd7;&#x2009;10[-3]). Histology scores decreased by&#x2009;~&#x2009;70% (4.0&#x2009;&#xb1;&#x2009;0.7 vs. 12.1&#x2009;&#xb1;&#x2009;0.8; p&#x2009;=&#x2009;3.1&#x2009;&#xd7;&#x2009;10[-6]), confirming mitigation of ulceration and inflammation. Treatment with Cs-Hyd-CM reduced TNF-&#x3b1; by&#x2009;~&#x2009;40% vs DSS-only (104.5&#x2009;&#xb1;&#x2009;6.8&#x2009;&#x2192;&#x2009;63.8&#x2009;&#xb1;&#x2009;8.7&#xa0;pg/mg; p&#x2009;=&#x2009;4.6&#x2009;&#xd7;&#x2009;10[-4]) while restoring IL-10 toward normal levels (p&#x2009;=&#x2009;3.0&#x2009;&#xd7;&#x2009;10[-3]). MPO activity dropped&#x2009;~&#x2009;52% (76.5&#x2009;&#xb1;&#x2009;3.4&#x2009;&#x2192;&#x2009;36.8&#x2009;&#xb1;&#x2009;5.3 U/mg; p&#x2009;=&#x2009;8.4&#x2009;&#xd7;&#x2009;10[-4]). Collectively, Cs-Hyd-CM significantly attenuated disease severity and promoted mucosal healing in DSS colitis.<br><br>CONCLUSIONS: Local intrarectal delivery of MSC-CM via chitosan hydrogel substantially alleviates experimental UC. This cell-free platform leverages MSC secretome functions, immunomodulation, barrier restoration, and controlled retention, while avoiding the complexities and risks of cell transplantation.}, }
@article {pmid41722622, year = {2026}, author = {Allen, SL and Breen, L and Lord, JM and Duggal, NA}, title = {Age-related sarcopenia and the gut microbiome: mechanistic insights into the gut-muscle axis and potential microbiome based therapeutic interventions.}, journal = {Ageing research reviews}, volume = {118}, number = {}, pages = {103065}, doi = {10.1016/j.arr.2026.103065}, pmid = {41722622}, issn = {1872-9649}, mesh = {Humans ; *Sarcopenia/microbiology/therapy/metabolism/physiopathology ; *Aging/physiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Muscle, Skeletal/metabolism ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Ageing is associated with a loss of skeletal muscle mass, strength and function, termed sarcopenia. The presence of sarcopenia is known to be problematic leading to an increased risk of falls, fractures and mortality. Age-related changes in the gut microbiome, characterized by reduced diversity and altered metabolite production, may compromise intestinal barrier function, leading to increased permeability. These age-associated changes in the gut microbiome led to changes in circulating microbial metabolites and toxins, such as a decrease in short-chain fatty acids, an increase in lipopolysaccharides and an imbalance in bile acid production. Together these alterations may contribute to the development of sarcopenia through impairments in muscle protein turnover. Currently, lifestyle-based approaches e.g., exercise and diet, alongside the use of pre-, pro- and post-biotics have been proposed as strategies to target the gut-muscle axis and combat the risk of sarcopenia in the expanding ageing population. However, little evidence is available to support their use within clinical settings. Several new strategies including the nutraceutical Urolithin A and faecal microbiome transplants (FMT) have been suggested to treat age-related sarcopenia. This review provides insight into the potential interactions of the gut microbiome and skeletal muscle with ageing and sarcopenia development, alongside potential new and existing countermeasures.}, }
@article {pmid41722699, year = {2026}, author = {Shang, A and Shen, J}, title = {Gut microbiota and their metabolites in stroke: From mechanistic study toward therapeutic perspectives.}, journal = {Pharmacological research}, volume = {225}, number = {}, pages = {108147}, doi = {10.1016/j.phrs.2026.108147}, pmid = {41722699}, issn = {1096-1186}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome ; *Stroke/microbiology/therapy/metabolism ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; *Bacteria/metabolism ; }, abstract = {Stroke is a medical emergency with high incidence, mortality, disability rate, and multiple complications, which place a serious burden on families and society. Clinically, gastrointestinal dysfunction has been observed in a significant percentage of stroke patients, suggesting that gut microbiota may be a viable target for stroke prevention and therapy. In this review, we summarized the alterations in the intestinal environment following stroke across clinical and preclinical models, highlighting the changes in the major bacterial communities, including Bacteroidetes, Firmicutes, Proteobacteria and Actinomycetota, etc. Considering the connection between the brain-gut axis, we discussed the therapeutic potential for treating ischemic stroke by modulating the gut microbiota, including protection of the blood-brain barrier (BBB) and the intestinal barrier, as well as the application of fecal microbiota transplantation (FMT). Furthermore, we highlighted the main mechanisms of regulating gut microbiota to improve stroke outcomes, involving intestinal metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and phenylacetylglutamine (PAGln), endotoxin, hormones, and amino acids, as well as factors related to immunity, inflammation, and oxidative stress. Finally, we summarized potential targeted therapeutic approaches, such as natural small molecules, engineered probiotics, and bile acid-nanoparticles, etc. Collectively, these insights support the gut microbiota as a promising target for mitigating stroke risk, attenuating acute injury, and enhancing recovery.}, }
@article {pmid41722712, year = {2026}, author = {Beales, JT and Mohanty, V and Seng, MM and Tapp, ZM and Sardesai, SD and Williams, NO and Gatti-Mays, ME and Stover, DG and Sudheendra, PK and Wesolowski, R and Bailey, MT and Ni, A and Cologna, SM and Pyter, LM}, title = {Gut microbiota and metabolite disruption during breast cancer chemotherapy is associated with peripheral neuropathy sensory symptoms and pain.}, journal = {Brain, behavior, and immunity}, volume = {135}, number = {}, pages = {106489}, pmid = {41722712}, issn = {1090-2139}, support = {R01 CA216290/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Peripheral Nervous System Diseases/chemically induced/microbiology/metabolism ; *Breast Neoplasms/drug therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects/physiology ; Middle Aged ; *Antineoplastic Agents/adverse effects/therapeutic use ; Adult ; *Pain/microbiology/metabolism ; Feces/microbiology ; Taxoids/adverse effects ; RNA, Ribosomal, 16S ; }, abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious adverse effect of chemotherapeutic agents such as taxanes, platinum compounds, and vinca alkaloids. Efforts to prevent and treat CIPN are impeded by an incomplete understanding of its pathogenesis. Recently, the gut microbiota has been causally linked to CIPN in rodent models. However, human studies exploring this connection are limited. Here, in a cohort of 70 patients with early-stage breast cancer, relationships between disruptions in the gut microbiota during chemotherapy and both participant CIPN symptoms and general pain symptoms were investigated. Study participants provided fecal samples (for 16S rRNA sequencing and targeted metabolomics), blood samples, and sensory symptom information during the three days prior to their first and their final chemotherapy (including a taxane drug) infusions. Sensory neuropathy symptoms increased during treatment, as did circulating levels of neurofilament light chain (NFL), a putative biomarker of CIPN. Decreases in microbiota alpha diversity during chemotherapy were associated with worse neuropathy symptoms during treatment, along with worsening of general pain, after controlling for pre-treatment baseline symptoms. Larger shifts in beta diversity from baseline to last infusion also coincided with more severe neuropathy symptoms. Bacterial producers of short-chain fatty acids were decreased in participants with neuropathy symptoms at the final chemotherapy infusion. Furthermore, decreases in fecal levels of short-chain fatty acids during treatment were related to worse neuropathy symptoms, suggesting a potential mechanism by which gut microbiota alterations could influence CIPN. Collectively, these findings corroborate preclinical work linking the gut microbiota to CIPN and provide evidence of potential microbiota involvement in general pain symptoms as well. Larger confirmatory studies in the future could support microbiota-targeted interventions for CIPN, such as fecal microbiota transplants or dietary interventions.}, }
@article {pmid41723572, year = {2026}, author = {Liang, H and Ding, X and Liu, S and Tong, S and Wang, X and Zhang, Z and Wang, W and Zhang, X and Yuan, Y and Jiang, Y and Sun, T}, title = {Aging-caused the changes of the gut microbiota drive intestinal barrier dysfunction and increase sepsis susceptibility.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2630475}, pmid = {41723572}, issn = {1949-0984}, mesh = {Animals ; *Sepsis/microbiology/physiopathology/metabolism ; Intestinal Barrier Function ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Aging ; Mice, Inbred C57BL ; Male ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Feces/microbiology ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Intestinal Mucosa/metabolism ; Disease Models, Animal ; }, abstract = {Physiological and pathological changes associated with aging contribute to deteriorating disease prognosis in sepsis. However, the mechanisms by which these disturbances exacerbate inflammation remain underexplored. In this study, fecal samples were collected from aged and young septic patients and mice and subsequently transplanted into young pseudo-germ-free mice via fecal microbiota transplantation. Fecal, colon tissue, and blood samples were collected to be used 16S rDNA sequencing to characterize the gut microbiota, histopathological examination, enzyme-linked immunosorbent assay and FITC-dextran intestinal permeability assay to assess gut injury and gut barrier function. Additionally, nontargeted and targeted metabolomics were used to identify differential metabolites in the feces of aged and young septic mice. To further validate the roles of specific bacterial strains and their metabolites in sepsis, genetically engineered bacteria were used in both in vivo and in vitro experiments. The results showed that an increased abundance of Klebsiella aerogenes (K. aero) in aged hosts, which led to elevated histamine (HA) production and exacerbated intestinal barrier dysfunction. Importantly, K. aero strains carrying a histidine decarboxylase gene variant were identified as major HA producers. Mechanistically, HA was shown to drive intestinal barrier dysfunction by inhibiting Nlrp6 expression and its subsequent binding to LC3, thereby impairing autophagy. Treatments that modulated HA levels or overexpressed Nlrp6 ameliorated inflammation in septic mice. These findings suggest that targeting the HA-Nlrp6-LC3 axis could offer a novel therapeutic approach for managing sepsis, particularly in aged populations.}, }
@article {pmid41723574, year = {2026}, author = {Benedé-Ubieto, R and Estévez-Vázquez, O and Acar, R and Leal-Lassalle, H and Gutierrez, AH and Redondo-Urzainqui, A and Iborra, S and Odintsova, VE and Tyakht, A and Herranz, JM and Firat, Z and Basol, M and Korkmaz, B and Sanz-García, C and Juanola, O and Caparrós, E and Francés, R and Ciudin, A and Pericàs, JM and Gómez-Santos, B and Aspichueta, P and Treichel, N and Clavel, T and Reißing, J and Bruns, T and Bartneck, M and Mazariegos, MS and Wolters, JC and Jorquera, G and Liedtke, C and Vaquero, J and Bañares, R and Cakan-Akdogan, G and Ávila, MA and Konu, O and Cubero, FJ and Nevzorova, YA}, title = {Alcohol consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): understanding the gut-liver crosstalk for clinical translation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2631834}, pmid = {41723574}, issn = {1949-0984}, mesh = {Animals ; Humans ; Mice ; *Liver/metabolism/pathology ; *Gastrointestinal Microbiome/drug effects ; *Alcohol Drinking/adverse effects/metabolism ; Male ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Zebrafish ; *Fatty Liver/metabolism/microbiology/etiology ; *Non-alcoholic Fatty Liver Disease/metabolism ; Diet, Western/adverse effects ; Female ; Hepatocytes/metabolism ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVE: In the present study, we investigated the role of the gut-liver crosstalk in the pathogenesis of steatotic liver disease (SLD) induced by the compounding and deleterious effects of alcohol and metabolic risk factors, and explored the potential translational aspects of microbiome-based interventions.<br><br>DESIGN: The effects of combined exposure to alcohol and a high-fat, high-cholesterol diet (HFHC) Western diet (WD) were tested in a dietary mouse DUAL model and compared to mice fed only with WD. Liver and gut phenotypes were evaluated via histochemistry, flow cytometry, gene expression, proteomic, and metabolomic analyses. The effects on the gut microbiota were studied in both DUAL mice and MASLD patients with a history of alcohol consumption. Antibiotic-induced microbiota depletion (AIMD) and microbiota modulation therapies (probiotics and fecal microbiota transplant (FMT)) were performed in mice. Primary human hepatocytes and HepG2 cells were used to study the underlying mechanisms. Zebrafish larvae exposed to alcohol and a HFHC diet were used as a validation model.<br><br>RESULTS: Alcohol in combination with WD synergistically exacerbated SLD. DUAL-diet-induced disruption of the intestinal barrier led to LPS leakage into the bloodstream and subsequent TLR4-mediated hepatic inflammation. This, together with enhanced intestinal fat absorption, and impaired intrahepatic lipid oxidation - particularly due to insufficient CPT-1 activity - contributed to prominent steatohepatitis. The DUAL-induced changes in the gut microbiota showed similarities to human dysbiosis in MASLD patients who consumed alcohol, including an increase in Bacteroides and Alistipes. AIMD improved pathology, indicating a causal role of the microbiota in the pathophysiology of DUAL steatohepatitis, whilst early microbiome modulation via FMT induced mild improvements in liver and gut physiology.<br><br>CONCLUSIONS: These results indicated that the microbiota&#x2012;gut&#x2012;liver axis plays a crucial role in the progression of SLD intensified by alcohol and concurrent metabolic risk factors, thus providing a promising translational target for potential therapeutic interventions.}, }
@article {pmid41724218, year = {2026}, author = {Liu, J and Liu, T and Nie, L and Zhou, L and Luo, J and Guo, L and Zhang, X and Gong, M and Chen, Z and Li, X and Fan, X}, title = {Semaglutide attenuates autistic-like behaviors in BTBR mice through the shaping of gut microbiota.}, journal = {Pharmacological research}, volume = {225}, number = {}, pages = {108149}, doi = {10.1016/j.phrs.2026.108149}, pmid = {41724218}, issn = {1096-1186}, mesh = {Animals ; Semaglutide ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Glucagon-Like Peptides/pharmacology/therapeutic use ; Male ; Social Behavior ; Disease Models, Animal ; *Autism Spectrum Disorder/drug therapy/microbiology/metabolism/psychology ; *Behavior, Animal/drug effects ; Hippocampus/drug effects/metabolism ; Neurogenesis/drug effects ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication and the presence of repetitive behaviors. The significance of the gut-brain axis in the pathogenesis of ASD often points to a relationship with gut dysbiosis and metabolic disruptions in affected individuals. This study investigates the potential of the glucagon-like peptide-1 receptor agonist, semaglutide, to modulate gut microbiota, metabolic pathways, and neurodevelopmental outcomes using the BTBR T(+) Itpr3(tf)/J (BTBR) mouse model of ASD. Our findings indicate that administration of semaglutide during an early neurodevelopmental stage leads to significant improvements in social behavior, cognitive function, and repetitive behaviors in BTBR mice. This therapeutic effect is associated with the restoration of gut microbiota, as demonstrated by fecal microbiota transplantation from C57BL/6 J controls and semaglutide-treated BTBR mice, which ameliorated the ASD behaviors in BTBR mice. Metabolomic profiling identified adrenic acid (AdA) as a crucial mediator; AdA levels in BTBR mice were lower but returned to normal following semaglutide treatment. Additionally, RNA sequencing revealed that hippocampal neurogenesis is associated with semaglutide treatment, and AdA supplementation restored social behaviors and hippocampal neurogenesis. These results highlight the critical role of the gut microbiota-brain axis in the therapeutic effects of semaglutide on ASD and suggest that targeting this axis alongside AdA may represent a promising strategy for ASD.}, }
@article {pmid41724232, year = {2026}, author = {Tang, H and Sulaiman, JE and Zhang, Y and Yang, Y and Wang, J and Zhong, W and Lei, H and Liu, Y}, title = {Cyanidin-3-O-glucoside alleviates aflatoxin B1-induced splenic immunotoxicity via gut microbiota remodeling.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {396}, number = {}, pages = {127856}, doi = {10.1016/j.envpol.2026.127856}, pmid = {41724232}, issn = {1873-6424}, mesh = {Animals ; *Aflatoxin B1/toxicity ; *Glucosides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Anthocyanins/pharmacology ; *Spleen/drug effects ; Male ; }, abstract = {While the hepatotoxicity of aflatoxin B1 (AFB1) is well characterized, its immunotoxicity remains overlooked. This study investigates whether cyanidin-3-O-glucoside (C3G), a bioactive polyphenolic flavonoid, can alleviate AFB1-induced immunotoxicity. Our results demonstrated that C3G significantly ameliorated AFB1-induced splenic injury, which was associated with the suppression of the NLRP3/caspase-1/GSDMD pyroptosis pathway and reduced expression of IL-1β and IL-18. Furthermore, C3G modulated the gut microbiota by enriching specific beneficial bacteria (e.g., Alistipes and Candidatus Saccharimonas) and reversed AFB1-induced metabolic disorders. Transplantation of fecal microbiota from C3G-pretreated donor mice reproduced the protective effect of C3G in mice exposed to AFB1, whereas sterile fecal filtrate transplantation only offered partial relief, indicating that the core mechanism depends on viable microbiota. In summary, C3G alleviates AFB1-induced splenic injury by restructuring the dysbiotic gut microbiota into a more enriched community. This remodeling restores metabolic homeostasis and inhibits NLRP3-mediated pyroptosis via the gut-spleen axis. Our findings demonstrate that C3G alleviates AFB1-induced splenic immunotoxicity by remodeling the gut microbiota via the gut-spleen axis, establishing a novel microbiota-dependent strategy mediated by natural polyphenols.}, }
@article {pmid41724956, year = {2026}, author = {Xu, Y and Huang, L and Sun, L and Li, C and Zhou, C and Liu, P and Zhang, Z and Deng, S and Mao, C and Hu, Z and Bao, X and Xia, S and Xu, Y}, title = {Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.}, journal = {Cellular &amp; molecular biology letters}, volume = {31}, number = {1}, pages = {}, pmid = {41724956}, issn = {1689-1392}, support = {82130036/823B2027//National Natural Science Foundation of China/ ; 2022ZD0211800//STI2030-Major Projects/ ; ZDXK202216//Jiangsu Province Key Medical Discipline/ ; }, abstract = {BACKGROUND: White matter injury (WMI) is the most prevalent lesion in cerebral small vessel disease and a major contributor to cognitive decline. Recent studies have highlighted the critical role of gut microbiota in regulating brain disorders. However, the role of gut microbiota in WMI-related cognitive decline remains unclear. METHODS: A bilateral carotid artery stenosis (BCAS) mouse model was established to mimic WMI and related cognitive decline. Fecal microbiota transplantation was employed to verify the causal relationship between gut microbiota dysbiosis and WMI. 16 S rRNA gene sequencing was used to analyze gut microbiota and its potential functions. Untargeted metabolomics was applied to identify differential metabolites. Cognitive function was assessed through Y-maze, novel object recognition, and fear conditioning tests. WMI was assessed using in vivo imaging, immunostaining, and electron microscopy. The changes in oligodendrocyte lineage cells, microglia, and blood-brain barrier were investigated using immunofluorescence staining, EdU cell proliferation assays, and Western blotting. Patients with ischemic WMI were included to examine the correlation between serum L-arginine (L-Arg) levels, brain imaging, and cognition. RESULTS: We discovered that BCAS mice exhibited gut microbiota dysbiosis and reduced arginine biosynthesis, with decreased L-Arg levels in serum and white matter. Fecal microbiota from BCAS mice resulted in WMI and related cognitive decline in normal mice. Serum L-Arg levels were reduced in patients with ischemic WMI and were closely associated with WMI and cognitive decline. Importantly, L-Arg supplementation improved WMI-related cognitive decline in BCAS mice. Mechanistically, L-Arg promoted oligodendrocyte precursor cell proliferation and differentiation, enhanced the anti-inflammatory activity of microglia, and reduced blood-brain barrier leakage, thereby mitigating WMI-related cognitive decline. Furthermore, Lachnospiraceae was identified as the main source of gut-to-brain L-Arg. Supplementation with Lachnospiraceae alleviates WMI-related cognitive decline. CONCLUSION: Overall, our study revealed the critical role of gut microbiota, particularly Lachnospiraceae, and L-Arg in improving WMI-related cognitive decline, providing novel strategies for understanding and treating WMI-related cognitive decline.}, }
@article {pmid41725847, year = {2026}, author = {Liu, G and Chen, L and Guan, M and Xiao, N}, title = {Global trends and future perspectives in autism spectrum disorder and gut microbiota research: a comprehensive bibliometric analysis.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1607951}, pmid = {41725847}, issn = {1662-4548}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. Increasing studies examine whether gut microbiota alterations and the gut-brain axis are linked to ASD-relevant phenotypes. As the literature expands rapidly, a quantitative mapping is needed to clarify influential work and evolving themes.<br><br>OBJECTIVE: To map global research on ASD and the gut microbiota, identify major contributors and knowledge bases, and characterize thematic evolution and emerging fronts.<br><br>METHODS: We analyzed 1,391 English-language articles and reviews indexed in the Web of Science Core Collection (1999-2024). CiteSpace, VOSviewer, and R were used to evaluate publication trends, collaboration networks, co-citation structure, keyword clustering, and burst detection.<br><br>RESULTS: Publication output increased slowly before 2010 and accelerated after 2018. The United States and China were leading contributors and key collaboration hubs. The co-citation core was anchored by landmark experimental and translational studies, including work on microbiome-to-behavior links and microbiome-targeted interventions. Keyword clustering and timeline views highlighted three prominent thematic directions: fecal microbiota transplantation, Rett syndrome, and maternal immune activation. Recurrent and burst keywords emphasized the gut-brain axis, short-chain fatty acids, gastrointestinal symptoms, and oxidative stress. Recent burst terms, including obesity, major depressive disorder, and glutamate, suggest increasing connections to metabolic and broader psychiatric dimensions.<br><br>CONCLUSION: ASD-microbiome research has shifted from descriptive comparisons toward mechanism-oriented and intervention-relevant questions. Future progress will benefit from standardized protocols, longitudinal designs, and multi-omics integration, together with rigorously designed trials to evaluate microbiome-targeted strategies.}, }
@article {pmid41727337, year = {2026}, author = {Toumazi, D and Charalambous, C and Constantinou, C and Nicolaou, N}, title = {From the gut to the brain: The involvement of the gut microbiota in the development and progression of glioblastoma.}, journal = {Neuro-oncology advances}, volume = {8}, number = {1}, pages = {vdaf267}, pmid = {41727337}, issn = {2632-2498}, abstract = {Glioblastoma (GB) is the most malignant tumor in the adult central nervous system (CNS), presenting substantial treatment challenges due to its infiltrative nature, heterogeneity and immunosuppressive environment it creates. Current therapeutic efforts are focused on enhancing our understanding of GB and developing effective therapies. An emerging area of interest is the bidirectional gut-brain axis, which mediates communication between gut microbiota and CNS. The gut-brain axis allows the microbiota to modulate the immune system and inflammatory pathways through microbial metabolites, such as short-chain fatty acids (SCFAs) and tryptophan derivatives, promoting or suppressing GB progression. Understanding these interactions can lead to microbiota-targeted therapies for GB patients. Novel therapies, such as fecal microbiota transplantation to enhance immunotherapy response and using bacterial toxins to cross the blood-brain barrier, show promise in improving treatment-resistant GB treatment. Additionally, the role of probiotics and antibiotics on GB prognosis is being investigated. While more research is needed to understand the gut microbiota's role in GB, recent findings suggest promising directions for future therapies. This review examines the interplay between key immune system components and the microbiota in GB development and explores how this understanding could facilitate the development of novel therapeutic interventions.}, }
@article {pmid41727556, year = {2026}, author = {Millar, BC and Cates, MJ and Torrisi, MS and Round, AJ and Warde, A and Lowery, CJ and Moore, JE}, title = {Antimicrobial Resistance: The Answers.}, journal = {British journal of biomedical science}, volume = {83}, number = {}, pages = {15559}, pmid = {41727556}, issn = {2474-0896}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; SARS-CoV-2 ; COVID-19 ; Pandemics ; *Drug Resistance, Bacterial ; *Drug Resistance, Microbial ; Betacoronavirus ; *Bacterial Infections/drug therapy ; }, abstract = {Antimicrobial resistance (AMR) has caused a global public health crisis, contributing to approximately five million deaths in 2019 and predicted deaths of approximately ten million annually by 2050. This equates to approximately 1.4-fold more deaths annually from AMR in 2050 than the entire COVID-19 pandemic to date. To tackle this AMR pandemic, regulatory and policy frameworks have been prepared at local, national and international levels with multi-faceted proposals and advances encompassing surveillance, diagnostics, infection prevention, antibiotic prescribing and variation of existing and novel treatment approaches. This narrative review primarily focuses on research and development which have been documented over the last five years in relation to therapeutic approaches at various stages in clinical development and the potential role that vaccines can play in the fight against AMR. This review provides an overview on antibacterial drugs, including novel classes of antibiotics, which have been recently approved, as well as combination antibiotic therapy and the potential of repurposed drugs. The potential role of novel antimicrobial, antibiofilm and quorum sensing inhibitors, such as antimicrobial peptides, nanomaterials and compounds from the extreme and natural environments, as well as ethnopharmacology including the antimicrobial effects of plants, spices, honey and venoms are explored. Novel therapeutic approaches are critically discussed in terms of their realistic clinical potential, detailing recent and ongoing trials to highlight the current interest of these approaches, including immunotherapy, bacteriophage therapy, antimicrobial photodynamic therapy (aPDT), antimicrobial sonodynamic therapy (aSDT), nitric oxide therapy and microbiome manipulation including faecal microbiota transplantation (FMT). The potential of predatory bacteria as living antimicrobial agents is also discussed. Importantly, there have been many technological developments which have enhanced bioprospecting and research and development of novel antimicrobials which this review draws attention to, including artificial intelligence, machine learning and Organ-on-a-Chip devices. Finally, key messages from the recent World Health Organization report into the role of vaccines against AMR provides an interesting perspective relating to prevention which can be of significance in tackling the AMR burden.}, }
@article {pmid41727680, year = {2026}, author = {Su, B and Cao, Y and Ma, L and Huang, J}, title = {BMI-stratified phenotypes of polycystic ovary syndrome: advances in gut microbiota research and personalized management strategies.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1734041}, pmid = {41727680}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy ; Female ; *Precision Medicine/methods ; *Gastrointestinal Microbiome/physiology ; *Body Mass Index ; Phenotype ; *Obesity/microbiology/complications ; Dysbiosis ; }, abstract = {Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder affecting 11%-13% of women of reproductive age. Based on body mass index (BMI), patients can be phenotypically classified into obese and non-obese subgroups: the obese PCOS is characterized by insulin resistance, hyperandrogenemia, and metabolic syndrome, with more pronounced metabolic risks; non-obese PCOS primarily manifests as reproductive endocrine dysfunction. In recent years, studies have shown that the Gut microbiota plays a key role in the pathogenesis of PCOS, and dysbiosis in the obese subgroup is generally more pronounced, potentially amplifying metabolic abnormalities through pathways such as short-chain fatty acids, bile acid disturbances, and endotoxin-related low-grade inflammation. This review systematically summarizes the clinically heterogeneous features of BMI-stratified PCOS and its gut microbiota characteristics, with a focus on elucidating the mechanistic differences between obese and non-obese individuals in terms of inflammation, metabolites, and endocrine regulatory pathways. Based on current evidence, individualized intervention strategies targeting different BMI subtypes are proposed, including dietary and lifestyle modifications, interventions with probiotics/prebiotics/synbiotics, and exploration of emerging precision microbiome therapies such as fecal microbiota transplantation. The interaction between BMI and gut microbiota provides new directions for stratified management and personalized treatment of PCOS; however, high-quality longitudinal and interventional studies are still needed to clarify causal relationships and optimize microbiota-targeted strategies.}, }
@article {pmid41729099, year = {2026}, author = {Zhang, B and Si, Y and Liu, Y and Wei, J and Li, M and Si, D and Li, H and Wang, X and Han, P and Wang, W and Bao, J and Cheng, L and Lei, Y and Ma, H and Liu, Y}, title = {Simulated microgravity induces cerebral dysfunction by disturbing protective microbiota-metabolite-microglia signaling across the gut‒brain axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2635820}, pmid = {41729099}, issn = {1949-0984}, mesh = {Animals ; *Weightlessness Simulation/adverse effects ; *Microglia/metabolism ; Rats ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Male ; Signal Transduction ; *Brain/physiopathology/metabolism ; Linoleic Acid/metabolism ; Rats, Sprague-Dawley ; Hippocampus/metabolism/physiopathology ; STAT1 Transcription Factor/metabolism ; Intestinal Barrier Function ; }, abstract = {Long-duration spaceflight characterized by microgravity adversely affects operator proficiency postlanding, yet the mechanisms by which microgravity induces cerebral dysfunction refractory to short-term recovery among astronauts remain poorly defined. Here, we demonstrate that simulated microgravity (SMG) leads to chronic behavior disorders and cognitive deficits via a microbiota-metabolite-brain axis. Fecal microbiota transplantation (FMT) from long-term SMG-treated donor rats to recipients (n = 5 per group) under normal gravity (NG) induces anxiety-like behaviors and spatial working memory disturbances by impairing synaptic plasticity in the hippocampus, reproducing the phenotype of SMG-exposed rats. SMG destroys intestinal barriers and alters the gut microbiota to a proinflammatory state with an increased abundance of Proteobacteria but decreased production of linoleic acid (LA) and LA-derived metabolites, which is highly associated with neuroinflammation in the hippocampus. Mechanistically, LA can be taken up by the hippocampus under NG conditions, and then block inflammatory microglial activation by interacting with signal transducer and activator of transcription 1 (STAT1) and inhibiting its phosphorylation at Tyr 701 and Ser 727. However, the Proteobacteria, especially Pseudomonas aeruginosa, tend to be the dominant phylum in gut microbiota under SMG conditions and consume large amounts of LA, breaking LA-dependent immune homeostasis in the central nervous system (CNS). Dietary supplementation with LA significantly mitigated SMG-induced neuroinflammation and cognitive impairment. Taken together, our findings in SD rats models reveal a critical role for gut microbiota dysbiosis in simulated microgravity-associated encephalopathy, offering a novel strategy for LA replenishment to improve brain function during spaceflight.}, }
@article {pmid41731480, year = {2026}, author = {Liu, P and Hu, P and Jin, M and Wan, Y and Wu, J and Sun, W and Tang, Y and Huang, L and Zhang, D and Shi, D and Xie, T and Tong, Y and Zheng, H and Wang, L and He, H and Xu, X}, title = {Gut microbiota dysbiosis contributes to diabetic nephropathy via affecting renal lipid deposition and inflammatory responses.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41731480}, issn = {1479-5876}, support = {82304948//National Natural Science Foundation of China/ ; No.2022MHCX01//School-level Project Innovation Project of Minhang Hospital Affiliated to Fudan University/ ; 24ZR1461700//Shanghai Natural Science Foundation/ ; 2024MZYS07//High-Level Specialist Physician Training Program under the Collaborative Health Service System of Medical Education and Research in Minhang District/ ; 2023MHBJ04//Minhang District Central Hospital Topnotch Project/ ; 2025MHZ035//Natural Science Research Project in Minhang District/ ; }, abstract = {BACKGROUND: Diabetic nephropathy (DN) patients exhibit distinct patterns of gut microbiota dysbiosis. Nevertheless, the causal relationship between gut microbiota dysbiosis and DN pathogenesis remains to be established.<br><br>METHODS: Fecal microbiota transplantation (FMT) was performed using donor samples from both DN patients and diabetic controls, with healthy donor microbiota serving as the control intervention in STZ/high-fat diet-induced DN model. Renal function was assessed by measuring biochemical indicators such as urinary protein and serum creatinine. Renal pathological changes were observed using PAS staining and Masson staining, and the composition of the intestinal microbiota was analyzed by 16&#xa0;S rRNA sequencing. Furthermore, the effects of FMT-HC on renal gene expression and lipid metabolism were investigated through transcriptome sequencing, Western blotting, and Oil Red O staining.<br><br>RESULTS: Compared with the control group, the renal function of mice with DN microbiota transplantation was significantly deteriorated, as evidenced by increased proteinuria and aggravated renal tubular interstitial fibrosis, accompanied by impaired intestinal barrier function and reduced abundance of Lactobacillus. After FMT-HC intervention, renal injury in DN mice was significantly alleviated, lipid deposition was reduced, inflammatory responses were downregulated, and beneficial bacteria such as L. johnsonii were significantly enriched in the intestine. In addition, RNA seq revealed that FMT-HC exert a protective effect on diabetic nephropathy by regulating the PPAR signaling pathway, thereby improving renal lipid metabolism disorders.<br><br>CONCLUSION: This study demonstrates that gut microbiota dysbiosis contributes to diabetic nephropathy. The regulation of renal lipid deposition and inflammatory responses might involve the process of DN.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07832-9.}, }
@article {pmid41732311, year = {2026}, author = {Makkieh, Y and Shah, HH and Imran, SB and Pathan, SMK and Saju, AC and Majooju, M and Garg, A and Naag, T and Islam, R and Fahima, C and Ali, R}, title = {The gut-heart axis: Exploring the role of the gut microbiome in cardiovascular health - A focused systematic review.}, journal = {American heart journal plus : cardiology research and practice}, volume = {61}, number = {}, pages = {100687}, pmid = {41732311}, issn = {2666-6022}, abstract = {This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding risk in patients taking oral anticoagulants. Limited evidence suggests that modulation of the microbiota may reduce chemotherapy-induced cardiotoxicity. However, only nine eligible studies met the inclusion criteria, reflecting the early and heterogeneous nature of this research area. Consequently, these findings should be interpreted as exploratory and hypothesis-generating. The focused review emphasizes the need for large-scale trials to validate microbiome-targeted strategies in CVD prevention and management. This focused systematic review is registered with PROSPERO (ID: CRD420251022190).}, }
@article {pmid41734860, year = {2026}, author = {Wu, QL and Zhou, YR and Chen, ZR and Liu, MX and Liu, MX and Liu, YF and Li, ZS and Zhao, QR and Zhang, YQ and Zhang, GQ and Zhang, Z and Gong, YT and Tang, C and Yang, T and Du, ZC}, title = {Roles of the gut microbiota in cancer immunotherapy: Mechanistic foundations and therapeutic opportunities.}, journal = {Critical reviews in oncology/hematology}, volume = {221}, number = {}, pages = {105230}, doi = {10.1016/j.critrevonc.2026.105230}, pmid = {41734860}, issn = {1879-0461}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; Dysbiosis/immunology ; Probiotics/therapeutic use ; Tumor Microenvironment/immunology ; }, abstract = {Cancer immunotherapy has revolutionized oncological treatment through diverse modalities including immune checkpoint blockade, adoptive cell therapy, therapeutic vaccines, and cytokine-based approaches. Despite these advances, clinical responses remain heterogeneous, with sustained benefit limited to a minority of patients. Emerging evidence now implicates gut microbiota as a critical systemic regulator of immunotherapy efficacy across multiple treatment platforms, mechanistically linking intestinal dysbiosis to antitumor immunity through the gut-immune-tumor axis. Specific commensal taxa and their metabolites, including short-chain fatty acids and tryptophan derivatives, regulate anti-tumor immunity through effector T cell enhancement, dendritic cell activation, and regulatory T cell suppression. This review systematically examines the microbial-metabolite-immune axis, elucidating mechanisms whereby intestinal microbes and metabolites mediate immunotherapy responses. We comprehensively evaluate microbiota-targeting strategies including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation, providing mechanistic insights and translational frameworks. We further discuss current challenges in transitioning from associative microbiome studies to mechanistic causality, standardizing intervention protocols, and integrating multi-modal microecological data, proposing future directions for engineered probiotics and precision microbial therapeutics to optimize outcomes under current immunotherapy.}, }
@article {pmid41735080, year = {2026}, author = {Yu, Y and Lu, L and Ji, G and Xu, H}, title = {Ecological battle of gut microbiota under drug intervention.}, journal = {Trends in microbiology}, volume = {34}, number = {3}, pages = {228-229}, doi = {10.1016/j.tim.2026.01.002}, pmid = {41735080}, issn = {1878-4380}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Ecological consequences of drug exposure in the gut microbiota remain difficult to predict. In a recent Cell study, Shi et al. have demonstrated that nutrient competition and interspecies antagonism drive drug-induced microbiome restructuring. Their predictive framework advances mechanistic understanding of drug-microbiome interactions and fecal microbiota transplantation.}, }
@article {pmid41735123, year = {2026}, author = {D'Arcangelo, G and Paparella, R and Gravina, A and Tarani, F and Tarani, L and Aloi, M and Petrella, C}, title = {Exploring novel biomarkers in pediatric ulcerative colitis: The role of Lipocalin-2, MMP-9, and MMP-9/LCN-2 complex.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {58}, number = {5}, pages = {630-637}, doi = {10.1016/j.dld.2026.01.224}, pmid = {41735123}, issn = {1878-3562}, mesh = {Humans ; *Colitis, Ulcerative/blood/diagnosis ; *Matrix Metalloproteinase 9/blood ; Child ; *Lipocalin-2/blood ; Biomarkers/blood ; Female ; Male ; Adolescent ; Prospective Studies ; Case-Control Studies ; Severity of Illness Index ; C-Reactive Protein/analysis ; Enzyme-Linked Immunosorbent Assay ; ROC Curve ; Acute-Phase Proteins ; }, abstract = {BACKGROUND AND AIMS: Lipocalin-2 (LCN-2), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/LCN-2 complex are emerging biomarkers for ulcerative colitis (UC). While extensively studied in adults, data in children are limited. This study aimed to evaluate their serum levels in children with newly diagnosed UC, compare them with healthy controls, and assess correlations with disease severity and extent.<br><br>METHODS: In this prospective case-control study, 32 children with UC (6-18 years) and 38 healthy controls were enrolled. Baseline clinical (Pediatric Ulcerative Colitis Activity Index/ PUCAI), laboratory (albumin, hemoglobin, Erythrocyte Sedimentation Rate, C-reactive protein/CRP, fecal calprotectin), and endoscopic (extent, Ulcerative Colitis Endoscopic Index of Severity/UCEIS) data were collected. Serum LCN-2, MMP-9, and MMP-9/LCN-2 complex levels were measured by ELISA.<br><br>RESULTS: Serum LCN-2, MMP-9, and MMP-9/LCN-2 levels were significantly higher in UC patients than controls. ROC analysis indicated LCN-2 had the best diagnostic performance. Higher LCN-2 and MMP-9 levels were observed in children with more severe endoscopic disease (UCEIS > 4) or pancolitis. LCN-2 levels inversely correlated with albumin, whereas MMP-9 positively correlated with CRP and UCEIS.<br><br>CONCLUSIONS: LCN-2 and MMP-9 are promising biomarkers in pediatric UC, reflecting disease severity and extent. Their measurement may have clinical utility in monitoring disease progression and guiding management in children.}, }
@article {pmid41736017, year = {2026}, author = {Junaid, M and Ahmad, A and Hu, Z and Xu, M and Shi, X and Qu, N and Du, T and Ding, H and Zhu, Y}, title = {The maternal and infant gut microbiome: implications for pregnancy outcomes, immune development, and health in the first 1000 days.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41736017}, issn = {1479-5876}, support = {2024Z034, 2024Z204//Science and Technology Innovation 2035 Major Project of Ningbo/ ; K. C. Wong Magna Fund in Ningbo University//K. C. Wong Magna Fund in Ningbo University/ ; }, abstract = {BACKGROUND: The maternal microbiota is recognized as an important regulator of pregnancy outcomes and early infant immune programming. Across gestation, microbial communities in the gut, vaginal, oral, and putative placental niches undergo dynamic changes driven by hormonal, metabolic, and environmental factors, with important consequences for maternal–fetal health. These microbial transitions shape maternal immune-metabolic balance and are associated with major pregnancy complications, including gestational diabetes mellitus, preeclampsia, intrahepatic cholestasis of pregnancy, fetal growth restriction, and preterm birth.<br><br>MAIN BODY: Emerging yet debated evidence suggests that microbial DNA signatures may be detected in the placenta and uterus, raising critical questions about in utero microbial transmission and its role in neonatal microbiota establishment. The first 1,000 days, spanning prenatal life through early childhood, represent a critical window during which the infant gut microbiota is established and immune programming begins. Maternal&#x2013;infant microbial transfer occurs through delivery, breastfeeding, and early-life environmental exposures, seeding the neonatal gut with beneficial taxa such as Bifidobacterium and shaping immune tolerance through mediators including IgA, TGF-&#x3b2;, and human milk oligosaccharides. Perturbations during this period via cesarean delivery, antibiotic exposure, or maternal dysbiosis have been associated with higher risks of allergy, autoimmunity, obesity, and neurodevelopmental abnormalities later in life. This review synthesizes current findings on maternal&#x2013;infant microbiome interactions, emphasizing their role in immune maturation and disease susceptibility. It also discusses emerging therapeutic strategies&#x2014;including probiotics and prebiotics, fecal microbiota transplantation, next-generation microbial ecosystem therapeutics, and CRISPR-based approaches that are under investigation for modulating the maternal and infant microbiome.<br><br>CONCLUSIONS: Despite significant advances, key gaps remain in establishing the existence of a true placental microbiome, the mechanisms of maternal immune&#x2013;microbial signaling, and the long-term efficacy of microbiome-targeted therapies. Understanding the intricate crosstalk between microbiota, hormones, and immunity provides a foundation for developing approaches to improve maternal and child health.}, }
@article {pmid41736135, year = {2026}, author = {Huang, H and Peng, S and Liu, Y and Chen, L and Wu, F}, title = {Fecal microbiota transplantation for advanced non-small cell lung cancer with secondary PD-1 resistance efficacy prognostic factors and microbiome diversity analysis.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41736135}, issn = {1479-5876}, support = {2025YLCE0054//Talent Program of Ganzhou Sci-Tech and Medical Joint Program/ ; 82560474//Regional Programs of the National Natural Science Foundation of China/ ; 82560461//Regional Programs of the National Natural Science Foundation of China/ ; 82360507//Regional Programs of the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Acquired resistance to programmed cell death protein 1 (PD-1) inhibitors represents a major therapeutic challenge in advanced non-small cell lung cancer (NSCLC). Increasing evidence suggests that gut microbiota dysbiosis contributes to immunotherapy resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to restore antitumor immunity, yet its role in PD-1–resistant NSCLC remains insufficiently explored.<br><br>METHODS: This prospective, single-arm phase II study enrolled patients with stage IIIB&#x2013;IV NSCLC who developed secondary resistance after prior PD-1&#x2013;based therapy. Patients received oral capsule-based FMT combined with PD-1 inhibitor rechallenge and chemotherapy. Treatment efficacy was assessed using objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Gut microbiota composition was analyzed by 16&#xa0;S rRNA sequencing, and immune cell subsets were evaluated by flow cytometry. Cox regression analysis was performed to identify prognostic factors.<br><br>RESULTS: A total of 27 patients were enrolled, of whom 8 achieved partial response, yielding an ORR of 29.6% and a disease control rate of 63.0%. Median PFS and OS were 6.8 months (95% CI: 2.1&#x2013;11.6) and 11.1 months (95% CI: 6.4&#x2013;15.9), respectively. Post-FMT, responders exhibited significantly increased gut microbial diversity and distinct microbial enrichment compared with non-responders. Enhanced infiltration of CD8&#x207a; T-cell subsets and reduced regulatory T-cell proportions were observed in responders. Multivariable analysis identified concomitant proton pump inhibitor use (HR: 12.67, P&#x2009;<&#x2009;0.001) and corticosteroid exposure during FMT (HR: 4.98, P&#x2009;=&#x2009;0.013) as independent predictors of shorter PFS. Treatment-related adverse events were common but mostly mild to moderate, with no FMT-related serious infections observed.<br><br>CONCLUSIONS: FMT combined with PD-1 inhibitor rechallenge and chemotherapy demonstrated encouraging antitumor activity and acceptable safety in advanced NSCLC patients with secondary PD-1 resistance. Gut microbiota modulation may enhance immunotherapy responsiveness, while concomitant use of PPIs and corticosteroids may adversely affect outcomes. These findings support further investigation of microbiome-based strategies in overcoming immunotherapy resistance.<br><br>TRIAL REGISTRATION: National Health Security Information Platform and Medical Research Information System of China, MR3622010054.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07885-w.}, }
@article {pmid41737395, year = {2026}, author = {Wen, D and Liu, S and Wu, Y and Zhang, H and Zhang, K}, title = {Fecal microbiota transplantation improves functional constipation through the gut microbiome-bile acid-receptor axis.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1751593}, pmid = {41737395}, issn = {2296-858X}, abstract = {Functional Constipation (FC) is a prevalent gastrointestinal motility disorder worldwide that markedly impairs patients' quality of life, yet the currently available treatment options often show limited efficacy. In recent years, research has gradually revealed the critical role of the gut microbiota and bile acid metabolism in the pathogenesis of FC. Fecal Microbiota Transplantation (FMT), which restores the intestinal microecological balance by transferring gut microbiota from healthy donors, has demonstrated clinical efficacy in promoting bowel movements, improving stool consistency, and enhancing patients' quality of life. However, its underlying mechanisms remain incompletely understood. Current evidence indicates that FMT restores microbial diversity, increases beneficial taxa, and partially reconstructs the bile acids (BAs) profile, thereby modulating Farnesoid X Receptor (FXR) and Takeda G Protein-Coupled Receptor 5 (TGR5) mediated signaling pathways to enhance intestinal secretion and alleviate constipation-related symptoms. The resulting microbiota-bile acid-receptor pathway elucidates the mechanistic link between microbial remodeling and host gastrointestinal motility, thereby offering theoretical support for the therapeutic application of FMT in functional constipation.}, }
@article {pmid41738638, year = {2026}, author = {Eriksen, LL and Støy, S and Mejlby Hansen, M and Porsborg Gatten, E and Erikstrup, C and Kelsen, J and Mullish, BH and Marchesi, JR and Thomsen, KL and Dahlerup, JF and Dahl Baunwall, SM and Hvas, CL}, title = {Dynamics in Circulating Immune Cell Subsets After Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical and translational gastroenterology}, volume = {17}, number = {5}, pages = {e01008}, pmid = {41738638}, issn = {2155-384X}, support = {8056-00006B//Innovationsfonden/ ; NNF22OC0074080//Novo Nordisk Fonden/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Male ; *Clostridium Infections/therapy/immunology/blood/microbiology ; Recurrence ; *Clostridioides difficile/immunology ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; Aged ; Vancomycin/therapeutic use/administration &amp; dosage ; Treatment Outcome ; T-Lymphocytes, Regulatory/immunology ; Natural Killer T-Cells/immunology ; Adult ; Combined Modality Therapy/methods ; Flow Cytometry ; Immunologic Memory ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial.<br><br>METHODS: Thirty-five patients with rCDI were randomized to vancomycin and FMT (n = 20) or vancomycin alone (n = 15). Blood samples were drawn before (wk0) and 1 week (wk1) after treatment. In 3 additional patients, blood samples were drawn before and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO + integrin&#x3b2;7 +) and effector (CD45RO - integrin&#x3b2;7 +) T cells were analyzed by flow cytometry.<br><br>RESULTS: FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid T regulatory cells dynamics. Natural killer T (NKT) cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in nonclassical monocytes and a shift in gut-homing memory to effector cells at wk1.<br><br>DISCUSSION: In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. T regulatory cells and NKT cells seemed responsive and should be further studied. Cure of Clostridioides difficile infection may be associated with an increase in circulating gut-homing T cells.}, }
@article {pmid41741396, year = {2026}, author = {Garcia-Guevara, F and Resink, T and Clasen, F and Uhlén, M and Achour, A and Shoaie, S}, title = {Temporal dynamics of gut biosynthetic gene clusters link persistent colonization and engraftment in fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2634469}, pmid = {41741396}, issn = {1949-0984}, abstract = {The human gut microbiome carries a large array of biosynthetic gene clusters (BGCs) that encode the production of secondary metabolites, yet their temporal dynamics and role during microbial colonization remain largely unexplored. Here, we tracked BGCs profile over time in a cohort of healthy adults, and identified two distinct groups: persistent, which are stable over time, and transient, which are more sporadic. Functional annotations indicated persistent gene clusters are enriched in antibiotic resistance mechanisms, while transient ones more frequently carry virulence-associated genes. We then examined colonization of these two groups in the context of fecal microbiome transplantation. Our results show that persistent gene clusters exhibit higher colonization rates than transient ones. These findings contribute to our understanding of how microbial metabolites influence host health, potentially guiding future therapeutic strategies targeting the microbiome.}, }
@article {pmid41743065, year = {2026}, author = {Ren, D and Chai, X and Xiang, C and Zhao, Y and Sun, P and Wang, M and Li, J and Wu, J and Yi, C and Chen, S and Li, E and Zhao, S}, title = {Acer truncatum Bunge seed oil attenuates learning and memory impairment in AD mouse model via modulating gut microbiota and metabolism.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1757330}, pmid = {41743065}, issn = {2296-861X}, abstract = {This study aimed to clarify the neuroprotective effect of Acer truncatum Bunge seed oil (ASO) and its interactions with the gut microbiota in transgenic mice with 5 × Familial Alzheimer's disease (5 × FAD). The AD-transgenic mice were fed with standard diet supplemented with 4% ASO from one to six months of age. The result show that ASO intervention can alleviate learning and memory impairment, enhance motor coordination and endurance, and reduce Aβ deposition in the brains. It also inhibit the proliferation of microglia and astrocytes, decrease the levels of IL-1β, IL-6, and TNF-α in the hippocampus and serum. Then, ASO could increase the Chao1 index and Shannon index, alter the gut microbiota composition, specifically, enhance the growth of gut bacteria correlated with the production of SCFAs, including Ruminococcaceae, Butyricicoccus, Sutterella and others, particularly those related to butyrate production. Additionally, ASO can increase the concentrations of SCFAs in fresh feces and serum, particularly butyric acid. ASO could primarily modulate the biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and sphingolipids metabolism in serum. At the same time, Fecal microbiota transplantation (FMT) could reduce Aβ deposition, enhance learning and memory. Finally, Supplementation of sodium Buty also mitigate learning and memory impairments. This study highlights the gut microbiota might be a potential therapeutic target for AD and provides a scientific foundation for developing novel pharmaceuticals or nutraceuticals.}, }
@article {pmid41743374, year = {2026}, author = {Marasco, G and Meacci, D and Sarnelli, G and Tosetti, C and Cremon, C and Savarino, EV and Barbara, G}, title = {Diarrhea management: from pathophysiology to microbiota modulation.}, journal = {Therapeutic advances in gastroenterology}, volume = {19}, number = {}, pages = {17562848261424324}, pmid = {41743374}, issn = {1756-283X}, abstract = {Diarrhea, whether acute or chronic, is a common clinical condition with numerous causes that collectively impose significant health, economic, social, and psychological burdens worldwide. Based on its duration, diarrhea is classified as acute when lasting less than 2 weeks and chronic when persisting for more than 4 weeks. From a pathophysiological standpoint, diarrhea can be categorized into four main types: osmotic, secretory, inflammatory, and motility-related. Acute diarrhea is most commonly caused by infectious gastroenteritis and tends to have a self-limited course. In contrast, chronic diarrhea presents a more complex diagnostic challenge due to its varied etiologies and clinical presentations. A shared feature among many causes of both acute and chronic diarrhea is an alteration in the gut microbiota, a condition referred to as dysbiosis. While acute infections often result in temporary microbial imbalance, chronic conditions such as irritable bowel syndrome and symptomatic uncomplicated diverticular disease are associated with persistent dysbiosis. This review aims to explore the most prevalent causes and underlying mechanisms of acute and chronic diarrhea, with a particular focus on the role of the gut microbiota. It will also examine the principal therapeutic strategies aimed at modulating intestinal microbiota, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation.}, }
@article {pmid41743795, year = {2026}, author = {Zhang, J and Ji, J and Dai, X and Li, B and Liu, T and Zhang, S and Yu, Y}, title = {Microplastics and Nanoplastics Cause Thyroid Dysfunction in Adolescent Mice through the Intestinal Microbiota-Mediated Hypothalamus-Pituitary-Thyroid Axis.}, journal = {Environment &amp; health (Washington, D.C.)}, volume = {4}, number = {2}, pages = {313-323}, pmid = {41743795}, issn = {2833-8278}, abstract = {Polypropylene (PP) and poly-(ethylene terephthalate) (PET) plastic products are widely used in diet packaging and may generate microplastics (MPs) and nanoplastics (NPs) during use. However, their effects and mechanisms on causing endocrine system diseases remain unclear. Here, we established a dietary exposure mouse model using micro and nanoplastics (MNPs) and found that MNPs caused a decrease in thyroid function in adolescent mice. Fecal microbiota transplantation (FMT) was used to reconstruct the intestinal microbiota of mice to reveal the mechanisms of thyroid dysfunction. The abundance of Bacteroides in the intestinal tract significantly changed after FMT. PP-MPs and NPs affected the levels of lysophosphatidylethanolamine and fatty acid esters of hydroxy fatty acids, respectively, which competitively bound to thyrotropin receptor (TSHR) on the thyroid gland, thus affecting the thyroid function. PET-MNPs affected the level of 4-hydroxy-3-methoxyphenylglycol sulfate, which regulated the activity of sympathetic nervous system by acting on the thyrotropin-releasing hormone receptor and TSHR in mice, thereby interfering with the regulatory function of the hypothalamus-pituitary-thyroid (HPT) axis on the synthesis and secretion of thyroid hormones. This study emphasizes the key role of intestinal microbiota-mediated HPT axis in thyroid dysfunction caused by MNP exposure and provides theoretical basis for the prevention of endocrine-related diseases during adolescence caused by MNPs.}, }
@article {pmid41743894, year = {2026}, author = {Jayathilaka, NS and Wijekoon, KJ and Sachinthani, SDD and Weththasinghe, AV and Ganamurali, N and Sabarathinam, S}, title = {Enteroendocrine hormones and gut microbiota in obesity: a systematic review from mechanistic insight to precision metabolic care.}, journal = {Journal of diabetes and metabolic disorders}, volume = {25}, number = {1}, pages = {73}, pmid = {41743894}, issn = {2251-6581}, abstract = {PURPOSE: This systematic review aims to synthesize current evidence on enteroendocrine cell alterations in obesity, elucidate the mechanisms by which gut microbial taxa and metabolites regulate gut hormone release, and assess therapeutic innovations targeting the microbiota-enteroendocrine axis for precision metabolic care.<br><br>METHODS: A systematic search of PubMed, Web of Science, Scopus, and Embase was conducted from January 2015 to July 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Studies examining enteroendocrine cell function, gut microbiota composition, and their metabolic interactions in human obesity, animal models, and cellular systems were included. Data were extracted on gut hormone levels, microbial community structure, short-chain fatty acid production, and therapeutic interventions. Quality assessment was performed using the Cochrane Risk of Bias tool for randomized controlled trials and Newcastle-Ottawa Scale for observational studies.<br><br>RESULTS: Microbial dysbiosis characterized by depletion of short-chain fatty acid-producing bacteria is associated with impaired gut hormone release and altered free fatty acid receptor signaling. Therapeutic strategies including glucagon-like peptide-1 receptor agonists are associated with substantial weight loss, whereas probiotics, prebiotics, and fecal microbiota transplantation show variable and generally modest metabolic effects in human studies.<br><br>CONCLUSION: The microbiota-enteroendocrine axis represents a promising therapeutic target for obesity management, supported by mechanistic and associative evidence.Multi-modal precision approaches integrating hormonal pharmacotherapy with microbiota modulation may enable more durable metabolic benefits and personalized obesity treatment.}, }
@article {pmid41744425, year = {2026}, author = {Sandeep, G and Pahari, S and Nayak, V and Gundamaraju, R and Mishra, P and Misra, A}, title = {The Gut-Prostate Axis: Decoding the Interplay of Environmental Factors, Microbial Metabolites, and Hormonal Regulation in Prostate Cancer Pathogenesis.}, journal = {Technology in cancer research &amp; treatment}, volume = {25}, number = {}, pages = {15330338261424322}, pmid = {41744425}, issn = {1533-0338}, abstract = {Prostate cancer remains one of the most common malignancies in men, with its progression strongly influenced by androgen signaling. While genetic alterations are well-documented in prostate cancer, growing evidence highlights the contribution of environmental factors, particularly diet and the gut microbiome, in modulating disease risk and therapy response. The gut microbiota plays a crucial role in regulating host metabolism, immune responses, and hormone activity. Recent findings suggest that specific microbial communities influence androgen biosynthesis and metabolism through enzymes such as β-glucuronidase, altering systemic androgen availability and imp acting tumor progression. Additionally, microbial metabolites, including short-chain fatty acids, secondary bile acids, and bacterial genotoxins, can affect inflammatory pathways and cellular signaling relevant to prostate tumorigenesis. Experimental studies also indicate that modifying the gut microbiota through dietary interventions, probiotics, or fecal microbiota transplantation can influence tumor growth and improve responses to immunotherapy and hormone-based treatments. In this review we present the current knowledge on gut-prostate axis, examine the mechanistic links between microbial activity and prostate cancer biology, and discuss emerging microbiome-based strategies as potential therapies. A deeper understanding of this bidirectional crosstalk could pave the way for microbiome-informed approaches to prevention, diagnosis, and personalized treatment of prostate cancer.}, }
@article {pmid41745080, year = {2026}, author = {Kumar, S and Himanshu,  and Gaur, P and Ahmad, S and Puri, P and Raj, VS and Pandey, RP}, title = {Microbiota Transplantation as a Future Novel Therapeutic Strategy Approach.}, journal = {Diseases (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {41745080}, issn = {2079-9721}, abstract = {Bacterial vaginosis (BV) is a leading cause of genital discomfort among women globally, and it arises from dysbiosis of the vaginal ecosystem characterized by the overgrowth of pathogenic bacteria. Current therapeutic strategies primarily rely on antibiotics and/or probiotics, which demonstrate clinical efficacy but are frequently associated with limitations such as antimicrobial resistance, high recurrence rates, and incomplete restoration of a healthy vaginal microbiota. Inspired by the success of fecal microbiota transplantation in gastrointestinal disorders, vaginal microbiome transplantation (VMT) from healthy donors has emerged as a potential alternative therapeutic approach for BV. However, experimental and early clinical studies indicate that VMT efficacy is not uniform across individuals, with considerable inter-individual variability in treatment outcomes. Host genetic factors, baseline vaginal microbial composition, immune status, and environmental influences are likely to modulate therapeutic success, underscoring the need for personalized interventions. This article critically evaluates the shortcomings of existing standardized treatments, highlights the potential advantages and challenges of VMT, and discusses emerging, precision-based therapeutic strategies for BV in light of recent research advances and ongoing clinical trials worldwide.}, }
@article {pmid41745224, year = {2026}, author = {Spaggiari, L and Tedeschi, G and Benatti, G and De Benedittis, M and Franzè, MT and Pinetti, D and Pericolini, E and Ardizzoni, A}, title = {Untargeted Metabolomic Analysis of Cell-Free Supernatants (CFSs) from Different Clinical Isolates of Saccharomyces cerevisiae and Their Effects on Candida albicans Virulence.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {41745224}, issn = {2309-608X}, support = {not applicable//FAR Dipartimentale 2024 (Ardizzoni) and FAR Dipartimentale 2025 (Pericolini)/ ; }, abstract = {Saccharomyces cerevisiae probiotic properties are effective for the treatment of infections by the opportunistic pathogen Candida albicans. Here, we assessed the anti-Candida effect of cell-free supernatants (CFSs) from three different fecal isolates and one ATCC strain of S. cerevisiae. We evaluated C. albicans growth inhibition through CFUs, and the impairment of virulence factors (adhesion, biofilm formation, and metabolic activity) by crystal violet and XTT assays. An untargeted metabolomic analysis of the CFSs was also performed. The CFSs moderately reduced C. albicans growth, but they could impair C. albicans virulence by reducing its capacity to adhere and to form a biofilm, and by decreasing the metabolic activity of biofilm-embedded fungal cells. The untargeted metabolomic analysis indicated an overexpression of N-acetyl-DL-tryptophan and other molecules derived from its metabolism (kynurenic acid and indole-3-acrylic acid), the dipeptides glycyl-L-leucine, prolyl-leucine, and γ-L-glutamyl-L-leucine, and the unconventional nucleotide inosine in the CFSs from fecal isolates, as compared to the reference strain. Further studies are warranted to better characterize the metabolome of these CFSs. Should the effects described here also be confirmed in vivo, the possible future employment of S. cerevisiae CFSs as a postbiotic aid to the current antifungal therapy may be considered.}, }
@article {pmid41745910, year = {2026}, author = {Cao, X and Zhou, L and Ding, Y and Ma, C and Chen, Q and Li, N and Ren, H and Yan, P and Jia, J}, title = {Study of Fecal Microbiota Transplantation Ameliorates Colon Morphology and Microbiota Function in High-Fat Diet Mice.}, journal = {Veterinary sciences}, volume = {13}, number = {2}, pages = {}, pmid = {41745910}, issn = {2306-7381}, support = {ZR2023MC164//the Natural Science Foundation of Shandong Province/ ; 2022KJ137//the Youth Innovation Team Project Program of Shandong Provincial Education Department/ ; }, abstract = {This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host-microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders.}, }
@article {pmid41745976, year = {2026}, author = {Németh, K and Tóth, I and Lányi, K and Schilling-Tóth, BM and Csorba, S and Žura Žaja, I and Sterczer, &#xc1;}, title = {The Collaborative Collapse: Bile Acid Dysmetabolism as a Central Pathogenic Driver in Canine and Feline Multi-Systemic Disorders-From Mechanisms to Precision Therapeutics.}, journal = {Veterinary sciences}, volume = {13}, number = {2}, pages = {}, pmid = {41745976}, issn = {2306-7381}, support = {SRF-003//University of Veterinary Medicine Budapest/ ; 2025-2.1.1-EK&#xd6;P-2025-00022//Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund/ ; }, abstract = {Veterinary metabolomics has redefined bile acids (BAs) from simple digestive surfactants to systemic endocrine signals within a microbial-host metabolic axis. This review aims to evaluate how BA dysmetabolism acts as a central pathogenic factor in canine and feline disease. We analyze the BA pool's integrity, which depends on a specialized functional guild, primarily Peptacetobacter hiranonis, responsible for 7α-dehydroxylation. We delineate two principal pathological profiles: (1) microbial collapse, characterized by secondary bile acid (SBA) depletion and compromised farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) signaling, which exacerbates inflammation in chronic enteropathy (CE), protein-losing enteropathy (PLE), and exocrine pancreatic insufficiency (EPI); and (2) hepato-biliary spillover, wherein host-induced dysfunction results in primary bile acid (PBA) excess. Recent data have linked these disruptions to skeletal health, feline renal fibrosis, cardiac remodeling in myxomatous mitral valve disease (MMVD), and neuroinflammation in epilepsy and hepatic encephalopathy. The discovery of microbially conjugated bile acids (MCBAs) and microbial extracellular vesicles (MEVs) reveals highly specific, vesicle-mediated communication pathways impacting systemic health. Diagnostic protocols should prioritize functional profiling, including the dysbiosis index (DI), serum conjugated BA analysis, and SBA/PBA ratios. Clinical management is moving beyond empirical fecal microbiota transplantation (FMT), towards precision synthetic microbial consortia (SynComs), neuroprotective BAs like tauroursodeoxycholic acid (TUDCA), and molecular postbiotics to restore the collaborative metabolome.}, }
@article {pmid41746368, year = {2026}, author = {Tsuzaka, S and Deie, K and Ebihara, M and Matsuda, R and Tsutsuno, T and Taki, S and Ogawa, S and Kondo, Y and Takezoe, T and Naya, I and Mizuta, K and Hosokawa, T and Kawashima, H}, title = {Association of preoperative ultrasonography with the bowel function at 5 years of age in low-type anorectal malformation: a retrospective cohort study.}, journal = {Surgery today}, volume = {}, number = {}, pages = {}, pmid = {41746368}, issn = {1436-2813}, abstract = {PURPOSE: Low-type anorectal malformation (LARM) is commonly associated with favorable fecal continence; however, some patients experience a suboptimal bowel function during early childhood. We evaluated whether the rectal pouch–perineum (P–P) distance, measured using preoperative ultrasonography, is associated with the postoperative bowel function. METHODS: Forty-seven children with LARMs who underwent surgery between 2006 and 2020 were analyzed over a 5-year follow-up. We measured the P–P distance on day 0/1 of life using transperineal ultrasonography. The bowel function at five years of age was assessed using the Japan Society of ARM Study Group evacuation score (ES). We conducted simple and multiple regression analyses to examine the association between the P and P distance and postoperative outcomes. RESULTS: A shorter P–P distance correlated with higher ES (B = − 0.833, P = 0.014), less soiling (B = − 0.282, P = 0.038), and less incontinence (B = − 0.357, P = 0.049). Lumbosacral malformations were independently associated with a lower ES, worse soiling, and urgency. CONCLUSION: Ultrasonographic measurement of the P–P distance is useful for surgical planning and it is associated with the bowel function at 5 years of age in patients with LARMs. Although a shorter P–P distance was associated with a better bowel function in early childhood, a longer follow-up is required to determine whether P–P distance is associated with the ultimate long-term functional outcomes.}, }
@article {pmid41746975, year = {2026}, author = {Wang, G and Liu, L and Zhang, H and Mao, P and Lu, S and Zhang, X and Li, X and Song, C}, title = {Effects of tacrolimus treatment on the gut microbiota and metabolites in liver transplant recipients.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0343817}, pmid = {41746975}, issn = {1932-6203}, mesh = {Humans ; *Tacrolimus/therapeutic use/adverse effects/pharmacology/administration &amp; dosage ; *Liver Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome/drug effects ; Male ; *Immunosuppressive Agents/therapeutic use/adverse effects ; Middle Aged ; Feces/microbiology ; Adult ; }, abstract = {BACKGROUND: Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.<br><br>METHODS: The study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.<br><br>RESULTS: As the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of Escherichia coli_D and Bacteroides stercoris rose. Additionally, the abundance of Brunovirus and Uetakevirus tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of Phocaeicola and Klebsiella increased, and the abundance of Peduovirus among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of Phocaeicola. With respect to the C/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2'-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0/16:0) showed substantial declines.<br><br>CONCLUSIONS: Tacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.}, }
@article {pmid41747725, year = {2026}, author = {Chen, K and Liu, Y and Rong, J and Dai, N and Xu, C and Li, H and Zhong, L and Wang, B and Ji, Z and Xie, S and Xu, Y and Yang, F and Wang, J and Li, D and Gu, Y and Zhou, X and Li, Y and Chen, M and Chen, Y and Li, W and Tang, Z and Cai, J and Xu, J and Xia, S and Zhan, Q and Zhou, Z}, title = {Strain-level genetic heterogeneity and colonization dynamics drive microbiome therapeutic efficacy.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {3}, pages = {393-405.e5}, doi = {10.1016/j.chom.2026.02.002}, pmid = {41747725}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Genetic Heterogeneity ; *Carcinoma, Non-Small-Cell Lung/therapy/microbiology ; *Lung Neoplasms/therapy/microbiology ; *Microbiota/genetics ; Metagenome ; Treatment Outcome ; *Gastrointestinal Microbiome/genetics ; Animals ; Bacteria/classification/genetics ; }, abstract = {Fecal microbiota transplantation (FMT) has shown immunotherapeutic promise, yet its efficacy in non-small-cell lung cancer (NSCLC) remains unclear. We demonstrate that FMT improves anti-PD-1 efficacy and progression-free survival in a single-arm trial of advanced PD-L1-negative NSCLC. Analyzing over 2,000 metagenomes from diverse disease cohorts and healthy controls via a high-resolution strain-tracking framework, we reveal that phylogenetically distinct strains within identical species exert opposing therapeutic effects, resolving prior inconsistencies. We identify conserved ecological principles where engraftment relies on species-intrinsic metabolic and immune evasion traits. Crucially, successful colonization by specific beneficial strain variants correlates with positive clinical outcomes. Finally, we identify 38 priority species with robust engraftment potential and significant heterogeneity as candidates for precision therapeutics. These findings establish a strain-function-efficacy paradigm, elucidating the mechanistic basis of variable outcomes and guiding next-generation microbiome drug development.}, }
@article {pmid41747877, year = {2026}, author = {Waghmare, A and Rahangdale, S and Khare, K and Taksande, B and Umekar, M and Mangrulkar, S}, title = {Interweaving microglial senescence and gut microbiome dynamics in Alzheimer's disease - Mechanisms and therapeutic frontiers.}, journal = {Molecular and cellular neurosciences}, volume = {136}, number = {}, pages = {104075}, doi = {10.1016/j.mcn.2026.104075}, pmid = {41747877}, issn = {1095-9327}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Alzheimer Disease/metabolism/microbiology/therapy/pathology ; Animals ; *Gastrointestinal Microbiome/physiology ; *Cellular Senescence ; Dysbiosis/metabolism ; }, abstract = {Alzheimer's disease (AD), a prevalent neurodegenerative disorder characterized by cognitive impairment and neuronal degeneration, is increasingly recognized as being driven not only by the traditional amyloid-beta and tau pathologies but also by persistent neuroinflammation and systemic immune dysregulation. Emerging evidence implicates microglia senescence and gut microbiota dysbiosis is critical contributors to the neuroinflammatory landscape. Senescent microglia marked by reduced phagocytic ability and a pro-inflammatory secretory profile, are unable to clear pathogenic stimuli, thereby intensifying neuronal damage. Simultaneously, gut dysbiosis, characterized by a reduction in beneficial bacteria and an increase in endotoxin-producing species, elevates systemic inflammation and compromises the intestinal and blood brain barrier. Microbial metabolites, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS), affect microglial activation through the gut-brain axis, primarily via the TLR4/NF-κB and NLRP3 inflammasome pathways, thus promoting microglial senescence and exacerbating AD pathology. Therapeutic approaches that target these interacting pathways are rejuvenation of microglia with senolytics and stimulation of TREM2; regulation of gut microbiota with probiotics, prebiotics, lifestyle modification, dietary intervention; and fecal microbiota transplantation. Precision medicine approaches incorporating microbiome profiling and immunogenetic analysis will enhance these treatments. This review combines mechanistic insight into microglial aging and gut-brain interaction, emphasizes their synergistic role in AD pathogenesis, and delineates integrated therapeutic strategies. Dissection of the gut-microglia axis can reveal novel targets for early intervention to counteract neuroinflammation, improve cognitive function, and slow disease progression in AD.}, }
@article {pmid41747917, year = {2026}, author = {Liu, X and Wang, Y and Medina, AA and Liu, D and Liu, J and Tang, W and Wang, M and Chen, X and Huang, K and Liu, M and Wang, C and Liu, Y}, title = {Probiotic-derived extracellular vesicles attenuate cholestatic liver damage via gut-liver axis.}, journal = {Pharmacological research}, volume = {225}, number = {}, pages = {108152}, doi = {10.1016/j.phrs.2026.108152}, pmid = {41747917}, issn = {1096-1186}, mesh = {Animals ; *Cholestasis/metabolism/microbiology/chemically induced ; *Probiotics/therapeutic use/pharmacology ; *Liver/metabolism/pathology/drug effects ; Mice, Knockout ; *Gastrointestinal Microbiome/drug effects ; *Extracellular Vesicles/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Male ; Mice ; Bile Acids and Salts/metabolism ; Receptor, Farnesoid X-Activated ; Mice, Inbred C57BL ; Pyridines ; Fibroblast Growth Factors/metabolism ; }, abstract = {Gut-liver axis disturbance is the unifying pathogenesis of cholestatic liver diseases. The purpose of this study was to explore the underlying mechanisms of the probiotic Lactobacillus amylovorus (LA) and its secreted extracellular vesicles (EVs) on liver damage and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and multidrug resistance protein 2 knockout (Mdr2[-/-]) mice. Direct replenishment of LA is sufficient to correct the DDC-fed and Mdr2[-/-]-induced liver damage and fibrosis. Mechanistic studies show that the secretion of EVs is required for the LA-induced liver protective effects. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with glutathione metabolism, microbial metabolism in diverse environments and inflammatory mediator regulation of TRP channels in DDC-fed mice. Our findings revealed that LAEVs reshaped the gut microbiota, which was associated with increased bile acids (BAs) deconjugation and fecal BAs excretion, repaired gut barrier function, activated intestinal Farnesoid X receptor/Fibroblast growth factor 15 (FXR/FGF-15) axis, reduced liver BAs and oxidative stress level, which ultimately mitigated liver damage and fibrosis in both DDC-fed and Mdr2[-/-] mice. Notably, LAEVs did not ameliorate DDC-induced liver damage or fibrosis in antibiotic-treated mice. Furthermore, LAEVs provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. LAEVs did not ameliorate DDC-induced liver damage or fibrosis in BSH inhibitor (CAPE)-treated mice. LAEVs also failed to improve liver damage and fibrosis in DDC-induced intestinal epithelial cell-specific FXR knockout (Fxr[△IE]) mice. This study revealed that LAEVs mitigated cholestatic liver fibrosis via regulating gut microbiota-bile acid-ROS axis in mice.}, }
@article {pmid41749264, year = {2026}, author = {Li, L and Cai, F and Liu, Z and Mo, W and Zhang, J and Qin, J and Liang, C and Xu, H and Liu, S and Tang, S and Peng, P and Liang, J and Ruan, H and Qin, R and Luo, F and Xiong, G and Yang, C and Zou, J and Liu, S and Geng, Y and Huang, J}, title = {Cross-kingdom microbial interactions in the gut during inflammatory bowel disease.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41749264}, issn = {1479-5876}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology ; Animals ; *Gastrointestinal Microbiome ; *Microbial Interactions ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing inflammation of the gastrointestinal tract. Recent studies emphasize the importance of gut microbiome dysbiosis in IBD pathogenesis, where interactions among bacteria, fungi, protozoa, and viruses contribute to inflammation, immune modulation, and epithelial barrier disruption.<br><br>METHODS: A comprehensive narrative literature review was conducted, focusing on human data and preclinical studies. Biomedical databases were searched for research related to microbial communities and their role in IBD development, specifically targeting microbial metabolites, gut fungi, protozoa, and viruses. Relevant studies were analyzed to assess their impact on immune pathways and microbial interactions.<br><br>RESULTS: The review reveals how different microbial kingdoms collaborate through bacteria-fungi, bacteria-protozoa, and phage-bacteria interactions, influencing metabolite production and immune system function. Specific microbial metabolites like short-chain fatty acids (SCFAs), indoles, bile acids, and others play significant roles in regulating mucosal immunity and barrier function. Disruptions in these interactions lead to chronic inflammation and contribute to disease progression. Multi-kingdom therapies, including probiotics, yeast-based treatments, and fecal microbiota transplantation (FMT), show promise but face challenges due to clinical variability.<br><br>CONCLUSION: Understanding IBD as a disruption of microbial ecosystems enables the development of personalized treatment strategies. Multi-omics studies and microbiome-based interventions targeting specific microbial interactions hold potential for more effective, individualized therapies in IBD management. However, further research and larger clinical trials are necessary for translating these findings into routine clinical practice.}, }
@article {pmid41749649, year = {2026}, author = {Pawłowski, P and Zaj, N and Iwaniszczuk, K and Grzelka, I and Makuch, W and Samardakiewicz-Kirol, E and Kościołek, A and Samardakiewicz, M}, title = {Personalizing Nutritional Therapy in Pediatric Oncology: The Role of Gut Microbiome Profiling and Metabolomics in Mitigating Mucositis and Enhancing Immune Response to Chemotherapy.}, journal = {Children (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {41749649}, issn = {2227-9067}, abstract = {INTRODUCTION: Intensive chemotherapy protocols and hematopoietic stem cell transplantation (HSCT) in children with cancer frequently lead to severe complications, such as mucositis and immune dysfunction. A growing body of evidence indicates that these complications are closely associated with the patient's nutritional status and the composition of the gut microbiome, which becomes profoundly destabilized as a result of cytotoxic therapy and antibiotic use.<br><br>BACKGROUND: The aim of this review is to critically evaluate the current state of knowledge on the interplay between gut dysbiosis, metabolomic profiles-with particular emphasis on short-chain fatty acids (SCFAs)-and treatment-related toxicity in pediatric patients, as well as to delineate pathways toward personalized nutritional therapy.<br><br>METHODS: A narrative review was conducted, including clinical and preclinical studies published between January 2015 and October 2025. PubMed/MEDLINE, Embase, Cochrane Library, and other databases were searched, focusing on changes in microbiome composition, correlations between gut-derived metabolites and the severity of complications (sepsis, graft-versus-host disease [GvHD], mucositis), and the effects of targeted nutritional interventions (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation [FMT]) on microbiome modulation during anticancer therapy.<br><br>RESULTS: The analysis demonstrates that pediatric oncologic treatment leads to a marked reduction in microbial diversity, including the loss of protective Clostridiales taxa (e.g., Faecalibacterium), accompanied by an overgrowth of Proteobacteria pathobionts. Metabolomic profiling indicates that low SCFA levels (e.g., butyrate < 20-50 &#xb5;mol/g) are a strong predictor of severe mucositis, prolonged neutropenia, and an increased risk of sepsis. Interventions aimed at restoring eubiosis and enhancing SCFA production show potential in strengthening the intestinal barrier, modulating immune responses, and enabling maintenance of the planned relative dose intensity (RDI) of chemotherapy by reducing treatment-related toxicity.<br><br>CONCLUSIONS: Gut microbiome profiling and fecal metabolomics represent promising prognostic tools in pediatric oncology. There is an urgent need for further research employing "omics"-based approaches to develop precise, individually tailored nutritional protocols. Such strategies, including postbiotics and FMT, may minimize treatment-related adverse effects and improve long-term clinical outcomes in pediatric patients.}, }
@article {pmid41751793, year = {2026}, author = {Ptáček, O and Musil, Z and Guarnieri, G and Vrbacká, A and Moudrá, P and Zlámalová, A and Röszlerová, P and Tonhajzer, M and Musil, V and Morelli, A and Zach, P}, title = {Amyotrophic Lateral Sclerosis: The State of the Art on Treatments and the Therapeutic Role of the Intestinal Microbiome in Human Studies.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41751793}, issn = {1422-0067}, support = {Cooperatio 39 - Oncology and Haematology//Charles University/ ; Cooperatio 33-Intensive Care Medicine//Charles University/ ; Cooperatio 36-Medical Diagnostics and Basic Medical Sciences//Charles University/ ; #NEXTGENERATIONEU//European Commission/ ; MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DR. 1553 11.10.2022)//Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder; to date, there is no long-term effective treatment. Recently, a relationship has been discovered between the human intestinal microbiome and the pathogenesis of ALS, on which basis faecal microbiota transplantation (FMT) has been proposed as a potential treatment for ALS. In this review, we compare three existing case studies examining the effect of FMT on the course of ALS, highlighting differences in methodology and results. In two of the studies, a halt in the progression of ALS symptoms was observed following FMT, accompanied by improvement in patient health. However, in the third and largest study, no significant effect of FMT was observed. The possible explanation for this discrepancy may be the intentional depletion of intestinal microorganisms using antibiotics prior to FMT in the third study. Future studies and/or completion of the ongoing clinical studies will help clarify the therapeutic effectiveness of FMT in ALS patients.}, }
@article {pmid41752118, year = {2026}, author = {Kurdi, MA and Alotaibi, H and Alkhuraymi, AT and Aldahery, LN and Alhawaj, AF and Aldali, HJ}, title = {Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752118}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/microbiology/therapy ; Animals ; C9orf72 Protein/genetics ; Superoxide Dismutase-1/genetics ; DNA-Binding Proteins/genetics ; RNA-Binding Protein FUS/genetics ; Genetic Therapy/methods ; Mutation ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut-brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.}, }
@article {pmid41752122, year = {2026}, author = {Wang, SJ and Nian, HY and Chen, ZH and Cui, L}, title = {Human Microbiota-Associated Pig Models for Translational Microbiome Research: A Scoping Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752122}, issn = {1422-0067}, support = {23141900100//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Animals ; Humans ; *Translational Research, Biomedical/methods ; Swine ; Fecal Microbiota Transplantation/methods ; *Microbiota ; *Gastrointestinal Microbiome ; Models, Animal ; }, abstract = {The human microbiota-associated (HMA) pig model provides a physiologically relevant platform that bridges preclinical and translational research. However, its use remains limited, with existing studies showing considerable variation in establishment methods. This scoping review systematically evaluates methodological frameworks, engraftment outcomes, and research applications of HMA pig models. Additionally, it highlights their strengths, limitations, and implications for future studies. We conducted a comprehensive literature search in PubMed, Web of Science, Scopus, and Directory of Open Access Journals, following PRISMA guidelines for Scoping Reviews. The review examines the methodological foundations of HMA pig model generation and proposes a minimal reporting framework to promote standardization. It synthesizes studies on human microbiota engraftment in pigs, identifying factors that influence colonization efficiency. Finally, it summarizes current applications, discusses persistent limitations and translational challenges, and outlines opportunities for future research. Overall, these integrated insights aim to foster standardized, reproducible protocols for HMA pig model preparation and guide advancements in the field.}, }
@article {pmid41752141, year = {2026}, author = {Wu, Y and Wong, OWH and Chen, S and Wang, Y and Zhang, G and Gao, Y and Chan, FKL and Ng, SC and Su, Q}, title = {Gut Microbiome Mediates the Causal Link Between Autism Spectrum Disorder and Dietary Preferences: A Mendelian Randomization Study.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752141}, issn = {1422-0067}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology/genetics/etiology ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome ; Female ; Male ; *Food Preferences ; Middle Aged ; Genetic Predisposition to Disease ; Cross-Sectional Studies ; Diet ; Genome-Wide Association Study ; Adult ; }, abstract = {Autism spectrum disorder (ASD) frequently co-occurs with malnutrition and gut dysbiosis, yet the underlying mechanisms remain poorly understood. Herein, this cross-sectional study first profiles dietary intake differences using dietary records from 210,874 participants (ASD = 232; non-ASD = 210,642; median age = 56.18) from the UK Biobank (UKB). Second, a bi-directional Mendelian Randomization (MR) approach serves to dissect relationships between ASD genetic susceptibility and dietary preferences by leveraging genome-wide association metadata from the iPSYCH-PGC (ASD) and UKB (dietary intake/food-liking traits). The same strategy is implemented to identify ASD-associated gut microbial species. Mediation analyses further assess the role of gut microbiota in the association between ASD and dietary preferences. Subjects with ASD exhibit higher consumption of cheese, processed meat, and oily fish, alongside lower intake of fruits, and demonstrate a preference for high-fat/salt and energy-dense foods. Additionally, the depletion of Turicibacter, Streptococcus, and Lachnospiraceae NK4A136 was causally related with ASD (all false discovery rate < 0.05; β = -0.15, β = -0.10, β = -0.093, respectively), which significantly mediates the ASD-associated elevated preference for high-fat/salt foods. In conclusion, ASD is associated with specific dietary preferences, likely mediated via gut microbiota, highlighting the future potential of gut microbiome-based therapeutics to modify eating disorders for ASD.}, }
@article {pmid41753607, year = {2026}, author = {Yuan, H and Yi, L and Jia, H and Song, G and Cheng, W and Xie, Y and Zhu, J and Zhao, S}, title = {Gut Microbiota-Derived Metabolites to Regulate Intramuscular Fat Deposition in Pigs.}, journal = {Microorganisms}, volume = {14}, number = {2}, pages = {}, pmid = {41753607}, issn = {2076-2607}, support = {2024YFD1800404//National Key Research and Development Program of China/ ; 32360808//National Natural Science Foundation of China/ ; 31760645//National Natural Science Foundation of China/ ; 31260592//National Natural Science Foundation of China/ ; 31060331//National Natural Science Foundation of China/ ; 32560790//National Natural Science Foundation of China/ ; 202202AE090032//Major Science and Technology Project of Yunnan Province/ ; 202501AS070086//Major Science and Technology Projects of Yunnan Province/ ; }, abstract = {Intramuscular fat (IMF) is a crucial determinant of pork quality, influencing tenderness, flavor, and consumer preferences, yet selective breeding has reduced its levels in modern pigs. This review explores the molecular and cellular mechanisms of IMF deposition, including progenitor cell differentiation via pathways like Wnt/β-catenin and PPARγ, and advances in non-invasive detection methods such as hyperspectral imaging and Raman spectroscopy. It highlights correlations and causal links between the gut microbiota composition and IMF, established through omics analyses, fecal microbiota transplantation, and germ-free models. Key microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids, modulate lipid metabolism bidirectionally via signaling receptors like GPR43, FXR, and TGR5. Future research should integrate multi-omics and develop probiotics to enhance IMF efficiency for sustainable pork production.}, }
@article {pmid41754077, year = {2026}, author = {Ashkanani, G and Rob, M and Yousef, M and Ashkanani, A and Al-Najjar, YA and Laws, S and Chaari, A}, title = {The Effects of Microbiome Modulating Therapies on Inflammatory Markers in Autoimmune Disease: A Systematic Review and Meta-Analysis.}, journal = {Nutrients}, volume = {18}, number = {4}, pages = {}, pmid = {41754077}, issn = {2072-6643}, mesh = {Humans ; *Autoimmune Diseases/therapy/microbiology/immunology/blood ; *Probiotics/administration &amp; dosage/therapeutic use ; Biomarkers/blood ; Synbiotics/administration &amp; dosage ; *Inflammation/therapy ; Prebiotics/administration &amp; dosage ; *Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; *Fecal Microbiota Transplantation ; Dietary Supplements ; Female ; }, abstract = {BACKGROUND: Autoimmune diseases (ADs) are a growing global health burden, driven by chronic inflammation and immune dysregulation. The gut-immune axis plays a central role in their pathogenesis, with dysbiosis linked to several conditions. This has prompted investigation into nutraceuticals such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as adjunctive therapies.<br><br>METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, and Web of Science for randomized controlled trials evaluating these interventions in autoimmune diseases.<br><br>RESULTS: Twenty-eight randomized control trials (RCTs) involving 2002 patients across 11 countries met inclusion criteria. Across the included RCTs, pooled analyses demonstrated significant reductions in c-reactive protein (CRP) (SMD -0.67, 95% CI -1.00 to -0.33; I[2] = 80.8%) and Tumor necrosis factor-alpha (TNF-&#x3b1;) (SMD -1.81, 95% CI -2.67 to -0.94; I[2] = 96%), a significant increase in Interleukin-10 (IL-10) (SMD 2.65, 95% CI 0.64 to 4.66; I[2] = 98%), and no overall significant effect on Interleukin-6 (IL-6) (SMD -0.89, 95% CI -1.99 to 0.22; p = 0.12). The strongest evidence of benefit was observed in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Pooled effects are limited by extreme between-study heterogeneity (I[2] 80-98%), leaving interpretation as exploratory rather than definitive. More limited or inconsistent findings were reported for systemic lupus erythematosus, hypothyroidism, axial spondylarthritis, and juvenile idiopathic arthritis. Heterogeneity in study design, probiotic strain selection, dosage, and treatment duration limited comparability across trials.<br><br>CONCLUSIONS: Overall, microbiome-targeted nutraceuticals appear promising for attenuating systemic inflammation in select autoimmune conditions, but results remain mixed. Larger, rigorously designed RCTs with standardized endpoints are needed to clarify efficacy, identify optimal formulations, and define patient populations most likely to benefit.}, }
@article {pmid41754110, year = {2026}, author = {Singh, N and Hosein, E and Virkud, YV and Keet, C and Kulis, M}, title = {The Gut Microbiome in the IgE-Mediated Food-Allergic Patient-A Narrative Review.}, journal = {Nutrients}, volume = {18}, number = {4}, pages = {}, pmid = {41754110}, issn = {2072-6643}, support = {T32 HD091058/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Food Hypersensitivity/immunology/therapy/microbiology ; *Immunoglobulin E/immunology ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; Omalizumab/therapeutic use ; Allergens/immunology ; Desensitization, Immunologic/methods ; }, abstract = {Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics.}, }
@article {pmid41754939, year = {2026}, author = {Cosimato, I and Brescia, A and Franci, G and Casolaro, V and Folliero, V}, title = {Emerging Therapeutic Approaches for Modulating the Intestinal Microbiota.}, journal = {Pharmaceutics}, volume = {18}, number = {2}, pages = {}, pmid = {41754939}, issn = {1999-4923}, abstract = {Background/Objectives: The gut microbiota is increasingly recognized as a key determinant of human health, playing a vital role in metabolism, immunity, and disease susceptibility. Dysbiosis, or microbial imbalance, is associated with gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridioides difficile infection (CDI), as well as extraintestinal conditions, including obesity, cardiovascular disease, and neuropsychiatric disorders. This review aims to provide an updated overview of emerging therapeutic strategies to modulate the gut microbiota to restore eubiosis and improve health outcomes. Methods: A narrative review of recent literature was conducted, focusing on preclinical and clinical studies investigating microbiota-targeted therapies. The review primarily covers innovative interventional approaches, including fecal microbiota transplantation (FMT), bacterial consortium transplantation (BCT), bacteriophage therapy and outer membrane vesicles (OMVs). Results: Evidence supports the role of probiotics, prebiotics, and synbiotics in remodeling microbial communities and improving host health, although their effects may be strain- and context-dependent. FMT has demonstrated high efficacy in the treatment of recurrent Clostridium difficile infections and is being studied for IBD, IBS and extraintestinal diseases, following the recent Food and Drug Administration approval of the first commercial FMT products. BCT offers a standardized alternative to donor-derived material, with early clinical successes such as FDA-approved SER-109. Phage therapy and OMVs represent promising frontiers, offering targeted microbial modulation and interactions with the immune system, although clinical data remain limited. Conclusions: Emerging gut microbiota modulation strategies offer new perspectives for precision medicine and could transform the prevention and treatment of many diseases, but further studies are needed to ensure their safety, standardization, and clinical application.}, }
@article {pmid41757041, year = {2026}, author = {Tschang, MA and Vuong, RD and Eilers, B and Chac, D and Waalkes, A and Penewit, K and Easton, A and Schuessler, B and Daniels, R and Weil, AA and Salipante, SJ and Gibbons, SM and Schindler, AG}, title = {If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41757041}, issn = {2692-8205}, abstract = {The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures. We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into pellets ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the pellets, and blood was collected to compare corticosterone levels relative to traditional gavage FMT. Plasma corticosterone levels were found to be significantly lower in mice receiving FMT via pellets compared to oral gavage. Furthermore, relative to gavage FMT, microbial signatures of mice receiving FMT via pellets were more similar to those of the donor pellets at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta-diversity distances. Together, these results establish effective antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.}, }
@article {pmid41757237, year = {2026}, author = {Wu, Q and Wang, M and Yang, J and Wang, J and Feng, S and Lu, S and Qin, Z and He, X and Wu, L}, title = {The influence of washed microbiota transplantation on menstruation in female patients of childbearing age.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1715020}, pmid = {41757237}, issn = {1664-2392}, mesh = {Humans ; Female ; Adult ; *Gastrointestinal Microbiome/physiology ; Quality of Life ; *Fecal Microbiota Transplantation/methods ; *Menstruation/physiology ; Young Adult ; Depression ; Anxiety ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND AND AIMS: Menstrual disorders are closely related to the disorder of gut microbiota. This study aims to explore the impact of Washed microbiota transplantation (WMT) on the quality of life, depression and anxiety scale scores, and menstrual conditions of female patients of childbearing age.<br><br>METHODS: The data of female patients of childbearing age who received WMT at the First Affiliated Hospital of Guangdong Pharmaceutical University from February 2023 to February 2025 were collected. A comparative analysis was conducted on the effects of SF-36, SDS, SAS and menstrual conditions in female patients of childbearing age before and after WMT treatment. The changes of gut microbiota before and after WMT were analyzed by 16S rRNA gene sequencing.<br><br>RESULTS: A total of 23 female patients of childbearing age were included in this study. WMT significantly improved the scores of GH, SF, MH, RE and VT in SF-36 of female patients of childbearing age and significantly reduced the scores of SDS and SAS (P < 0.05). The MDQ score was negatively correlated with the PF, BP, GH, VT, RE and MH scores in SF-36, and positively correlated with the SDS and SAS scores (P < 0.05). WMT enhanced the &#x3b1; diversity of gut microbiota in female patients of childbearing age, and the Chao1 and Shannon indices were statistically significant (P < 0.05). At the same time, the relative abundance of Dialister, Bifidobacterium, Faecalibacterium, Roseburia and Fusobacterium increases. The relative abundances of Bacteroides, Agathobacter, Prevotella, Escherichia-Shigella and Ruminococcus decreased.<br><br>CONCLUSIONS: WMT treatment can effectively improve the quality of life score of female patients of childbearing age and reduce the scores of depression and anxiety scales. WMT can increase the diversity and abundance of gut microbiota in female patients of childbearing age and improve menstrual conditions, which provides new ideas for future clinical treatment.}, }
@article {pmid41759265, year = {2026}, author = {Qu, Y and Wang, P and Wang, D and Li, B and Yang, F}, title = {Intermittent fasting protects MPTP-induced Parkinson's disease mouse model through regulating gut microbiota dysbiosis.}, journal = {International immunopharmacology}, volume = {175}, number = {}, pages = {116447}, doi = {10.1016/j.intimp.2026.116447}, pmid = {41759265}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Dysbiosis ; Intermittent Fasting ; Mice ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Cytokines/metabolism ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; }, abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by gut microbiota dysbiosis and excessive inflammatory responses. Intermittent fasting (IF) exerts neuroprotective effects on neurodegenerative diseases. However, the impact of IF on PD and its mechanisms still need to be elucidated. In the present study, we found that 13-week IF regimen (designed as alternate-day fasting) mitigated motor impairment, α-synuclein aggregation, and loss of dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Meanwhile, IF attenuated intestinal dysfunctions, intestinal pro-inflammatory cytokines (tumor necrosis factor-αlphα (TNF-α) and interleukin-1 beta (IL-1β)) levels, and gut barrier destruction. Furthermore, IF alleviated brain barrier impairment and suppressed the activation of astrocytes and microglia. Mechanistic studies revealed that IF suppressed the toll-like receptor 4 (TLR4)/NF-κB signaling pathway both in the colon and substantia nigra. 16S rRNA sequencing demonstrated that IF alleviated MPTP-induced microbiota dysbiosis, decreasing harmful bacteria abundances (Proteobacteria, Burkholderiales, Sutterellaceae, Parasutterella, Burkholderiales_bacterium, and Desulfovibrio_fairfieldensis) while increasing probiotic bacteria abundances (Oscillospirales, Rikenellaceae, and Lactobacillus_murinus), which were significantly correlated with the anti-inflammatory effects of IF. Gas chromatography-mass spectrometry (GC-MS) revealed that IF induced the levels of fecal short chain fatty acids (SCFAs). Antibiotics intervention abolished the beneficial effects of IF, suggesting that gut microbiota contributed to the neuroprotection of IF for PD. These findings suggest that IF regimen may serve as a novel therapeutic strategy for PD, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.}, }
@article {pmid41759374, year = {2026}, author = {Zhou, H and Huang, Y and Chen, C and Song, M and Hylemon, PB}, title = {Gut microbiome and bile acid metabolism in liver disease: Mechanisms, clinical implications, and therapeutic opportunities.}, journal = {Pharmacological reviews}, volume = {78}, number = {2}, pages = {100120}, pmid = {41759374}, issn = {1521-0081}, support = {IS1 BX005517/BX/BLRD VA/United States ; R01 AA030180/AA/NIAAA NIH HHS/United States ; I01 BX005730/BX/BLRD VA/United States ; P01 CA275740/CA/NCI NIH HHS/United States ; IS1 BX004777/BX/BLRD VA/United States ; R01 DK115377/DK/NIDDK NIH HHS/United States ; R21 AA026629/AA/NIAAA NIH HHS/United States ; IK6 BX004477/BX/BLRD VA/United States ; R01 DK104893/DK/NIDDK NIH HHS/United States ; R01 DK057543/DK/NIDDK NIH HHS/United States ; I01 BX004033/BX/BLRD VA/United States ; R56 DK115377/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Bile Acids and Salts/metabolism ; Animals ; *Liver Diseases/metabolism/microbiology/therapy/drug therapy ; *Gastrointestinal Microbiome ; Liver/metabolism ; }, abstract = {The intricate interplay between the gut microbiome and bile acid metabolism via the gut-liver axis is fundamental to hepatic homeostasis. Perturbations in this axis are increasingly implicated in the pathogenesis of diverse liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and hepatocellular carcinoma. This review integrates current understanding of hepatic bile acid synthesis, enterohepatic circulation, and gut microbial bile acid transformations, detailing how bile acids function as signaling molecules through nuclear receptors including farnesoid X receptor, pregnane X receptor, vitamin D receptor, constitutive androstane receptor, and G-protein-coupled receptors; G protein-coupled bile acid receptor 1 (also known as Takeda G protein-coupled receptor 5), and sphingosine-1-phosphate receptor 2. We explore disease-specific alterations in gut microbiota composition and bile acid profiles in metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and liver cancers, focusing on mechanisms linking gut dysbiosis, impaired intestinal barrier function, altered bile acid signaling, inflammation, and immune modulation to liver injury and progression. Furthermore, we discuss the clinical implications, highlighting the potential of microbiome signatures and bile acid profiles as diagnostic and prognostic biomarkers. Therapeutic strategies targeting the gut-liver axis, including probiotics, fecal microbiota transplantation, farnesoid X receptor agonists, and fibroblast growth factor 19 analogs, are reviewed. Finally, we address current challenges and future directions, emphasizing the need for multiomics integration, functional studies, and personalized medicine approaches to leverage the gut-liver axis for improved liver disease management. SIGNIFICANCE STATEMENT: Disruption of the gut microbiome-bile acid-liver axis is now recognized as a unifying mechanism driving multiple liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and hepatocellular carcinoma. Unraveling the molecular and microbial interactions within this axis offers fundamental insights into disease pathogenesis and reveals novel therapeutic opportunities. Integrating multiomics technologies with artificial intelligence-based analytics will accelerate the discovery of predictive biomarkers and personalized interventions, advancing the field toward precision-based liver disease treatment protocols.}, }
@article {pmid41759744, year = {2026}, author = {Waghmare, PV and Kolekar, KA and Bashir, B and Kumbhar, PS and Patil, KS and Gupta, G and Prasher, P and Jha, SK and Disouza, J and Gurav, SS and Dua, K and Singh, SK}, title = {Advocating gut-retina connection and microbiota mediated pathways in management of age-related macular degeneration: Preclinical to clinical perspective.}, journal = {Ageing research reviews}, volume = {117}, number = {}, pages = {103071}, doi = {10.1016/j.arr.2026.103071}, pmid = {41759744}, issn = {1872-9649}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; *Aging ; Probiotics/therapeutic use ; *Retina/metabolism/pathology/microbiology ; Dysbiosis ; }, abstract = {Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis) cause lowered microbial diversity, enhanced gut permeability, and pro-inflammatory species, leading to macular damage. The healthy gut microbiota containing Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Faecalibacterium prausnitzii, are responsible for maintaining gut homeostasis, protecting the retina, and preventing ARMD progression. In contrast, the elevated population of pathogenic species such as Escherichia coli, Prevotella, Desulfovibrio, Enterococcus faecalis, and Streptococcus salivarius in gut dysbiosis is involved in ARMD progression. This review explores gut microbiota and their dynamics in ageing. The age-dependent gut microbiota variations and potential biological implications for the progression of ARMD are discussed. The review also discusses observations from experimental animals and explores potential microbiome-centered treatment avenues, covering probiotics, synbiotics, dietary remedies, metabolite-based treatment, and fecal microbiota transplantation for managing ARMD. Furthermore, various challenges in the management of gut microbiota-driven ARMD are also briefed with future directions. Thus, a gut microbiota-focused paradigm can offer novel choices for ARMD prevention and treatment.}, }
@article {pmid41760447, year = {2026}, author = {Martin, M and Nguyen, VM and Puyade, M and Broca, F and Roblot, P}, title = {Faecal incontinence in systemic sclerosis: A narrative review.}, journal = {La Revue de medecine interne}, volume = {47}, number = {4}, pages = {194-199}, doi = {10.1016/j.revmed.2026.02.001}, pmid = {41760447}, issn = {1768-3122}, mesh = {Humans ; *Scleroderma, Systemic/complications/epidemiology/therapy ; *Fecal Incontinence/etiology/therapy/epidemiology/diagnosis ; Quality of Life ; }, abstract = {Although associated with impaired health-related quality of life, faecal incontinence (FI) is underscreened in cases of systemic sclerosis (SSc). Its pathophysiology is complex and multifactorial, encompassing vasculopathy, fibrosis and probably (autoimmune) neuropathy. FI prevalence in SSc seems to be 5-6-fold higher than in the age- and sex-matched general population and is severe in nearly 15% of cases. FI is associated with diarrhoea, small intestinal bacterial overgrowth, constipation, urinary incontinence, anticentromere positivity and some features of vasculopathy. FI should be regularly screened in all SSc patients. Simple self-questionnaires are useful tools, completed by meticulous digital rectal exam for anal and puborectalis tone and by neurological examination. In case of unexplained chronic constipation or diarrhoea, endoscopic explorations are mandatory first to search for organic cause. Anorectal manometry is recommended in case of suspected anorectal dysfunction. Management should be multidisciplinary and, in general, follows the recommendations applied to the general population. It consists mainly in diet and lifestyle modifications and biofeedback therapy. Loperamide or laxative/transanal irrigation could be proposed as options in case of chronic diarrhoea or terminal constipation respectively. Nerve stimulation and faecal microbiota transplantation require further studies before conclusions can be drawn.}, }
@article {pmid41761056, year = {2026}, author = {Wang, H and Gao, Q and Dang, G and Zhang, S and Zhong, R and Chen, L and Zhang, H}, title = {Pooled feces reduce the inter-sample variation of microbiota in pig models.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41761056}, issn = {1471-2180}, support = {2022YFD1300605//National Key R&amp;D Program of China/ ; CXGC2024F11//Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences/ ; 2022TSGC2029//Shandong Province Science and Technology Small and Medium-sized Enterprises Innovation Ability Improvement Project/ ; 202228037//Jinan introductory innovation team project/ ; }, abstract = {BACKGROUND: For in vitro batch fermentation or fecal microbiota transplantation, preparation of inoculum was recommended by pooled feces to minimize inter-individual variation. However, the impact of pooling on microbiota variability remains unclear. The present study investigated the changes in inter-sample variation of microbial community in fecal samples after pooling from different numbers of donors, and verified the hypothesis that the variation of microbiota in feces affects the fermentation outcomes in vitro using fecal inoculum.<br><br>RESULTS: The pooled feces from different pigs increased the microbial richness (Sobs and Ace indexes, P&#x2009;<&#x2009;0.05). The PCoA indicated that the microbiota composition was not distinct among the treatments, however, the distance of the sample within group was reduced as the incremental number of feces in the mixed samples. Microbial composition analysis indicated the variation of microbiota abundance was reduced with the increasing number of feces in mixed samples. The in vitro fermentation results suggested that the coefficient variation (CV), especially inter-bath and total CV, the kinetic parameters of gas production, in vitro fermentability of dry matter (IVDMF), and SCFA production reduced as the number of mixture donors increased.<br><br>CONCLUSIONS: Collectively, pooled feces originating from different donors can reduce the variation of microbiota between samples, and it is proposed that the fecal samples should be mixed, derived from 5 to 10 pigs, and then prepared as an inoculum to improve the reproducibility of in vitro fermentation.}, }
@article {pmid41761083, year = {2026}, author = {Mo, C and Shao, R and Shi, Z and Lou, X and Xue, J and Ning, D and Liu, Y and Jiang, W and Wei, X and Xiao, J and Wang, F and Chen, G}, title = {Fecal microbiota transplantation reduces susceptibility to post-antibiotic CLP-induced sepsis by modulating the gut microbiota and its metabolites.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41761083}, issn = {1471-2180}, support = {202401AS070017//Yunnan Provincial Basic Research Program/ ; 202302AA310042//The Yunnan Provincial Major Program in Biomedicine/ ; 8256080235//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Sepsis/therapy/microbiology/etiology ; *Fecal Microbiota Transplantation/methods ; *Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Intestinal Barrier Function ; Mice ; Dysbiosis/chemically induced/therapy ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Cecum/injuries ; Ligation/adverse effects ; Signal Transduction ; Punctures/adverse effects ; }, abstract = {Sepsis remains a leading cause of mortality in intensive care units, and antibiotics continue to serve as the cornerstone of treatment. However, their potentially detrimental effects on gut health are often overlooked. Although antibiotic exposure may increase susceptibility to disease, its contribution to the progression of sepsis has not been fully elucidated. In this study, we investigated the effects of antibiotics on the gut microbiota, microbial metabolites, and intestinal barrier integrity in healthy mice, and further evaluated their impact on subsequent sepsis outcomes. Using a cecal ligation and puncture (CLP)-induced sepsis model, we demonstrated that antibiotic-induced gut dysbiosis exacerbated intestinal barrier damage and significantly increased mortality. In contrast, fecal microbiota transplantation (FMT) markedly improved survival and restored intestinal barrier function. Mechanistically, the protective effects of FMT were associated with modulation of the Hippo signaling pathway, which was accompanied by reduced intestinal permeability. Collectively, these findings highlight the critical role of antibiotic-induced gut dysbiosis in the pathogenesis of sepsis and support FMT as a potential therapeutic strategy to alleviate intestinal barrier damage and improve survival in sepsis.}, }
@article {pmid41761093, year = {2026}, author = {Qureshi, A and Wahid, A and Qazi, S and Shahzad, MK and Kiani, HM and Asif, MDA}, title = {DynaBiome: interpretable unsupervised learning of gut microbiome dysbiosis via temporal deep models.}, journal = {BMC bioinformatics}, volume = {27}, number = {1}, pages = {}, pmid = {41761093}, issn = {1471-2105}, abstract = {PURPOSE: Gut microbiome dysbiosis is a critical determinant for autologous fecal microbiota transplantation (Auto-FMT) eligibility, yet current classification approaches rely predominantly on supervised learning with manually annotated sequencing labels, which are often scarce. This study proposes DynaBiome, a framework designed to predict gut dysbiosis by leveraging unsupervised learning and clinical phenotypic proxies as a scalable alternative to ground-truth genomic labeling. METHODS: Our framework employs an LSTM autoencoder architecture to capture temporal microbiome dynamics within 14-day windows. The model reconstructs normal microbiome patterns, where high reconstruction errors signal potential dysbiosis. To ensure rigorous evaluation and prevent data leakage, the dataset was partitioned via a strict patient-level split. Unsupervised anomaly signals were refined via phenotypic proxy labels (e.g., fever, neutropenia) via weak supervision, and ensemble learning methods were applied to optimize classification performance. RESULTS: The initial LSTM autoencoder successfully flagged dysbiotic sequences but required refinement to reduce false positives. Ensemble learning significantly enhanced predictive accuracy. The stacked ensemble (with Logistic Regression meta-learner) demonstrated optimal performance with an ROC AUC of 0.8908 and a Weighted F1-score of 0.7909. This approach significantly outperformed the standard One-Class SVM baseline (ROC AUC 0.6033), confirming the superiority of deep temporal modeling over static anomaly detection. Critically, the model achieved performance levels comparable to fully supervised baselines, confirming the efficacy of the proxy-label framework. CONCLUSION: Integrating unsupervised temporal feature extraction with stacked ensemble methods provides a viable framework for dysbiosis prediction. These results demonstrate that leveraging phenotypic via weak supervision can effectively approximate supervised baselines, thereby reducing the reliance on comprehensive metagenomic annotations for longitudinal patient monitoring.}, }
@article {pmid41761296, year = {2026}, author = {Ye, H and Yang, X and Zheng, M and Dong, W and Chen, X and Chen, J and Hu, M and Zhou, M and Zheng, P and Shen, L and Wu, Y and Zheng, K and Huang, XF and Yu, Y}, title = {Early risperidone exposure impairs cognitive function by perturbation of the gut microbiome and bile acids/tyrosine-PTP1B axis.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {41761296}, issn = {2049-2618}, mesh = {Animals ; *Risperidone/adverse effects ; Mice ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Cognition/drug effects ; *Tyrosine/metabolism ; Male ; Dysbiosis/chemically induced/microbiology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Cognitive Dysfunction/chemically induced ; *Antipsychotic Agents/adverse effects ; Hippocampus/drug effects ; Intestinal Barrier Function ; Bacteria/classification/genetics/drug effects/isolation &amp; purification ; Taurochenodeoxycholic Acid ; }, abstract = {BACKGROUND: Second-generation antipsychotics (SGAs) are increasingly being utilized in children and adolescents. Risperidone, one of the most commonly prescribed SGAs in this population, has been found to adversely affect cognitive function; however, limited knowledge exists regarding the impact of risperidone on the gut microbiome-brain axis. We hypothesized that the cognitive impairment induced by risperidone is mediated by alterations in the gut microbiome and its metabolites.<br><br>RESULTS: In this study, we found that early-life risperidone exposure impaired cognition in mice, including deficits in behavior tests and hippocampal dendritic architecture. The risperidone-exposed mice also exhibited gut microbiota dysbiosis along with damage to the intestinal barrier. Fecal microbiota transplantation (FMT) from treated donors to recipients demonstrated the causal role of the gut microbiome in risperidone-induced cognitive deficits. Of note, risperidone increased the abundance of species Escherichia coli, Eggerthella lenta, Ruminococcus gnavus, Clostridium perfringens, Clostridium difficile, and Blautia hydrogenotrophica. These altered species are identified to encode 7&#x3b1;-HSDH, 3&#x3b2;/&#x3b1;-HSDH, TyrB, and porA, the key enzymes in secondary bile acid metabolism and tyrosine metabolism. Furthermore, a significant reduction in tauroursodeoxycholic acid (TUDCA, the metabolite of bile acid metabolism) and accumulation of p-cresol (the metabolite of tyrosine metabolism) were observed in the brains of mice exposed to risperidone. Mechanically, TUDCA prevented cognitive impairment and endoplasmic reticulum (ER) stress in the hippocampus induced by risperidone, while p-cresol induced neuronal ER stress. Knockout of protein tyrosine phosphatase 1B (PTP1B, ER stress-associated protein) in neurons ameliorated cognitive impairment and neurological damage induced by risperidone.<br><br>CONCLUSIONS: This study, for the first time, reveals that early risperidone exposure induces gut microbiome dysbiosis and disturbs the bile acids/tyrosine-PTP1B axis to impair cognitive function. These findings alert the risk of gut and neurological side effects of SGAs treatment and highlight that it is crucial to maintain gut homeostasis during the brain developmental phases of children and adolescents with SGAs exposure. Video Abstract.}, }
@article {pmid41761646, year = {2026}, author = {Chen, Y and Jie, W and Xu, Y and Chen, X and Zhu, S and Ma, Y and Hu, L and Chen, C and Liu, B and Xu, D and Cai, D and Liu, Z}, title = {Correlation study between gut microbiota and intestinal permeability in cerebral small vessel disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {110}, number = {2}, pages = {922-936}, doi = {10.1177/13872877261418554}, pmid = {41761646}, issn = {1875-8908}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Cerebral Small Vessel Diseases/microbiology/metabolism ; Male ; Female ; Aged ; Intestinal Barrier Function ; Mice ; Dysbiosis ; Permeability ; Mice, Inbred C57BL ; Cognitive Dysfunction/microbiology ; Fecal Microbiota Transplantation ; Middle Aged ; Feces/microbiology ; Mannitol/urine ; }, abstract = {BackgroundDysbiosis of gut microbiota and increased intestinal permeability are associated with various diseases, and their relationship with cognitive dysfunction such as cerebral small vessel disease (CSVD) and Alzheimer's disease remains to be elucidated.ObjectiveThis study investigates the role of gut microbiota dysbiosis and its relationship with intestinal permeability in patients with cognitive impairment associated with CSVD (CSVD-CI).MethodsIntestinal permeability was detected in 21 patients with CSVD-CI and 20 healthy controls by testing urine lactulose/mannitol, and correlation analysis was performed between the test results and cognitive function assessment. 16S rRNA sequencing was used to analyze the different combination of gut microbiota. Feces of the patients or controls were gavaged into C57 mice, and gut barrier function, behavior, and metabolites were assessed.ResultsPatients with CSVD-CI have a higher incidence of hypertension, higher homocysteine levels, higher scores for white matter hyperintensities, and worse cognitive function. Their urinary mannitol recovery rate is higher, which is correlated with lower scores of cognitive function assessment. Alterations in the gut microbiota involve a reduction in Prevotella-9 alongside increases in Proteobacteria and Fusobacteria. Fecal microbiota transplantation (FMT) from patients with CSVD-CI increases intestinal permeability in mice, but does not change their cognitive function; meanwhile, fecal metabolomics analysis has identified alterations in bile acids and vitamins, which are associated with shifts in the gut microbiota.ConclusionsPatients with CSVD-CI have gut microbiota imbalance and increased intestinal permeability, which are associated with cognitive decline. FMT from these patients can cause intestinal leakage and the production of harmful metabolites in mice.}, }
@article {pmid41761700, year = {2026}, author = {Pepke, ML and Hansen, SB and Limborg, MT}, title = {The ageing holobiont: crosstalk between telomere dynamics, oxidative stress and the gut microbiome.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/brv.70152}, pmid = {41761700}, issn = {1469-185X}, support = {DNRF143//Danmarks Grundforskningsfond/ ; CF21-0356//Carlsbergfondet/ ; }, abstract = {The gut tissue is at the frontline of early onset of ageing. It exhibits high cell turnover rates and rapid telomere shortening, which can have systemic effects on the developing or senescing organism. We conducted a literature review of studies on the crosstalk between telomere length dynamics, telomerase activity, oxidative stress, and gut microbiota composition and activity in animals. Studies mainly on humans and animal models include correlations between telomere dynamics and gut microbiome components, particularly under pathogenic conditions, but also manipulations of either the gut microbiome through faecal microbiota transplantations or of telomere dynamics using telomerase knockout models. This synthesis reveals that components of the gut microbiome including microbial metabolites and pathogenic bacteria can affect telomere dynamics through oxidative-stress-inducing processes, and that telomere maintenance is critical in maintaining gut barrier and tissue integrity, which link inflammation and gut dysbiosis. Some of the interactions between the gut microbiome and host telomere dynamics are bidirectional and important in maintaining intestinal homeostasis. However, many of the causal molecular or cellular mechanisms - and how they translate into organismal senescence - remain to be identified. Furthermore, we highlight how recent advances in whole genome sequencing capacities and bioinformatic tools represent an often-unexploited resource for measuring telomere lengths and may be particularly valuable tools within the hologenomic framework outlined here. Investigating the role of telomere dynamics in mediating gut microbiota-host interactions in different species will improve our understanding of how crosstalk between these hallmarks of ageing shape holobiont physiology in general and the ageing phenotype in particular.}, }
@article {pmid41761979, year = {2026}, author = {Guo, Z and Gao, Z and Zhao, Y and Ni, X and Zhang, W and Li, L and Ren, S and Li, Q and Guo, D and Yue, L and Liu, Y and Lin, L and Fan, S and Hai, X}, title = {Administering Bifidobacterium pseudolongum With Arsenic Trioxide Attenuates Acute Promyelocytic Leukemia in Mice by Restoring Immune Microenvironment and Intestinal Homeostasis.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {2}, pages = {48584}, doi = {10.31083/FBL48584}, pmid = {41761979}, issn = {2768-6698}, support = {82274028//National Natural Science Foundation of China/ ; 2022ZX02C09//Heilongjiang Key R&amp;D Program/ ; //Fundamental Research Funds for the Provincial Universities in Heilongjiang Province (2025)/ ; JJ2025PL0189//Natural Science Foundation of Heilongjiang Province/ ; 2024M10//Innovation Fund of the First Affiliated Hospital of Harbin Medical University/ ; 2024M25//Innovation Fund of the First Affiliated Hospital of Harbin Medical University/ ; 230000253533210000086//2025 Central Government Fiscal Subsidy Fund for Medical Care Compliance and Capacity Enhancement (Traditional Chinese Medicine Undertakings and Inheritance and Development Component)/ ; }, mesh = {*Arsenic Trioxide/pharmacology/administration &amp; dosage/therapeutic use ; Animals ; *Leukemia, Promyelocytic, Acute/immunology/drug therapy/microbiology/therapy ; Humans ; Homeostasis/drug effects ; Mice ; *Bifidobacterium ; Gastrointestinal Microbiome/drug effects ; Intestines/drug effects/microbiology/immunology ; Dysbiosis ; *Antineoplastic Agents/pharmacology ; RNA, Ribosomal, 16S/genetics ; *Probiotics/administration &amp; dosage ; Tumor Microenvironment/drug effects/immunology ; }, abstract = {OBJECTIVE: Arsenic trioxide (ATO) is a cornerstone of acute promyelocytic leukemia (APL) therapy but induces severe gut microbiota dysbiosis, limiting its efficacy and safety. This study investigated whether adjunctive Bifidobacterium pseudolongum (BP) could mitigate these adverse effects and enhance therapeutic outcomes.<br><br>METHODS: 16S rRNA gene sequencing data of gut microbiota were obtained from a cohort of 22 APL patients treated with ATO-based regimens (20 of 22 data were obtained and analysis further), accessible under BioProject ID PRJNA935705. To evaluate the within-sample microbial community richness and evenness, alpha and beta diversity indices were calculated. Using a murine APL model, we compared ATO monotherapy with ATO+BP co-treatment. Analyses included fecal metagenomic sequencing, single-cell RNA sequencing (sc-RNA-seq), flow cytometric immune profiling, and assessment of intestinal tight junction proteins (claudin-1, occludin, and ZO-1) via immunofluorescence.<br><br>RESULTS: ATO treatment significantly reduced gut microbial diversity and depleted beneficial taxa. Sc-RNA-seq data showed that ATO could orchestrate the APL immune microenvironment mainly through functional activation of CD8+ T cells and monocytes. BP supplementation restored microbial homeostasis and synergistically enhanced ATO's antileukemic effect, reducing the leukemic burden in peripheral blood by 72% and in bone marrow by 64% compared to ATO alone. Mechanistically, BP preserved intestinal barrier integrity by upregulating tight junction protein expression and modulated anti-tumor immunity, notably increasing bone marrow CD8+ T cells by 2.21-fold.<br><br>CONCLUSIONS: BP is an effective adjunct to ATO therapy, counteracting gut dysbiosis, intestinal damage, and the immune microenvironment while synergistically improving antileukemic efficacy. Targeting the gut-leukemia axis with BP represents a promising strategy for improving the precision and safety of APL treatment.}, }
@article {pmid41762317, year = {2026}, author = {Altan, ZB and Ihlamur, M}, title = {The relationship between gut microbiota and neurodegenerative diseases: a genetic and epigenetic perspective.}, journal = {Metabolic brain disease}, volume = {41}, number = {1}, pages = {}, pmid = {41762317}, issn = {1573-7365}, abstract = {Gut microbiota (GM) is a complex and dynamic structure that can have a wide range of effects on human health. Studies in recent years have shown that microbiota is not only related to the gastrointestinal tract (GIT) but also to the immune and endocrine systems. It causes various effects on host physiology, especially through genetic and epigenetic mechanisms. It shows that microbiota-derived metabolites can play a role in the development of neurological diseases by changing gene expression. In this review article, the relationship between GM and neurodegenerative diseases (NDs) is explained in terms of genetics and epigenetics. In terms of the gut–brain axis (GBA); the role of systems such as short-chain fatty acids (SCFA), vagus nerve, inflammatory responses and intestinal permeability in the pathogenesis of NDs such as Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and Multiple Sclerosis (MS) is discussed. In addition, experimental studies have drawn attention to the effects of changes in microbiota on neuroinflammation and cognitive impairment. In terms of treatment strategies; Probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT) and nutritional interventions targeting microbiota seem to be promising strategies. However, the fact that microbiota structure varies between individuals indicates that studies in this area should be conducted in a more personalized manner. This article aims to provide a basis for future research by approaching the relationship between microbiota and NDs in a holistic manner.}, }
@article {pmid41762381, year = {2026}, author = {Sasidharan Pillai, S and Ashraf, AP}, title = {Gut Microbiota and Metabolic Health: From Dysbiosis to Therapeutics.}, journal = {Diabetes therapy : research, treatment and education of diabetes and related disorders}, volume = {17}, number = {4}, pages = {483-497}, pmid = {41762381}, issn = {1869-6953}, abstract = {The gut microbiota (GM) is a pivotal regulator of host metabolism and a contributor to the pathophysiology of obesity, type 2 diabetes (T2D), and metabolic syndrome (MS). Disruptions in GM composition and function are collectively termed dysbiosis. This review synthesizes current evidence on GM dysbiosis, moving beyond simple taxonomic associations, to examine functional drivers of metabolic dysfunction. Dysbiosis impairs metabolic health through several interconnected pathways: enhanced dietary energy extraction, compromised intestinal barrier integrity leading to metabolic endotoxemia, chronic low-grade "meta-inflammation," and the disruption of circadian rhythms and neuro-immune signaling. Beyond bacteria, dysbiosis of the gut virome and mycobiota may further modulate metabolic risk. Animal and emerging human studies indicate that reduced virome diversity and altered phage-bacteria interactions can amplify dysbiosis, promote inflammatory signaling, and impair metabolic homeostasis. Recognition of GM dysbiosis as a contributor to metabolic disease has prompted development of therapeutic strategies aimed at restoring microbial balance and function. These interventions span a spectrum from established clinical approaches with indirect microbiota effects to experimental therapies designed to directly manipulate microbial composition or activity. We evaluate the clinical readiness of GM-targeted therapies, including dietary patterns, prebiotics, probiotics, and fecal microbiota transplantation. While established metabolic treatments such as glucagon-like peptide-1 (GLP-1) receptor agonists and bariatric surgery significantly reshape the GM, direct microbial manipulations often yield variable results in human trials. We conclude that the future of metabolic management lies in personalized microbiomics, utilizing artificial intelligence and precision-based interventions to restore specific functional microbial deficits tailored to the individual host profile.}, }
@article {pmid41763136, year = {2026}, author = {Guo, Y and Xu, X and Han, A and Song, F and Zhang, Y and Jiang, X and Yu, W}, title = {Isorhamnetin alleviates diet induced MASLD in mice by modulating gut microbiota and bile acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {153}, number = {}, pages = {157987}, doi = {10.1016/j.phymed.2026.157987}, pmid = {41763136}, issn = {1618-095X}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Quercetin/analogs &amp; derivatives/pharmacology ; Diet, High-Fat/adverse effects ; Male ; Mice ; *Gastrointestinal Microbiome/drug effects ; Lipid Metabolism/drug effects ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/metabolism ; *Fatty Liver/drug therapy/metabolism/etiology ; Receptor, Farnesoid X-Activated ; Liver/metabolism/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: With the increasing prevalence of sedentary lifestyles and high-fat, high-sugar diets, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has continued to rise. Although the natural flavonoid compound isorhamnetin (ISO) has been shown to improve dyslipidemia in MASLD mice, its mechanism of action in regulating lipid metabolism via the gut microbiota and its metabolites remains unclear.<br><br>OBJECTIVE: This study investigates whether ISO can ameliorate high-fat diet-induced MASLD in mice in a dose-dependent manner and explores the mediating role of the gut microbiota in this process.<br><br>METHODS: Physiological monitoring, biochemical markers assessment, tissue section analysis, 16S rRNA sequencing, bile acid (BA) targeted metabolomics, and molecular analysis were performed on mouse tissues. In addition, fecal microbiota transplantation (FMT) from mice fed a high-dose of ISO further validated the regulatory role of the gut microbiota in MASLD mice. Molecular dynamics simulations and in vitro assays were performed to evaluate the interaction between ISO and FXR.<br><br>RESULTS: ISO dose-dependently reduced body weight and hepatic lipid content, inhibited lipid synthesis and promoted lipid oxidation. ISO reshaped the gut microbiota, increasing the relative abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae. These changes altered the BA pool composition by increasing the proportion of primary and conjugated BAs, activated the hepatic-ileal Farnesoid X Receptor (FXR) signaling axis, accelerated enterohepatic BA circulation, and reduced dietary fat absorption. Concurrently, ISO enhanced intestinal barrier integrity and alleviated hepatic inflammation. Fecal microbiota transplantation from ISO-treated mice partially reproduced these metabolic benefits. Molecular dynamics simulations and in vitro experiments further verified that ISO interacts with FXR and consequently enhances FXR signaling.<br><br>CONCLUSION: ISO alleviates MASLD by synergistically regulating gut microbiota and FXR signaling, highlighting its potential as a mild, multi-target natural therapeutic candidate for MASLD therapy.}, }
@article {pmid41763137, year = {2026}, author = {Zhou, S and Su, F and Gao, Q and Wang, M and Duan, J and Li, J}, title = {Cordyceps cicadae polysaccharides ameliorate ulcerative colitis by modulating the gut microbiota and regulating the bile acid/FXR/NF-κB signaling pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {153}, number = {}, pages = {158007}, doi = {10.1016/j.phymed.2026.158007}, pmid = {41763137}, issn = {1618-095X}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology/metabolism ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; Signal Transduction/drug effects ; Mice ; *Polysaccharides/pharmacology ; Receptors, Cytoplasmic and Nuclear/metabolism ; NF-kappa B/metabolism ; Receptor, Farnesoid X-Activated ; Male ; Dextran Sulfate ; *Cordyceps/chemistry ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease, closely linked to dysbiosis of the intestinal microbiota and abnormal bile acid homeostasis. Polysaccharides derived from Paecilomyces cicadae (CCP) exhibit immunomodulatory and anti-inflammatory effects. However, their therapeutic potential and underlying mechanisms in UC remain poorly elucidated.<br><br>PURPOSE: This research seeks to evaluate the therapeutic efficacy of CCP in the treatment of UC and utilizing the "microbiota-bile acid metabolism-immunity" axis, elucidates the mechanisms by which CCP enhances intestinal barrier integrity and ameliorates inflammation via modulation of the gut microbiota-mediated farnesoid X receptor (FXR)/NF-&#x3ba;B signaling pathway.<br><br>METHODS: The physicochemical properties of CCP were characterized by FTIR spectroscopy, HPLC, and SEM analyses. A dextran sulfate sodium (DSS)-induced colitis mouse model was used to evaluate the ameliorative effects of CCP. Gut microbial alterations were profiled by 16S rDNA sequencing, while targeted metabolomics enabled comprehensive quantification of bile acid profiles in serum and fecal samples. Fecal microbiota transplantation (FMT) was conducted to validate the microbiota-mediated actions of CCP. Downstream molecular mechanisms were examined using Western blotting and immunofluorescence assays to assess modulation along the microbiota-bile acid axis.<br><br>RESULTS: CCP is primarily composed of glucose, mannose, and galactose, exhibiting a characteristic polysaccharide structure with a uniform molecular weight distribution. Treatment with CCP significantly ameliorated DSS-induced colitis in mice, as evidenced by reduced weight loss, preserved colon length, and decreased histopathological damage. 16S rDNA analysis demonstrated CCP-driven restoration of intestinal microbial diversity and a marked increase in Clostridium Kas107-2 (cluster XIVa). Metabolomics revealed normalization of bile acid metabolism, with elevated synthesis of secondary bile acids (deoxycholic acid, lithocholic acid, 12-keto LCA) and reduced levels of primary bile acids (&#x3b1;/&#x3b2;-MCA). Mechanistically, CCP activated FXR signaling, suppressed I&#x3ba;B&#x3b1; phosphorylation, downregulated NF-&#x3ba;B signaling, and reduced production of pro-inflammatory cytokines (TNF-&#x3b1;, IL-1&#x3b2;, IL-6). Enhanced expression of tight junction proteins (ZO-1, Occludin, Claudin-1) indicated improved epithelial barrier function. Notably, FMT from CCP-treated donors replicated these protective effects, confirming colitis attenuation, bile acid restoration, and inhibition of FXR/NF-&#x3ba;B signaling.<br><br>CONCLUSIONS: CCP ameliorate experimental UC by promoting the proliferation of Clostridium cluster XIVa, modulating bile acid metabolism to facilitate secondary bile acid biosynthesis, activating FXR pathways, and suppressing NF-&#x3ba;B-driven inflammatory responses, thereby reinforcing intestinal epithelial barrier integrity.}, }
@article {pmid41763794, year = {2026}, author = {Wei, K and Peng, L and Wei, Q and Wei, Y and Wang, L and Zhu, Y and Wei, Y and Wei, X}, title = {Amelioration of colitis by donor microbiota modulated with tea active ingredients: A fecal microbiota transplantation study.}, journal = {Food research international (Ottawa, Ont.)}, volume = {229}, number = {}, pages = {118473}, doi = {10.1016/j.foodres.2026.118473}, pmid = {41763794}, issn = {1873-7145}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Tea/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Colitis/therapy/chemically induced/microbiology ; Mice ; Polyphenols/pharmacology ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; Disease Models, Animal ; Intestinal Barrier Function ; Feces/microbiology ; Polysaccharides/pharmacology ; *Colitis, Ulcerative/therapy ; Fatty Acids, Volatile/metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) using donor microbiota modulated by tea represents an emerging approach to ameliorate ulcerative colitis (UC). This study aims to demonstrate the amelioration of dextran sulfate sodium (DSS)-induced colitis by donor microbiota modulated with tea-derived bioactive ingredients-tea polyphenols (TPP), tea polysaccharides (TPS), or theabrownin (TB). Following transplantation of fecal microbiota modulated by TPP, TPS, or TB from donors into colitis mice, significant reductions in Disease Activity Index (DAI) were observed, alongside attenuated intestinal histopathological damage. Additionally, gut barrier integrity was enhanced, as indicated by upregulated expression of occludin and Muc2. Fecal microbiota modulated by TPP and TPS showed superior efficacy in alleviating colitis compared with TB-modulated microbiota. The mechanism involved that marked enrichment of beneficial genera, including Akkermansia (TPP-enriched) and Allobaculum/Lactobacillus (TPS-enriched), which promoted the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids, while reducing primary bile acids levels. These metabolic changes enhanced intestinal barrier function and suppressed suppressing pro-inflammatory cytokines through the modulation of TLR4/NF-κB p65 and Nrf2/ARE signaling pathways. This study not only elucidates the mechanism of tea bioactive ingredients-modulated donor microbiota alleviates colitis through regulation of the gut-microbiota-metabolite axis, but also provides a foundation for FMT-based strategies in colitis intervention.}, }
@article {pmid41764528, year = {2026}, author = {Zhang, W and Su, Q and Shi, H and Sun, Y and Li, X and Li, M and Wang, H and Yu, J and Wong, N and Chan, FKL and Zhang, J and Ng, SC}, title = {Discovery and characterization of Christensenella hongkongensis as a novel bacterium in the adenoma-carcinoma progression.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41764528}, issn = {1479-5876}, abstract = {BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and commonly starts from a pre-cancerous stage. This study aimed to identify potential fecal bacterial candidates associated with progression of CRC from the adenoma-carcinoma sequence and to explore underlying mechanisms of carcinogenesis.<br><br>METHODS: Publicly metagenomic datasets were analyzed using MaAsLin2 to identify bacterial species enriched in CRC patients compared to healthy controls. Additionally, we established a large cohort in mainland China, consisting of 686 subjects, including 285 CRC patients, 73 advanced adenoma patients (AA), 134 non-advanced adenoma patients (nAA), and 194 healthy controls (NC). Fecal samples from this cohort were analyzed by duplex quantitative polymerase chain reaction (qPCR) to validate the abundance of key bacterial candidate and its association with tumor node metastasis (TNM) stages. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of Christensenella hongkongensis (C. hongkongensis) alone and in combination with fecal immunochemical test (FIT) across different CRC stages. In vitro experiments and transcriptome sequencing were performed to explore the effects of C. hongkongensis and its mechanisms in CRC progression.<br><br>RESULTS: MaAsLin2 analysis identified seven bacterial species were significantly more abundant in fecal samples of CRC patients than in healthy controls (p&#x2009;<&#x2009;0.05). Among them, C. hongkongensis, an obligately anaerobic, catalase-positive, motile, non-sporulating, gram-positive coccobacillus was distinguished by its lowest abundance in healthy controls and significant enrichment in CRC patients. Validation in our recruited cohort showed that the abundance of C. hongkongensis progressively increased from non-advanced adenomas to advanced adenomas and CRC. For classifying AA from nAA, C. hongkongensis yielded an area under the ROC curve (AUC) of 0.60 (95% CI 0.53&#x2013;0.68), with 45.2% sensitivity and 85.8% specificity. A combined model integrating C. hongkongensis abundance and FIT further improved diagnostic performance, increasing AUCs from 0.77 to 0.81 for AA vs NC (p&#x2009;<&#x2009;0.05) and from 0.76 to 0.82 for AA vs nAA (p&#x2009;<&#x2009;0.001). Linear regression analysis revealed a significant positive association between C. hongkongensis and TNM stages in CRC. In vitro experiments showed that C. hongkongensis promoted CRC cell proliferation, inhibited apoptosis, and enhanced the growth of patient-derived CRC organoids. RNA-seq analysis identified activation of the Wnt/&#x3b2;-catenin signaling pathway, which was further validated by elevated protein levels of active &#x3b2;-catenin, reduced phosphorylation of GSK3&#x3b2;, and the upregulation of downstream targets c-Jun and Cyclin-D1.<br><br>CONCLUSIONS: Our findings suggest that C. hongkongensis promotes colorectal tumorigenesis via Wnt/&#x3b2;-catenin activation, and highlight its potential as a novel non-invasive bacterial marker for early detection and monitoring of CRC progression.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07886-9.}, }
@article {pmid41764851, year = {2026}, author = {Guo, Q and He, Y and Cao, T and Lin, C and Deng, M and Wu, R and Cai, H}, title = {Tryptophan-kynurenine metabolism: A link between the gut microbiota dysbiosis and cognitive impairment.}, journal = {Microbiological research}, volume = {307}, number = {}, pages = {128481}, doi = {10.1016/j.micres.2026.128481}, pmid = {41764851}, issn = {1618-0623}, mesh = {*Kynurenine/metabolism ; Humans ; *Dysbiosis/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Tryptophan/metabolism ; *Cognitive Dysfunction/microbiology/metabolism ; Animals ; Brain/metabolism ; Probiotics/therapeutic use ; Metabolic Networks and Pathways ; Fecal Microbiota Transplantation ; }, abstract = {Cognitive impairment is a central feature of neuropsychiatric and neurodegenerative disorders, significantly diminishing patients' quality of life. Emerging evidence underscores the role of gut microbiota dysbiosis in the progression of cognitive decline. The gut microbiota influences brain function through various mechanisms, with the kynurenine pathway standing out as a key biochemical route linking peripheral metabolism to central nervous system function, thereby impacting cognitive performance. Dysregulation of the kynurenine pathway has been closely associated with neurotransmitter imbalances, exacerbated neuroinflammation, and metabolic dysfunction, all of which contribute to the onset and progression of cognitive impairment. Recent studies suggest that interventions targeting the gut microbiota, such as probiotics, antibiotics, and fecal microbiota transplantation, may improve cognitive function by modulating the kynurenine pathway. This review examines the complex relationship between gut microbiota, the kynurenine pathway, and cognition, highlighting the potential of targeting kynurenine pathway-related enzymes and microbiota modulation as therapeutic strategies. Despite promising findings, the precise mechanisms and therapeutic potential of these interventions remain under investigation, offering new avenues for the treatment of cognitive disorders.}, }
@article {pmid41769404, year = {2026}, author = {Zhao, Y and Chen, D and Qi, K}, title = {The role of gut microbiota in Hirschsprung's disease: from pathogenic mechanisms to microbiota-targeted therapies.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20854}, pmid = {41769404}, issn = {2167-8359}, mesh = {Humans ; *Hirschsprung Disease/therapy/microbiology/physiopathology/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Intestinal Barrier Function ; Animals ; Enteric Nervous System ; }, abstract = {Hirschsprung's disease (HSCR) is a common congenital disorder characterized by abnormal enteric nervous system development. Recent studies have demonstrated that gut microbiota and their metabolites play a significant role in the pathogenesis of HSCR. This review systematically examines the interplay between gut dysbiosis and pathophysiological alterations in HSCR, including disruptions in microbial composition, aberrant metabolite profiles, impaired intestinal barrier function, and dysregulated neuro-immune modulation. Research indicates that HSCR patients exhibit a characteristic gut microbial imbalance, which may influence the development and function of the enteric nervous system by altering the intestinal microenvironment, including metabolic profiles and immune status. Furthermore, this review explores the potential therapeutic value of microbiota-targeted interventions, such as probiotics and fecal microbiota transplantation (FMT), in HSCR treatment, providing a theoretical foundation for novel therapeutic strategies. These findings not only enhance the understanding of HSCR pathogenesis but also offer new perspectives for clinical prevention and treatment.}, }
@article {pmid41769611, year = {2026}, author = {Li, X and Xu, S and Li, Y and Wang, R and Qin, C and Wang, X}, title = {Research Progress on the Mechanisms of Gut Microbiota Dysbiosis Associated With Idiopathic Pulmonary Fibrosis: A Review.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102429}, pmid = {41769611}, issn = {2168-8184}, abstract = {Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease with an incompletely understood pathogenesis. In recent years, growing evidence has highlighted the critical role of gut microbiota dysbiosis in the onset and progression of IPF. This review comprehensively summarizes the characteristics of gut microbiota alterations associated with IPF, explores the underlying mechanisms driving these changes, and examines their impact on disease development. Particular emphasis is placed on the emerging concept of the "gut-lung axis," which elucidates the bidirectional communication between the intestinal microbiome and pulmonary health. The review further discusses microbial metabolites and immune modulation as key mediators linking gut dysbiosis to pulmonary fibrosis. Additionally, current advances in microbiota-targeted therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation, are analyzed for their potential in IPF management. By systematically integrating recent findings, this article aims to deepen the understanding of IPF pathophysiology and provide a theoretical foundation for novel treatment targets centered on gut microbiota regulation.}, }
@article {pmid41771438, year = {2026}, author = {Lynch, SV and Nagler, CR and Rachid, R}, title = {Microbial Therapeutics for the Prevention and Treatment of Food Allergy.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {14}, number = {4}, pages = {780-785}, doi = {10.1016/j.jaip.2026.02.024}, pmid = {41771438}, issn = {2213-2201}, mesh = {Humans ; *Food Hypersensitivity/therapy/prevention &amp; control/immunology/microbiology ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *Probiotics/therapeutic use ; Immune Tolerance ; T-Lymphocytes, Regulatory/immunology ; Dysbiosis ; Desensitization, Immunologic ; }, abstract = {Food allergy affects approximately 8% of children and 11% of adults in the United States. Available treatments, including oral immunotherapy and anti-IgE, are not known to lead to remission. There is now increasing evidence implicating the gut microbiome as a key regulator of allergic inflammation. Distinct microbial and metabolomic alterations characterize food-allergic individuals, and gnotobiotic mouse models show that fecal microbiota from food-allergic donors transfer allergic sensitization, whereas microbiota from healthy donors protect from anaphylaxis through induction of tolerogenic Foxp3[+]RORγt[+] regulatory T cells (Tregs). Goblet cell-derived resistin-like molecule beta induces food allergy through modulation of the gut microbiome and depletion of indole-producing species. These findings have inspired the development of 5 microbial therapeutic approaches: probiotics, rationally defined bacterial consortia, fecal microbiota transplantation, metabolite-based approaches, and biologics targeting dysbiosis-associated pathways. Early-phase clinical studies support feasibility, yet long-term safety, durability, and reproducibility remain uncertain. Major challenges include interindividual variability, ecological complexity, and regulatory standardization. Microbiome-directed therapeutics hold promise to transform food allergy management from temporary desensitization toward remission and durable immune tolerance. The application of systems biology approaches integrating metabolomics, transcriptomics, and immune phenotyping will be essential to unravel the complex host-microbial interactions that underlie the efficacy of these approaches.}, }
@article {pmid41772613, year = {2026}, author = {Zeng, L and Zhou, W}, title = {Deciphering the mitochondria-gut microbiota axis in irritable bowel syndrome: pathogenic insights and therapeutic frontiers.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41772613}, issn = {1479-5876}, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder involving multiple pathogenic mechanisms. Gut microbiota dysbiosis and mitochondrial dysfunction are key drivers of IBS, as they weaken the intestinal barrier, promote inflammation, and alter metabolism. However, the underlying mechanisms of crosstalk between these factors remain largely understudied, which hinders the clinical translation of targeted therapeutic strategies.<br><br>MAIN BODY: Drawing on recent literature, this review clarifies the intricate interplay between mitochondrial health and gut microbiota balance in IBS. We summarize the core pathophysiological mechanisms of IBS including neuroendocrine, immune-inflammatory, and gastrointestinal motility-related pathways. We further elaborate on the individual roles of mitochondrial dysfunction and gut microbiota dysbiosis in IBS pathogenesis, discussing the bidirectional crosstalk between mitochondria and the gut microbiota, and the regulatory role of diet in this axis. Current therapeutic approaches targeting IBS, such as Western medications; probiotics; fecal microbiota transplantation; low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; traditional Chinese medicine; and mitochondria-targeted interventions, are also reviewed. Building on this, the review summarizes the advantages and limitations of existing research on the mechanisms and therapies for IBS and identifies the challenges and directions for future basic and clinical research.<br><br>CONCLUSIONS: The interplay between mitochondrial dysfunction and gut microbiota dysbiosis is a critical research focus for understanding IBS pathophysiology. Elucidating the underlying mechanisms of their crosstalk provides a foundation for future research and facilitates the development of innovative therapeutic strategies targeting mitochondrial health and gut microbiota balance. This multifaceted approach holds promise for improving IBS management and enhancing the quality of life of affected patients.}, }
@article {pmid41772743, year = {2026}, author = {He, J and Wang, MN and Chen, HJ and Zuo, GY and Li, JL and Yin, WF and Pan, XG and Cheng, YC and Xia, CY and Xu, JK and Zhang, WK}, title = {Muribaculum intestinale alleviates depressive-like behaviors by inhibiting Th17 cell differentiation and M1 microglia polarization.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {41772743}, issn = {2049-2618}, support = {ZRZC2025-KCC03//National High Level &amp; Elite Medical Professionals Project of China-Japan Friendship Hospital/ ; 2025-NHLHCRF-JBGS-A-WZ-10; ZRJY2024-BJ01//National High Level &amp; Elite Medical Professionals Project of China-Japan Friendship Hospital/ ; 82474100//National Natural Science Foundation of China/ ; 82474100, 82273815, 82273809, 82073731//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Th17 Cells/drug effects/cytology/immunology ; *Microglia/drug effects ; Mice ; *Depression/therapy/microbiology/drug therapy ; Male ; Cell Differentiation/drug effects ; Gastrointestinal Microbiome/drug effects ; *Antidepressive Agents/pharmacology ; *Iridoids/pharmacology/administration &amp; dosage ; Fecal Microbiota Transplantation ; Disease Models, Animal ; *Actinobacteria/physiology ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Behavior, Animal/drug effects ; Fatty Acids, Volatile/metabolism ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis has been implicated in the pathogenesis of depression. Our previous studies identified loganin as a potential antidepressant agent; however, its oral bioavailability is low. Whether loganin alleviates depression via modulation of the gut microbiota remains unclear.<br><br>METHODS: Chronic unpredictable stress mice model was used to evaluate the antidepressant-like effects of loganin. To determine the role of gut microbiota, mice were treated with an antibiotic cocktail (ABX) to deplete microbiota. Fecal microbiota transplantation (FMT) from loganin-treated donors and Muribaculum intestinale (M. intestinale) were performed to assess microbial contributions.<br><br>RESULTS: Loganin exerted antidepressant-like effects by modulating gut microbiota, as evidenced by reduced efficacy in ABX-treated mice and behavioral improvements in recipients of FMT from loganin-treated donors. Loganin modulated gut microbiota composition particularly increasing the abundance of Muribaculum, and increased short-chain fatty acids (SCFAs). M. intestinale alleviated depressive-like behaviors, prompted the butyrylation of ROR&#x3b3;t, inhibited Th17 cells differentiation, and suppressed M1 microglia polarization. Importantly, overexpression of ROR&#x3b3;t attenuated the behavioral benefits of M. intestinale.<br><br>CONCLUSION: Loganin exerts antidepressant-like effects by enriching Muribaculum and SCFAs, thereby inhibiting Th17 cell differentiation and M1 microglia polarization. M. intestinale may represent a promising microbial-based therapeutic strategy for depression.}, }
@article {pmid41774188, year = {2026}, author = {Yadav, A and Melkani, GC}, title = {Microbes, mood, and metabolism/obesity: Pharmacological insights into the gut-obesity-depression triad.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {83}, number = {1}, pages = {}, pmid = {41774188}, issn = {1420-9071}, support = {P30 AG050886/AG/NIA NIH HHS/United States ; AG065992//National Institute of Aging/ ; }, abstract = {The global rise in obesity and depression, two highly prevalent and often comorbid disorders has intensified interest in the gut–brain axis as a shared biological link. Mounting evidence indicates that the gut microbiota profoundly influences both metabolic and neuropsychiatric regulation, positioning it as a promising therapeutic target for these interconnected conditions. This review explores the complex interactions among microbial dysbiosis, host metabolism, and mood regulation, emphasizing pharmacological strategies that harness this triad for treatment. Gut-derived hormones such as glucagon-like peptide-1 (GLP-1) and microbiome-produced metabolites, including short-chain fatty acids (SCFAs) and bile acids, have demonstrated potential to modulate appetite, insulin sensitivity, inflammation, and brain function. GLP-1 receptor agonists like semaglutide originally developed for diabetes and obesity also exhibit antidepressant properties, highlighting their dual therapeutic promise. Emerging microbiome-based interventions, such as precision probiotics, engineered psychobiotics, and fecal microbiota transplantation (FMT), are being investigated to restore microbial balance and improve both metabolic and mood outcomes. Furthermore, combination therapies pairing microbiota-targeted agents with conventional antidepressants or anti-obesity drugs may offer synergistic benefits, enhance efficacy while minimize adverse effects. Despite this promise, significant challenges remain, including ensuring safety, understanding long-term impacts, navigating regulatory hurdles for live biotherapeutics, and addressing ethical concerns about altering the human microbiome. A deeper understanding of the gut–microbiome–brain axis may ultimately enable personalized, microbiota-guided therapies that treat both the physiological and psychological dimensions of obesity and depression, marking a major step toward holistic and precision medicine.}, }
@article {pmid41774771, year = {2026}, author = {Han, X and Yu, H and Gao, Q and Wang, X and Zhang, L and Zhao, Q and Yu, L and Zhang, Y and Sui, M and Li, Y}, title = {Gut microbiota dysbiosis promotes chronic kidney disease-associated atrial fibrillation through activation of the NLRP3 inflammasome.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {28}, number = {3}, pages = {}, pmid = {41774771}, issn = {1532-2092}, support = {2024YFA1307001//National Key R&amp;D Program of China/ ; 82400375//National Natural Science Foundation of China/ ; 82330014//National Natural Science Foundation of China/ ; 82200413//National Natural Science Foundation of China/ ; PL2024H031//Heilongjiang Provincial Natural Science Foundation/ ; 2022M721525//Postdoctoral Science Foundation of China/ ; }, mesh = {Animals ; *Dysbiosis ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/complications/microbiology/metabolism ; Disease Models, Animal ; *Atrial Fibrillation/microbiology/etiology/metabolism/prevention &amp; control/physiopathology ; Male ; Fecal Microbiota Transplantation ; *Inflammasomes/metabolism ; Toll-Like Receptor 4/metabolism ; Intestinal Barrier Function ; Rats, Sprague-Dawley ; Indican/blood ; Rats ; Signal Transduction ; Lipopolysaccharides/blood ; *Bacteria/metabolism/growth &amp; development ; }, abstract = {AIMS: Chronic kidney disease (CKD) significantly increases the risk of atrial fibrillation (AF). Although alterations in the gut microbiota have been linked to CKD progression, its exact involvement in CKD-associated AF remains unclear. We aim to investigate the role of gut microbiota in the development of CKD-associated AF and to uncover potential mechanisms that could serve as effective targets for prevention and treatment.<br><br>METHODS AND RESULTS: A rat model of CKD was induced by an adenine-enriched diet. 16S rRNA sequencing and faecal microbiota transplantation (FMT) were utilized to study the involvement of gut microbiota. AST-120, gut barrier protectants, and mono-colonization experiments were performed to investigate potential mechanism. CKD rats exhibited gut microbiota dysbiosis and a significantly increased susceptibility to AF. FMT from CKD rats transferred this heightened AF susceptibility to healthy recipient rats, linked to the activation of the NLRP3 inflammasome. Mechanistically, gut dysbiosis in CKD patients leads to elevated indoxyl sulphate (IS) levels, causing gut barrier dysfunction and increased circulating lipopolysaccharide (LPS). Elevated LPS activates atrial Toll-like receptor 4 (TLR4) receptors, triggering NLRP3 inflammasome activation, which contributes to AF pathogenesis. Treatment with the IS scavenger AST-120 or gut barrier protectants successfully prevented CKD-associated AF. Furthermore, supplementation with Lactobacillus gasseri reduced circulating IS levels and mitigated AF susceptibility in CKD rats.<br><br>CONCLUSION: This study demonstrates that gut dysbiosis-driven elevation of IS and subsequent activation of the atrial NLRP3 inflammasome are key mechanisms in CKD-associated AF. Modulating the gut microbiota could provide a new therapeutic strategy for CKD-associated AF.}, }
@article {pmid41776098, year = {2026}, author = {Xiang, X and Zhu, J and Jiang, J and Ding, P and Zhu, Y and Cheng, K and Ming, Y}, title = {Unique gut microbiota and metabolomic profiling as biomarker of post-transplant recovery in acute-on-chronic liver failure after liver transplantation.}, journal = {Applied microbiology and biotechnology}, volume = {110}, number = {1}, pages = {}, pmid = {41776098}, issn = {1432-0614}, support = {81771722 and 82570782//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Liver Transplantation/adverse effects ; *Acute-On-Chronic Liver Failure/microbiology/surgery/metabolism ; Biomarkers/analysis ; *Gastrointestinal Microbiome ; Metabolomics ; Feces/microbiology ; *Metabolome ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Carcinoma, Hepatocellular ; Liver Neoplasms ; Multiomics ; }, abstract = {Acute-on-chronic liver failure (ACLF) is a severe condition arising from chronic liver disease, characterized by acute decompensation, organ failure, and high short-term mortality. Poor outcomes have also been observed in patients with ACLF after liver transplantation (LT). Emerging evidence, including a study from our center, suggests that gut microbiota plays an important role in ACLF. Patients who underwent LT at our center between October 2022 and June 2024 were included. Fecal samples were collected within 1 month post-LT for 16S rRNA and untargeted metabolomic sequencing. In this study, 144 samples from 69 patients with ACLF, cirrhosis, or hepatocellular carcinoma (HCC) were analyzed. Distinct microbiota and metabolic profiles were observed among the groups. ACLF patients exhibited significantly altered beta diversity, with notable depletion of g__Anaerostipes. Metabolomic analysis revealed substantial differences, including enrichment of tangeritin and depletion of candesartan in the ACLF group. Network analysis identified g__Anaerostipes as a key node linking differential taxa and metabolites. A random forest model based on these features effectively distinguished patient groups, with the highest classification accuracy observed in HCC. Multi-omic signatures were also associated with early allograft dysfunction (EAD), particularly g__Lachnoclostridium. Several microbial and metabolic features, including g__Lachnoclostridium, showed significant correlations with clinical indicators. The gut microbiome after LT is closely associated with ACLF. This study offers valuable insights for further investigation into the pathogenesis and post-LT prognosis. KEY POINTS: • ACLF patients have a unique gut microbiota and metabolic profile after LT • g__Anaerostipes is the prominent biomarker of ACLF's multi-omics signature • g__Lachnoclostridium is a promising indicator of recovery after LT.}, }
@article {pmid41776310, year = {2026}, author = {Kim, M and Wang, J and Pilley, SE and Lu, RJ and Xu, A and Kim, Y and Liu, M and Fu, X and Booth, SL and Mullen, PJ and Benayoun, BA}, title = {Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.}, journal = {Nature aging}, volume = {6}, number = {3}, pages = {682-702}, pmid = {41776310}, issn = {2662-8465}, support = {#00034120//Pew Charitable Trusts/ ; T32 AG052374/AG/NIA NIH HHS/United States ; No. 58-1950-7-707//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; }, mesh = {Animals ; Female ; *Ovary/physiology ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; Mice ; *Aging/physiology ; *Menopause/physiology ; Mice, Inbred C57BL ; Transcriptome ; Fertility ; }, abstract = {The decline in ovarian function with age affects fertility and is associated with increased risk of age-related diseases, including osteoporosis and dementia. Notably, earlier menopause is linked to shorter lifespan, yet the molecular mechanisms underlying ovarian aging remain poorly understood. Recent evidence suggests the gut microbiota may influence ovarian health. Here we show that ovarian aging is associated with distinct gut microbial profiles in female mice and that the gut microbiome can directly influence ovarian health. Using fecal microbiota transplantation from young or estropausal female mice, we demonstrate that heterochronic microbiota transfer remodels the ovarian transcriptome, reduces inflammation-related gene expression and induces transcriptional features consistent with ovarian rejuvenation. These molecular changes are accompanied by enhanced ovarian health and increased fertility. Integrating metagenomics-based causal mediation analyses with serum untargeted metabolomics, we identify candidate microbial species and metabolites that may contribute to the observed effects. Our findings reveal a direct link between the gut microbiota and ovarian health.}, }
@article {pmid41776699, year = {2026}, author = {Song, Y and Wen, S and Guan, LL}, title = {Unraveling the dynamic changes in the intestinal microbiome: impacts on pre-weaning calf health and productivity.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {}, pmid = {41776699}, issn = {1674-9782}, abstract = {The early life gut microbial colonization in pre-weaning calves plays a pivotal role in shaping their health, growth, and productivity. This review delves into the dynamic changes of intestinal microbiota during early life, emphasizing key factors such as colostrum management, feeding strategies, roughage supplementation, and microbial interventions including probiotics, prebiotics, and fecal microbiota transplantation (FMT), and non-nutritional stressors that can shape the early life microbial colonization. We highlight the microbiota's critical functions in nutrient metabolism, immune development, gut barrier integrity, and gut-brain axis regulation. Additionally, the consequences of microbial dysbiosis on calf health and its long-term effects on production performance in beef and dairy cattle are discussed. While current research has provided valuable insights, understanding causal mechanisms remains a challenge. This review aims to guide practical strategies for targeted microbial management, offering a pathway to optimize early-life interventions for improved calf health and productivity.}, }
@article {pmid41776845, year = {2026}, author = {Cai, Y and Sun, J and Chen, S and Wang, D and Jing, Y and Jin, X and Li, Z and Li, C and Ban, X}, title = {Agarotriose Alleviates Colitis by Promoting Akkermansia muciniphila-Derived Spermidine Production to Suppress PI3K/AKT/NF-κB Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {10}, pages = {8451-8472}, doi = {10.1021/acs.jafc.5c16297}, pmid = {41776845}, issn = {1520-5118}, mesh = {Animals ; *Colitis/microbiology/drug therapy/genetics/metabolism ; Signal Transduction/drug effects ; *Spermidine/biosynthesis/metabolism ; Mice ; *NF-kappa B/genetics/metabolism/immunology ; *Phosphatidylinositol 3-Kinases/genetics/metabolism/immunology ; *Proto-Oncogene Proteins c-akt/genetics/metabolism/immunology ; Humans ; *Akkermansia/metabolism ; Mice, Inbred C57BL ; *Trisaccharides/administration &amp; dosage ; Gastrointestinal Microbiome/drug effects ; Male ; }, abstract = {Agarotriose (A3), a marine-derived oligosaccharide from agar, has shown anti-inflammatory potential, yet the involvement of gut microbiota remains incompletely understood. Using a dextran sulfate sodium-induced colitis mouse model combined with antibiotic depletion and fecal microbiota transplantation, we found that the protective effects of A3 were largely dependent on the gut microbiota. Integrated multiomics analyses indicated that A3 preferentially enriched Akkermansia muciniphila and was associated with increased intraluminal spermidine levels. Spermidine abundance correlated with A. muciniphila enrichment and improvement of colitis-related phenotypes. In vitro, A3 promoted the growth of A. muciniphila and enhanced spermidine production. Transcriptomic and cellular analyses further suggested that spermidine attenuated inflammatory responses, at least in part, through modulation of the PI3K/AKT/NF-κB signaling pathway. Collectively, these results support a potential "A3-A. muciniphila-spermidine-host signaling" axis and suggest that A3 may serve as a promising marine-derived prebiotic for intestinal health.}, }
@article {pmid41777702, year = {2026}, author = {Zhang, YW and Li, RY and Wu, Y and Wang, P and Zhou, QR and Su, JC}, title = {Gut microbiota and bone aging: Focusing on the gut-X axis modes.}, journal = {Journal of orthopaedic translation}, volume = {57}, number = {}, pages = {101064}, pmid = {41777702}, issn = {2214-031X}, abstract = {UNLABELLED: As studies have continuously advanced, cross-linking interplay between various organs in aging individuals have continuously emerged as research hotspots. The role of gut microbiota in bone aging-related diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, has been extensively probed. This review first summarized the inseparable association between gut microbiota and osteoporosis, osteoarthritis, and intervertebral disc degeneration, which then explored potential mechanisms of gut-X axis through neuromodulation (microbiota-gut-brain-bone axis), immunomodulation (Th17 and Treg balance), endocrine regulation (gut-derived hormones and 5-HT), metabolite-mediated regulation (SCFAs), bacterial extracellular vesicles, and changes in microbial niche and gut microbiome-associated biomarkers. Moreover, potential intervention strategies including diet, probiotics, fecal microbiota transplantation, and physical activity were summarized to enhance clinical translation applicability. This review creatively exhibited integrated concept of "gut-X axis" to explore common, patterned mechanisms underlying "gut-bone axis", "gut-joint axis", and "gut-disc axis". Furthermore, it delves into potential mechanisms by which this shared pattern regulates bone aging-related diseases and prospectively outlines therapeutic strategies for bone aging based on this axis.<br><br>This review presents crucial role and regulatory significance of gut-X axis modes in common bone-aging related diseases. By anchoring the gut-X axis as intervention targets, the thinking of gut microbiota and its related metabolites in basic studies and clinical prevention and treatment of bone aging-related diseases might be expanded, and its clinical application transformation and development could be innovated.}, }
@article {pmid41778019, year = {2026}, author = {Huang, J and Zhang, Y and Zheng, W and Li, G}, title = {Gut microbiota contributes to gestational diabetes mellitus by interfering with bile acid metabolism and resistin.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1675560}, pmid = {41778019}, issn = {2235-2988}, mesh = {Female ; Animals ; *Bile Acids and Salts/metabolism ; Pregnancy ; *Resistin/metabolism ; Humans ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/physiology ; *Diabetes, Gestational/microbiology/metabolism ; RNA, Ribosomal, 16S/genetics ; Mice ; Adult ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics ; Disease Models, Animal ; Matrix Metalloproteinase 9/metabolism ; Lipopolysaccharides/blood ; }, abstract = {INTRODUCTION: Gestational diabetes mellitus (GDM) affects 6% to 15% of pregnancies globally, as a severe metabolic disorder that impairs offspring health. Mounting evidence highlights the critical role of gut microbiota in metabolic regulation, yet the causal relationship between gut microbiota and GDM pathogenesis remains unclear. This study aimed to clarify this causal link and explore the underlying mechanisms.<br><br>METHODS: An innovative human microbiota transplantation approach was adopted. Gut microbiota from GDM patients was transplanted into antibiotic-treated C57BL/6J mice. 16S rRNA sequencing was used to analyze the structural changes of gut microbiota in recipient mice, and metabolomics was employed to detect changes in circulating bile acid levels. For mechanism exploration, Luminex assay was used to detect multiple inflammatory factors, enzyme-linked immunosorbent assay (ELISA) was applied to measure lipopolysaccharide (LPS) levels, and Western blot (WB) was utilized to determine the expression of intestinal barrier protein.<br><br>RESULTS: Transplantation of gut microbiota from GDM patients directly induced glucose intolerance in pregnant antibiotic-treated C57BL/6J mice. 16S rRNA sequencing showed significant structural reorganization of the gut microbiota in GDM microbiota recipients, characterized by decreased abundance of Lachnospiraceae_FCS020_group and increased abundance of Akkermansia, Faecalibaculum, and Bilophila. These microbiota dysregulations led to reduced expression of the intestinal barrier protein Claudin-1, elevated serum lipopolysaccharide (LPS) levels, and increased resistin and matrix metalloproteinase 9 (MMP-9) levels. Metabolomic analysis revealed decreased circulating primary bile acids (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary bile acid deoxycholic acid (DCA). Correlation analysis indicated a positive correlation between Faecalibaculum and DCA, CDCA, as well as resistin. DCA and CDCA were significantly negatively correlated with HOMA-IR, while resistin was significantly positively correlated with GTT-AUC, FINS, and HOMA-&#x3b2;%.<br><br>CONCLUSION: These findings suggest that the imbalance in bile acid metabolism and mild inflammatory response caused by dysregulated gut microbiota is an adjustable environmental driving factor in the pathophysiological process of GDM.}, }
@article {pmid41778022, year = {2026}, author = {Tan, Z and Young, E and Rajagopalan, A}, title = {Push Enteroscopic Jejunal and Ileoscopic Delivery of Fecomicrobiota Transplantation (FMT) for Treatment of Clostridioides difficile Enteritis in a Patient With a Total Colectomy and Ileal Pouch-Anal Anastomosis (IPAA): A Case Report.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {10}, number = {3}, pages = {e70381}, pmid = {41778022}, issn = {2397-9070}, abstract = {Clostridioides difficile infection (CDI) is recognized as the leading cause of antibiotic-associated diarrhea. There are several case reports of C. difficile enteritis in patients who have undergone colectomy and end ileostomy or ileal pouch-anal anastomosis. This case report describes a unique case of recurrent C. difficile enteritis following proctocolectomy and ileoanal pouch, treated successfully with faecal microbiota transplantation (FMT) via anterograde and retrograde delivery into the small bowel.}, }
@article {pmid41778620, year = {2026}, author = {Wang, Y and OuYang, J and Zhang, H and Shen, Y and Guo, Z and Lv, W}, title = {The Efficacy of Gut Microbiome-Modulating Therapies on Liver Cirrhosis: A Systematic Review and Network Meta-Analysis.}, journal = {Clinical and translational gastroenterology}, volume = {17}, number = {5}, pages = {e01010}, pmid = {41778620}, issn = {2155-384X}, support = {No. HLCMHPP2023086//High Level Chinese Medical Hospital Promotion Project of China/ ; }, mesh = {Humans ; *Liver Cirrhosis/therapy/microbiology/blood/immunology ; *Probiotics/administration &amp; dosage/therapeutic use ; *Gastrointestinal Microbiome/immunology ; *Prebiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Disease Progression ; }, abstract = {INTRODUCTION: Gut microbiome-modulating therapies are potential strategies for managing liver cirrhosis, yet head-to-head comparisons to determine the optimal intervention are lacking. This study aimed to evaluate and rank the therapeutic efficacy of these therapies on liver function and disease progression in patients with liver cirrhosis.<br><br>METHODS: We searched major databases (PubMed, Web of Science, Embase, Cochrane Library) for randomized controlled trials (RCTs) published from January 1, 2000, to December 30, 2024. Interventions included probiotics, prebiotics, synbiotics, and fecal microbiota transplantation vs placebo or standard care. Primary outcomes were hepatic function indicators; secondary outcomes included inflammatory markers. Data were analyzed using random-effects frequentist network meta-analyses. The study was registered on Prospective Register of Systematic Reviews (CRD420251000506).<br><br>RESULTS: Seventeen studies comprising 1,051 individuals were included. Synbiotics demonstrated the most significant efficacy among all interventions, showing superior reduction in blood ammonia levels compared with placebo (mean difference [MD] -5.57), probiotics, and prebiotics. Prebiotics showed significant differences in lowering endotoxin levels compared with placebo (MD: -3.29) and probiotics. Furthermore, relative to placebo, prebiotics significantly reduced tumor necrosis factor-alpha (MD: -2.30) and interleukin-6 levels (MD: -4.60).<br><br>DISCUSSION: This network meta-analysis advances current knowledge by establishing an evidence-based hierarchy of efficacy. Synbiotics are most effective for reducing blood ammonia, whereas prebiotics demonstrate superior efficacy in lowering endotoxin and inflammatory markers. These results support a personalized therapeutic approach: prioritizing synbiotics for patients with hyperammonemia and prebiotics for those characterized by systemic inflammation. Future high-quality RCTs are needed to standardize specific strain combinations.}, }
@article {pmid41778780, year = {2026}, author = {Mambuque, E and Del Amo-de Palacios, A and Huete, SG and Marsh, CC and Theron, G and García-Basteiro, AL and Serrano-Villar, S}, title = {Beyond bacilli: integrating the microbiome into the TB research agenda.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2638004}, pmid = {41778780}, issn = {1949-0984}, support = {K43 TW012302/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *Tuberculosis/microbiology/therapy/diagnosis ; Dysbiosis/microbiology ; Multiomics ; *Gastrointestinal Microbiome ; *Microbiota ; Animals ; Metabolomics ; Antitubercular Agents/therapeutic use ; Lung/microbiology ; }, abstract = {Tuberculosis (TB) remains a leading infectious killer, with growing evidence that the human microbiome-particularly in the gut and lungs-shapes susceptibility, progression, and treatment outcomes. Over the past decade, studies have reported that TB-associated dysbiosis, which is more common in the gut than in the lung, is often marked by the loss of short-chain fatty acid-producing taxa and the expansion of opportunistic microbes. However, findings are frequently confounded by diet, antibiotic exposure, comorbidities, geography, and methodological variability. Most research has relied on compositional profiling, offering limited insight into functional mechanisms. This narrative review synthesizes recent evidence, emphasizing the need to integrate multiomics approaches-metagenomics, metatranscriptomics, and metabolomics-and experimental validation to uncover causal links between microbiome alterations and TB pathogenesis or therapy response. We discuss potential clinical applications, including microbiome-based diagnostics (such as stool-based microbial or metabolite signatures for TB risk stratification), prognostic indicators (such as gut microbiome recovery predicting immune normalization during therapy), and adjunctive interventions (including microbiome-derived products to reduce drug-induced liver injury or fecal microbiota transplantation, which has been shown to be safe in people with HIV on stable ART) to mitigate drug toxicity or enhance immune recovery. Key priorities include methodological standardization, confounder control, mechanistic studies, and the inclusion of high-burden settings. By moving beyond descriptive surveys toward functional, translational research, integrating insights from different microbiome methods into TB prevention, diagnosis, and treatment could redefine the clinical research agenda and open new avenues for precision medicine in this global disease.}, }
@article {pmid41778924, year = {2026}, author = {Lawenius, L and Hägg, D and Horkeby, K and Nilsson, KH and Wu, J and Grahnemo, L and Ohlsson, C and Sjögren, K}, title = {Gut microbiota transplantation from young adult mice fails to restore low bone and muscle mass in old mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {330}, number = {4}, pages = {E461-E470}, doi = {10.1152/ajpendo.00522.2025}, pmid = {41778924}, issn = {1522-1555}, support = {2021&#x2009;-&#x2009;01739//Swedish Research Council/ ; 2020&#x2009;-&#x2009;01392//Swedish Research Council/ ; 2024 - 02412//Swedish Research Council/ ; ALFGBG-720331//ALF-agreement/ ; LFGBG-965235//ALF-agreement/ ; LU2021-0096//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; LU2024-0110//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; NNF 190C0055250//Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)/ ; NNF 22OC0078421//Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)/ ; KAW 2015.0317//Knut och Alice Wallenbergs Stiftelse (kawforskning)/ ; KAW 2020.0230//Knut och Alice Wallenbergs Stiftelse (kawforskning)/ ; ERC//European Union/ ; }, mesh = {Animals ; Mice ; *Aging/physiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Male ; Mice, Inbred C57BL ; *Bone Density/physiology ; *Muscle, Skeletal ; *Bone and Bones ; Age Factors ; Body Composition ; }, abstract = {Aging is associated with reduced lean and bone mass, as well as alterations in gut microbiota composition. We previously demonstrated that gut microbiota composition differs between young adult and old mice, and that transplanting gut microbiota from old donors into young germ-free mice reduces lean mass, but not bone mass, compared with transplantation from young adult donors. In this study, we investigated whether the reduced lean and bone mass observed in old mice could be restored through gut microbiota transplantation from young adult donors. Old mice (18-mo old) were treated with antibiotics to deplete their gut microbiota and subsequently transplanted with gut microbiota from either young adult (5-mo old) or old (21-mo old) donors. Recipient mice colonized with gut microbiota from young adult donors showed distinct beta and alpha diversity compared with those colonized with gut microbiota from old donors, demonstrating successful transplantation. However, no differences in lean or bone mass were observed between old mice transplanted with gut microbiota from young adult donors and those receiving gut microbiota from old donors. In conclusion, our findings demonstrate that gut microbiota composition differs in mice transplanted with young adult compared with old gut microbiota but neither reduced lean mass nor reduced bone mass in old mice can be restored through gut microbiota transplantation from young adult donors.NEW &amp; NOTEWORTHY Aging is associated with reduced lean and bone mass and changes in gut microbiota (GM). We tested whether transplanting young adult GM could reverse these age-related conditions in old mice. GM transplantation resulted in distinct GM compositions between mice receiving young adult versus old donor GM, but neither lean nor bone mass was restored in old mice. These findings suggest that GM from young adult mice cannot restore musculoskeletal deficits in aging.}, }
@article {pmid41780589, year = {2026}, author = {Sowulewski, O and Leszkowicz, J and Sakowska, M and Spychalski, P and Szlagatys-Sidorkiewicz, A}, title = {Definitive surgery for Hirschsprung Disease between 3 and 12 months achieves best outcomes: A systematic review with meta-analysis.}, journal = {Journal of pediatric surgery}, volume = {61}, number = {6}, pages = {163039}, doi = {10.1016/j.jpedsurg.2026.163039}, pmid = {41780589}, issn = {1531-5037}, mesh = {Humans ; *Hirschsprung Disease/surgery ; Infant ; Treatment Outcome ; Postoperative Complications/epidemiology ; Age Factors ; Infant, Newborn ; *Digestive System Surgical Procedures/methods ; Colorectal Surgical Procedures ; Time Factors ; }, abstract = {INTRODUCTION: Optimal age for definitive pull-through in Hirschsprung disease (HD) is debated. Both early and delayed interventions may influence short- and long-term outcomes, but current guidelines do not provide a clear recommendation.<br><br>METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nineteen studies published between 1998 and 2025, including 3980 pediatric patients with HD undergoing definitive pull-through surgery, were included. Age at surgery was stratified using predefined thresholds (neonatal, <3 months, <6 months, <12 months, <4 years, and above). Short- and long-term outcomes were extracted and synthesized. Risk of bias was assessed using the Newcastle-Ottawa Scale.<br><br>RESULTS: Short-term outcomes were reported in 15 studies. Hirschsprung-associated enterocolitis (HAEC) was the most frequently reported complication (0-69.1 %), occurring more often in neonates than in non-neonates (22.4 %, 78/348 vs. 15.5 %, 125/808) and in patients operated before 3 months of age compared with those operated later (20.7 %, 68/328 vs. 13.6 %, 60/442). Neonatal surgery was also associated with higher rates of anastomotic leakage (7.1 %, 10/140 vs. 1.5 %, 6/412). Long-term outcomes were assessed in 14 studies. Patients operated during the neonatal period had higher rates of fecal incontinence (30.0 %, 55/183 vs. 17.8 %, 56/314) and constipation (25.2 %, 39/155 vs. 12.8 %, 43/336). Similarly, surgery performed before 3 months of age was associated with increased rates of fecal incontinence (18.0 %, 36/200 vs. 8.6 %, 20/232) and constipation (23.5 %, 47/200 vs. 13.8 %, 32/232) at long-term follow-up.<br><br>CONCLUSIONS: Timing of definitive surgery in Hirschsprung disease is associated with differences in postoperative outcomes. Neonatal surgery and surgery performed during early infancy (<3 months) were more often associated with higher complication rates, whereas procedures performed during infancy showed more balanced results.}, }
@article {pmid41780895, year = {2026}, author = {Ma, X and Xu, Y and Nian, Y and Luo, R and Chen, T and Su, K and Li, T and Shen, C and Xie, B and Dai, H and Zhao, J and Ma, Y}, title = {Dietary carboxymethylcellulose metabolite promotes heart allograft rejection through induction of proinflammatory macrophages via lysophosphatidic acid.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajt.2026.02.030}, pmid = {41780895}, issn = {1600-6143}, abstract = {Carboxymethylcellulose (CMC), a common food emulsifier, induces microbiota dysbiosis and systemic inflammation; however, its impact on transplant immunity remains unclear. Allogenic heart rejection was observed in CMC-fed recipient mice, with increased abundance of lysophosphatidic acid (LPA)-producing bacteria and increased serum LPA concentration. CMC-induced transplant rejection was caused by the gut microbiota, as confirmed by fecal microbiota transplantation and gut microbiota depletion. Furthermore, LPA-treated macrophages demonstrated a proinflammatory ability to accelerate allograft rejection in cytotoxic T lymphocyte-associated protein 4 immunoglobulin-induced allograft survival by upregulating glycolysis. Conversely, the administration of a glycolysis inhibitor resulted in allograft survival and abrogated the detrimental effect of LPA. Mass spectrometry and single-cell RNA sequencing confirmed that transplant patients with rejection showed significantly elevated serum LPA levels and LPA receptor 6 (LPAR6) expression in graft-infiltrate macrophages. Mechanistically, LPA preferentially promoted LPAR6 expression, which interacted with Rho-associated protein kinase 2 to activate the mammalian target of rapamycin/hypoxia-inducible factor 1-alpha pathway, thereby enhancing glycolysis and inducing proinflammatory macrophage polarization. Treatment with Ki16425, an LPAR antagonist, prolonged allograft survival in CMC-fed recipients. Our findings reveal a major detrimental effect of CMC on macrophage physiology and suggest that controlling LPAR6 expression or glycolysis in macrophages may improve allograft survival in transplant recipients.}, }
@article {pmid41780914, year = {2026}, author = {Cheng, M and Zhi, S and Zheng, M and Zhang, S and Hong, J}, title = {Gut Microbiota-Induced CTLA4 Expression on CD8 [+] T Cells Impairs Antitumor Immunity and Promotes Colorectal Cancer Progression.}, journal = {Immunology}, volume = {178}, number = {3}, pages = {455-480}, doi = {10.1111/imm.70128}, pmid = {41780914}, issn = {1365-2567}, support = {25A180025//The Key Scientific Research Project Plan of Higher Education Institutions in Henan Province/ ; 252300423545//The Youth Fund of Natural Science Foundation of Henan Province/ ; }, mesh = {*CTLA-4 Antigen/genetics/metabolism/immunology ; *Colorectal Neoplasms/immunology/microbiology/pathology/metabolism/therapy/genetics ; Animals ; *Gastrointestinal Microbiome/immunology ; Humans ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; Tumor Microenvironment/immunology ; Disease Progression ; Dysbiosis/immunology ; Mice ; Fecal Microbiota Transplantation ; T-Cell Exhaustion ; Cell Line, Tumor ; Tumor Escape ; Lymphocyte Activation ; Male ; Female ; Mice, Inbred C57BL ; }, abstract = {This study reveals a novel gut microbiota-CD8[+] T cell axis driving immunosuppression in colorectal cancer. Analysis of 16S rRNA sequencing identified significant gut dysbiosis in CRC patients, with marked enrichment of Phocaeicola and Bacteroides. Single-cell transcriptomics uncovered substantial T cell depletion and elevated CTLA4[+]PD1[+] immune cells within the tumour microenvironment. Critically, spatial transcriptomics demonstrated co-localization of CTLA4[+]CD8[+] T cells with tumour cells, indicating direct immunosuppressive interactions. Functional validation confirmed CTLA4 overexpression impairs CD8[+] T cell effector capacity, accelerating CRC cell proliferation and invasion. In vivo models demonstrated that faecal microbiota transplantation (FMT) promoted CTL activation, reduced Bacteroides abundance, decreased the formation of CD8[+]CTLA4[+] T cells and ameliorated CRC symptoms. Additionally, CTLA4 knockdown inhibited tumour growth and metastasis. These findings establish a mechanistic pathway: gut dysbiosis induces chronic inflammation, triggering CTLA4 upregulation on CD8[+] T cells to promote T cell exhaustion and tumour immune evasion. The study provides immunological evidence for targeting the microbiota-CTLA4 axis in CRC immunotherapy.}, }
@article {pmid41780918, year = {2026}, author = {Patel, RK and Teja, R and Hermann, K and Franz, R and Wong, K and Kao, D}, title = {Engaging Patient and Caregiver Partners in Codeveloping a Patient Educational Video for Improving Clostridioides difficile Infection Education: Participatory Co-Design Study.}, journal = {JMIR formative research}, volume = {10}, number = {}, pages = {e81643}, pmid = {41780918}, issn = {2561-326X}, mesh = {Humans ; *Patient Education as Topic/methods/standards ; *Caregivers/psychology/education ; *Clostridium Infections/therapy/psychology ; Female ; Male ; Focus Groups/methods ; Middle Aged ; Adult ; Aged ; Fecal Microbiota Transplantation ; *Patients/psychology ; Clostridioides difficile/pathogenicity ; Video Recording ; }, abstract = {BACKGROUND: Patients with recurrent Clostridioides difficile infection (rCDI) and their caregivers often face considerable uncertainty regarding medical management, including the use of fecal microbiota transplantation (FMT), largely due to the scarcity of accessible and credible educational resources. Codeveloping educational materials with patients and caregivers offers a structured way to address these gaps and ensure that resources reflect the informational, psychological, and emotional needs of patients.<br><br>OBJECTIVE: The study team sought to cocreate an educational resource through an iterative process including patient and caregiver partners with lived experience of rCDI to improve C difficile infection education.<br><br>METHODS: This study examined the cocreation process of a patient-centered educational resource between the study team and patient or caregiver participants through a series of focus group (FG) sessions. Five participants took part in 3 serial FG sessions (3-5 participants each) over 13 months. Each FG session was audio recorded, transcribed, and analyzed using the NVivo (version 14) quantitative analysis software. A semantic thematic analysis framework was applied to interpret the results. Key areas of concern and preferred formats were identified following the first FG session. The first version of the educational resource was developed by the study team to address areas of concern and was iteratively refined following feedback from subsequent FG sessions with the study participants.<br><br>RESULTS: Participants expressed concerns about the lack of credible information on treatment options and their associated risks, especially with regard to FMT. They noted inadequate coverage of C difficile infection recurrence and its physical, psychological, and emotional impacts. Participants expressed a preference for educational resources in video format. On the basis of further feedback, refinements were made to improve pacing, consistency of animation, and narration, incorporating emotional and mental health considerations. The codeveloped video was well received and valued for its clear language, messaging, step-by-step guidance, and overall accessibility and clarity.<br><br>CONCLUSIONS: Our study demonstrated the feasibility and utility of patient and caregiver involvement in cocreating an educational resource on the management of rCDI, with FMT being a treatment option. Despite efforts to address knowledge gaps and preferences expressed for a video format, uncertainties remain regarding the most effective educational resource format. The integration of patient, caregiver, and study team perspectives contributed to a codeveloped video that addresses unmet needs and is patient centered. However, diverse patient experiences remain underrepresented. Future research should consider including more diverse participants as well as evaluating the effectiveness of knowledge improvement through various educational resource formats and patient health care experiences and levels of satisfaction.}, }
@article {pmid41782164, year = {2026}, author = {Sørensen, KM and Jensen, CH and Möller, S and Qvist, N and Andersen, DC and Sørensen, JA}, title = {Repairing Peri-Anal Fistulas with regenerative cell therapeutics: study protocol for a double-blinded randomized controlled phase I-II trial from Denmark (REP-PAF).}, journal = {Trials}, volume = {27}, number = {1}, pages = {}, pmid = {41782164}, issn = {1745-6215}, support = {NNF21OC0071847//Novo Nordisk Fonden/ ; NNF19OC0055353//Novo Nordisk Fonden/ ; }, mesh = {Humans ; *Rectal Fistula/surgery/physiopathology/diagnostic imaging ; Double-Blind Method ; Denmark ; Treatment Outcome ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase I as Topic ; Equivalence Trials as Topic ; *Adipose Tissue/cytology/transplantation ; Wound Healing ; *Regeneration ; Quality of Life ; *Stem Cell Transplantation/adverse effects/methods ; Time Factors ; Debridement/methods/adverse effects ; Female ; *Anal Canal/surgery/physiopathology ; Recovery of Function ; Randomized Controlled Trials as Topic ; Adult ; }, abstract = {BACKGROUND: Surgical treatment of high anal fistulas is challenging and associated with a relatively high rate of complications and failure. Stem cell therapy has shown promising results for fistulas associated with Crohn's disease but remains less studied in cryptoglandular fistulas. This clinical trial is being performed to evaluate the outcome of treating complex cryptoglandular perianal fistulas (PAFs) using minimal surgical debridement combined with either non-cultured (autologous) or cultured (allogeneic) adipose-derived regenerative cells (ADRCs). The primary outcome is the clinical healing rate after 12 months. Secondary outcomes include functional outcomes regarding quality of life and anal continence (measured by the 36-Item Short Form Health Survey [SF-36] and the Wexner Fecal Incontinence Score), risk factors for fistula recurrence, radiological healing assessed by magnetic resonance imaging, and comparison of autologous versus allogeneic ADRCs with respect to cell characterization, immune responses, and efficacy.<br><br>METHODS: This is a double-blinded, randomized interventional non-inferiority, phase I-II clinical trial using two approved investigational medicinal products. The study will be conducted at the surgical department, Odense University Hospital OUH, in Odense, Denmark. Inclusion criterion is an adult patient (&#x2265;&#x2009;18&#xa0;years) with complex PAF (high transsphincteric or suprasphincteric), involving more than 30% of the anal sphincter. Key exclusion criteria are ongoing suppuration, simple anal fistula, ano- or rectovaginal fistula, inflammatory bowel disease, body mass index (BMI) of&#x2009;<&#x2009;18.5&#xa0;kg/m[2], known allergy to penicillin or streptomycin, pregnancy, and verified syphilis, human immunodeficiency virus (HIV), or hepatitis on screening test. The primary investigator (PI) is responsible for participants' recruitment. Eligible patients will undergo 1-day surgery, including debridement of the fistula tract and closure of the internal orifice, liposuction from the anterior abdominal wall, injection of 30-40&#xa0;mL of autologous microfat around the fistula tract, and injection of 30 million stem cells (either autologous ADRCs or allogeneic ADRC001) according to randomization (1:1 allocation ratio). Patients who receive treatment will attend follow-up visits at 3, 6, and 12&#xa0;months postoperatively. Serious adverse events will be reported including large abscess formation, wound dehiscence causing fecal incontinence, sepsis, major bleeding, and serious allergic reactions. The trial has been approved by the European Medicines Agency EMA and is monitored by the Good Clinical Practice (GCP) Unit at OUH. A total of 75 patients will be included. Recruitment began in October 2024, with a planned duration of 3&#xa0;years.<br><br>DISCUSSION: The trial intervention is designed as a minimally invasive treatment with the potential to shorten and ease recovery, enable a quicker return to daily activities and work, and avoid sphincter damage, thereby preserving function. The trial is expected to provide evidence on whether allogeneic ADRCs combined with microfat are a viable alternative to autologous ADRCs with microfat for the treatment of PAF.<br><br>TRIAL REGISTRATION: Clinical Trials Information System (CTIS) EU CT 2022-502659-73-01. Registered on 18 November 2023.<br><br>CLINICALTRIALS: org NCT0&#xa0;6303752. Registered on 25 February 2024.}, }
@article {pmid41782495, year = {2026}, author = {Loublier, C and Taminiau, B and Seidel, L and Moula, N and Tano, C and Cesarini, C and Costa, M and Lecoq, L and Daube, G and Amory, H}, title = {Survey on Faecal Microbiota Transplantation and Probiotic Use in Equine Practice in France and Belgium.}, journal = {Veterinary medicine and science}, volume = {12}, number = {2}, pages = {e70854}, pmid = {41782495}, issn = {2053-1095}, support = {40005849//Fonds De La Recherche Scientifique - FNRS/ ; }, mesh = {Belgium ; Animals ; *Fecal Microbiota Transplantation/veterinary/statistics &amp; numerical data ; Horses ; France ; *Probiotics/therapeutic use ; Cross-Sectional Studies ; *Horse Diseases/therapy ; Surveys and Questionnaires ; *Veterinarians/statistics &amp; numerical data/psychology ; Female ; Male ; *Health Knowledge, Attitudes, Practice ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) and probiotics are used in equine practice. Understanding veterinarians' perceptions and practices is crucial for effective implementation.<br><br>OBJECTIVE: (1) Evaluate the prevalence, usage patterns and perceived effectiveness of probiotics and FMT among equine veterinarians in France and Belgium. (2) Assess their knowledge, practices and influencing factors across demographics and settings. (3) Explore links between FMT protocols and treatment satisfaction.<br><br>STUDY DESIGN: Cross-sectional survey.<br><br>METHODS: An online survey collected demographic data and responses on the use of probiotics and FMT. Analyses included descriptive statistics, chi-square tests and logistic regression models.<br><br>RESULTS: Ninety-six equine veterinarians participated, practicing in Belgium (52.1%), France (39.6%) or both (8.3%). Probiotic use was reported by 82.1%, more frequent in field than clinical practice (odds ratio [OR]&#xa0;=&#xa0;3.61, 95% CI [1.09, 12.02], p&#xa0;=&#xa0;0.036) and in France than Belgium (OR&#xa0;=&#xa0;5.08, 95% CI [1.44, 17.94], p&#xa0;=&#xa0;0.012). Probiotics were used for chronic diarrhoea (88.0%), acute diarrhoea (67.6%) and inflammatory bowel diseases (45.9%). Most veterinarians (83.3%) defined probiotics well, but 16.7% misidentified non-probiotic products. FMT was used by 76.0%, mainly occasionally and therapeutically, more in clinical than field practice (OR&#xa0;=&#xa0;4.79, 95% CI [1.03, 22.27], p&#xa0;=&#xa0;0.046). In theory, 58.3% prioritized infection-free donors, but only 22.5% tested donors before FMT, mostly using coprology (93.8%). Those who tested donors reported higher perceived efficacy (p&#xa0;=&#xa0;0.0029).<br><br>MAIN LIMITATIONS: Potential selection bias, as participation was voluntary. Generalizability might be limited by focus on France and Belgium. Sample size, while informative, should be expanded.<br><br>CONCLUSION: Probiotics and FMT were commonly used therapeutically by equine veterinarians in France and Belgium. Although probiotic use was widespread, some misunderstandings remained. FMT protocols varied, with donor faeces often untested. Treatment satisfaction was generally positive but estimated success rates varied. Standardized FMT protocols are needed to improve outcomes and consistency.}, }
@article {pmid41783924, year = {2026}, author = {Luo, S and Lou, F and Yang, P and Zhang, Y and Yan, L and Dong, Y and Yang, B and Wang, H and Liu, Y and Pu, J and Cannon, RD and Xie, P and Ji, P and Jin, X}, title = {Dysregulation of Oral Microbial Eicosapentaenoic Acid Induced by Chronic Restraint Stress Exacerbates Periodontitis via M1 Macrophage Polarization.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {28}, pages = {e21346}, pmid = {41783924}, issn = {2198-3844}, support = {82370968//National Natural Science Foundation of China/ ; 2026MSXM055//Chongqing medical scientific research project (Joint project of the Chongqing Health Commission and the Science and Technology Bureau)/ ; CSTB2022NSCQ-MSX1148//Natural Science Foundation of Chongqing/ ; 2025JYJ099//Project of Luzhou Science and Technology Bureau/ ; }, mesh = {Animals ; *Eicosapentaenoic Acid/metabolism ; Mice ; *Macrophages/metabolism ; *Periodontitis/metabolism/microbiology/etiology ; *Stress, Psychological/complications/metabolism/microbiology ; Male ; Restraint, Physical ; *Microbiota/physiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Dysbiosis ; }, abstract = {The intricate interplay between chronic psychological stress and periodontitis, mediated by oral microbiota and macrophage polarization, remains largely enigmatic. Here, we demonstrate that chronic restraint stress (CRS) exacerbates periodontitis by inducing oral microbial dysbiosis and a consequential shift in host metabolism. Clinical observations reveal a significant correlation between depressive symptoms and the severity of periodontitis, which is underpinned by a distinct oral microbiome. Crucially, fecal microbiota transplantation from CRS-exposed mice into germ-free mice was sufficient to transmit the heightened periodontitis phenotype, establishing a causal role for the stress-altered microbiota. Metabolomic profiling identified a depletion of eicosapentaenoic acid (EPA) in stressed, ligature-induced periodontitis mice. Mechanistically, supplementation with EPA ameliorates periodontitis by suppressing the NF-κB signaling pathway, thereby inhibiting the pro-inflammatory M1 polarization of macrophages. Our findings unveil a novel gut-oral axis mediated by microbiota and metabolites under stress, and position the omega-3 fatty acid EPA as a promising therapeutic agent for mitigating stress-aggravated inflammatory disorders.}, }
@article {pmid41785475, year = {2026}, author = {Dinan, TG and Cryan, JF}, title = {Faecal Transplants for Bipolar Depression: Moving out of the Periphery?.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437261428007}, pmid = {41785475}, issn = {1497-0015}, }
@article {pmid41785480, year = {2026}, author = {Shekarriz, S and Vigod, SN and Bianco, T and Bala, A and Hao, C and Allard, JP and Hota, S and Poutanen, S and Surette, MG and Taylor, VH}, title = {The Safety, Efficacy, and Feasibility of Fecal Microbiota Transplantation in a Population With Bipolar Disorder During Depressive Episodes: A Pilot Parallel Arm Randomized Controlled Trial: Sécurité, efficacité et faisabilité de la transplantation de microbiote fécal chez une population atteinte de troubles bipolaires, au cours d'épisodes dépressifs : essai pilote contrôlé à répartition aléatoire et à groupes parallèles.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437261420877}, pmid = {41785480}, issn = {1497-0015}, abstract = {BackgroundThe gut microbiome has been proposed as a potential modifiable target to treat mental illness. This double-blind randomized control trial investigated fecal microbiota transplant (FMT) in bipolar disorder (BD) to assess efficacy, safety, and feasibility. The primary outcome evaluated the effectiveness of standard approved therapy for BD depression + FMT in individuals not responding to standard treatment, measured by change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 24. Secondary outcomes included FMT's impact on anxiety, global function, side-effects, and safety. The feasibility of this novel intervention was also assessed. Microbial analysis utilized whole-genome shotgun metagenomic sequencing, comparing outcomes between allogenic (donor) and autologous (participants own) FMT.MethodsA total of 35 participants (28 women and 7 men) with at least moderate depressive-phase BD (MADRS) were randomized to receive either allogenic FMT (n = 17) or autologous FMT (n = 18) via colonoscopy and were followed for 24 weeks.ResultsMADRS scores significantly improved from baseline to the last visit in both treatment arms. There was no significant difference between allogenic FMT (16.74-point improvement) and autologous FMT (15.4-point improvement) regarding clinical efficacy (t = -0.47, p-value = .64, 95% confidence interval [CI] = -7.3-4.6). Microbiota analysis showed that allogenic FMT let to a bacterial profile similar to the healthy donor and increased bacterial diversity at the 6-month mark, whereas those receiving autologous FMT did not. The intervention was well tolerated with no significant adverse events. Recruitment, randomization, and retention metrics support feasibility of a larger trial.ConclusionFeasibility and tolerability data indicate further investigation into microbial manipulation in BD is warranted. The absence of efficacy differences between the two types of FMT, despite microbial change, highlights the importance of a true placebo in future studies, as well as the importance of understanding exactly what bacteria are linked to improvements. ClinicalTrials.gov, NCT0327922.}, }
@article {pmid41785672, year = {2026}, author = {Chen, Q and Feng, X and Wang, J and Zhu, H and Bo, Z and Wang, B and Zhao, Z}, title = {Impact of gut microbiota on hepatocellular carcinoma: Pathogenesis, diagnosis, prognosis, and therapeutic prospective.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {237}, number = {}, pages = {116581}, doi = {10.1016/j.ejca.2026.116581}, pmid = {41785672}, issn = {1879-0852}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/diagnosis/microbiology ; *Liver Neoplasms/therapy/diagnosis/microbiology ; *Gastrointestinal Microbiome ; Prognosis ; Dysbiosis ; }, abstract = {Advances in sequencing technology have elucidated the complex role of the gut microbiota in hepatocellular carcinoma (HCC). Communication between the gut and the liver occurs via the gut-liver axis, and dysbiosis of the gut microbiota has been implicated in both the promotion and suppression of HCC. Furthermore, through interactions with host metabolism and immune system, the gut microbiota significantly influences treatment responses and prognostic outcomes of HCC. Despite progress in therapeutic strategies, clinical efficacy remains suboptimal, underscoring the need for a deeper understanding of the gut microbiota's role. This review highlights the potential of gut microbiota as novel biomarkers for the diagnosis and prognostic prediction of HCC, and explores its therapeutic implications. We summarize current insights into the molecular mechanisms underlying the gut microbiota-HCC interplay, and emphasize the relationship between gut microbiota and the efficacy of various treatments, including surgery, chemotherapy, radiotherapy, immunotherapy, and targeted agents. Microbiome-targeting interventions like probiotics, fecal microbiota transplantation (FMT), and dietary changes as emerging adjuvant strategies are also discussed in detail to provide potential resources for advancing translational hepatology. Although challenges remain, this review aims to provide valuable perspectives for developing individualized therapeutic strategies in HCC management.}, }
@article {pmid41785880, year = {2026}, author = {Petersen, A&#xd8; and Damholt, B and Grove, M and Hink, J and Marotte-Hurbon, T and Söderqvist, J and Troy, A and Zdravkovic, M and Bayer, L and Brunner, K and Bryde, T and Clube, J and Gencay, YE and Gram, A and Haaber, JK and Hallström, B and Jasinskytė, D and Pascal, R and Petersen, M and Semsey, S and Torio, AS and Turcu, IC and Smrekar, F and Taur, Y and Satlin, MJ and Sommer, MOA and van der Helm, E and Grøndahl, C}, title = {Safety, recovery, and pharmacodynamics of CRISPR-Cas therapeutic SNIPR001: a phase 1, randomised, double-blind, first-in-human, dose-escalation study.}, journal = {The Lancet. Microbe}, volume = {7}, number = {4}, pages = {101257}, doi = {10.1016/j.lanmic.2025.101257}, pmid = {41785880}, issn = {2666-5247}, mesh = {Humans ; Adult ; Double-Blind Method ; Male ; Middle Aged ; Female ; Young Adult ; Adolescent ; Aged ; *Escherichia coli/virology/drug effects ; *Bacteriophages/genetics ; Feces/microbiology ; Healthy Volunteers ; }, abstract = {BACKGROUND: Patients with haematological cancer who receive stem-cell transplantation are at risk of bloodstream infections, often caused by multidrug resistant gut pathogens such as Escherichia coli. SNIPR001 is a cocktail of four CRISPR-Cas-armed bacteriophages that reduce colonisation of E coli in the gastrointestinal tract in animal models and is designed to not affect other members of the commensal microbiota. We aimed to investigate the safety and tolerability of SNIPR001 in healthy participants.<br><br>METHODS: In this randomised, placebo-controlled, double-blind, first-in-human, dose-escalation trial conducted at a single centre (Medpace Clinical Pharmacology Unit; Cincinnati, OH, USA), we sequentially enrolled healthy participants (aged 18-65 years) with more than 10[7]E coli colony-forming units per gram of stool into cohorts 1, 2, and 3, pending a safety review of the previous enrolment group where applicable. Participants in each cohort were randomly assigned to treatment or placebo using a unique three-digit participant identification number. Participants were orally administered 10[8] plaque-forming units (PFU) per dose (cohort 1), 10[10] PFU per dose (cohort 2), and 10[12] PFU per dose (cohort 3) of SNIPR001 or placebo (phosphate-buffered saline buffer), twice daily for 7 days. All personnel, except for a pharmacy staff member who prepared both SNIPR001 and placebo vials, were masked to the administered dose and assignment; masking was ensured by fully covering the surface of each vial. Participants were followed up to day 187. The primary outcome was the incidence and severity of adverse events and medically attended adverse events from the first administration of the study drug until 4 weeks after the last dose administration on day 35 of the study. Recovery and biodistribution of SNIPR001 in faeces, blood, and urine; pharmacodynamics, including the ability of SNIPR001 to reduce E coli levels in stool (assessed using a linear mixed-effects model); and microbiome composition (using Bray-Curtis dissimilarity) were secondary outcomes. Primary safety analyses were assessed per-protocol (ie, all enrolled participants who received at least one administration of the study drug). This trial was conducted under an Investigational New Drug application from the US Food and Drug Administration, is registered with ClinicalTrials.gov (NCT05277350), and is closed to new participants.<br><br>FINDINGS: The trial was carried out between March 24, 2022, and Nov 30, 2022. 36 eligible participants were randomly assigned to receive SNIPR001 or placebo in cohorts 1 (six assigned to 10[8] PFU per dose and two assigned to placebo), 2 (six to 10[10] PFU per dose and two to placebo), and 3 (12 to 10[12] PFU per dose and eight to placebo). The mean age of participants was 42&#xb7;1 years (SD 13&#xb7;8), with 14 (39%) female participants and 22 (61%) male participants. During the trial and 4-week follow-up period, only mild and moderate adverse events were observed, with most adverse events occurring in the placebo group (13, six, one, and nine for participants receiving either placebo or SNIPR001 at 10[8], 10[10], and 10[12] PFU twice a day, respectively). The number of participants who had adverse events was not significantly higher in treatment groups than in the placebo group (p=0&#xb7;94, one-sided Fisher's exact test). The most frequently reported adverse events were headaches and diarrhoea. No grade 3-4 adverse events were reported and no serious adverse events were reported in the SNIPR001 dose groups. During and after the dosing period, the gut microbiota composition did not significantly differ between the treatment and placebo groups (p>0&#xb7;05, two-sided Mann-Whitney U test of Bray-Curtis distances, false discovery rate [FDR]-corrected). Functional SNIPR001 was recovered from stool samples in concentrations proportional to the administered dose but was not meaningfully detected in plasma (only one sample) or urine (only one sample). SNIPR001 was undetected in all samples 6 months after the last dosing, which is a favourable pharmacokinetic property and meets regulatory expectations. We observed the largest reduction in E coli levels compared with placebo 2 weeks after treatment initiation at day 14 (78%; -0&#xb7;65 log10 [SE 0&#xb7;64] for 10[12] PFU SNIPR001 twice-daily group), according to a linear mixed-effects model for the highest dose population; however, this change was not statistically significant (p=0&#xb7;811, linear mixed-effects model, FDR-corrected).<br><br>INTERPRETATION: This first-in-human study of SNIPR001 supported its safety, tolerability, and restriction to the gastrointestinal tract, while not systemically disrupting the gut microbiome. These results justify further clinical development of SNIPR001 in an ongoing phase 1b/2a trial.<br><br>FUNDING: Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and SNIPR Biome.}, }
@article {pmid41786065, year = {2026}, author = {Wang, X and Liu, R and Liu, J and Lin, Y and Zhou, M}, title = {Gut microbiota-derived indole metabolites in depression: mechanisms and therapeutic potential.}, journal = {European journal of pharmacology}, volume = {1019}, number = {}, pages = {178720}, doi = {10.1016/j.ejphar.2026.178720}, pmid = {41786065}, issn = {1879-0712}, mesh = {Humans ; Animals ; *Indoles/metabolism ; *Depression/microbiology/metabolism/therapy ; *Gastrointestinal Microbiome ; Antidepressive Agents/therapeutic use/pharmacology ; Brain/metabolism ; Tryptophan/metabolism ; }, abstract = {Depression, a prevalent neuropsychiatric disorder with complex pathophysiology and often insufficient treatment efficacy, is increasingly associated with disruptions in the gut-brain axis. This review focuses on the underappreciated role of the microbial indole pathway, a key route in tryptophan metabolism orchestrated by the gut microbiota. We synthesize recent evidence demonstrating that gut microbiota-derived indole metabolites, such as indole-3-propionic acid (IPA) and indole-3-aldehyde (IAld), are significantly reduced in depression. These metabolites exert multifaceted antidepressant effects by enhancing intestinal and blood-brain barrier integrity, suppressing neuroinflammation, and promoting neuroplasticity. Furthermore, we explore the therapeutic potential of targeting this axis through interventions like specific probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation to restore microbial ecology and indole metabolite levels. By highlighting the microbiota-indole-brain pathway as a critical mechanistic and therapeutic frontier, this review provides a novel perspective on the pathogenesis and treatment of depression, moving beyond conventional monoaminergic theories.}, }
@article {pmid41786895, year = {2026}, author = {Hu, S and Liu, H and Song, F and Huang, D and Wei, Q}, title = {CFD protein deficiency induce slow transit constipation is correlated with gut microbial dysbiosis.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41786895}, issn = {2045-2322}, abstract = {UNLABELLED: Dysregulation of complement factor D (CFD) has been associated with various diseases, such as metabolic, cardiovascular, and renal disorders. However, its role in intestinal function has been less studied. Our research found that CFD-deficient (Cfd[–/–]) mice exhibited spontaneous slow transit constipation (STC) compared to wild-type (WT) mice. Moreover, the fecal weight and water content in Cfd[–/–] mice were significantly reduced, despite no specific changes in feeding behavior. Reduced C-kit protein expression, colon injury, complement dysfunction and dysbiosis of the fecal microbiota are also observed in Cfd[–/–] mice. After microbiota transplantation from WT mice into Cfd[–/–] mice, reduced stool output, water content, decreased C-kit protein expression and colon injury were significantly improved. These results indicate that CFD is critical for controlling microbial homeostasis in the colon and, in its absence, leads to colon injury and promotes slow transit constipation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-41597-x.}, }
@article {pmid41787060, year = {2026}, author = {Li, X and Tian, X and Liu, P and Yuan, J and Liu, P and Ying, X and Guo, H and Ma, C and Zhao, D and Xuan, R and Zhao, Q and Li, B and Qiu, Y and Yan, X}, title = {Gut Microbiota Remodeling after Fecal Microbiota Transplantation Is Associated with Reduced Inflammation and Cardiac Injury in Fluoride-Arsenic Co-Exposed Rats.}, journal = {Biological trace element research}, volume = {}, number = {}, pages = {}, pmid = {41787060}, issn = {1559-0720}, support = {SD2417//Shanxi Medical University Provincial Doctoral Research Fund/ ; XD2312//Shanxi Medical University Doctoral Start-up Fund/ ; 202403021212261//the Shanxi Province Basic Research Program/ ; No.82103961//National Natural Science Foundation of China/ ; No.82173644//National Natural Science Foundation of China/ ; YDZJSX2024D064//Shanxi Province Central-Guided Local Science and Technology Development Fund Project/ ; }, abstract = {Groundwater co-contamination with arsenic and fluoride (AsF) has emerged as a widespread environmental and public health concern. Although the individual toxicities of arsenic and fluoride have been extensively studied, the mechanisms responsible for their combined cardiotoxic effects are still unclear. To address this gap, we first conducted an integrated network toxicology analysis to predict the potential molecular pathways involved in AsF-induced cardiotoxicity. The analysis identified inflammatory signaling, particularly the TLR4/NF-κB pathway, as a potential key mediator. Based on these findings, we established an animal model with fecal microbiota transplantation (FMT) intervention to investigate the interactive effects of AsF exposure and the microbiota-mediated molecular mechanisms involoved. The results clearly show that FMT in AsF-exposed rats is associated with improvements in cardiac parameters, reductions in LPS and cytokine levels, and significant changes in gut microbial composition. The TLR4/NF-κB pathway is implicated as a plausible mediating mechanism in this process. Concurrently, shifts in the abundance of Bacteroidetes were associated with changes in blood pressure. Collectively, these findings provide a new perspective for understanding the cardiotoxicity of environmental co-contaminants and offer experimental support for therapeutic strategies targeting the gut-heart axis.}, }
@article {pmid41789426, year = {2026}, author = {Xiao, Y and Li, J and Xiang, L and Xiu, W}, title = {The role of gut microbiota in liver metastasis of small cell lung cancer: mechanisms and therapeutic implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1767998}, pmid = {41789426}, issn = {2235-2988}, mesh = {Humans ; *Liver Neoplasms/secondary/therapy/immunology ; *Gastrointestinal Microbiome ; *Lung Neoplasms/pathology ; *Small Cell Lung Carcinoma/pathology/therapy ; Tumor Microenvironment/immunology ; Animals ; Dysbiosis ; }, abstract = {Small cell lung cancer (SCLC) with liver metastases (LM), represents a highly aggressive clinical challenge characterized by significant morbidity, poor durable responses to chemoimmunotherapy, and limited therapeutic options. While most research has focused on tumor-intrinsic driver mutations and the local liver microenvironment, the remote influence of the gut microbiota on LM-SCLC pathogenesis remains a largely unexplored area. Emerging evidence from other cancer types suggests that the gut microbiota composition and its derived metabolites can modulate systemic immune tolerance, influence hepatic immune surveillance, and affect the efficacy and toxicity of anticancer therapies. This review synthesizes current knowledge on the gut-liver axis in cancer metastasis, with a specific focus on its pathogenesis. We discuss the molecular and immunological pathways through which gut microbial dysbiosis may promote an immunosuppressive liver microenvironment, facilitate the formation of a pro-metastatic niche, and impair anti-tumor responses. Specifically, we detail how translocated microbial products, such as lipopolysaccharide (LPS), and pro-tumorigenic secondary bile acids (SBAs) activate key hepatic immune cells (Kupffer cells, KCs) and stromal cells (hepatic stellate cells, HSCs). This activation modulates key signaling cascades and promotes the survival and outgrowth of circulating SCLC cells. Furthermore, we explore promising microbiota-based therapeutic strategies-including probiotics, prebiotics, fecal microbiota transplantation (FMT), and next-generation microbial therapeutics (NGMTs)-as novel approaches to augment standard-of-care treatments. A deeper understanding of the interplay between the gut microbiota and LM-SCLC is essential for opening new avenues for personalized combination therapies and improving outcomes for this high-risk patient population.}, }
@article {pmid41789806, year = {2026}, author = {Nair, AV}, title = {Friend and Foe: Microbes in Orchestrating Immunity and Shaping Infection Dynamics.}, journal = {ACS infectious diseases}, volume = {12}, number = {4}, pages = {1218-1232}, doi = {10.1021/acsinfecdis.5c00709}, pmid = {41789806}, issn = {2373-8227}, mesh = {Humans ; *Microbiota/immunology ; Animals ; Probiotics/administration &amp; dosage ; Prebiotics ; *Communicable Diseases/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Host-Pathogen Interactions ; }, abstract = {Microbial communities, or microbiota, are fundamental regulators of host immunity and infection outcomes across diverse body sites, including the gut, skin, respiratory tract, and vagina. Despite advances, infectious diseases remain a global challenge, exacerbated by antimicrobial resistance and emerging pathogens. This review explores the dynamic interplay between microbiota, host immune responses, and pathogens, highlighting how microbial interactions shape immune homeostasis and colonisation resistance. The review discusses therapeutic approaches leveraging probiotics, prebiotics, defined microbial consortia, and fecal microbiota transplantation to enhance resistance against bacterial, viral, fungal, and parasitic infections. These microbiome-based strategies represent promising, sustainable alternatives to conventional antibiotics, offering scalable and mechanism-driven interventions. This review further underscores the potential of microbiota-informed therapies to contribute to effective infectious disease prevention and management while addressing global health challenges.}, }
@article {pmid41791695, year = {2026}, author = {Chandra, QM and Clister, D and Halim, P and Dalimunthe, A and Ichwan, M and Sari, DK and Umaya, C and Aktary, N and Rani, A and Park, MN and Kim, B and Syahputra, RA}, title = {Harnessing the gut-heart axis for cardiovascular drug innovation: microbiome, metabolites, and personalized treatment strategies.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {587}, number = {}, pages = {120941}, doi = {10.1016/j.cca.2026.120941}, pmid = {41791695}, issn = {1873-3492}, mesh = {Humans ; *Precision Medicine ; *Cardiovascular Diseases/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Cardiovascular Agents/pharmacology/therapeutic use/metabolism ; Animals ; *Heart/drug effects ; }, abstract = {Cardiovascular disease (CVD) remains the leading cause of mortality worldwide despite major advances in pharmacotherapy. Emerging evidence reveals a pivotal role for the gut-heart axis, wherein gut microbiota are and their metabolites influence CV physiology, pathology, and drug responsiveness. Dysbiosis in conditions such as hypertension, atherosclerosis, and heart failure has been associated with altered production of bioactive metabolites including trimethylamine N-oxide, short-chain fatty acids, bile acids, and tryptophan derivatives. These metabolites have been shown to modulate inflammation, endothelial function, lipid metabolism, and myocardial remodeling. This review synthesizes current knowledge on microbiome-drug interactions in CV pharmacology, including how gut bacteria may metabolize drugs (e.g., digoxin, aspirin, warfarin) and how CV agents can shape microbial communities. We further explore microbiome-targeted therapeutic strategies-probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and small-molecule inhibitors of harmful metabolites-highlighting their mechanisms, preclinical evidence, and translational potential. Integrating microbiome profiling with multi-omics platforms and artificial intelligence may enable personalized treatment strategies that optimize CV outcomes. While the gut-heart axis presents an exciting frontier for drug innovation, challenges remain in establishing causality, addressing inter-individual microbiome variability, managing confounding factors such as diet and medication use, and meeting regulatory requirements. Harnessing this bidirectional relationship holds promise for transforming CV pharmacotherapy from a one-size-fits-all approach to precision medicine grounded in host-microbe interactions.}, }
@article {pmid41792228, year = {2026}, author = {Kim, DJ and Lee, YJ and Choi, JW and Lee, HS and Lee, WS and Park, HS and Choi, EJ and Park, H and Lee, JH and Lee, JH and Lee, SB and Choi, Y and Koh, SJ}, title = {Early fecal metabolomic profiling for predicting acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-38818-8}, pmid = {41792228}, issn = {2045-2322}, support = {2025IP0061-1//Grants from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea/ ; 2025//International Congress of BMT, funded by the Korean Society of Blood and Marrow Transplantation/ ; 26-2021-0060//Seoul National University Hospital Research Fund/ ; }, }
@article {pmid41792366, year = {2026}, author = {Ikram, S and Ullah, M and Lee, J and Hasan, N and Yoo, JW and Khan, R and Naeem, M}, title = {Fecal microbiota transplantation in inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials (2020-2025).}, journal = {Inflammopharmacology}, volume = {34}, number = {4}, pages = {2593-2605}, pmid = {41792366}, issn = {1568-5608}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic/methods ; *Inflammatory Bowel Diseases/therapy ; Remission Induction/methods ; Treatment Outcome ; Colitis, Ulcerative/therapy ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a therapeutic strategy for Inflammatory Bowel Disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). Although multiple randomized controlled trials (RCTs) have been published in recent years, evidence remains fragmented regarding safety and efficacy. This systematic review and meta-analysis evaluated the efficacy and safety of microbiome-based interventions in Inflammatory Bowel Disease (IBD).<br><br>METHODS: A systematic search of PubMed, Cochrane CENTRAL and Embase was conducted for randomized controlled trials (RCTs) published between January 2020 and May 2025. Eligible studies compared donor FME with placebo, autologous FMT or standard therapy in adult patients with IBD. Primary outcomes were clinical remission and endoscopic improvement; secondary outcomes included maintenance of remission and adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analyses were performed in R using the meta and meta for packages. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using common-effects and random-effects models.<br><br>RESULTS: Six RCTs involving 220-230 patients were included (majority UC patients, two trials CD). For induction of clinical remission, FMT was associated with significantly higher rates vs controls (OR&#x2009;=&#x2009;3.24, 95% CI 1.43-7.41, p&#x2009;=&#x2009;0.005) under a common-effect model; random-effects model showed similar point estimate but wide CI overlapping unity. Endoscopic response was strongly increased with FMT (OR&#x2009;=&#x2009;6.80, 95% CI 2.96-15.63, p&#x2009;<&#x2009;0.0001). Serious adverse events were more common in FMT arms but not statistically significant (common-effects OR&#x2009;~&#x2009;2.05, 95% CI 0.72-5.81, p&#x2009;=&#x2009;0.18). Evidence for maintenance of remission from two trials was limited and inconsistent.<br><br>CONCLUSION: Microbiome-based therapies, particularly FMT, significantly improved clinical and endoscopic remission in IBD (especially in UC) compared with control interventions, but safety signals and maintenance efficacy remain uncertain. Larger and strictly designed UC and CD-specific RCTs are needed to confirm long-term efficacy, clarify safety and define the role of microbiome-targeted therapies in IBD management.}, }
@article {pmid41792768, year = {2026}, author = {Zhang, S and Tang, S and Han, H and Xu, Y and Liu, D and Wang, H and Zhong, R and Chen, L and Zhang, H}, title = {Lactobacillus reuteri SKLAN202402ZF inhibited by early-life lincomycin exposure alleviate intestinal damage and inflammation sensitivity.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {41792768}, issn = {2049-2618}, mesh = {Animals ; *Lincomycin/adverse effects ; *Limosilactobacillus reuteri/physiology/drug effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Inflammation/chemically induced ; *Anti-Bacterial Agents/adverse effects ; Swine ; *Intestines/microbiology/drug effects/pathology ; Feces/microbiology ; Lipopolysaccharides ; *Probiotics/administration &amp; dosage ; Male ; }, abstract = {BACKGROUND: Early-life lincomycin and related antibiotics exposure affected gut microbiota composition and intestinal health, but which microbes play a dominant role in this process remains unclear.<br><br>RESULTS: Lactobacillus reuteri was suppressed in piglets exposed to lincomycin. Meanwhile, early-life lincomycin exposure caused intestinal morphological damage and decreased the expression of Claudin-1, Occludin, and ZO-1. Mice transplanted with lincomycin-exposed piglet fecal microbiota showed more severe inflammation and weight loss after LPS infection, and decreased colon Lactobacillus abundance. Furthermore, mice supplemented with Lactobacillus reuteri SKLAN202402ZF showed reduced lincomycin-related intestinal damage and inflammation after LPS infection. Specifically, Lactobacillus reuteri SKLAN202402ZF inhibits the expression of TLR4, MyD88, and NLRP3, and thus reduced the release of inflammatory factors such as IL-1&#x3b2;, IL-18, IL-17.<br><br>CONCLUSIONS: Lincomycin exposure affects the composition of gut microbes and increases subsequent susceptibility to LPS, while Lactobacillus reuteri SKLAN202402ZF has protective potential against antibiotic- associated intestinal inflammation.}, }
@article {pmid41794382, year = {2026}, author = {Lowry, DE and Cho, NA and Sampsell, K and Sales, KM and Noye Tuplin, EW and Biddle, M and Wang, W and Chleilat, F and Chow, MR and Buzatto, AZ and Reimer, RA}, title = {Prebiotics partially protect offspring from maternal antibiotic-induced obesity risk by altering maternal milk microbiota and gut colonization in Sprague-Dawley rats.}, journal = {The Journal of nutritional biochemistry}, volume = {153}, number = {}, pages = {110337}, doi = {10.1016/j.jnutbio.2026.110337}, pmid = {41794382}, issn = {1873-4847}, mesh = {Animals ; Female ; Rats, Sprague-Dawley ; *Prebiotics/administration &amp; dosage ; *Obesity/prevention &amp; control/chemically induced/microbiology ; *Anti-Bacterial Agents/adverse effects ; Pregnancy ; Male ; *Milk/microbiology ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Prenatal Exposure Delayed Effects ; Mice ; Lactation ; Oligosaccharides ; Liver/metabolism ; }, abstract = {Maternal antibiotic use can increase obesity risk in offspring. Co-administering prebiotics mitigates the risk in rats. How prebiotics and antibiotics interact to affect obesity risk is unknown, but could involve altered milk microbiota that influences offspring gut colonization. Sprague-Dawley rat dams were exposed to antibiotics (low-dose penicillin) and/or prebiotics (oligofructose) during gestation and lactation. Gut and milk microbiota were measured using 16S rRNA sequencing, and metabolic measurements were taken for dams and offspring at weaning (day 21) and 10 days postweaning (day 31). Germ-free mice were transplanted with maternal cecal microbiota to assess the causal role of vertically transmitted microbiota. Offspring maternally exposed to antibiotics showed relatively accelerated taxonomic maturation in the gut pre- and postweaning. Milk composition (fat, protein, hormone, microRNA, and cytokines) was unchanged, but milk-derived bacteria differed between maternal treatments and contributed to offspring gut microbial structure. Male offspring were especially affected by maternal antibiotic exposure and had increased body weight, fat mass, caloric intake, and hepatic triglycerides by day 31. All but hepatic triglycerides were attenuated with maternal prebiotic coconsumption. fecal microbiota transplants of maternal cecal matter into germ-free mice replicated male offspring body weight and hepatic outcomes. Untargeted hepatic lipidomics and network analysis revealed strong connections between several bacteria and lipid species potentially of bacterial origin that were enriched in prebiotic offspring microbiota and livers. These data confirm the role of milk microbiota in seeding offspring microbiota and implicate maternal antibiotic-associated gut microbiota as causally implicated in compromising early-life offspring hepatic metabolism that may lead to later metabolic disorders.}, }
@article {pmid41794466, year = {2026}, author = {Huang, S and Ding, H and Su, Y and Chen, Z and He, W and Chen, ZY and Zhu, H}, title = {Alpha-lipoic acid improves intestinal homeostasis and ameliorates colitis through modulation of gut microbiota and production of short chain fatty acids in mice.}, journal = {Food research international (Ottawa, Ont.)}, volume = {230}, number = {}, pages = {118582}, doi = {10.1016/j.foodres.2026.118582}, pmid = {41794466}, issn = {1873-7145}, mesh = {Animals ; *Thioctic Acid/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colitis/chemically induced/drug therapy/microbiology/metabolism ; *Fatty Acids, Volatile/metabolism/biosynthesis ; Male ; Mice, Inbred C57BL ; *Homeostasis/drug effects ; Mice ; Dextran Sulfate ; Intestinal Barrier Function ; Oxidative Stress/drug effects ; Disease Models, Animal ; NF-kappa B/metabolism ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; *Intestines/drug effects ; Intestinal Mucosa/metabolism ; }, abstract = {α-Lipoic acid (ALA) is a natural antioxidant present in both plants and animal foods. It has attracted growing attention for its potential role in maintenance of intestinal homeostasis. This study was to investigate the protective effects of dietary ALA on experimental colitis, and to evaluate its modulating effect on gut microbiome in mice. Male C57BL/6 J mice with dextran sulfate sodium (DSS)-induced acute colitis were administered ALA (40 or 80 mg/kg) dissolved in corn oil. Results showed that dietary ALA ameliorated colitis severity, improved intestinal barrier integrity, and attenuated inflammation by reducing oxidative stress and suppressing NF-κB pathway activation and pro-inflammatory cytokines expression. Moreover, dietary ALA increased the microbial diversity (Shannon index), reshaped gut microbiota composition by suppressing pathogenic bacteria and promoting beneficial taxa such as Akkermansia, and elevated levels of short chain fatty acids (SCFA). Fecal microbiota transplantation (FMT) further confirmed that ALA could modulate gut microbiota and protect against colitis in mice. In conclusion, ALA could effectively maintain the intestinal homeostasis and ameliorate colitis at least in mice. Such protective effect of ALA in gut health was mediated through modulation of gut microbiota and enhancement of SCFA production.}, }
@article {pmid41797510, year = {2026}, author = {Sajid, S and Huang, J and Kong, S and Lai, C and Tan, Z and Shao, Y and Guo, L}, title = {A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice.}, journal = {Aging cell}, volume = {25}, number = {3}, pages = {e70433}, pmid = {41797510}, issn = {1474-9726}, support = {82273757//National Natural Science Foundation of China/ ; 82574226//National Natural Science Foundation of China/ ; 2023B1515020106//Natural Science Foundation of Guangdong Province/ ; 4SG25295G//Discipline Construction Project of Guangdong Medical University/ ; 4SG25239G//Discipline Construction Project of Guangdong Medical University/ ; }, mesh = {Animals ; *Aging/metabolism ; Mice ; Oxidation-Reduction ; *Gastrointestinal Microbiome ; Male ; Mice, Inbred C57BL ; Oxidative Stress ; }, abstract = {Aging disrupts systemic metabolism, but the mechanisms by which gut microbial metabolites drive tissue-specific decline remain unclear. We conducted a multi-organ, multi-omics atlas across the gut, serum, liver, lung, and cortex in young and early-aged mice to address this. We identified a conserved aging signature marked by the microbiota-associated depletion of protective circulating metabolites, such as lysophosphatidylcholines (LPCs), concurrently with the systemic accumulation of pro-oxidative microbial catabolites, specifically trimethylamine N-oxide (TMAO) and indole-3-acetic acid (IAA). This microbial-metabolic drift disrupted systemic lipid transport and redox balance, leading to distinct organ-level vulnerabilities: hepatic lipid retention and ferroptosis susceptibility, pulmonary immune-redox activation, and cortical neurochemical dysregulation. To establish functional relevance, we conducted an integrated meta-analysis of 40 independent studies encompassing natural aging models, fecal microbiota transplantation (FMT), and probiotic interventions. This quantitative synthesis provided convergent evidence that microbial remodeling is a functionally relevant correlate associated with systemic aging phenotypes by restoring intestinal barrier integrity (upregulating ZO-1, MUC2), suppressing tissue inflammatory factors (IL-6, IL-1β, TNF-α), and mitigating oxidative stress (reducing MDA and restoring SOD/GSH). Together, our findings highlight gut-derived metabolic reprogramming as a modifiable, upstream driver of systemic aging, offering tractable targets for therapeutic intervention.}, }
@article {pmid41797849, year = {2026}, author = {Jalalifar, S and Bajelan, B and Mohammadi, R and Ghafoury, R and Kalhori, Z and Pooshang-Bagheri, K and Nekouian, R and Faranoush, M}, title = {The impact of gut microbiota on leukemia and prospects for novel therapies.}, journal = {Infectious medicine}, volume = {5}, number = {1}, pages = {100239}, pmid = {41797849}, issn = {2772-431X}, abstract = {The Human Microbiome Project has underscored the pivotal role of the gut microbiome in human health, revealing its potential influence on leukemia development, progression, and treatment response. This review summarizes evidence on microbiome-targeted therapies such as probiotics, fecal microbiota transplantation, antimicrobial peptides, and nanoparticles. These approaches may improve leukemia treatment outcomes through immune and metabolic modulation and reduced toxicity. Although emerging data suggest beneficial effects, most findings remain correlative and limited by small, heterogeneous studies. Further mechanistic and clinical research is required to clarify causal pathways, standardize interventions, and evaluate long-term safety. Personalized microbiome-based strategies that integrate molecular and immunologic profiling may ultimately refine leukemia management and improve survival.}, }
@article {pmid41798257, year = {2026}, author = {Liu, J and Wu, X}, title = {Fecal microbiota transplantation in ulcerative colitis: evidence, mechanisms, and practice considerations.}, journal = {Therapeutic advances in gastroenterology}, volume = {19}, number = {}, pages = {17562848261426284}, pmid = {41798257}, issn = {1756-283X}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease strongly associated with intestinal dysbiosis, reduced microbial diversity, and disrupted microbial metabolite profiles. Fecal microbiota transplantation (FMT) aims to restore microbial homeostasis and has shown a signal of benefit for induction of remission in some trials, but results are heterogeneous and long-term maintenance efficacy remains uncertain. In this narrative review, we synthesize randomized controlled trials (RCTs), systematic reviews/meta-analyses, and recent guideline and regulatory updates on FMT in UC, and integrate mechanistic insights from microbiome and metabolomics research. Across RCTs, intensive lower-gastrointestinal regimens using pooled, multidonor material, and/or anaerobic processing have most consistently achieved modestly higher steroid-free clinical and endoscopic remission than placebo in mild-to-moderate UC (approximately 25%-32% vs 5%-10% in representative studies), whereas upper-gastrointestinal delivery or oral lyophilized formulations and highly restrictive donor selection have yielded mixed or negative results. Mechanistically, responders commonly demonstrate engraftment of short-chain fatty acid producing taxa and restoration of secondary bile acid pathways. Safety profiles in trials are generally comparable to placebo for common mild adverse events, but rare severe transmissions (e.g., multidrug-resistant Escherichia coli and SARS-CoV-2) have driven stricter donor screening and have limited routine use outside regulated programs. Current guidelines recommend against FMT for UC outside clinical trials. Future work should prioritize standardized protocols, biomarker-guided personalization, combination strategies (diet/priming), and development of defined microbial therapeutics to improve efficacy and safety.}, }
@article {pmid41798939, year = {2026}, author = {Le, G and Wen, R and Huang, Z and Fang, H and Zheng, J and Wang, Y and Luo, H}, title = {Integrating network pharmacology, microbiomics, and metabolomics to uncover the therapeutic effect of Liubao tea on osteoarthritis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1746350}, pmid = {41798939}, issn = {1664-3224}, mesh = {Animals ; Mice ; *Metabolomics/methods ; *Gastrointestinal Microbiome/drug effects ; *Osteoarthritis/metabolism/drug therapy/microbiology ; *Tea/chemistry ; Male ; Network Pharmacology ; Disease Models, Animal ; *Plant Extracts/pharmacology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Pyrimidines/metabolism ; Cytokines/metabolism ; *Anti-Inflammatory Agents/pharmacology ; }, abstract = {BACKGROUND: Osteoarthritis (OA) is a debilitating joint disorder for which with no effective disease-modifying drugs are currently available. Liubao tea, a traditional Chinese post-fermented tea, exhibits diverse bioactivities, including anti-inflammatory properties and the ability to regulate gut microbiota. However, its potential therapeutic efficacy and underlying mechanism in the context of OA remain insufficiently elucidated.<br><br>METHODS: A mouse model of osteoarthritis (OA) induced by destabilization of the medial meniscus (DMM) was established, and the mice were treated with low- and high-dose Liubao tea extract. Micro-CT, histological staining (H&amp;E, Safranin O-Fast Green), and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate joint structure, cartilage damage, and inflammatory cytokine levels. 16S rRNA sequencing, fecal microbiota transplantation (FMT), and untargeted serum metabolomics were conducted to explore gut microbiota and metabolic changes. Additionally, Brequinar, a de novo pyrimidine synthesis inhibitor, was used to verify the role of pyrimidine metabolism. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of Liubao tea. Network pharmacology was employed to identify the active components and their potential targets in OA treatment. Molecular docking was performed to evaluate the interactions between key components and hub targets.<br><br>RESULTS: Liubao tea treatment significantly ameliorated DMM-induced OA progression, as evidenced by improved subchondral bone microarchitecture (increased bone volume/total volume [BV/TV], trabecular number [Tb.N], trabecular thickness [Tb.Th]; decreased trabecular separation [Tb.Sp]), the reduced cartilage erosion (lowered the modified Mankin and OARSI scores), and the suppressed systemic inflammation (decreased interleukin [IL]-6, IL-1&#x3b2;, tumor necrosis factor [TNF]-&#x3b1; levels). Liubao tea remodeled gut microbiota homeostasis (increased &#x3b1;-diversity and altered bacterial taxa), and fecal microbiota transplantation (FMT) from Liubao tea-treated mice recapitulated its anti-OA effects. Metabolomic analysis revealed that Liubao tea significantly downregulated the pyrimidine metabolism pathway, and Brequinar treatment mimicked its therapeutic benefits, confirming the role of pyrimidine metabolism suppression in OA alleviation. UPLC-MS/MS and network pharmacology analyses identified 1,989 metabolites in Liubao tea, including 273 bioactive components (e.g., flavonoids, lignans) that targeted 324 OA-related genes. The molecular docking results demonstrated that Eupatilin, 5,6,7,8-Tetramethoxyflavone, and 5-Hydroxy-6,7,3',4',5'-Pentamethoxyflavone exhibited potential interactions with the hub targets TP53, IL6, and TNF.<br><br>CONCLUSION: Liubao tea attenuates OA progression by modulating the composition of the gut microbiota and inhibiting the pyrimidine metabolism pathway, highlighting its potential as a novel natural therapeutic agent for OA.}, }
@article {pmid41800020, year = {2026}, author = {Park, U and Heo, JY and Chun, SM and Lee, JC and Lee, SH and Lee, SW}, title = {Harnessing the Gut Microbiota to Improve Cancer Immunotherapy: Focus on Lung Cancer.}, journal = {Immune network}, volume = {26}, number = {1}, pages = {e7}, pmid = {41800020}, issn = {1598-2629}, abstract = {The gut microbiota has emerged as a key orchestrator of systemic immunity, capable of reshaping the tumor microenvironment and modulating responses to cancer immunotherapy via the gut-lung axis. While immune checkpoint blockade (ICB) has revolutionized lung cancer treatment, a significant proportion of patients fail to respond. Accumulating evidence suggests that intestinal microbial composition modulates antitumor immunity, yet clinical associations between specific microbial taxa and ICB outcomes often show inconsistencies across cohorts. In this review, we synthesize current mechanistic insights into how gut microbial metabolites and structural components modulate pulmonary immune surveillance. We critically examine the clinical landscape of microbiome signatures in non-small cell lung cancer (NSCLC), highlighting how species- and strain-level heterogeneity contributes to divergent findings. Finally, we discuss translational strategies-ranging from fecal microbiota transplantation to rationally designed bacterial consortia and engineered probiotics-and propose a roadmap for integrating multi-omics with microbiome engineering to overcome current limitations and optimize precision immunotherapy.}, }
@article {pmid41800246, year = {2026}, author = {Liu, Y and Wang, S and Xiang, X and Du, Y and Xue, Q and Niu, Y and Peng, W and Ye, L and Zhou, Q}, title = {Gut-Lung Microbiota Axis Shapes the Immune Microenvironment and Immunotherapeutic Response in Lung Cancer.}, journal = {International journal of biological sciences}, volume = {22}, number = {5}, pages = {2265-2284}, pmid = {41800246}, issn = {1449-2288}, mesh = {Humans ; *Lung Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods ; *Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/physiology/immunology ; *Lung/microbiology/immunology ; Animals ; }, abstract = {The gut-lung axis microbiota plays a pivotal role in shaping the tumor immune microenvironment (TIME) and regulating immunotherapeutic responses in lung cancer. This review highlights that pulmonary and gut microbial dysbiosis drives lung cancer development through inducing chronic inflammation, remodeling the immune microenvironment, and reprogramming metabolism. Lung cancer patients exhibit distinct microbial signatures characterized by altered microbiotal diversity and enrichment of specific taxa like Streptococcus, Veillonella, and Bacteroidetes in the airways, along with gut microbial shifts involving decreased Firmicutes/Bacteroidetes ratio. These microbial alterations promote tumor progression via activation of pro-inflammatory pathways (e.g., interleukin-17 (IL-17)/interleukin-23 (IL-23) axis) and suppression of antitumor immunity.Notably, the gut-lung microbiome exerts a profound impact on immunotherapeutic efficacy: responders are enriched with beneficial microbes like Akkermansia muciniphila and Bifidobacterium that enhance CD8[+] T cell responses, while non-responders show elevated levels of Gammaproteobacteria and Fusobacterium associated with immunosuppression. Regulatory mechanisms include systemic immune modulation by microbial metabolites such as short-chain fatty acids, as well as activation of key signaling pathways including cGAS-STING and CD40L-CD40/NF-κB. Emerging translational applications encompass lung cancer diagnosis and immunotherapeutic response prediction via microbial biomarkers, as well as therapeutic interventions including fecal microbiota transplantation (FMT) and probiotic supplementation. Future studies should clarify microbe-host interaction mechanisms and develop personalized microbiota-based strategies to overcome immunotherapy resistance, offering the potential to revolutionize precision oncology through integrating microbiota modulation with conventional therapies.}, }
@article {pmid41800260, year = {2026}, author = {Zhang, J and Yan, S and Gao, T and Li, M and Li, Y and Li, L and Ji, D and Bian, Z and Huang, W and Hou, J and Lu, T and Su, L}, title = {Gut Microbiota-driven Tryptophan Metabolism Towards the Indole Pathway Mediates Schisandra Chinensis Polysaccharide's Alleviation of Ulcerative Colitis and Comorbid Depression via Aryl Hydrocarbon Receptor.}, journal = {International journal of biological sciences}, volume = {22}, number = {5}, pages = {2557-2580}, pmid = {41800260}, issn = {1449-2288}, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism ; *Tryptophan/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; *Polysaccharides/therapeutic use/pharmacology ; Mice ; *Schisandra/chemistry ; *Indoles/metabolism ; *Gastrointestinal Microbiome/drug effects/physiology ; *Depression/drug therapy/metabolism ; Male ; Mice, Inbred C57BL ; }, abstract = {Patients with ulcerative colitis (UC) exhibit heightened depression risk, linked to microbiota-gut-brain axis dysfunction. This study isolated a novel low-molecular-weight Schisandra chinensis polysaccharide (SCP) that ameliorated UC and comorbid depression by remodeling gut microbiota, redirecting tryptophan (Trp) metabolism toward the indole pathway, and activating aryl hydrocarbon receptor (AhR). Structurally, SCP features a →4)-α-D-Glcp backbone with O-6 branched chains. In dextran sulfate sodium-induced UC mice, SCP mitigated colonic inflammation, restored intestinal barrier integrity, and improved depression-like behaviors by repairing blood-brain barrier, reducing neuroinflammation, preserving hippocampal neurons, and modulating synaptic plasticity. Multi-omics revealed SCP enriched beneficial microbiota (e.g., Limosilactobacillus reuteri) and rebalanced Trp metabolism along the gut-brain axis. SCP suppressed the hyperactive kynurenine (Kyn) pathway (reduced Kyn/Trp ratio) while elevating indole-3-propionic acid (IPA) levels in colon, serum, and hippocampus. Functioning as a pivotal molecule, IPA exerted dual anti-inflammatory effects in both colon and hippocampus via AhR activation and NF-κB inhibition. Antibiotic depletion and fecal microbiota transplantation validated SCP's microbiota-dependent efficacy, while IPA supplementation recapitulated SCP's benefits. AhR inhibition abolished SCP's therapeutic actions, confirming AhR as the critical target. Collectively, these findings propose a novel therapeutic strategy for UC and associated depression, highlighting SCP's potential value in targeting the Trp metabolism-AhR axis.}, }
@article {pmid41801218, year = {2026}, author = {Zhang, Y and Teng, M and He, W and Li, L and Zhang, Y and Wang, S and Wang, C and Wang, D}, title = {4-Hydroxybenzyl Alcohol Mitigates Hyperlipidemia-Associated Depression by Inhibiting Neuroinflammation via the NKIRAS2/NF-κB Pathway.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {27}, pages = {e17873}, pmid = {41801218}, issn = {2198-3844}, support = {20240101212JC//Natural Science Foundation of Jilin Province/ ; }, mesh = {Animals ; Mice ; *NF-kappa B/metabolism ; *Hyperlipidemias/complications/metabolism/drug therapy ; *Depression/drug therapy/etiology/metabolism ; Signal Transduction/drug effects ; Male ; *Benzyl Alcohols/pharmacology ; Mice, Inbred C57BL ; *Neuroinflammatory Diseases/drug therapy/metabolism ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; }, abstract = {Epidemiological data link hyperlipidemia to increased depression susceptibility. This study investigates the potential involvement of 4-hydroxybenzyl alcohol (4-HBA), a bioactive molecule known for its neuroprotective and anti-inflammatory effects, in the pathophysiology of hyperlipidemia-associated depression. High-fat diet (HFD)-fed mice develop concurrent hyperlipidemia and depression-like behaviors, with 4-HBA identified as a key modulated brain metabolite in fecal microbiota transplantation recipients. In HFD-fed mice, 4-HBA treatment simultaneously improves lipid metabolism and significantly alleviates depression-like behaviors, accompanied by suppression of the nuclear factor κB (NF-κB) signaling pathway in the brain. In LPS-stimulated BV2 cells, 4-HBA inhibits NF-κB activation through NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), thereby coordinating the downregulation of inflammatory responses. Conditioned medium from 4-HBA-treated BV2 cells enhances neuronal viability and reduces inflammatory responses in HT22 neurons in co-culture. Importantly, silencing Nkiras2 in BV2 cells and organotypic brain slice cultures negated the anti-inflammatory and neuroprotective actions of 4-HBA. These findings demonstrate that the NKIRAS2/NF-κB pathway is a molecular mediator underlying the biological effects of 4-HBA. These findings position 4-HBA as a dual-action metabolite capable of concurrently mitigating metabolic and psychiatric manifestations through neuroinflammatory regulation.}, }
@article {pmid41802308, year = {2026}, author = {Han, JY and Kim, MJ and Park, JW and Jeong, SY}, title = {Gut microbiome in colorectal cancer: recent advances and clinical implications.}, journal = {Annals of coloproctology}, volume = {42}, number = {1}, pages = {72-85}, pmid = {41802308}, issn = {2287-9714}, abstract = {The gut microbiome is not just a bystander of colorectal carcinogenesis but is an active driver of colorectal cancer (CRC). CRC-associated microbiome contributes in the tumorigenesis through chronic inflammation, formation of toxic metabolite and genotoxins, oncogenic signal activation, immune evasion, and barrier disruption-all reinforcing a tumor microenvironment. In contrast, beneficial microbiome supports the barrier-immune-metabolic axis by maintaining mucosal integrity and balanced immune tone. Despite extensive studies of microbiome-based CRC biomarkers, microbiome-based CRC biomarkers have not been yet ready for routine clinical use due to variation across populations and lack of standardization of key steps such as sampling, analysis, cutoffs, and interpretation. Microbiome-based therapies aim to change the overall intestinal ecosystem rather than simply adding or removing single strains. At present, dietary modulation and prebiotics are considered supportive measures, while probiotics or synbiotics are in preclinical stage. Fecal microbiota transplantation (FMT) still faces important challenges in effectiveness, standardization and safety. By its role in reshaping the tumor-host immune environment, FMT is viewed as a potential option for cancer therapy after further development through well-controlled clinical trials with careful safety monitoring.}, }
@article {pmid41802647, year = {2026}, author = {Luo, J and Jin, X and Cui, M and He, H and Liao, J and Wen, W and Li, W and Cao, Y}, title = {Wulingsan alleviates metabolic dysfunction-associated steatotic liver disease through regulating gut microbiota-bile acid axis.}, journal = {Prostaglandins &amp; other lipid mediators}, volume = {183}, number = {}, pages = {107067}, doi = {10.1016/j.prostaglandins.2026.107067}, pmid = {41802647}, issn = {1098-8823}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; Rats ; Male ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; *Fatty Liver/metabolism/drug therapy ; Liver/drug effects/metabolism/pathology ; Fecal Microbiota Transplantation ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy ; }, abstract = {BACKGROUND: Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is closely linked to gut microbiota disorders and bile acid imbalance. Wulingsan (WLS) have shown promise in regulating these pathways, but its mechanism of action unclear. This study aimed to evaluate the therapeutic effect of WLS on the rat MASLD model from the perspectives of intestinal microbiota composition and bile acid homeostasis.<br><br>METHODS: The MASLD model was induced by a high-fat diet (HFD) and treated with different doses of WLS. Body weight and serum lipid profiles were monitored, inflammation were assessed to ELISA and RT-qPCR. H&amp;E staining to evaluate histopathological changes. The 16S rRNA sequencing and LC-MS/MS analysis of gut microbiota composition and bile acid profiles. The fecal microbiota transplantation (FMT) experiment verified the effect of WLS on the gut microbiota.<br><br>RESULTS: WLS treatment reduces the body weight of MASLD rats, improves lipid indicators, and inhibits inflammation and liver damage. The results of the FMT experiment indicated that transplantation of fecal microbiota from WLS-treated donors regulated the gut microbial composition and restored bile acid metabolic homeostasis in recipient rats.<br><br>DISCUSSION: This study demonstrates that WLS treats MASLD by modulating multiple pathological pathways. Its effects in improving lipid metabolism and reducing hepatic inflammation align with the pathophysiological mechanisms of MASLD, indicating direct hepatoprotective actions. WLS intervention significantly restored gut microbiota diversity, increased the proportion of beneficial bacteria, suppressed potentially harmful bacterial genera, and corrected dysbiosis. FMT experiments further confirmed that gut microbes play a crucial role in mediating the therapeutic benefits of WLS. When microbiota from WLS-treated donors were transplanted into recipient rats, significant improvements were observed in metabolic markers, hepatic histopathology, and bile acid homeostasis. Collectively, the data support that WLS improves MASLD through a multi-targeted strategy centered on the gut-liver axis.<br><br>CONCLUSION: WLS has an effective therapeutic effect on MASLD by improving lipid metabolism, reducing liver inflammation, reshaping the intestinal microbiota and normalizing bile acid homeostasis.}, }
@article {pmid41803498, year = {2026}, author = {Zhou, H and Sun, R and Nie, X and Xia, L and Dong, H and Liu, Y and Hou, S and Dong, W and Zhu, X and Yao, Y and Zhao, GP and Lu, S and Wang, Y and Yang, C}, title = {A clinic-responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice.}, journal = {Nature microbiology}, volume = {11}, number = {4}, pages = {993-1007}, pmid = {41803498}, issn = {2058-5276}, support = {82241228//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32230060//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31925001//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82073152//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82241227//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82030045//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Mice ; Humans ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; *Immunotherapy/methods ; Fecal Microbiota Transplantation ; *Carcinoma, Non-Small-Cell Lung/therapy/immunology ; *Gastrointestinal Microbiome ; *Lung Neoplasms/therapy/immunology ; Feces/microbiology ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Cell Line, Tumor ; Female ; *Immune Checkpoint Inhibitors/therapeutic use ; Mice, Inbred C57BL ; CD8-Positive T-Lymphocytes/immunology ; }, abstract = {Targeting the gut microbiota is a promising strategy to enhance the efficiency of cancer immunotherapy; however, success has been limited. Here we combined metagenomic analysis and in silico prediction to identify bacterial species associated with immunotherapy response in patients with non-small-cell lung cancer. We constructed a defined consortium (RCom) of 15 bacterial species, most of which were isolated from responder patient faeces, associated with improved clinical response to anti-programmed cell death protein 1 (PD-1) treatment. Metabolic models and in vitro experiments revealed that RCom is a stable and cooperative community, and in vivo experiments showed that RCom engrafts and produces immunomodulatory metabolites. Oral administration of RCom improved the anti-tumour activity of anti-PD-1 by increasing the intratumoural infiltration and cytotoxic function of CD8[+] T cells in syngeneic tumour models and across mice with heterogeneity in baseline gut microbiota composition. RCom supplementation also limited anti-PD-1 resistance in mice conferred by faecal microbiota transplantation from individual non-responsive patients. These findings suggest that RCom is a potential adjuvant to improve responsiveness to anti-PD-1 therapy in cancer.}, }
@article {pmid41803870, year = {2026}, author = {Wang, Y and Tian, W and Ye, Z and Liao, Y and Huang, C and Qi, D and Wang, Y and Chen, Y and Zhou, Y}, title = {Based on the gut-heart axis: Polygonum capitatum improves atherosclerosis by modulating gut microbiota and TMAO, supporting MCPIP1/p53-associated endothelial protection.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {}, pmid = {41803870}, issn = {1749-8546}, support = {2024YJSKYJJ376//Guizhou Provincial Postgraduate Education Innovation Program project funding/ ; 82160099//National Natural Science Foundation of China/ ; Qian-ke-he basic talents-GCC[2023]085//Guizhou High-level Innovative Talents Project/ ; Qiankehe support [2022] generally 263//Science and Technology Plan Project of Guizhou Province/ ; }, abstract = {Polygonum capitatum (PC), known as "Tou Hua Liao" (Chinese name), is an essential source of Hmong medicinal plants, which has been used for treating various human diseases. This study examined whether PC has lipid-lowering and anti-atherosclerotic effects and explored the underlying mechanisms. We focused on PC's influence on gut microbiota-derived metabolites. First, we analyzed animal-derived serum containing PC components and the botanical compounds of PC by UPLC-MS/MS to identify potential bioactive constituents. Second, we treated high-fat diet-fed hamsters with PC to determine whether the treatment improved plasma lipids and attenuated atherosclerosis progression. We then assessed PC's effects on the gut microbiota by 16S rDNA sequencing and performed fecal microbiota transplantation in hamster models. Finally, we used human umbilical vein endothelial cells (HUVECs) to probe molecular mechanisms by which PC might inhibit oxidative stress and apoptosis. In a diet-induced atherosclerotic hamster model, PC treatment reduced atherosclerosis by decreasing lipid accumulation, oxidative stress, and apoptosis, and it restored gut microbiota balance while markedly lowering the abundance of TMAO-producing bacteria. PC also exerted antioxidant and anti-apoptotic effects and inhibited endothelial apoptosis via an MCPIP1-dependent mechanism. Together, these results indicate that PC suppresses atherosclerosis through two likely pathways: reduction of gut microbiota-derived TMAO production and inhibition of oxidative stress-driven endothelial apoptosis. Network pharmacology analysis of PC-specific blood-absorbed components supports these findings.}, }
@article {pmid41803890, year = {2026}, author = {Liu, J and Ning, X and Yuan, J and Yu, Z and Qin, Y and Xing, Y and Zhao, J and Sun, S}, title = {Gut dysbiosis in kidney injury: therapeutic potential of fecal microbiota transplantation.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-026-04100-w}, pmid = {41803890}, issn = {2047-783X}, abstract = {Chronic kidney disease (CKD) poses a substantial global health burden. The gut-kidney axis has become a critical area of research, given the influence of gut microbiota on the kidney. CKD exhibits a distinct gut dysbiosis signature, comprising an altered microbial architecture divergent from healthy individuals and specific microbial changes that exhibit distinct associations with the degree of renal impairment. Preclinical studies lend support to the therapeutic capacity of fecal microbiota transplantation (FMT) in CKD, demonstrating its efficacy in reshaping gut dysbiosis, rehabilitating the gut barrier, rectifying immune imbalance, and reducing fibrosis. These mechanistic insights are complemented by observations of its synergistic effects when combined with standard therapeutics in other conditions, underscoring its potential to improve human kidney outcomes. This review synthesizes current knowledge on CKD-associated dysbiosis, impaired intestinal barrier, and the therapeutic potential of FMT in mitigating the progression of CKD.}, }
@article {pmid41804658, year = {2026}, author = {Lin, H and Feng, Z and Tu, Q and Li, H and Zhang, Y and Wei, X and Yi, Q and Zhang, H and Wang, Y and Li, X and Li, Y and Huang, J and Chen, Z and Shentu, H and Wang, A and Chen, Y and He, X and Cao, X}, title = {Advance Microbiota Transplantation: A Novel Addition-Subtraction Paradigm for Optimising Faecal Microbiota Transplantation.}, journal = {Microbial biotechnology}, volume = {19}, number = {3}, pages = {e70323}, pmid = {41804658}, issn = {1751-7915}, support = {2024YFA1307102//National Key Research and Development Program of China/ ; C2501011//Shenzhen Medical Research Fund/ ; ZDSYS20220606100800002//Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Science and Technology Program (Strategic Emerging Industries Special Project)/ ; LCYSSQ20220823091405012//Shenzhen Science and Technology Program (Young Scientists Project in Industrial Fields)/ ; SZSM202411029//Sanming Project of Medicine in Shenzhen/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Clostridium Infections/therapy ; }, abstract = {Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but yields inconsistent benefits in chronic indications. As a crude whole-microbiota transplant, FMT contains numerous undefined active components, complicating efforts to ensure treatment predictability and stability. Therefore, we propose Advance Microbiota Transplantation (AMT), a comprehensive, phase-based hypothesis that employs an addition-subtraction strategy throughout the pre-, peri- and post-transplant stages. AMT comprises donor and recipient pre-treatment, procedural optimisation and post-transplant adjuvant interventions to mitigate donor variability, ecological resistance, procedural heterogeneity and unstable engraftment. Through a systematic synthesis of current evidence-based FMT research, we explored how the addition-subtraction strategy can be operationalised to shape the AMT concept and define testable, phase-specific levers, thereby providing a foundation for future clinical translation. In parallel, we appraised the reporting quality using the Preferred Reporting Items for Microbiotherapy (PRIM) and identified six persistently under-reported items that limit the interpretability, comparability, and reproducibility of FMT research. This review aims to facilitate the integration of AMT into clinical practice.}, }
@article {pmid41804768, year = {2026}, author = {Fan, S and Yin, G and Ren, Y and Fan, X and Liang, Y and Ma, N and Luo, Y and Deng, Y and Zhang, C and Xiang, T and Zuo, J and Tang, J and Luo, D and Fan, X}, title = {Epigallocatechin-3-gallate ameliorates LPS-induced ARDS by modulating Akkermansia-associated SCFAs metabolism and inhibiting the JAK2/STAT3 candidate signaling pathway.}, journal = {Food &amp; function}, volume = {17}, number = {7}, pages = {3186-3211}, doi = {10.1039/d5fo05380c}, pmid = {41804768}, issn = {2042-650X}, mesh = {Animals ; *Catechin/analogs &amp; derivatives/pharmacology ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; *Respiratory Distress Syndrome/drug therapy/chemically induced/metabolism ; Lipopolysaccharides/adverse effects ; Male ; *STAT3 Transcription Factor/metabolism ; *Janus Kinase 2/metabolism ; *Akkermansia/metabolism/drug effects ; Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; }, abstract = {Acute respiratory distress syndrome (ARDS) is a leading cause of acute respiratory failure and mortality, characterized by significant inflammation and damage to the alveolar-capillary membrane, which disrupts gas exchange. Although the triggers of ARDS vary, uncontrolled inflammation plays a central role in its progression, with current treatment options being limited. Dysbiosis of the gut microbiota fuels systemic inflammation via the gut-lung axis and acts as a key driver of ARDS onset and progression. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent derived from green tea, with known anti-inflammatory effects, and microbiota-modulating properties, holds potential as a therapeutic intervention for ARDS. This study investigated the mechanism of EGCG's intervention in ARDS and its impact on gut microbiota using C57BL/6J mice. The mice were divided into groups receiving different doses of EGCG pretreatment, followed by intratracheal instillation of lipopolysaccharide (LPS)-induced ARDS. Various techniques, including pathological examination, ELISA, and immunohistochemistry (IHC), were employed to assess pulmonary inflammation and examine intestinal tight junction integrity. Gut microbiota composition was analyzed via 16S rRNA sequencing. To further elucidate the role of the gut microbiota, fecal microbiota transplantation (FMT) was performed following gut microbiota depletion. Feces from EGCG-treated donor mice were transplanted into recipient mice, with results compared to the EGCG-pretreated group. A more focused investigation involved the transplantation of Akkermansia muciniphila (AKK), and its effects on pulmonary inflammation and intestinal tight-junction integrity were observed. Additionally, GC-MS analysis confirmed that AKK-derived metabolites were short-chain fatty acids (SCFAs), and the effects of SCFAs were compared to those of EGCG pretreatment. Network pharmacology and transcriptomic analysis suggested that SCFAs likely exert their effects through the JAK2/STAT3 signaling pathway. The effects of SCFAs and EGCG pretreatment were further validated using specific inhibitors to assess pulmonary and intestinal conditions. In the LPS-induced ARDS model, EGCG significantly reduced the inflammatory response, decreased inflammatory cell infiltration, and inhibited pro-inflammatory cytokine production, thereby limiting lung and intestinal tissue damage. Mechanistically, EGCG enriched the gut microbiota, particularly increasing AKK abundance, which promoted SCFAs production. These SCFAs entered systemic circulation, reached the lungs, and modulated the JAK2/STAT3 candidate signaling pathway to suppress inflammation, ultimately alleviating ARDS pathology. In conclusion, EGCG mitigates ARDS-related inflammatory damage by increasing Akkermansia muciniphila abundance and enhancing SCFAs production, which inhibits the JAK2/STAT3 candidate pathway. This study introduces a novel gut microbiota-based approach for ARDS treatment and offers new insights into the role of gut-derived metabolites in ARDS pathogenesis.}, }
@article {pmid41807298, year = {2026}, author = {Huang, J and Qin, Q and Li, X and Jiang, K and Xu, J and Mao, Y and Kang, W and Gao, R and Cheng, Y and Zhao, W and Ke, J and Mou, X}, title = {Bacteroides-associated NAD[+] depletion correlates with exacerbated radiation-induced colorectal injury and impaired mucosal proliferative capacity.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2641260}, pmid = {41807298}, issn = {1949-0984}, mesh = {Animals ; *NAD/metabolism ; Humans ; *Bacteroides/metabolism/genetics ; *Intestinal Mucosa/pathology/radiation effects/metabolism/microbiology ; Mice ; Cell Proliferation ; *Radiation Injuries/microbiology/metabolism/pathology ; Female ; *Proctitis/microbiology/metabolism/pathology ; Gastrointestinal Microbiome ; Feces/microbiology/chemistry ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {Radiation proctitis (RP) is a frequent complication of pelvic radiotherapy that compromises treatment delivery and patient quality of life, yet the factors shaping injury severity remain incompletely defined. We prospectively profiled pretreatment fecal microbiomes and metabolomes from 55 patients and stratified them by outcome into mild versus severe RP. Baseline microbial composition showed Bacteroidales enriched in severe RP and Firmicutes enriched in mild cases. Multi-omics integration highlighted nicotinate/nicotinamide pathways; severe RP was characterized by concomitant reductions in both fecal and tissue NAD[+] levels, along with an enrichment of microbial nicotinate/nicotinamide metabolism genes, primarily contributed by Bacteroides ovatus, B. xylanisolvens, and B. fragilis. In mice, fecal microbiota transplantation from severe-RP donors exacerbated radiation-induced colorectal injury and decreased colorectal NAD[+], supporting a causal role for the microbiota. Gavage with Bacteroides similarly worsened pathology and lowered NAD[+], whereas nicotinamide mononucleotide (NMN) supplementation attenuated the injury. Mechanistically, Bacteroides gavage reduced mitochondrial membrane potential, decreased the Lgr5[+] stem-cell proportion and proliferative indices, associated with Wnt pathway modulation. NMN reversed these effects in parallel with NAD[+] restoration. Together, these results identify a microbiota‒metabolite association wherein Bacteroidales enrichment is associated with NAD[+] depletion, reduced mucosal proliferative capacity, and exacerbated radiation-induced colorectal injury. The work deepens insight into RP pathogenesis and suggests a potential basis for microbiome- and metabolite-targeted approaches to attenuate severe RP.}, }
@article {pmid41807473, year = {2026}, author = {Cheng, L and Li, Y and Zhang, Y and Qin, C and Yang, L and Yan, X and Nie, G}, title = {Cetobacterium somerae as a microbial correlate of improved muscle quality after intestinal microbiota transplantation in Yellow River carp (Cyprinus carpio).}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41807473}, issn = {2055-5008}, support = {U22A20532//National Natural Science Foundation of China/ ; HARS-22-16-S//Special Fund for Henan Agriculture Research System/ ; }, mesh = {Animals ; *Carps/microbiology/growth &amp; development ; *Gastrointestinal Microbiome ; *Muscles/physiology ; Animal Feed/analysis ; Bacteria/classification/genetics/isolation &amp; purification ; *Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Diet ; }, abstract = {Dietary faba bean enhances fish muscle quality but concurrently reduces growth performance. The gut microbiota critically modulates muscle growth and quality. However, the specific microbial taxa, metabolites, and regulatory mechanisms responsible remain to be elucidated. This study established a differential gut microbiota model in faba-bean-fed Yellow River carp (Cyprinus carpio), used whole-intestinal microbiota transplantation (WIMT) to directly test its effect on muscle quality, and supplemented the key bacterium and its metabolite to confirm their contribution. After a 6-week faba bean diet, growth performance declined, whereas muscle texture improved (P < 0.05). This improvement was concomitant with a higher abundance of the genera Aeromonas and Cetobacterium in the gut. Following 8 weeks of daily WIMT from faba-bean-fed donors, Yellow River carp maintained normal growth performance (P > 0.05) and simultaneously showed improved muscle texture, characterized by more small-diameter fibers, lower fat content, and higher collagen levels (P < 0.05), recapitulating the donor's key muscle phenotype. Meanwhile, WIMT reshaped the gut microbiome composition and its metabolic profile, and the marker species Cetobacterium somerae and its metabolite acetic acid showed associations with improvements in muscle quality. Further in vivo validation indicated that C. somerae reduced fat deposition and improved muscle texture, an effect possibly linked to activation of the AMPK-PGC-1α-FoxO pathway, and its metabolite acetic acid mirrored these changes. This study reveals the direct impact of gut microbiota on muscle quality through WIMT in Yellow River carp, provides novel evidence of the fish gut-muscle axis, and offers a scientific basis for improving muscle quality.}, }
@article {pmid41808568, year = {2026}, author = {Sharma, S and Parashar, M and Lal, K and Naik, M and Tanwar, SS}, title = {Doxorubicin-Induced Cardiotoxicity: Comprehensive Pathway Insights and Advanced Preclinical Therapeutics.}, journal = {Journal of applied toxicology : JAT}, volume = {46}, number = {6}, pages = {1801-1837}, doi = {10.1002/jat.70131}, pmid = {41808568}, issn = {1099-1263}, mesh = {Humans ; Animals ; *Cardiotoxicity/etiology ; *Doxorubicin/toxicity/adverse effects ; Oxidative Stress/drug effects ; *Antibiotics, Antineoplastic/toxicity ; Autophagy/drug effects ; Lipid Peroxidation/drug effects ; }, abstract = {Doxorubicin, a secondary metabolite of Streptomyces peucetius var. caesius and a member of the anthracycline family, exerts anticancer effects via DNA intercalation and topoisomerase II inhibition in tumor cells. However, its clinical application is limited by dose-dependent and cumulative cardiotoxicity. The mechanisms underlying doxorubicin-induced cardiotoxicity (DIC) include oxidative stress, lipid peroxidation, mitochondrial dysfunction, calcium dysregulation, disrupted iron homeostasis, nitric oxide release, and inflammatory mediator production. Emerging evidence highlights autophagy dysregulation, with doxorubicin upregulating cardiac autophagy by suppressing GATA4 and ribosomal protein S6 kinase beta-1(S6K1). Mitochondria-dependent ferroptosis also plays a significant role, driven by downregulation of glutathione peroxidase 4 (GPX4), lipid peroxidation via DOX-Fe[2+] complexes, and dysregulated iron metabolism. Additionally, DOX triggers pyroptosis in cardiomyocytes, involving proteins such as NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), caspase-3, and gasdermin D (GSDMD). Epigenetic alterations, including DNA hypomethylation (via downregulation of DNMT1 (DNA (cytosine-5)-methyltransferase 1), changes in microRNA levels (e.g., upregulation of miR-520h targeting HDAC19 (histone deacetylase 1), and histone deacetylase inhibition, exacerbate cardiac damage. Recent studies also emphasize the role of gut microbiota in doxorubicin-induced cardiotoxicity. Doxorubicin induces dysbiosis, leading to cardiomyocyte apoptosis and elevated myocardial enzyme levels. Interventions such as dietary modifications, fecal microbiota transplantation, probiotics, and natural compounds like glabridin and emodin show promise. Glabridin reduces inflammation by modulating colonic macrophage polarization, while emodin inhibits ferroptosis via gut microbiota remodeling mediated by Nrf2. This review explores oxidative stress, lipid peroxidation, ferroptosis, apoptosis, inflammation, autophagy, epigenetics, and gut microbiota in DIC, alongside promising pharmacological strategies to mitigate its effects.}, }
@article {pmid41809160, year = {2026}, author = {Mishra, A and Juneja, D}, title = {Decolonizing the gut from multidrug-resistant bacteria: Current strategies and future perspectives.}, journal = {World journal of methodology}, volume = {16}, number = {1}, pages = {108646}, pmid = {41809160}, issn = {2222-0682}, abstract = {The rise of multidrug-resistant organisms (MDROs) represents a serious global health crisis, with the gastrointestinal tract serving as a major reservoir for these pathogens. This review highlights the burden of gut colonization by MDROs, its role in spreading antimicrobial resistance, and explores current and emerging strategies for decolonization. Various non-antibiotic approaches such as probiotics, prebiotics, bacterial consortia, selective digestive decontamination, faecal microbiota transplantation, bacteriophage therapy, and Clustered Regularly Interspersed Short Palindromic Repeats-CRISPR-associated protein systems along with dietary interventions have been assessed for their potential to restore microbial balance and reduce MDRO carriage. While promising results have emerged from early studies and animal models, most interventions remain investigational. Rigorous clinical trials, standardized protocols, and safety assessments are essential before these approaches can be integrated into routine practice for MDRO management.}, }
@article {pmid41809178, year = {2026}, author = {Mundhra, SK and Kochhar, R}, title = {Methodological insights into fecal microbiota transplantation: Dissecting key approaches for success.}, journal = {World journal of methodology}, volume = {16}, number = {1}, pages = {108875}, pmid = {41809178}, issn = {2222-0682}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a revolutionary treatment strategy for restoring gut microbiota in recurrent Clostridioides difficile infection and has also been explored across a broader range of dysbiosis-related diseases such as inflammatory bowel disease where it has demonstrated promising results and potential therapeutic benefits. The success of FMT largely depends on the careful implementation of best practices, which include selecting appropriate donors, preparing the stool properly, and choosing the right delivery methods. This mini-review explores the evolution of FMT methodologies, including donor screening protocols, advances in stool preparation, and innovations in administration routes. We also discuss emerging approaches, such as synthetic microbiota and microbiome engineering, alongside the challenges and future directions for standardizing FMT. These methodological advancements aim to enhance safety, efficacy, and accessibility of FMT, establishing it as a key player in microbiome-based therapies.}, }
@article {pmid41809453, year = {2026}, author = {Zhao, X and Zhang, W and Zhang, Y and Liu, XA}, title = {Gastrointestinal dysfunction after brain injury: Mechanisms and the role of the brain-gut axis.}, journal = {World journal of gastroenterology}, volume = {32}, number = {10}, pages = {115731}, pmid = {41809453}, issn = {2219-2840}, mesh = {Humans ; *Brain-Gut Axis/physiology ; *Gastrointestinal Diseases/etiology/therapy/physiopathology ; Dysbiosis/etiology/physiopathology/therapy ; *Brain Injuries/complications/physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Animals ; Enteric Nervous System/physiopathology ; Intestinal Barrier Function ; Probiotics/therapeutic use ; Brain/physiopathology ; Quality of Life ; Gastric Emptying/physiology ; Gastrointestinal Tract/innervation/physiopathology ; }, abstract = {Brain injury (BI) encompasses traumatic BI and stroke, and is a leading cause of mortality and morbidity worldwide. In addition to primary brain damage, BI can cause a series of sequelae, of which gastrointestinal (GI) dysfunction is one of the most important affecting patient outcomes. GI dysfunction, including delayed gastric emptying, increased intestinal permeability, and gut dysbiosis, is common among patients with BI. GI dysfunction not only impairs nutrient absorption and increases the risk for infection, but also enhances secondary BI by aggravating the systemic inflammatory response. The brain-gut axis refers to the bidirectional communication network between the central nervous system and enteric nervous system. This article provides an overview of the mechanisms underlying GI dysfunction after BI and the close relationship with the brain-gut axis. Furthermore, the potential mechanisms underlying brain-gut modulation by probiotics, fecal microbiota transplantation, and vagus nerve stimulation are discussed, which may provide new insights into the treatment of GI dysfunction in patients with BI. An in-depth understanding of the interaction between the brain and GI system is essential to develop more effective therapeutic strategies to alleviate patient suffering and improve survival and quality of life.}, }
@article {pmid41809597, year = {2026}, author = {Chen, N and Ma, T and Chen, R and Zhang, Y and Tang, X and Sun, Y}, title = {Transcutaneous electrical nerve stimulation treated anterior talo-fibular ligament injured rat through the gut-joint axis and intestinal microbiota.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1770614}, pmid = {41809597}, issn = {1664-302X}, abstract = {OBJECTIVE: This study demonstrated that transcutaneous electrical nerve stimulation (TENS) and its induced fecal microbiota transplantation (FMT) could treat anterior talo-fibular ligament (ATFL) injury rat and modify the intestinal microbiota via the gut-joint axis.<br><br>METHODS: An ATFL injury model was duplicated and treated with low, medium, or high-intensity of TENS. After 1, 2, and 3&#x202f;weeks of TENS treatment, the improvements and the expression levels of NOD2/IL-6/NF-&#x3ba;B/BMP-2/TGF-&#x3b2; were measured. The intestinal microbiota was analyzed via 16S rDNA sequencing. After FMT which induced by TENS, the improvement of ATFL injury rat was analyzed.<br><br>RESULTS: After TENS treatment, compared with the model control group, the bio-mechanical, gait, bone mineral density (BMD), etc. parameters were elevated in the TENS groups (p&#x202f;<&#x202f;0.05); the expression of NOD2/IL-6 decreased and the BMP-2/TGF-&#x3b2; increased in the TENS groups (p&#x202f;<&#x202f;0.05). The intestinal microbiota was altered, including increases in the abundances of Erysipelotrichaceae, Lachnospira, Eubacterium, Phascolarctobacterium, and Alloprevotella. After FMT, similar improvements were found in ATFL injury rats.<br><br>CONCLUSION: TENS ameliorated ATFL injury rat by regulating the NOD2/IL-6/NF-&#x3ba;B/BMP-2/TGF-&#x3b2; and changed the intestinal microbiota through the gut-joint axis. Dominant intestinal microbiota was associated with FMT and could improve ATFL injury rat.}, }
@article {pmid41809655, year = {2026}, author = {Zhou, B and Parekh, Z and Phung, C and Rodriguez, SH and Skondra, D}, title = {The gut-retina axis in age-related macular degeneration: immune crosstalk and metabolite production.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10847}, pmid = {41809655}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/immunology/microbiology/pathology/metabolism ; *Gastrointestinal Microbiome/immunology/physiology ; Animals ; *Retina/pathology/immunology/metabolism ; Dysbiosis/immunology ; }, abstract = {Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.}, }
@article {pmid41812936, year = {2026}, author = {Lv, J and Zhang, Y and Yue, Y and Huang, S and Zhang, S and Fu, Y and Dai, C and Han, C and Hao, Z}, title = {Lianweng formula alleviates colonic inflammation through gut microbiota-mediated inactivation of the PTGS2/AKR1C3/ALOX5 pathway and subsequent suppression of arachidonic acid metabolism.}, journal = {Journal of ethnopharmacology}, volume = {364}, number = {}, pages = {121512}, doi = {10.1016/j.jep.2026.121512}, pmid = {41812936}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arachidonic Acid/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Male ; Rats, Sprague-Dawley ; *Colitis, Ulcerative/drug therapy/microbiology/pathology/metabolism ; Rats ; Cyclooxygenase 2/metabolism ; Colon/drug effects/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Metabolomics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Current clinical management of ulcerative colitis (UC) is often limited by inadequate efficacy and adverse effects. Our previous studies identified Lianweng formula (LW) as a promising therapeutic candidate and preliminarily elucidated its bioactive components. However, the integrated mechanism involving the interplay between gut microbiota and host metabolism remains obscure.<br><br>PURPOSE: This study aimed to elucidate the regulatory mechanism of LW on arachidonic acid (AA) metabolism in UC rats, with a specific focus on the mediating role of gut microbiota.<br><br>METHODS: The therapeutic efficacy of LW was first evaluated in a UC rat model by assessing inflammatory cytokines, histological injury, and mucosal barrier integrity. Integrated 16S rRNA sequencing and untargeted metabolomics were performed to map the alterations in gut microbiota and colonic metabolic profiles. Crucially, antibiotic cocktail (ABX) depletion and fecal microbiota transplantation (FMT) were employed to verify the causal role of gut microbiota in mediating LW's efficacy. Finally, targeted metabolomics was conducted to decipher the specific crosstalk between microbial composition and the AA metabolic pathway.<br><br>RESULTS: Oral administration of LW significantly alleviated colonic pathological damage and restored intestinal barrier integrity, while effectively suppressing the inflammatory response in UC rats. Furthermore, LW effectively restored gut microbiota homeostasis by increasing the abundance of beneficial genera, such as g_Odoribacter and g_Rikenella, and decreasing the abundance of harmful genera, including g_Desulfovibrio and g_Paludicola, among others. Untargeted metabolomics highlighted the AA metabolic pathway as a critical target of LW, exhibiting strong correlations with the altered gut microbiota. Notably, gut microbiota depletion via ABX significantly compromised the therapeutic efficacy of LW and nullified its regulation of AA metabolism, identifying gut microbes as essential mediators. This causal link was further corroborated by FMT, which demonstrated that LW-modulated microbiota successfully recapitulated the suppression of AA metabolism and the therapeutic benefits. These findings were consistently validated by quantitative targeted metabolomics profiling.<br><br>CONCLUSION: Our findings demonstrate that LW significantly mitigates colonic inflammation in UC rats, primarily by inhibiting the arachidonic acid metabolic pathway. Notably, this metabolic regulation and the consequent anti-inflammatory effects are critically dependent on LW-induced gut microbiota remodeling. This study offers novel therapeutic insights into UC treatment by highlighting the pivotal role of microbiota-metabolite crosstalk in the mechanism of action of LW.}, }
@article {pmid41814325, year = {2026}, author = {Zhang, J and Zhou, Y and Mei, X and Yan, S and Mao, J and Li, Y and Bian, Z and Li, L and Ji, D and Lu, T and Chen, J and Su, L}, title = {Molecular mechanisms and therapeutic potential of tryptophan metabolism in gut-brain signaling transduction: a narrative review.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {}, pmid = {41814325}, issn = {1742-2094}, support = {2023YFC3504200//National Key Research and Development Program of China/ ; ZYXYL2024-006//The "leading plan" project of the first-class discipline of Nanjing University of Chinese Medicine/ ; 82304723//National Natural Science Foundation of China/ ; }, abstract = {As an essential amino acid, tryptophan (Trp) serves as a pivotal mediator in gut-brain axis (GBA) communication through three primary metabolic pathways: kynurenine (Kyn), indole, and serotonin (5-HT), which together regulate neuroimmune and neuroendocrine homeostasis via the vagus and spinal afferent nerves, circulatory system, and hypothalamic-pituitary-adrenal (HPA) axis. This review systematically examines Trp metabolism’s critical roles in GBA, emphasizing molecular pathways, rate-limiting enzymes, and receptor-mediated signaling. We discuss the bidirectional interplay between gut microbiota and host Trp metabolism, encompassing microbial modulation of host enzyme activities such as indoleamine 2,3-dioxygenase and direct production of bioactive indole derivatives like indole-3-propionic acid. Characteristic disruptions in Trp metabolism patterns are identified across GBA-associated disorders including irritable bowel syndrome, inflammatory bowel disease, depression, Alzheimer’s disease, schizophrenia and Parkinson’s disease, marked by aberrant neurotoxic to neuroprotective metabolite ratios and enzymatic dysregulation. The aryl hydrocarbon receptor (AhR) emerges as a molecular hub connecting Trp metabolites to GBA functions, with distinct metabolites eliciting opposing effects through AhR activation. Therapeutic strategies targeting Trp metabolism are critically evaluated, including fecal microbiota transplantation, probiotic supplementation, metabolite administration, and enzyme inhibitors. Future research directions address mechanistic gaps and translational challenges in restoring GBA homeostasis via Trp pathway modulation.}, }
@article {pmid41814703, year = {2025}, author = {Huang, YJ and Xie, YL and Mo, PY and Tan, ZX and Wu, XM and Wang, SL}, title = {[Anti-depressant mechanism of Bupleuri Radix in regulating hippocampal FGFR1-5-HT_(1A)R heterodimer formation via intestinal flora-short-chain fatty acids].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {50}, number = {24}, pages = {6947-6956}, doi = {10.19540/j.cnki.cjcmm.20250825.801}, pmid = {41814703}, issn = {1001-5302}, mesh = {Animals ; Mice ; *Hippocampus/metabolism/drug effects ; *Fatty Acids, Volatile/metabolism ; *Bupleurum/chemistry ; Male ; *Antidepressive Agents/administration &amp; dosage ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/administration &amp; dosage ; *Receptor, Fibroblast Growth Factor, Type 1/metabolism/genetics/chemistry ; *Depression/drug therapy/metabolism/microbiology/genetics ; *Receptor, Serotonin, 5-HT1A/metabolism/genetics/chemistry ; }, abstract = {Based on the "gut-brain" axis, this study investigated the molecular mechanism of the antidepressant effect of Bupleuri Radix. The effect of Bupleuri Radix on human intestinal flora cultured in vitro was analyzed by 16S rRNA sequencing. Differential bacteria were identified by real-time quantitative PCR(qPCR). Short-chain fatty acid(SCFA) content was determined by the GC-FID method. A depression-like mouse model was established using the "triple-one" compound stress method. Mice were administered the aqueous extract of Bupleuri Radix by gavage, transplanted with Bacteroides acidifaciens or spore-forming bacteria, or gavaged with SCFAs. Behavioral changes were assessed. SCFA content in feces was measured by GC-FID. Hippocampal(fibroblast growth factor 21, FGF21) protein expression was detected by Western blot. The formation of fibroblast growth factor receptor 1-5-hydroxytryptamine receptor 1A(FGFR1-5-HT_(1A)R) heterodimers was examined using the Duolink PLA method. The results showed that Bupleuri Radix significantly increased the abundance of the three spore-forming bacterial genera Ruminococcus, Dorea, and Blautia(P<0.05), as well as B. acidifaciens(P<0.001). Administration of Bupleuri Radix(P<0.001 or P<0.05) and transplantation of B. acidifaciens(P<0.01) both increased the levels of SCFAs such as acetic acid and butyric acid in bacterial metabolites. Treatment with Bupleuri Radix, transplantation of B. acidifaciens, or high doses of SCFAs significantly improved depression-like behaviors in mice, increased hippocampal FGF21 expression(P<0.05, P<0.01, or P<0.001), and promoted FGFR1-5-HT_(1A)R heterodimer formation(P<0.05 or P<0.01), whereas transplantation of spore-forming bacteria showed no obvious antidepressant effect. In conclusion, the antidepressant effect of Bupleuri Radix is mediated by intestinal bacteria such as B. acidifaciens, which regulate the synthesis and metabolism of SCFAs, thereby modulating hippocampal FGF21 expression and activating FGFR1-5-HT_(1A)R heterodimers.}, }
@article {pmid41815180, year = {2026}, author = {Kumar, SE and Selvarajan, S and Varghese, T and Bharadwaj, PK and Lakshmi, KS and Hanmantgad, S and Dutta, AK and Joseph, AJ and Mathews, V and George, B}, title = {Fecal Calprotectin as a biomarker for early diagnosis and prediction of steroid response in Acute Gastrointestinal Graft versus Host Disease.}, journal = {Blood cell therapy}, volume = {9}, number = {1}, pages = {31-40}, pmid = {41815180}, issn = {2432-7026}, abstract = {BACKGROUND: Acute gastrointestinal graft-versus-host disease (GI-GVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) that requires early diagnosis. Fecal calprotectin (FC) is a biomarker of intestinal inflammation. We studied the role of FC in differentiating GI-GVHD from other diarrhea.<br><br>METHODS: We prospectively studied allogeneic HSCT recipients between 2017 and 2020. FC levels were measured pre-transplant, on post-transplant day 14, on day 1 of diarrhea, and post-steroid treatment (day 3-7 of steroid treatment).<br><br>RESULTS: We studied 116 patients with median age 14.5 (5-29) years; 84 were male (72.4%). Fifty-seven patients (49.1%) developed diarrhea post-HSCT, 34 (59.7%) patients had GI-GVHD, and 23 patients (40.3%) developed other diarrheal illnesses. FC level on day1 of diarrhea among GI-GVHD patients (n=33) was higher (63 &#x3bc;g/g [Q1-Q3:25.6-358.5]) compared to other diarrhea (27.5 &#x3bc;g/g [21.1-60.4], p=0.045). FC cut-off > 53.7 &#x3bc;g/g had sensitivity (78.6%) and specificity (57.9%) with area under the receiver operating characteristic curve of 0.67 to predict GI-GVHD on day 1 of diarrhea. FC levels in steroid non-responders (n=7) were higher (311.5 &#x3bc;g/g [40.5-1,291.5]) than responders (n=11) (31.2 &#x3bc;g/g [20.8-137.2] &#x3bc;g/g); p=0.03. Haplomatch, severe GI-GVHD, and coexisting skin GVHD were significant predictors of poor treatment response.<br><br>CONCLUSION: A higher FC value on day 1 of diarrhea aids in the diagnosis of acute GI-GVHD and predicts poor response to treatment.}, }
@article {pmid41816110, year = {2026}, author = {Li, Z and Yan, J and Zeng, Z and Zhao, L}, title = {The role of gut microbiota and its metabolites in preventing oncogenesis.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1790063}, pmid = {41816110}, issn = {2296-634X}, abstract = {The gut microbiota is increasingly recognized as a key determinant of cancer susceptibility, functioning as a dynamic interface between environmental exposures and host physiology. Dysbiosis disrupts immune homeostasis, epithelial integrity, and metabolic equilibrium, thereby fostering a microenvironment conducive to oncogenesis. Conversely, a balanced microbial ecosystem and its metabolites exert potent anti-tumor effects through immune modulation, maintenance of mucosal barrier function, and detoxification of carcinogens. This Review synthesizes emerging mechanistic insights into how commensal microbes and their metabolic products coordinate host defense pathways to suppress malignant transformation. We further discuss translational strategies-ranging from probiotics, prebiotics, and synbiotics to fecal microbiota transplantation and dietary interventions-that leverage microbiome modulation for cancer prevention. Despite compelling preclinical evidence, clinical translation remains constrained by inter-individual variability and incomplete mechanistic understanding. Integration of multi-omics analyses, gnotobiotic models, and precision microbial engineering offers a path toward microbiota-based interventions as a cornerstone of personalized cancer prevention and immunomodulation.}, }
@article {pmid41816239, year = {2026}, author = {Li, M and Zhai, H and Qiao, L and Wang, Z and Yang, L and Zheng, X and Shi, H and Geng, W and Wang, J}, title = {Targeting the gut microbiota: the application and prospects of probiotics, fecal microbiota transplantation, and natural products in MASLD.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1735669}, pmid = {41816239}, issn = {2296-861X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver condition globally. Studies have revealed distinct differences in the gut microbiota (GM) composition between healthy individuals and MASLD patients, suggesting a crucial role of GM in disease initiation and progression. This review summarizes characteristic gut microbial alterations in MASLD, examines the relationship between GM and their metabolites in MASLD pathogenesis, and discusses potential mechanistic pathways. Furthermore, we summarize the possible therapeutic applications of probiotics, fecal microbiota transplantation (FMT), and natural products in managing MASLD through GM modulation. Although current evidence indicates these interventions may slow or prevent MASLD progression, most research remains limited to animal experiments and small-scale clinical studies. The scarcity of high-quality clinical evidence has created a significant gap between theoretical research and clinical application. Therefore, this article aims to summarize existing findings, explore the prospects of GM-targeted strategies for MASLD treatment, and propose future research directions in this field.}, }
@article {pmid41816323, year = {2026}, author = {Huang, Z and Liu, J and Zheng, X and Geng, X and Tan, J and Ai, Y and Li, H and Zhou, D}, title = {Integrating bioinformatic prediction and the "gut microbiota-inflammation-skin axis" to decipher the mechanisms of quercetin (from Evodia rutaecarpa) in diabetic wound healing.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1755280}, pmid = {41816323}, issn = {1664-3224}, mesh = {Animals ; *Wound Healing/drug effects ; *Quercetin/pharmacology ; Rats ; Humans ; Mice ; Male ; *Gastrointestinal Microbiome/drug effects ; *Diabetes Mellitus, Experimental/complications ; RAW 264.7 Cells ; Computational Biology/methods ; Inflammation/drug therapy ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Skin/drug effects/metabolism/pathology ; Human Umbilical Vein Endothelial Cells ; Vascular Endothelial Growth Factor A/metabolism ; *Diabetic Foot/drug therapy ; }, abstract = {BACKGROUND: Diabetic foot ulcer (DFU) is a serious complication of diabetes with impaired healing. This study focused on the herbal medicine Evodia rutaecarpa as a case to investigate the mechanisms of diabetic wound healing via the "gut microbiota-inflammation-skin axis". We specifically aimed to elucidate the role of its core bioactive flavonoid, quercetin (Que), whose therapeutic potential in this context remains underexplored.<br><br>METHODS: In vitro, the direct interaction between Que and HIF1&#x3b1; was assessed by cellular thermal shift assay, and its functional effect on the HIF1&#x3b1;/VEGF pathway was evaluated in a lipopolysaccharide-induced RAW264.7/HUVEC co-culture system. In vivo, a streptozotocin-induced diabetic rat model with full-thickness dorsal wounds was treated with Que. Wound healing rates, metabolic parameters, systemic inflammation, and gut microbiota composition were analyzed. The causal role of the gut microbiota was further tested using fecal microbiota transplantation from Que-treated donors to diabetic recipient rats, and the biological activity of resulting drug-containing serum was assessed in HUVEC and RAW264.7 cell cultures.<br><br>RESULTS: Que was identified as a principal active component of E. rutaecarpa with predicted binding affinity for key targets involved in inflammatory and hypoxic responses. In vitro, Que directly bound to and stabilized HIF1&#x3b1; protein and upregulated the expression of both HIF1&#x3b1; and VEGF in HUVECs under inflammatory co-culture conditions. In diabetic rats, Que treatment significantly accelerated wound closure, improved systemic glucose and lipid metabolism, reduced serum levels of TNF-&#x3b1; and IL-1&#x3b2;, and modulated the gut microbiota structure. FMT from Que-treated rats replicated the pro-healing effects, enhancing angiogenesis and collagen deposition in wounds, and reducing tissue inflammation. Consistently, serum derived from the FMT-Que group promoted HUVEC migration and tube formation, and attenuated the pro-inflammatory cytokine expression in RAW264.7 cells.<br><br>CONCLUSION: This study demonstrated that Que promoted diabetic wound healing by modulating the "gut microbiota-inflammation-skin axis", thereby reducing systemic inflammation and enhancing local angiogenesis.}, }
@article {pmid41816355, year = {2026}, author = {Wang, X and Xu, Z and Yao, Y and Jia, H and Du, M and Wang, S and Yan, F and Li, L}, title = {Periodontitis promotes intestinal inflammation through gut microbiota-mediated suppression of GPR109A.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1761932}, pmid = {41816355}, issn = {2235-2988}, mesh = {Animals ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Periodontitis/microbiology/complications/pathology ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Mice ; *Inflammation/pathology/microbiology ; Male ; Colon/pathology/microbiology/metabolism ; Disease Models, Animal ; *Receptors, Nicotinic/metabolism/genetics ; Intestinal Mucosa/pathology/metabolism/microbiology ; Fatty Acids, Volatile/analysis ; Zonula Occludens-1 Protein/metabolism ; Occludin/metabolism ; Intestinal Barrier Function ; }, abstract = {OBJECTIVE: To determine whether periodontitis promotes intestinal inflammation through gut microbiota-mediated suppression of the GPR109A receptor.<br><br>METHODS: Periodontitis was induced by ligatures in C57BL/6J mice under normal chow or high-fructose diet. Periodontal destruction was evaluated by micro-computed tomography and hematoxylin and eosin staining. Colonic GPR109A expression, intestinal epithelial integrity, as well as intestinal and systemic inflammation were assessed by histology and immunostaining, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Short-chain fatty acids (SCFAs) in colonic contents were quantified by GC-MS/MS. Further, the probiotic strain CBM588 was supplemented to two groups of mice (CP/LP group) to alleviate periodontitis-induced inflammation, and GPR109A expression was detected. To investigate the role of periodontitis-associated gut microbiota, fecal microbiota from control (GF-CON) and ligatured (GF-LIG) mice were transplanted into germ-free recipients, and colonic GPR109A levels and inflammatory responses were analyzed. Finally, GPR109A function was modulated by administration of GSK256073 and mepenzolate bromide in ligatured mice, and corresponding changes in tight junctional integrity as well as intestinal and systemic inflammation were evaluated.<br><br>RESULTS: Periodontitis significantly downregulated the expression of colonic GPR109A and disrupted the localization of ZO-1 and Occludin. Probiotic supplementation restored GPR109A expression and rescued ZO-1 distribution. Fecal microbiota transplantation from periodontitis donors led to GPR109A suppression, tight junction impairment, and inflammatory upregulation in germ-free mice, confirming a microbiota-dependent mechanism. Activation of GPR109A reversed barrier disruption and reduced pro-inflammatory cytokine levels.<br><br>CONCLUSION: Periodontitis promotes colonic inflammation by gut microbiota-induced suppression of GPR109A receptor, leading to the destruction of the epithelial barrier. Activation of GPR109A restores barrier function and attenuates inflammation.}, }
@article {pmid41816663, year = {2026}, author = {Li, Y}, title = {Gut microbiota in the pathogenesis and treatment of inflammatory bowel disease: a critical review of mechanisms and therapeutic advances.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1738292}, pmid = {41816663}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a complex, recrudescent chronic gastrointestinal disease. The prevalence of IBD has increased globally year by year, and the exact pathogenesis remains incompletely understood. Evidence indicates that there is a strong correlation between dysbiosis of gut microbiota and the occurrence and progression of IBD. This review systematically describes recent advances in understanding the role of gut microbiota in IBD, with a particular focus on how dysbiosis contributes to pathogenesis. In addition, this review synthesizes the latest research progress and challenges of therapies of IBD targeting the gut microbiota, highlighting both their therapeutic potential and current limitations. Importantly, literature is based on targeted selection of high-quality sources, including clinical trials, meta-analyses, systematic reviews, and regulatory documents, to provide a balanced and up-to-date perspective. Emphasis is laid on the potential of microbiota-targeted therapies in IBD management.}, }
@article {pmid41817170, year = {2026}, author = {Loeven, AM and Pacheco, FA and Brown, AN and Fadool, DA}, title = {Lack of Structural Change in Olfactory Circuitry Following Fecal Microbiome Transplant From Donors Subjected to Diet-induced Obesity.}, journal = {Journal of neurochemistry}, volume = {170}, number = {3}, pages = {e70396}, pmid = {41817170}, issn = {1471-4159}, support = {T32 DC000044/NH/NIH HHS/United States ; //Robinson Family and the Tallahassee Memorial Hospital/ ; F31 DC019867/DC/NIDCD NIH HHS/United States ; R01 DK133464/NH/NIH HHS/United States ; R01 DK133464/DK/NIDDK NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; F31 DC019867/NH/NIH HHS/United States ; }, mesh = {Animals ; *Obesity/metabolism/pathology/therapy/etiology ; Male ; *Diet, High-Fat/adverse effects ; Mice ; Female ; *Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/physiology ; *Olfactory Receptor Neurons/pathology/metabolism ; *Olfactory Bulb/pathology/metabolism ; }, abstract = {Obesity and fatty diets are known to damage the structure and function of chemosensory systems. Consumption of a moderately high-fat diet (MHF) induces loss of olfactory sensory neurons (OSNs) and reduces the density of associated axonal projections to the olfactory bulb that are central in the coding of odor information. Previous work has demonstrated reduced alpha diversity, as well as signature changes in microbiome composition when mice are challenged with a MHF diet that precipitates diet-induced obesity. Herein, we tested the hypothesis that a dysbiotic gut microbiome is sufficient to induce olfactory damage. Male and female donor mice were randomly assigned to a control-fat (CF) or MHF diet for 5 months duration, followed by baseline measurements of body weight, body composition (EchoMRI), glucose tolerance, and metabolic phenotyping via indirect calorimetry. We next performed fecal microbiome transplantation (FMT) from these donors to CF-maintained recipient mice. After 8 weeks post FMT, we observed no difference in body weight, glucose clearance, body composition, or fat pad weights as a consequence of transfer from MHF-maintained donors. Following FMT, recipient male mice exhibited increased Erysipelotrichaceae abundance and decreased Lactobacillaceae abundance, similar to MHF-fed donors. Recipient brains were processed for tissue clearing using immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) and then imaged using high resolution light sheet microscopy. The volume of olfactory glomeruli expressing Olfr160 odor receptors could be visualized using genetic reporters; the FMT from MHF-maintained donors failed to evoke structural changes to these defined olfactory synapses. We conclude that diet-induced obesity, associated adiposity, and metabolic dysfunctions drive functional loss and structural changes to the olfactory system, but that gut microbiome dysbiosis alone is not sufficient to yield olfactory circuitry deficits.}, }
@article {pmid41818727, year = {2026}, author = {Li, G and Shen, Q and Ma, C and Wang, C and Song, B and Cao, Y}, title = {Gut microbiota and neurotransmitter metabolic profiling in a rat model simulating hypoactive sexual desire disorder.}, journal = {The journal of sexual medicine}, volume = {23}, number = {4}, pages = {}, doi = {10.1093/jsxmed/qdag067}, pmid = {41818727}, issn = {1743-6109}, support = {82201777//National Natural Science Foundation of China/ ; JK20245//Basic and the Project of MOE Key Laboratory of Population Health Across Life Cycle/ ; }, mesh = {Animals ; Female ; Rats ; *Neurotransmitter Agents/metabolism ; Rats, Sprague-Dawley ; *Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; Sexual Behavior, Animal/physiology ; Fecal Microbiota Transplantation ; *Sexual Dysfunctions, Psychological/microbiology/metabolism/therapy ; Prefrontal Cortex/metabolism ; }, abstract = {BACKGROUND: Hypoactive Sexual Desire Disorder (HSDD) is a highly prevalent, clinically impactful female sexual health condition whose pathogenesis is closely associated with disrupted excitation-inhibition homeostasis in the central nervous system, while the mechanistic role of gut microbiota in this pathological process via the gut-brain axis remains largely unelucidated.<br><br>AIM: To explore gut microbiota-neurotransmitter interactions in an HSDD-simulating rat model and verify their causal role via fecal microbiota transplantation (FMT).<br><br>METHODS: Female Sprague-Dawley rats were stratified into high copulatory behavior, normal copulatory behavior (NCB), and reduced copulatory behavior (RCB) groups via quantified mating behavioral assays, with the RCB phenotype used to establish a preclinical rat model simulating the core features of human HSDD. FMT was performed in four experimental groups: RCB-FMT-RCB, NCB-FMT-NCB, RCB-FMT-NCB, and NCB-FMT-RCB. Gut microbial composition was characterized by 16S rRNA gene sequencing, and prefrontal cortex (PFC) neurotransmitter levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sexual behavioral parameters were assessed following FMT administration.<br><br>OUTCOMES: Determined gut microbial and PFC neurotransmitter differences between RCB and normal rats, and validated FMT's regulatory effects on recipients' copulatory behavior, gut microbiota, and neurotransmitter balance.<br><br>RESULTS: Compared with NCB rats, RCB rats exhibited a distinct microbial biomarker profile, characterized by enrichment of Oscillibacter and Bacteroides and depletion of Jeotgalicoccus. In the PFC, RCB rats had elevated levels of inhibitory neurotransmitters (5-HT, GABA) and 5-HIAA, alongside reduced levels of excitatory neurotransmitters (DOPA, Glu). FMT induced phenotypic transfer: NCB-FMT-RCB rats displayed diminished sexual desire and developed RCB-like microbial and neurotransmitter profiles, while RCB-FMT-NCB rats exhibited improved copulatory behavioral endpoints and partial normalization of PFC neurotransmitter levels. Spearman's correlation analysis demonstrated that Oscillibacter and Bacteroides abundances were correlated with neurotransmitter imbalance in the PFC.<br><br>CLINICAL IMPLICATIONS: This study provides novel preclinical insights into the role of the gut-brain axis in HSDD, supporting further exploration of gut microbiota as a potential research target for HSDD.<br><br>STRENGTHS AND LIMITATIONS: Strengths include a validated RCB rat model, bidirectional FMT for causality; limitations involve the inability to assess subjective distress in rodents, rat-human physiological differences, PFC-only neurotransmitter analysis, unclear molecular pathways, and lack of long-term data.<br><br>CONCLUSIONS: Gut microbial dysbiosis contributes to RCB (simulating human HSDD) in female rats via modulating prefrontal cortex neurotransmitter excitation-inhibition homeostasis, with Oscillibacter and Bacteroides as key functional genera. These findings provide preliminary preclinical evidence for the gut-brain axis in sexual behavior regulation and human HSDD pathogenesis.}, }
@article {pmid41819520, year = {2026}, author = {Peng, Z and Liao, C and Liu, B and Yu, W and Huang, J and Chen, S and Li, L and Liang, H}, title = {Gut microbiota-derived eicosapentaenoic acid alleviates kidney fibrosis in diabetic nephropathy following acute kidney injury.}, journal = {European journal of pharmacology}, volume = {1019}, number = {}, pages = {178741}, doi = {10.1016/j.ejphar.2026.178741}, pmid = {41819520}, issn = {1879-0712}, mesh = {Animals ; *Eicosapentaenoic Acid/metabolism/pharmacology/therapeutic use ; *Diabetic Nephropathies/pathology/microbiology/complications/drug therapy/metabolism ; Fibrosis ; *Kidney/pathology/drug effects/metabolism ; Male ; *Acute Kidney Injury/pathology/microbiology/chemically induced/complications/metabolism/drug therapy ; Mice ; *Gastrointestinal Microbiome/drug effects ; Macrophages/drug effects/pathology/metabolism ; Fecal Microbiota Transplantation ; Myofibroblasts/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; Folic Acid ; }, abstract = {Acute kidney injury (AKI) superimposed on diabetic nephropathy (DN) accelerates fibrosis progression to end-stage renal disease, but the underlying mechanisms remain poorly understood. Since gut microbiota and their metabolites are pivotal contributors to diabetic pathogenesis and fibrotic development, we examined the role of gut microbiota-derived metabolites in the regulation of fibrosis following AKI-on-DN. Using a murine model of folic acid-induced AKI in diabetic nephropathy, we revealed that folic acid injury exacerbated kidney dysfunction and fibrosis, which was associated with macrophage to myofibroblast transition (MMT). Integrative multi-omics profiling identified dysbiosis of intestinal flora as a critical pathological amplifier. Fecal microbiota transplantation blunted MMT and attenuated kidney fibrosis in diabetic kidney mice following folic acid stress. Furthermore, Metabolomic profiling identified a robust decline of gut microbiota-derived eicosapentaenoic acid (EPA) in AKI-on-DN mice, paralleled by reduced EPA levels in both serum and feces. EPA supplementation substantially impeded MMT and alleviated kidney fibrosis in AKI-on-DN mice. Notably, macrophage depletion considerably diminished MMT and collagen deposition in injured kidneys of AKI-on-DN mice. Collectively, our findings demonstrate that EPA plays a crucial role in regulating macrophage to myofibroblast transformation, thereby driving kidney fibrosis following AKI superimposed on diabetic nephropathy.}, }
@article {pmid41820001, year = {2026}, author = {Chen, D and Zhang, B and Zhang, X and Huang, J and Wang, O}, title = {[Effects of different feeds on intestinal microbiota and fat deposition in rats colonized with normal triglycerides individuals].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {55}, number = {1}, pages = {86-91}, doi = {10.19813/j.cnki.weishengyanjiu.2026.01.015}, pmid = {41820001}, issn = {1000-8020}, mesh = {Animals ; Male ; Rats ; Rats, Sprague-Dawley ; *Triglycerides/blood/metabolism ; *Gastrointestinal Microbiome ; *Diet, High-Fat ; *Adipose Tissue/metabolism ; *Intestines/microbiology ; Lipid Metabolism ; *Animal Feed ; Feces/microbiology ; }, abstract = {OBJECTIVE: To study the changes in intestinal microbiota, intestinal microbiota and fat deposition in rats with normal triglyceride(TG) colonization under different feed conditions.<br><br>METHODS: 10-week-old male sterile SD rats were randomly divided into 2 groups according to body weight, with 6 rats in each group, namely the high-fat diet group and the normal diet group. Rats were given fecal bacterial solution by gavage at a dose of 1 mL/100 g of body weight, every other day, for a total of 3 times, followed by 2 weeks of adaptive growth of the microbiota. After the transplantation was completed, the rats were respectively fed with high-fat diet and normal diet for 9 weeks. Their body weight was weighed every week, and feces were collected every 3 weeks. At the end of the experiment, the rats were sacrificed, and the liver, perirenal fat, subcutaneous fat and brown fat were weighed. Oil red O staining and lipid biochemical index detection were performed on the liver, and high-throughput sequencing was used to analyze the changes in intestinal microbiota of the rats.<br><br>RESULTS: After the experiment, compared with the normal feed group, the final body weight, perirenal fat and subcutaneous fat of rats in the high-fat feed group all increased significantly(P<0.05). The serum total cholesterol(TC)and the low density lipopro-tein cholesterol(LDL-C)level was extremely significantly increased(P<0.01). Obvious lipid deposition can be seen in the liver.16 S RNA sequencing analysis of the intestinal microbiota revealed that there were differences and changes in the diversity of Alpha and Beta of the intestinal microbiota, as well as the types and quantities of the microbiota in the high-fat diet group compared with the normal diet group. From the perspective of the phylum level analysis, the abundance of Bacteroidetes in the high-fat feed group decreased from 63.59% at week 0 to 30.94% at week 9, the abundance of Firmicutes decreased from 30.57% to 25.08%, and the F/B value increased from 0.48 at week 0 to 0.81 at week 9. At the genus level, after a 9-week feeding cycle, the abundance of Prevotella&#xff3f;9 and Phascolarctobacterium in the intestinal tract of rats in the high-fat diet group decreased. The abundance of pathogenic bacteria such as Parabacteroides has increased.<br><br>CONCLUSION: In normal TG population rats with colonized intestinal flora, significant changes occurred in lipid metabolism and the composition of intestinal flora under different feeds.}, }
@article {pmid41820416, year = {2026}, author = {Ichimura, R and Tanaka, K and Song, I and Shimizu, E and Ogawa, Y and Tsubota, K and Fukuda, S}, title = {Association between bone marrow donor origin and gut microbiota composition following fecal microbiota transplantation in mice.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41820416}, issn = {2045-2322}, support = {22H03541//JSPS KAKENHI/ ; JP23gm1010009//AMED-CREST/ ; JPMJER1902//JST ERATO/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; *Bone Marrow Transplantation ; Feces/microbiology ; Tissue Donors ; Mice, Inbred C57BL ; Male ; }, abstract = {Fecal microbiota transplantation (FMT) has been reported as a method to directly alter the recipient's gut microbiota in order to normalize its composition and confer therapeutic benefits. It is essential to maintain a consistent gut microbiota in FMT donors. However, various environmental factors influence the maintenance of gut microbiota composition. We investigated whether bone marrow transplantation (BMT) donor origin, presumably affecting the resultant recipient immune environment, may influence FMT outcomes by conducting a study combining BMT and FMT treatments in mice. Our results show that the origin of the bone marrow donor affected the extent to which the FMT recipient microbiota resembled that of the FMT donor. However, these changes did not reduce the overall microbiota dissimilarity compared to FMT alone. Among the affected microbes, the relative abundance of a mucus-associated bacterium in the family Muribaculaceae was higher, suggesting sensitivity to the combined influence of BMT and FMT donor origins. These findings are consistent with the possibility that bacterial proximity to the intestinal epithelium could modulate persistence patterns in response to distinct post-BMT environments. Altogether, the observed trends suggest that differences associated with bone marrow donor origin may shape post-FMT microbial retention.}, }
@article {pmid41821793, year = {2023}, author = {Almeida, C and Gonçalves-Nobre, JG and Alpuim Costa, D and Barata, P}, title = {The potential links between human gut microbiota and cardiovascular health and disease - is there a gut-cardiovascular axis?.}, journal = {Frontiers in gastroenterology (Lausanne, Switzerland)}, volume = {2}, number = {}, pages = {1235126}, pmid = {41821793}, issn = {2813-1169}, abstract = {The gut-heart axis is an emerging concept highlighting the crucial link between gut microbiota and cardiovascular diseases (CVDs). Recent studies have demonstrated that gut microbiota is pivotal in regulating host metabolism, inflammation, and immune function, critical drivers of CVD pathophysiology. Despite a strong link between gut microbiota and CVDs, this ecosystem's complexity still needs to be fully understood. The short-chain fatty acids, trimethylamine N-oxide, bile acids, and polyamines are directly or indirectly involved in the development and prognosis of CVDs. This review explores the relationship between gut microbiota metabolites and CVDs, focusing on atherosclerosis and hypertension, and analyzes personalized microbiota-based modulation interventions, such as physical activity, diet, probiotics, prebiotics, and fecal microbiota transplantation, as a promising strategy for CVD prevention and treatment.}, }
@article {pmid41821822, year = {2023}, author = {Silva, R and Dinis, L and Peris, A and Novais, L and Calhau, C and Pestana, D and Marques, C}, title = {Fecal microbiota transplantation-could stool donors' and receptors' diet be the key to future success?.}, journal = {Frontiers in gastroenterology (Lausanne, Switzerland)}, volume = {2}, number = {}, pages = {1270899}, pmid = {41821822}, issn = {2813-1169}, abstract = {Fecal microbiota transplantation (FMT) is indicated in many countries for patients with multiple recurrences of Clostridioides difficile infection (CDI) for whom appropriate antibiotic treatments have failed. Donor selection is a demanding and rigorous process in view of the implementation of FMT programs worldwide. One of the most noteworthy factors that has been shown to affect FMT outcomes is the microbial diversity of the stool donor. A detailed assessment of the donor's microbiota is crucial, as the microbiota is complex, dynamic, and resilient, and a healthy microbiota has several dimensions in addition to the absence of pathogens. Diet is one of the most important factors that modulates the composition and function of the gut microbiome (GM) and has a critical role in orchestrating the host-microbiota crosstalk throughout life. The diversity of the human GM seems to be related to variations in dietary patterns. Currently, the dietary patterns of stool donors and receptors are not taken into consideration in any way for FMT. In this study, we reflect on the importance of including this type of assessment in the stool donor screening process and knowing the impact of diet on the GM, as well as the importance of monitoring receptors' diet to ensure the engraftment of the transplanted microbiota.}, }
@article {pmid41822071, year = {2022}, author = {Bibbò, S and Fusco, S and Ianiro, G and Settanni, CR and Ferrarese, D and Grassi, C and Cammarota, G and Gasbarrini, A}, title = {Gut microbiota in anxiety and depression: Pathogenesis and therapeutics.}, journal = {Frontiers in gastroenterology (Lausanne, Switzerland)}, volume = {1}, number = {}, pages = {1019578}, pmid = {41822071}, issn = {2813-1169}, abstract = {Depression and anxiety disorders represent a burdensome clinical issue. Considering the unsatisfactory clinical response of some patients to antidepressant therapy, new personalized approaches are being studied. In recent years, pre-clinical and clinical studies have investigated the role of intestinal microbiota demonstrating the importance of the gut-brain axis in these diseases. Indeed, gut microbes are able to interact with the brain interfering with behavior through some mechanisms such as amino acid metabolism, short-chain fatty acids, vagus nerve, endocrine signaling and immune responses. Experiments of gut microbiota transfer from subjects with major depression to animal models corroborated the causative role of intestinal microbes in mood disorders and anxiety. Furthermore, the incidence of dysbiosis in patients with anxiety and depression suggests a potential role for gut microbiota modulators in the treatment of these disorders. In particular, several probiotics and synbiotics have been shown to be effective in improving clinical symptoms, promising results have emerged also from fecal microbiota transplantation, but the evidence is still limited. These promising results switch on the use of gut microbiota modulators as an adjunctive tool to anti-depressant therapy. Developing pharmaceutical or nutraceutical strategies to modify the composition of gut microbiota may offer novel and personalized therapeutic tools against anxiety and depression.}, }
@article {pmid41822072, year = {2022}, author = {Masi, L and Ciuffini, C and Petito, V and Pisani, LF and Lopetuso, LR and Graziani, C and Pugliese, D and Laterza, L and Puca, P and Di Vincenzo, F and Pizzoferrato, M and Napolitano, D and Turchini, L and Amatucci, V and Schiavoni, E and Privitera, G and Minordi, LM and Mentella, MC and Papa, A and Armuzzi, A and Gasbarrini, A and Scaldaferri, F}, title = {Innovative, complementary and alternative therapy in inflammatory bowel diseases: A broad 2020s update.}, journal = {Frontiers in gastroenterology (Lausanne, Switzerland)}, volume = {1}, number = {}, pages = {1022530}, pmid = {41822072}, issn = {2813-1169}, abstract = {Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-α antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.}, }
@article {pmid41822330, year = {2026}, author = {Luo, L and Xue, M and Sun, L and Dai, Z}, title = {Gut microbiota in obesity management: from microbial clocks to precision microbial therapies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1705021}, pmid = {41822330}, issn = {2235-2988}, mesh = {Humans ; *Obesity/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Circadian Rhythm/physiology ; Animals ; Circadian Clocks ; *Obesity Management/methods ; }, abstract = {The gut microbiota exhibits robust circadian oscillations that synchronize with host metabolic cycles. Disruption of these microbial rhythms is increasingly recognized as a factor contributing to the pathogenesis of obesity. Clinical evidence supports that chrono-modulated interventions, including chrono-nutrition, temporal fecal microbiota transplantation (FMT), and engineered microbial systems, represent promising approaches in obesity management. This review synthesizes the features of gut microbiota circadian dynamics, the intrinsic and extrinsic factors regulating microbiota oscillations, and the precise microbial intervention measures targeting temporal patterns. Through the integration of insights into the microbiota-clock-metabolism axis, this review emphasizes the necessity of time-specific strategies in translating microbial circadian biology into effective, personalized obesity therapies.}, }
@article {pmid41822494, year = {2026}, author = {Chen, H and Yu, S and Zhang, M and Tian, B and Yang, L and Lu, J}, title = {Gut microbial metabolites in inflammatory bowel disease: immunological mechanisms regulating Treg/Th17 balance and therapeutic potential.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1780865}, pmid = {41822494}, issn = {1664-3224}, mesh = {Humans ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Th17 Cells/immunology/metabolism ; *Inflammatory Bowel Diseases/immunology/metabolism/therapy/microbiology/etiology ; Animals ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder resulting from a combination of genetic susceptibility, environmental factors, and an abnormal immune response of the intestinal immune system to commensal microorganisms. The gut microbiota and its metabolites play a pivotal role in maintaining intestinal immune homeostasis. Recent advances indicate that dysbiosis of the microbiota is accompanied by alterations in its metabolic functions. Abnormal levels of key metabolites, particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids, are closely associated with the pathogenesis of IBD. These metabolites act as G protein-coupled receptor ligands, nuclear receptor ligands, or epigenetic modifiers, deeply involved in the differentiation, function, and dynamic balance between regulatory T cells (Tregs) and T helper 17 cells (Th17). Disruption of the Treg/Th17 balance is a central driver of intestinal immune inflammation in IBD. This review systematically explores the molecular networks through which major microbial metabolites regulate the differentiation and function of Treg and Th17 cells, including their profound effects on cellular metabolic reprogramming, the epigenetic landscape, and the local immune microenvironment. Furthermore, it analyzes how the disturbance of the microbial metabolome in the pathological state of IBD leads to the attenuation of beneficial immunoregulatory signals and the generation of potential pro-inflammatory signals, thereby contributing to a vicious cycle of immune tolerance deficiency and chronic inflammation. Based on these mechanisms, this article evaluates therapeutic strategies targeting the microbiota-metabolism-immune axis, such as dietary interventions, probiotics/prebiotics, postbiotics, engineered bacterial therapies, fecal microbiota transplantation, and small-molecule receptor modulators, discussing their current status and challenges. Finally, the limitations of current research are outlined, and future directions are proposed, including the use of integrated multi-omics analyses, spatial biology technologies, and organoid models to advance the development of personalized precision medicine.}, }
@article {pmid41822725, year = {2024}, author = {Mpountouridis, A and Tsigalou, C and Bezirtzoglou, I and Bezirtzoglou, E and Stavropoulou, E}, title = {Gut microbiome in non-alcoholic fatty liver disease.}, journal = {Frontiers in gastroenterology (Lausanne, Switzerland)}, volume = {3}, number = {}, pages = {1534431}, pmid = {41822725}, issn = {2813-1169}, abstract = {Non-alcoholic fatty liver disease (NAFLD) has a rapidly growing incidence worldwide, affecting approximately one-third of world population. The disturbance of gut commensal bacteria impacting host's homeostasis is referred to as gut dysbiosis. The gut microbiome contributes to the pathogenesis of NAFLD through various pathways. Gut microbiota is at constant interactions with the intestinal epithelial barrier and affects its integrity. Through gut-liver axis, gut microbiota may influence liver immune function. The release of lipopolysaccharides (LPS) from intestines to portal vein which are transported to the liver, may trigger hepatic inflammation, steatosis and even fibrosis. Moreover, the gut microbiome induces the conversion of primary bile acids (BAs) to secondary BAs, which activates intestinal receptors, such as FXR and TGR5. FXR activation decreases fat absorption and thus reduces hepatic lipid accumulation, while TGR5 activation promotes the release of glucagon-like peptide-1 (GLP-1) in blood. Furthermore, gut ethanol-producing bacteria has been implicated in NAFLD development. Additionally, in NAFLD there is a reduction in intestinal levels of short-chain fatty acids, such as butyrate, propionate and acetate. Many bacterial alterations have been observed in NAFLD, including the increased Bacteroidetes and decreased Firmicutes. Many probiotics have been tried in NAFLD prevention and management, including a plethora of strains from Lactobacilli, Bifidobacteria and Streptococcus and some of them have promising perspectives. There is also some promising data from the administration of prebiotics (such as inulin and fructo-oligosaccharides) and symbiotics (probiotics plus prebiotics). Faecal microbiota transplantation (FMT) is yet to be evaluated for its efficacy against NAFLD.}, }
@article {pmid41823302, year = {2026}, author = {Al, KF and Jia, S and Silverman, M and Reid, G and Burton, JP and Parvathy, SN}, title = {Prebiotic modulation of FMT donor microbiota enhances MASLD-relevant taxa and functions in an in vitro gut model.}, journal = {Journal of applied microbiology}, volume = {137}, number = {4}, pages = {}, doi = {10.1093/jambio/lxag074}, pmid = {41823302}, issn = {1365-2672}, support = {//Lawson/ ; //Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {*Prebiotics/analysis ; Humans ; Inulin/metabolism ; *Gastrointestinal Microbiome/drug effects ; Oligosaccharides/pharmacology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Glucuronates ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Fatty Acids, Volatile/metabolism ; }, abstract = {AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease) is a prevalent and progressive condition closely linked to gut microbiota composition. Fecal microbiota transplantation (FMT) may help restore a health-associated microbiome, but its efficacy is often limited by inconsistent engraftment of beneficial taxa. Prebiotics may selectively support keystone microbes associated with reduced MASLD risk. This study evaluated two prebiotics, inulin and xylooligosaccharides (XOS), for their ability to modulate the microbiota of healthy FMT donors in an in vitro gut model, focusing on enriching beneficial taxa and functions associated with MASLD resilience.<br><br>METHODS AND RESULTS: Stool from eight clinically qualified FMT donors was cultured anaerobically for 24 h with or without prebiotics. Microbiota composition was assessed by 16S rRNA gene sequencing and short-chain fatty acid (SCFA) concentrations were measured using nuclear magnetic resonance. Functional potential was inferred using predictive metagenomic analysis. Prebiotic responses were highly donor-specific, yet both inulin and XOS consistently enriched Bifidobacterium and Bacteroides-genera associated with SCFA production and metabolic health. XOS preferentially enriched Lactobacillus and Parabacteroides, while inulin enhanced Holdemanella and Mediterraneibacter. Functional pathways relevant to MASLD pathophysiology were enriched, including carbohydrate metabolism, vitamin biosynthesis, fatty acid metabolism, and tryptophan degradation. Both prebiotics significantly increased acetate levels, while butyrate showed a donor-dependent increasing trend.<br><br>CONCLUSIONS: These findings suggest that prebiotic supplementation can selectively enrich MASLD-relevant microbial taxa and functions in donor-derived FMT material, supporting their potential as adjuvants to enhance the efficacy and disease-specificity of FMT interventions for MASLD.}, }
@article {pmid41824007, year = {2026}, author = {Zhu, S and Zou, M and Wu, Q and Zou, Y and Tan, T and Huang, Z and Gong, Z and Luo, H and Dong, X}, title = {The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease: From Mechanistic Insights to Precision Therapeutics.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {6}, pages = {e71687}, pmid = {41824007}, issn = {1530-6860}, support = {2024GXNSFAA010247//Guangxi Natural Science Fundation/ ; 2024GXNSFBA010227//Guangxi Youth Science Fun Project/ ; QYY-GCRC-202301//Research Foudation for Advanced Talents of The people's and Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Science/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Precision Medicine/methods ; *Liver/metabolism ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Dysbiosis ; *Fatty Liver/therapy/metabolism/microbiology ; *Non-alcoholic Fatty Liver Disease/therapy/metabolism/microbiology ; *Metabolic Diseases/therapy ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver condition globally, shifting the diagnostic paradigm toward an affirmative, metabolism-focused framework. The gut-liver axis is a central pathophysiological pathway. This review aims to synthesize revolutionary advances from 2023 to 2025 in understanding and treating MASLD by focusing on the gut microbiome's role. This comprehensive review analyzes cutting-edge research published between 2023 and 2025. We examined evidence from landmark clinical trials, developments in next-generation probiotics, the integration of artificial intelligence (AI) with multiomics for diagnostics, and studies clarifying the interplay between host genetics and the microbiome in MASLD pathogenesis. Causal links between gut dysbiosis and MASLD pathology are now firmly established. Fecal microbiota transplantation (FMT) effectively prevents hepatic encephalopathy recurrence, and next-generation probiotics like Akkermansia muciniphila have entered MASLD-specific trials. AI-driven diagnostic tools have achieved regulatory qualification from the European Medicines Agency. Furthermore, host genetics, particularly PNPLA3 variants, are shown to not only predispose to MASLD but also shape specific microbial communities that functionally contribute to disease progression. The field is rapidly advancing from correlative observations to causal evidence, enabling the development of microbiome-based biomarkers and personalized therapies. The future of MASLD management lies in precision strategies, such as bacteriophage therapy and functionally defined probiotics, which integrate metabolic, microbial, and genetic factors into individualized care, heralding a new therapeutic era.}, }
@article {pmid41826266, year = {2026}, author = {Wu, K and Yu, H and Cao, K and Dai, B and Yuan, Y and Qian, X and Zhong, H and Qu, Y and Jiang, H and Chen, T}, title = {Overconsumption of fructose aggravates acute GVHD by inducing gut dysbiosis and promoting macrophage-mediated inflammatory response.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2642459}, pmid = {41826266}, issn = {1949-0984}, mesh = {Animals ; *Fructose/adverse effects/administration &amp; dosage/metabolism ; *Dysbiosis/microbiology/immunology ; *Macrophages/immunology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Graft vs Host Disease/microbiology/immunology/pathology ; Mice, Inbred C57BL ; Cytokines/metabolism/immunology ; Fecal Microbiota Transplantation ; Bacterial Translocation ; Intestinal Barrier Function ; Inflammation ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Disease Models, Animal ; T-Lymphocytes/immunology ; Macrophage Activation ; }, abstract = {Increased fructose intake is a triggering factor in a series of inflammatory diseases. However, the pathogenic role of fructose overconsumption in acute graft-versus-host disease (aGVHD) has not yet been clarified. In this study, we found that a high-fructose diet (HFR) aggravated the severity and mortality of aGVHD in mice and enhanced gut dysbiosis and bacterial translocation with impairment of the intestinal epithelial barrier. Fecal microbiota transplantation experiments further demonstrated that the microbiota derived from HFR-fed aGVHD mice was sufficient to reproduce intestinal barrier disruption and bacterial translocation in aGVHD recipients. HFR exacerbated the severity of aGVHD after depletion of the gut microbiota by antibiotics. Given the results that in vitro cultivated T-cells do not respond to fructose stimulation, we further investigated whether fructose overexposure affects macrophage activation. In fructose-treated bone marrow-derived macrophages (BMDMs), HIF-1α was stabilized by mitochondrial reactive oxygen species production, resulting in increased glycolysis and subsequently augmented expression of the inflammatory cytokines IL-6, IL-12, TNF-α, and IL-1β. Interestingly, we found that macrophages derived from HFR-fed aGVHD mice were able to enhance T-cell proliferation and Th1/Th17 differentiation. In parallel, correlation analysis integrating 16S rRNA and metabolomics sequencing data revealed that the abundances of Akkermansiaceae and Erysipelotrichaceae were positively correlated with the levels of indole-5,6-quinone and 6,7-dimethyl-8-(D-ribityl)lumazine. After depletion of macrophages and the gut microbiota in host mice, GVHD severity was significantly reversed even after HFR treatment. Taken together, our data reveal that high fructose intake exacerbated aGVHD by inducing a gut microbiota imbalance and promoting inflammatory macrophage activation. This provides a potential therapeutic strategy to alleviate aGVHD via precise adjustment of the fructose dietary.}, }
@article {pmid41826284, year = {2026}, author = {Zhang, R and Feng, R and Wang, J and Chen, Y and Liu, H and Zhu, Q and Tian, H and Qin, C and Teng, J and Tang, B and Wu, M and Zeng, J and Wu, E and Ding, X and Wang, X}, title = {Gut microbiota modulation via repeated donor fecal transplantation improves motor and gastrointestinal symptoms in drug-naïve Parkinson's disease: a randomized phase 2 trial.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {}, pmid = {41826284}, issn = {2059-3635}, support = {82201407//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82122022,82471272, 82171248, 82471350, 82201407//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82130035, 82371308//National Natural Science Foundation of China (National Science Foundation of China)/ ; R04017//Sun Yat-sen University (SYSU)/ ; }, mesh = {Humans ; *Parkinson Disease/therapy/microbiology/pathology/physiopathology ; *Fecal Microbiota Transplantation ; Female ; Male ; Middle Aged ; Aged ; *Gastrointestinal Microbiome ; *Constipation/therapy/microbiology ; Double-Blind Method ; Quality of Life ; }, abstract = {The gut-brain axis is increasingly recognized as a critical contributor to Parkinson's disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor fecal microbiota transplantation (dFMT) in de novo PD. FMT was administered for seven days (200 mL on days 1-3; 50 mL on days 4-7) per 4-week cycle. Seventy-two patients were randomized 1:1 to receive dFMT or autologous FMT (aFMT), and 66 completed the trial. At 35 weeks, the dFMT group showed significant improvement in motor symptoms (mean change in Unified Parkinson's Disease Rating Scale [UPDRS] III: -3.8 vs. +0.1; p = 0.0001) and a substantially greater reduction in constipation severity (dFMT vs. aFMT: -6.5 vs. -0.7; p < 0.0001), accompanied by improved quality-of-life scores. Microbiome profiling revealed greater similarity to donor composition and a marked reduction in Escherichia-Shigella, correlating with decreased colonic α-synuclein aggregation (r = 0.3775, p = 0.0277), supporting a gut-brain mechanistic link. Biochemical analyses showed elevated fecal dopamine and 3,4-dihydroxyphenylacetic acid levels, while histological assessments demonstrated strengthened epithelial barrier integrity with increased E-cadherin expression. All adverse events were mild and self-limited; no serious treatment-related events were observed. These findings demonstrate that repeated dFMT is safe, well tolerated, and yields clinically meaningful motor and gastrointestinal improvements in drug-naïve PD, providing integrated mechanistic and clinical evidence that microbiota-targeted modulation represents a promising nonpharmacologic therapeutic strategy for neurodegenerative disease. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200064151.}, }
@article {pmid41826399, year = {2026}, author = {Wang, L and Zhang, S and Liu, Y and Li, D and Tian, G and Li, X and Li, Y}, title = {A study on the efficacy and safety of fecal microbiota transplantation as an adjunctive therapy for treating depressive episodes.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41826399}, issn = {2045-2322}, support = {2025ZL480//Traditional Chinese Medicine Scientific Research Fund Project (A)/ ; 2022ZA150//Traditional Chinese Medicine Scientific Research Fund Project (A)/ ; }, abstract = {UNLABELLED: This study aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) as an adjunctive therapy for depressive episodes. This study recruited 46 participants aged 18–65 from January 2022 to December 2023 who were diagnosed with depression according to the International Classification of Diseases, 10th edition. They were randomly divided into two groups to receive different treatments, including FMT combined with medication group (test group, n = 23) and the medication-only group (control group, n = 23). Assessments were performed before and two weeks after treatment. Ten predominant gut microbiota species were analyzed, and the Hamilton’s Depression Scale-24(HAMD-24) was used to evaluate depressive symptoms. Adverse events related to treatment were assessed using an adverse event scale and laboratory tests. The main evaluation indicators included the reduction rate of HAMD-24 scores, treatment efficacy rate, and changes in the indicators of the ten predominant intestinal bacteria before and after transplantation. Safety assessment indicators included adverse events, blood routine, biochemistry, electrocardiogram, immunological parameters (immunoglobulins and complement), hypersensitive C-reactive protein(hs-CRP), thyroid function, and glycated hemoglobin. The rank-sum test was performed to compare differences in microbiota before and after FMT treatment. The relationship between gut microbiota and depression severity was examined by means of correlation analysis. The baseline HAMD-24 scores showed no significant difference between the test and control groups (P > 0.05). After two weeks treatment, the reduction in HAMD-24 scores (P = 0.048) and the HAMD-24 reduction rate (P = 0.016) were significantly higher in the test group than control group (P < 0.05). Following FMT treatment, Enterococcus, Lactobacillus, Bifidobacterium, and Butyricicoccus levels significantly increased compared to baseline (P < 0.05). Linear discriminant analysis(LDA) revealed a significant post-treatment increase in Enterococcus relative abundance (P = 0.02). In the test group, baseline-enriched Clostridium prausnitzii (P = 0.040), Butyricicoccus (P = 0.029), and Eubacterium rectale (P = 0.004) showed significant negative correlations with HAMD-24 scores, whereas post-treatment Enterococcus was correlated with HAMD-24 scores (P = 0.030). Adverse event incidence was 28.6% in the test group and 30% in the control group, with no significant difference (P = 0.928). Reported discomforts during FMT treatment—nausea, vomiting, and nasopharyngeal discomfort—were mild and self-resolving, with no serious adverse events observed. The administration of FMT as an adjunctive therapy demonstrates superior improvement in depressive symptoms and is deemed safe with no apparent adverse reactions. There was no change in the composition of gut microbiota structure before and after FMT in patients with depression. Enterococcus showed a significant relative abundance increase in the gut after FMT. The post-treatment Enterococcus was correlated with HAMD-24 scores.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-41801-y.}, }
@article {pmid41826553, year = {2026}, author = {Garcia-Peterson, LM and Wellman, AS and Xu, X and Ji, M and Duval, C and Shats, I and Wu, X and Randall, TA and Bostan, H and Cunefare, D and Ganta, CK and Sifre, M and Xu, X and Blumberg, RS and Li, JL and Li, X}, title = {Paneth cell SIRT1 deficiency increases intestinal stress resistance by modulating the gut microbiota.}, journal = {EMBO reports}, volume = {27}, number = {7}, pages = {1830-1857}, pmid = {41826553}, issn = {1469-3178}, support = {Z01 ES102205//HHS | NIH | National Institute of Environmental Health Sciences (DEHS)/ ; 1FI2GM143339-01//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DK088199//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Sirtuin 1/deficiency/genetics/metabolism ; *Paneth Cells/metabolism ; Mice ; *Gastrointestinal Microbiome ; Colitis/chemically induced/microbiology/pathology/metabolism/genetics ; Intestinal Mucosa/metabolism/microbiology ; *Stress, Physiological ; Mice, Knockout ; Endoplasmic Reticulum Stress ; Wnt Signaling Pathway ; }, abstract = {Paneth cells, intestine-originated innate immune-like cells, are important for maintenance of the intestinal stem cell niche, gut microbiota, and gastrointestinal barrier. Dysfunctional Paneth cells under pathological conditions are a site of origin for intestinal inflammation. However, mechanisms underlying stress-induced Paneth cell dysregulation remain unclear. Here, we report that SIRT1, the most conserved mammalian NAD[+]-dependent protein deacetylase and a well-known genetic repressor of inflammation, cell-autonomously suppresses Paneth cell function and sensitizes the gut epithelium to environmental stress. Specifically, deletion of Paneth cell SIRT1 in mice elevates Wnt signaling and ATF4/endoplasmic reticulum stress pathway in Paneth cells. These molecular alterations are coupled with increased Paneth cell abundance and enhanced anti-microbial peptide production in young mice, improved protection against intestinal immune cell expansion in aged mice, and increased resistance to chemically induced colitis. Using microbiota-depleted mice with or without fecal transplantation, we further demonstrate that Paneth cell SIRT1 deficiency ameliorates colitis by interacting with the gut microbiota. Collectively, our findings uncover an unanticipated function of Paneth cell SIRT1 in conferring stress sensitivity in the gut epithelium.}, }
@article {pmid41828467, year = {2026}, author = {Shen, H and Yu, X and Wang, Z and Zhou, S and Jiang, J and Guo, H and Han, Y}, title = {Gut Microbiota Remodeling Mediates the Therapeutic Effects of a Plant-Based Medicine on DSS-Induced Ulcerative Colitis in Mice via the Butyrate-SVCT1-Vitamin C Axis.}, journal = {International journal of molecular sciences}, volume = {27}, number = {5}, pages = {}, pmid = {41828467}, issn = {1422-0067}, support = {No. 2025-I2M-KJ-016//the CAMS Innovation Fund for Medical Sciences/ ; No. 3332025150//the Fundamental Research Funds for Central Universities, Peking Union Medical College/ ; No. 2024-I2M-ZH-012//the CAMS Innovation Fund for Medical Sciences/ ; No. 20230484467//the Beijing Nova Program from Beijing Municipal Science &amp; Technology Commission/ ; }, mesh = {Animals ; *Ascorbic Acid/metabolism ; Mice ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate/toxicity/adverse effects ; *Butyrates/metabolism ; *Sodium-Coupled Vitamin C Transporters/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; Colon/metabolism ; Fecal Microbiota Transplantation ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising global incidence in recent years. Dengzhan shengmai (DZSM), a plant-based formulation clinically used in the management of cerebrovascular diseases, possesses documented anti-inflammatory and antioxidant properties; however, its effects on UC are unclear. In this study, we investigated the therapeutic potential and underlying mechanism of DZSM in a dextran sulfate sodium (DSS)-induced murine colitis model. Our results showed that DZSM significantly alleviated UC-related parameters. Mechanistically, DZSM remodeled gut microbiota dysbiosis, specifically enriching the abundance of short-chain fatty acid (SCFA)-producing bacteria and elevating colonic levels of SCFAs. Notably, butyrate upregulated the expression of the sodium-dependent vitamin C transporter 1 (SVCT1) in colonic epithelial cells, thereby enhancing cellular vitamin C (VitC) uptake. The accumulated VitC synergized with butyrate to exert potent antioxidant and anti-inflammatory effects, further reinforcing epithelial barrier function. Importantly, fecal microbiota transplantation (FMT) confirmed that the protective effects of DZSM on UC were achieved by modulating gut microbiota, at least partially. Collectively, our findings demonstrate for the first time that DZSM alleviates DSS-induced colitis in mice through a novel butyrate-SVCT1-VitC axis driven by gut microbiota remodeling, providing new mechanistic insights into the microbiota-dependent efficacy of plant-based medicine.}, }
@article {pmid41828553, year = {2026}, author = {Alba, C and Palomino, L and Vergara, B and Rodríguez-Belvis, MV and Aragón, A and Zaghlul, MADC and Jurado, R and Martín-Fernández, C and Vázquez-Gómez, JA and González-Vicent, M and Molina-Angulo, B and Sánchez-Llorente, P and García-Hernández, P and Rodríguez, JM and Muñoz-Codoceo, RA and Herranz, C}, title = {Metataxonomic Analysis and Fatty Acid Profiling of Feces from Children Undergoing Hematopoietic Stem Cell Transplantation.}, journal = {International journal of molecular sciences}, volume = {27}, number = {5}, pages = {}, pmid = {41828553}, issn = {1422-0067}, support = {XVIII//Mutua Madrile&#xf1;a/ ; PR17/24-31883//Comunidad de Madrid/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Feces/microbiology/chemistry ; *Graft vs Host Disease/etiology/microbiology ; RNA, Ribosomal, 16S/genetics ; *Fatty Acids, Volatile/analysis/metabolism ; Male ; Female ; Child ; *Gastrointestinal Microbiome ; *Fatty Acids/metabolism/analysis ; Child, Preschool ; Adolescent ; Infant ; *Metabolomics/methods ; Transplantation, Homologous ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (HSCT) is a medical procedure to treat hematologic malignancies and restore bone marrow function. However, this approach may lead to graft-versus-host disease (GvHD), a major cause of mortality and morbidity after allogeneic HSCT. Some studies have suggested the involvement of gut microbiota in the development and prognosis of GvHD. In this context, the main objective of this study was to compare the fecal microbiome composition and short-chain profile of pediatric patients who underwent successful HSCT, developed GvHD or died. The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) were quantified by gas chromatography. Fecal samples at engraftment were mainly characterized by a loss of bacterial diversity, a depletion of sequences belonging to the genus Blautia and significantly lower concentrations of fecal butyrate and acetate compared with those obtained before HSCT and 100 days after HSCT. Our findings confirm that children experiencing GvHD after HSCT have distinct gut microbiota and SCFA profiles, which might contribute to developing new microbiota-targeted strategies for GvHD prevention during HSCT procedures.}, }
@article {pmid41828959, year = {2026}, author = {Liang, Y and Huang, P and Li, J and Manafu, Z and Wang, R and Chen, X and Zhang, X and Wu, Y and Malajiang, X and Yiming, A and Duishan, S and Wusiman, A}, title = {The Protective Effects and Underlying Mechanisms of Taraxacum kok-saghyz Polysaccharides Against Intestinal Dysbiosis-Induced Mastitis Were Elucidated Using a Murine Model of the "Gut-Mammary" Axis.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {5}, pages = {}, pmid = {41828959}, issn = {2076-2615}, support = {XJRC-2025-KJ-KJQY-002//Adelijiang Wusiman/ ; }, abstract = {The gut-mammary axis represents a promising therapeutic target for mastitis. Although plant-derived polysaccharides exhibit immunomodulatory properties, their capacity to modulate this axis-and specifically to ameliorate dysbiosis-induced mastitis-remains unexplored. Here, we investigated the therapeutic potential of Taraxacum kok-saghyz leaf-derived polysaccharides (TKP-L) against mastitis in a murine model of gut dysbiosis, with dysbiosis induced by fecal microbiota transplantation (FMT) from donor cows. Pregnant mice (n = 60) with antibiotic-depleted microbiota received FMT suspensions prepared from the feces of healthy dairy cows or cows with clinical mastitis (based on somatic cell count). Mice were randomly divided into five groups: Control (vehicle), M-FMT (mastitis-cow FMT, disease model), H-FMT (healthy-cow FMT), TKP-L (M-FMT + oral TKP-L, 500 mg/kg/day), and Ciprofloxacin (M-FMT + ciprofloxacin, positive Control). After FMT establishment, TKP-L or ciprofloxacin was administered for 14 days. We assessed histopathology, pro-inflammatory mediators (IL-6, IL-1β, TNF-α, MPO), tight junction proteins (occludin, ZO-1, Claudin-3), and bacterial translocation using GFP-E. coli, and gut/milk microbiota via 16S rRNA sequencing. Compared to the M-FMT group, TKP-L treatment significantly alleviated mammary inflammation and pathology, inhibited pro-inflammatory cytokine expression, and enhanced the expression of tight junction proteins in both intestinal and mammary tissues, correlating with reduced bacterial translocation to the mammary gland. Microbiota analysis showed that TKP-L restored microbial homeostasis in the gut and milk, concurrently increasing the relative abundance of beneficial bacteria such as Limosilactobacillus. TKP-L alleviates gut dysbiosis-induced mastitis in mice by concurrently modulating the gut-mammary axis through microbial remodeling, enhancement of epithelial barriers, and anti-inflammatory actions. These findings highlight TKP-L as a promising gut microbiota-targeting candidate for mastitis intervention.}, }
@article {pmid41831535, year = {2026}, author = {Chen, J and Xiao, C and Cao, M and Hu, Y and Yan, Y and Tong, J and Cheng, C and Huang, J}, title = {Association between gut virome and prenatal stress-induced changes in behavior and immune responses in male offspring.}, journal = {Brain, behavior, and immunity}, volume = {135}, number = {}, pages = {106532}, doi = {10.1016/j.bbi.2026.106532}, pmid = {41831535}, issn = {1090-2139}, mesh = {Animals ; Female ; Pregnancy ; *Prenatal Exposure Delayed Effects/immunology/microbiology ; *Stress, Psychological/immunology/microbiology ; *Gastrointestinal Microbiome/physiology/immunology ; Anxiety/immunology ; Male ; *Virome/immunology/physiology ; Fecal Microbiota Transplantation ; Behavior, Animal/physiology ; }, abstract = {Maternal stress during gestation is associated with an increased risk of neurodevelopmental disorders in offspring. The gut-brain axis is considered a potential mediating pathway. As a key component of the gut microbiome, the bacteriophages can remodel bacterial community structure and function. However, whether gut viruses contribute to prenatal stress-induced behavioral alterations in offspring remains unclear. Here, we reported that prenatal stress induces anxiety-like behaviors and alters the gut virome and bacteriome specifically in male offspring. By comparing the gut virome and bacteriome between dams and their offspring, we found that the gut microbial profile of male offspring is more similar to that of their mothers than that of female offspring. To investigate whether changes in the gut virome are causally linked to stress-related behavioral or physiological outcomes, we transplanted gut viromes from control offspring into the offspring exposed to maternal prenatal stress. The results showed that transplantation of the gut virome from control offspring alleviated anxiety-like behaviors, restored the gut microbiome, and modulated immune responses in prenatally stressed offspring. Our findings highlight the critical role of gut bacteriophages in mediating prenatal stress-induced behavioral changes and demonstrate that fecal virome transplantation (FVT) can mitigate such alterations. Thus, we establish a causal link between prenatal stress, the gut virome, immune function, and behavior, pointing to FVT as a potential therapeutic strategy for certain neurodevelopment-related behavioral abnormalities.}, }
@article {pmid41832194, year = {2026}, author = {Arshad, M and Zhang, CY and Gao, ZK and Sun, H and Xu, DQ and Fan, CY and Zhang, BW and Geng, JX and Li, Y and Kotusov, A and Liu, SL and Zhang, N and Mu, XQ}, title = {Capecitabine combined with fecal microbiota transplantation prevents colorectal cancer progression through correction of microbial dysbiosis and immune regulation.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41832194}, issn = {2045-2322}, support = {NSFC82020108022, NSFCU23A20521//National Natural Science Foundation of China/ ; NSFC81903631//National Natural Science Foundation of China/ ; UNPYSCT14 2018065//Youth Innovation Fund of University in Hei Longjiang/ ; }, abstract = {UNLABELLED: The significant economic burden of colorectal cancer (CRC) necessitates the development of innovative therapeutic approaches. Interest in the gut microbiota’s role in CRC has increased. Capecitabine, as a chemotherapy, may disrupt the balance of the intestinal microbiota. This study investigated the anticancer effects of capecitabine combined with fecal microbiota transplantation (FMT) in a CRC mouse model caused by azoxymethane and dextran sodium sulfate. FMT was achieved with fecal microbiota from healthy mice through enema. Capecitabine decreased the number and diameter of cancer foci in CRC mice, while FMT supplementation had a more noticeable impact, indicated by increased body weight and survival rate. Capecitabine significantly reduced the abundance of pathogenic bacteria in mice with CRC, such as Bacteroides, Enterorhabdus, Monoglobus, Rodentibacter, uncultured_rumen_bacterium, Turicibacter, and Streptococcus. The supplementation of FMT more effectively reversed the gut microbiota dysbiosis in CRC mice, as demonstrated by the ACE and Chao 1 indices, PCoA analysis, and enhanced normal biological pathways. Microbial dysbiosis induced immunological dysfunction in CRC mice, indicated by abnormal immune cell recruitment and excessive cytokine production. Capecitabine treatment reduced immune cell infiltration, including CD3[+] T cells, CD4[+] T cells, and CD49b[+] NK cells, as chemotherapy often suppresses the immune system. The supplement of FMT increased the proportion of CD4[+] T cells, CD49b[+] NK cells, CD8[+] T cells, and LY6G[+] neutrophils, indicating improved immune responses against CRC. Moreover, capecitabine therapy alone reduced the overexpression of IL1a, IL6, IL12a, IL12b, IL17, IL22, FOXP3, STAT3, IFN-γ, TNF-α, TGF-β, GZMA, CXCR4, OPN, PD-1 and PD-L1. FMT supplementation resulted in a higher immune response to CRC, as it had a greater inhibitory effect on the overexpression of inflammatory cytokines and enhanced the production of IL10, IFN-γ, and CXCR4. These cytokines were positively correlated with Azospirillum_sp._47_25, Romboutsia, Lactococcus, Rikenella_sp._Marseille_P3215 and Turicibacter and negatively correlated with Parabacteroids, unclassified_Oscillospiraceae, Marvinbryantia, unclassified_Clostridia_vadinBB60_group, unclassified_Erysipelatoclostridiaceae, A2, Roseburia, Rikenellaceae_RC9_gut_group, Acetatifactor and unclassified_Clostridia. The combination of capecitabine and FMT is more effective at preventing CRC than capecitabine alone, as it reverses gut microbial abnormalities and boosts immune responses to CRC.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-43626-1.}, }
@article {pmid41833674, year = {2026}, author = {Wang, X and Shao, J and Dong, X and Ding, H and Ma, Z}, title = {Bletilla striata polysaccharide alleviates obesity by remodeling the gut microbiota-metabolite-liver axis and suppressing the hepatic AMPK-SREBP2/SQLE signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {354}, number = {}, pages = {151416}, doi = {10.1016/j.ijbiomac.2026.151416}, pmid = {41833674}, issn = {1879-0003}, mesh = {Animals ; *Polysaccharides/pharmacology/chemistry ; *Liver/metabolism/drug effects ; *Obesity/metabolism/drug therapy/microbiology/etiology ; *Gastrointestinal Microbiome/drug effects ; *Signal Transduction/drug effects ; Mice ; *Orchidaceae/chemistry ; Male ; *AMP-Activated Protein Kinases/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Obesity is a global health crisis, yet the precise biochemical relay underlying the anti-obesity effects of Bletilla striata polysaccharides (BSP) remains to be fully elucidated. We investigated the metabolic effects of BSP in a high-fat diet (HFD)-induced obese mouse model. Using an integrative multi-omics strategy combined with fecal microbiota transplantation (FMT) and functional validation, we aimed to decipher the "gut microbiota-metabolite-liver" regulatory axis. BSP supplementation significantly attenuated HFD-induced weight gain, improved glucose and lipid homeostasis, and mitigated systemic inflammation, oxidative stress, and hepatic steatosis in a dose-dependent manner. Multi-omics analyses revealed that BSP selectively remodeled the gut microbiota by suppressing obesity-associated genera while enriching beneficial taxa such as Allobaculum, Ileibacterium valens, and Dubosiella. These microbial shifts were accompanied by a reduction in deleterious bile acids and, crucially, a significant increase in the production and systemic circulation of short-chain fatty acids, providing a definitive physiological link between intestinal alterations and distal host responses. Hepatic transcriptomic and protein analyses further revealed that these gut-derived metabolites triggered the phosphorylation-mediated activation of AMPK signaling, which subsequently suppressed squalene epoxidase (SQLE)-mediated cholesterol biosynthesis. Causal evidence was established through FMT, where recipient mice phenocopied the metabolic benefits of BSP donors. Furthermore, loss- and gain-of-function experiments using pharmacological inhibitors and AAV8-mediated gene delivery confirmed that SQLE is a necessary mediator of BSP's anti-obesity action. Collectively, our findings demonstrate that BSP alleviates obesity by orchestrating a microbiota-metabolite-host axis connecting gut microbial remodeling to the hepatic AMPK-SREBP2/SQLE signaling cascade, highlighting its potential as a targeted functional dietary intervention.}, }
@article {pmid41833765, year = {2026}, author = {Yang, C and Zhang, X and Bie, J and Kang, W and Sun, G and Zhao, Q and Li, L and Hu, Q}, title = {Gut microbiota drives dietary lignans to improve perimenopausal depression via activating hippocampal ERβ/GluN2A/PSD95 pathway.}, journal = {Pharmacological research}, volume = {227}, number = {}, pages = {108161}, doi = {10.1016/j.phrs.2026.108161}, pmid = {41833765}, issn = {1096-1186}, mesh = {Animals ; Female ; *Hippocampus/metabolism/drug effects ; *Gastrointestinal Microbiome ; *Estrogen Receptor beta/metabolism/genetics ; Humans ; *Depression/metabolism/microbiology/drug therapy/diet therapy/psychology ; *Lignans/pharmacology/administration &amp; dosage/therapeutic use ; *Disks Large Homolog 4 Protein/metabolism ; *Perimenopause/psychology/metabolism ; Mice, Inbred C57BL ; Signal Transduction ; Middle Aged ; Mice ; Dietary Supplements ; *Antidepressive Agents ; Fecal Microbiota Transplantation ; }, abstract = {Dietary lignans (Diet-LIG) are a class of estrogenic plant polyphenols whose improve potential for perimenopausal depression (PMD), a condition driven by estrogen deficiency, remains unexplored. This study aims to investigate whether Diet-LIG intake can alleviate perimenopausal depressive symptoms and to explore the underlying mechanisms. The randomized controlled trial conducted in the study revealed that one-month supplementation significantly alleviated depressive and anxiety symptoms and elevated serum estradiol in perimenopausal women. This clinical benefit was associated with increased fecal levels of gut bacterial metabolites (enterolactone and enterodiol) the enzyme β-glucuronidase, and the enrichment of specific bacteria, notably Bacteroides ovatus. Animal studies showed that Diet-LIG upregulated ERβ protein expression in the hippocampal tissue of PMD mice. KEGG analysis of hippocampal proteomics showed that differentially expressed proteins between the Diet-LIG intervention and PMD groups were primarily enriched in the glutamatergic synapse pathway. Golgi staining and Western blot analysis confirmed that Diet-LIG supplementation improved neuronal plasticity, with significantly increased expression of GluN2A and PSD95 proteins. Humanized fecal microbiota transplantation experiments and in vitro cell interventions with Bacteroides ovatus monoculture medium revealed that the antidepressant effects of Diet-LIG are not directly mediated solely by the modulated gut microbiota, but instead rely on the bioactivity of metabolites produced through gut microbiota-driven conversion. In vitro validation experiments, the knockdown of ERβ in HT22 cells significantly suppressed GluN2A and PSD95 expression and blocked their induction by Diet-LIG metabolites. In conclusion, gut microbiota drives Diet-LIG to activate hippocampal ERβ, which regulates the GluN2A/PSD95 pathway and enhances hippocampal neuronal plasticity, thereby ameliorating perimenopausal depressive symptoms. (Chinese Clinical Trial Registry [ChiCTR], ID Number: ChiCTR2400082537.).}, }
@article {pmid41834217, year = {2026}, author = {Yuan, X and Gong, H and Zhang, L and Liu, Y and Zhou, M and Liu, Y and Tang, J and Pan, S and Xu, X and Wang, Y and Zhang, X and Zhang, T and Song, J}, title = {T2DM-Induced Gut Dysbiosis Exacerbates Periodontitis Through Intestinal Barrier Disruption and Redox Imbalance.}, journal = {Journal of clinical periodontology}, volume = {53}, number = {5}, pages = {821-833}, doi = {10.1111/jcpe.70116}, pmid = {41834217}, issn = {1600-051X}, support = {U22A20314//National Natural Science Foundation of China/ ; 82170968//National Natural Science Foundation of China/ ; 82301082//National Natural Science Foundation of China/ ; 2022YFC2504200//National Key Research and Development Program of China/ ; 2025MD774176//China Postdoctoral Science Foundation/ ; YXQN202401//Chongqing Youth Talent Support Program/ ; }, mesh = {Animals ; *Dysbiosis/complications ; *Periodontitis/microbiology/etiology/metabolism ; *Diabetes Mellitus, Type 2/complications ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Intestinal Barrier Function ; Oxidative Stress ; Male ; Disease Models, Animal ; }, abstract = {AIM: To investigate the potential role and underlying mechanisms of gut microbiota in type 2 diabetes mellitus (T2DM)-exacerbated periodontitis.<br><br>MATERIALS AND METHODS: A T2DM-associated periodontitis model was established in C57BL/6 mice and analysed using multi-omics sequencing (16S rRNA, metagenomics and metabolomics). Faecal microbiota transplantation (FMT) from T2DM donors was carried out in recipient mice to investigate the impact of gut dysbiosis on periodontitis. FMT from healthy donors, supplementation of intestinal barrier protectant or the metabolite oleic acid (OA) was administered to mice with T2DM-associated gut dysbiosis to examine their ameliorative effects on periodontal damage.<br><br>RESULTS: T2DM-associated gut dysbiosis, independent of hyperglycaemia, triggered intestinal barrier disruption, which disturbed systemic redox-related metabolisms and elevated oral oxidative stress, thereby aggravating periodontitis. Restoring gut microbiota via FMT from a healthy donor or protecting the intestinal barrier ameliorated periodontitis. Exogenous supplementary metabolite OA rescued periodontal damage by activating the SIRT1/FoxO1 pathway and enhancing antioxidant enzymes in mice with T2DM-associated gut dysbiosis.<br><br>CONCLUSIONS: T2DM-induced gut dysbiosis exacerbates periodontitis through intestinal barrier disruption and redox imbalance. These findings provide new adjunctive therapeutic perspectives including microbiota restoration, intestinal barrier protection and antioxidant supplementation for managing patients with T2DM-induced periodontitis.}, }
@article {pmid41834408, year = {2026}, author = {Zhu, R and Li, L and Zhao, M and Zhang, B and Zhang, Z and Li, M and Yu, L and Song, Z and Gu, N}, title = {Polysaccharide from Ribes nigrum L. Ameliorates Diabetic Kidney Injury in Mice by Modulating the GUDCA/GPBAR1 Axis through the Remodeling of the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {11}, pages = {9370-9386}, doi = {10.1021/acs.jafc.5c16173}, pmid = {41834408}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; Male ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Polysaccharides/administration &amp; dosage ; *Diabetic Nephropathies/drug therapy/metabolism/genetics/microbiology ; Humans ; *Ribes/chemistry ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; *Plant Extracts/administration &amp; dosage ; Kidney/metabolism/drug effects ; NF-kappa B/genetics/metabolism ; Transforming Growth Factor beta/genetics/metabolism ; Bacteria/isolation &amp; purification/classification/genetics ; Akkermansia ; }, abstract = {Diabetic nephropathy (DN) is a major microvascular complication of diabetes, requiring effective therapies. This study showed polysaccharide from Ribes nigrum L. (blackcurrant polysaccharides (BCP)) exerted therapeutic effects in high-fat diet/streptozotocin-induced diabetic mice, improving glucose homeostasis and alleviating renal inflammation and fibrosis. 16S rRNA sequencing revealed BCP altered gut microbiota and notably enriched Akkermansia muciniphila, which was validated via fecal microbiota transplantation and exogenous A. muciniphila administration. Combined 16S rRNA sequencing and metabolomic analysis identified a positive correlation between A. muciniphila and glycoursodeoxycholic acid (GUDCA). Exogenous A. muciniphila supplementation significantly increased the level of serum GUDCA in DN mice. Elevated GUDCA activated the bile acid receptor GPBAR1 in the kidney, suppressing NF-κB/NLRP3 inflammasome and TGF-β-mediated fibrosis. BCP improves renal outcomes by regulating bile acid metabolism through gut microbiota modulation, supporting its potential as a novel dietary strategy for DN.}, }
@article {pmid41834856, year = {2026}, author = {He, Z and Liu, B and Gong, A and Jia, X}, title = {The role of Western diet and gut microbiota in the pathogenesis of cardiovascular diseases.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1608563}, pmid = {41834856}, issn = {1664-302X}, abstract = {The Western diet (WD) is characterized by high fat, high sugar, high salt and low fiber. WD can disrupt the homeostasis of the intestinal flora and become an important factor in the occurrence and development of Cardiovascular Diseases (CVD). This review elucidates the core mechanism through which WD-induced intestinal flora dysbiosis contributes to the development of CVD. Specifically, the disruption of intestinal barrier function promotes the generation of pathogenic metabolites, such as trimethylamine-N-oxide (TMAO), while simultaneously suppressing the production of beneficial metabolites, including short-chain fatty acids (SCFAs). This metabolic shift subsequently triggers systemic inflammatory responses, oxidative stress, and metabolic disturbances, thereby accelerating the progression of CVD-related conditions, such as atherosclerosis and hypertension. Meanwhile, this review systematically summarizes key intervention strategies targeting the gut microbiota. Accumulating evidence indicates that interventions such as probiotics, prebiotics, the Mediterranean diet, and fecal microbiota transplantation (FMT) can effectively restore intestinal microbial homeostasis, enhance the production of SCFAs, and mitigate the risk of CVD. Notably, long-term dietary patterns have demonstrated significant efficacy in reshaping the gut ecosystem, underscoring the importance of sustainable lifestyle modifications. Therefore, this study aims to integrate current knowledge regarding the underlying molecular mechanisms and provide a theoretical basis for developing precise interventions to prevent and treat CVD through modulation of the gut microbiota.}, }
@article {pmid41834861, year = {2026}, author = {Zhang, Z and Hu, X and Ma, Y}, title = {Gut microbiota and ulcerative colitis: a bibliometric analysis of knowledge structure, research hotspots, and future directions.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1765748}, pmid = {41834861}, issn = {1664-302X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a globally prevalent immune-mediated colonic disorder, is fundamentally linked to intestinal dysbiosis. Despite the exponential growth in related papers, systematic, data-driven bibliometric analyses including global productivity trends, international collaboration networks, citation impact distributions, and the temporal evolution of research topics remain lacking.<br><br>METHODS: We conducted a comprehensive bibliometric analysis of 5,879 articles and reviews sourced from the Web of Science Core Collection (WOSCC) and Dimensions (2004-2025). Publication outputs, international collaboration networks, institutional productivity, and keyword evolution were visualized using R-bibliometrix, VOSviewer, and CiteSpace. Lotka's law and Bradford's law were applied to assess author and journal productivity distributions, respectively. Burst detection algorithms identified emerging research frontiers.<br><br>RESULTS: Annual publications demonstrated exponential growth, escalating from 36 in 2004 to a projected 819 in 2024. Geographically, China dominated absolute output (n = 2,559), followed by the USA (n = 1,181), with these two nations collectively accounting for 63.6% of global publications, justifying their prominence as the two major hubs in this research field. Harvard Medical School exhibited the highest citation efficiency (296.6 citations per publication), contrasting with volume leaders like Zhejiang University (92 publications). Co-occurrence clustering revealed 18 distinct knowledge domains, converging on five accelerating frontiers: "fecal microbiota transplantation (FMT)," "short-chain fatty acids," "traditional Chinese medicine," "intestinal barrier mechanisms," and "nanoparticle-based microbiota modulation." Burst analysis confirmed these themes-initiated citation surges post-2017, with "nanoparticles" and "intestinal barrier" exhibiting the strongest recent momentum (2023-2025), indicating a paradigm shift from descriptive microbiome profiling to mechanistic, precision-targeted interventions.<br><br>CONCLUSION: The UC-microbiome research agenda has transitioned from correlative association studies to multi-layered therapeutic modulation. Future efforts should prioritize standardizing FMT protocols through randomized controlled trials, establishing multi-ethnic longitudinal cohorts to address population-specific microbiome signatures, elucidating dose-response relationships of microbial metabolites, and converging nanodelivery systems with microbiome engineering to optimize therapeutic precision and sustain remission.}, }
@article {pmid41836291, year = {2026}, author = {Mi, F and Guo, J and Zheng, W and Shen, J and Ye, H}, title = {Fecal microbiota transplantation alleviates steatosis and inflammation in high-fat and high-sugar diet-induced fatty liver in mice.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1723128}, pmid = {41836291}, issn = {2296-634X}, abstract = {AIM: To investigate whether fecal microbiota transplantation (FMT) could alleviate high-fat and high-sugar (HFCS) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in mice and explore potential mechanisms underlying gut microbiota modulation.<br><br>METHODS: A MAFLD mouse model was established by feeding mice a HFCS diet for 20 weeks, followed by an 8-week intervention with FMT or saline, continuing for a total of 28 weeks. Gut microbiota composition, serum biochemical markers, liver histopathology, and inflammatory cytokine expression were evaluated.<br><br>RESULTS: The HFCS diet induced significant changes in gut microbiota, including increased Firmicutes and decreased Bacteroidetes and Bifidobacterium. FMT partially restored microbiota composition to resemble that of control mice. Mice receiving FMT showed reduced body weight and a consistent trend toward improvement in serum alanine transaminase and total cholesterol levels, although these changes did not reach statistical significance. Liver histology showed amelioration of steatosis and inflammation, as evidenced by reduced MAFLD activity score and decreased intrahepatic expression of IL-1&#x3b2; and IL-17&#x3b1; mRNA. To further explore potential mechanisms, we analyzed a public liver transcriptomic dataset (GSE151220) involving FMT from dysbiotic donors. Differentially expressed genes were enriched in lipid metabolism and extracellular matrix-related pathways, processes known to be involved in MAFLD progression.<br><br>CONCLUSION: These results suggest that FMT is associated with modulation of the gut-liver axis and partial alleviation of HFCS-induced MAFLD features in mice. FMT may serve as a potential adjunctive strategy for managing MAFLD.}, }
@article {pmid41836406, year = {2026}, author = {Guo, Z and Yang, J and Zang, R and Yang, Y and Wang, Q and Xu, C}, title = {The brain-gut-skin axis in inflammatory and disfiguring skin diseases: mechanistic insights, clinical correlations, and therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1737303}, pmid = {41836406}, issn = {1664-3224}, mesh = {Humans ; *Skin Diseases/therapy/etiology/metabolism/immunology/microbiology ; *Skin/immunology/metabolism ; Animals ; *Gastrointestinal Microbiome/immunology ; *Brain-Gut Axis ; Inflammation ; *Brain/metabolism ; }, abstract = {Emerging evidence suggests that the brain-gut-skin axis (BGSA) plays a critical role in the pathogenesis of inflammatory and disfiguring skin diseases. Conditions such as acne, atopic dermatitis, psoriasis, rosacea, vitiligo, and alopecia areata, once regarded as localized disorders driven mainly by cutaneous immune dysfunction, are now recognized as systemic conditions associated with neuroendocrine stress responses, gut microbial dysbiosis, and chronic low-grade inflammation. Mechanistic studies elucidate the intricate interorgan communication mediated by microbial metabolites (e.g., short-chain fatty acids and tryptophan derivatives), cytokine networks, neuropeptides, and hypothalamic-pituitary-adrenal (HPA) axis signaling. Building on these insights, therapeutic strategies are evolving rapidly. Microbiome-directed interventions (probiotics, postbiotics, dietary modification, and fecal microbiota transplantation), together with psychoneuroimmunological approaches, have shown potential to alleviate disease severity. Integrative therapies, including traditional herbal medicine, offer promising effects; however, we emphasize that mechanistic depth and robust clinical validation for these modalities are currently limited. This review integrates mechanistic findings, clinical correlations, and emerging therapeutic approaches, while critically distinguishing between correlation and causation. Future studies should emphasize longitudinal multi-omics analyses and standardized clinical trials to clarify causal pathways and guide precision, patient-centered management for systemic and cutaneous health.}, }
@article {pmid41839386, year = {2026}, author = {Zhou, J and Zheng, L and Zheng, Z and Ding, K and Fu, Z and Ni, Y}, title = {The characteristic of microglia and gut-microglia-brain axis: Implications for cognitive impairment and therapeutic strategies.}, journal = {The Journal of nutritional biochemistry}, volume = {154}, number = {}, pages = {110351}, doi = {10.1016/j.jnutbio.2026.110351}, pmid = {41839386}, issn = {1873-4847}, mesh = {*Microglia/physiology/metabolism ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain ; *Cognitive Dysfunction/therapy/microbiology ; Fecal Microbiota Transplantation ; Aging ; Exosomes/metabolism ; }, abstract = {Aging-associated cognitive impairment (CI) is a core feature of neurodegenerative diseases, profoundly affecting the daily life of patients. Microglial dysfunction significantly contributes to the pathogenesis of CI. The gut-brain axis serves as a pivotal regulator of microglial functions, making it a promising target for halting the development and progression of CI. Deciphering the mechanisms of the gut-microglia-brain (GMB) axis may help devise potential therapeutic strategies to mitigate CI. This review first describes the recent progress in the development and functions of microglia, including the latest advancements in this field. Subsequently, the dynamic and complex communications between microglia and the gut microecosystem, including intestinal cells, gut microbiota, gut microbiota-derived metabolites, gut-derived exosomes, and intestinal bacteriophages, were discussed. Finally, current therapeutic strategies targeting the GMB axis to mitigate CI, such as lifestyle interventions, fecal microbiota transplantation, phages, exosomes, and pharmacological therapies, were summarized. The understanding of GMB axis-mediated cognitive function may pave the way for the identification of novel therapeutic strategies to mitigate aging-associated CI.}, }
@article {pmid41839398, year = {2026}, author = {Kawuribi, V and Awere-Duodu, A and Adjei, FA and Osman, AH and Bomansaan, H and Madadi, MM and Tampuri, JU and Adu-Amankwaah, J}, title = {The gut-tumor metabolic axis: A comprehensive exploration of bidirectional crosstalk in cancer immunotherapy.}, journal = {Critical reviews in oncology/hematology}, volume = {222}, number = {}, pages = {105280}, doi = {10.1016/j.critrevonc.2026.105280}, pmid = {41839398}, issn = {1879-0461}, mesh = {Humans ; *Neoplasms/therapy/metabolism/immunology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Animals ; Tumor Microenvironment/immunology ; }, abstract = {The gut-tumor metabolic axis represents a bidirectional immunometabolic network in which tumor-derived metabolites reshape microbial ecology, while gut microbiome-derived metabolites recalibrate systemic and intratumoral immunity, ultimately influencing cancer progression and immunotherapy outcomes. Tumor aerobic glycolysis generates excess lactate and acidity that suppress cytotoxic immune function, remodel the tumor immune microenvironment, and indirectly perturb intestinal microbial composition. In turn, microbial metabolites including short-chain fatty acids, bile acid derivatives, tryptophan catabolites, inosine, and trimethylamine N-oxide signal through defined host pathways such as GPR109A, AHR, and adenosine A2A receptors to regulate antigen presentation, T-cell differentiation, macrophage polarization, and immune checkpoint sensitivity. Preclinical and emerging clinical evidence demonstrates that dietary modulation, rational probiotics, and fecal microbiota transplantation can enhance immune checkpoint inhibitor efficacy in selected contexts. However, metabolite effects are highly context dependent, with dose, timing, tumor type, and immune state critically shaping therapeutic benefit or resistance. This review integrates mechanistic insights and clinical evidence, highlights translational challenges including safety, donor heterogeneity, and biomarker validation, and proposes a framework for biomarker-guided microbiome-based strategies to advance precision cancer immunotherapy.}, }
@article {pmid41844477, year = {2026}, author = {Hui, H and Guzailiayi, A and Sirui, H and Danping, L and Xiaoyan, L and Abudukelimu, A and Pengbo, W}, title = {Sleep deprivation exacerbates hepatic steatosis by promoting hepatic inflammation and oxidative stress through gut microbiota dysbiosis in metabolic dysfunction-associated fatty liver disease rat.}, journal = {Biochemical and biophysical research communications}, volume = {813}, number = {}, pages = {153588}, doi = {10.1016/j.bbrc.2026.153588}, pmid = {41844477}, issn = {1090-2104}, mesh = {Animals ; *Oxidative Stress ; *Sleep Deprivation/complications/microbiology ; Rats, Sprague-Dawley ; Male ; *Gastrointestinal Microbiome ; *Dysbiosis/complications/microbiology ; Rats ; *Fatty Liver/pathology/microbiology/metabolism ; Inflammation/pathology/microbiology ; Liver/pathology/metabolism ; Diet, High-Fat/adverse effects ; }, abstract = {OBJECTIVE: The study aimed to explore the impact of sleep deprivation on hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MASLD) and its possible mechanisms.<br><br>METHODS: Forced exercise was used to establish sleep deprivation(SD) models in Sprague-Dawley rats. After 8 weeks of modeling, lipid profile, liver function, pathological feature, inflammatory cytokines, oxidative stress markers, and gut microbiota were determined.<br><br>RESULTS: Sleep deprivation exacerbated hepatic steatosis in MASLD rats, as evidenced by significant alteration in morphological analysis and pathological features, accompanied by more severe metabolic disorders and liver injury. Moreover, sleep deprivation dramatically enhanced the secretion of pro-inflammatory cytokines and oxidative stress damage in the liver of MASLD rats. The results of 16S rRNA analysis confirmed a novel causal role of gut microbiota dysbiosis in driving the development of MASLD. Furthermore, sleep deprivation exacerbated gut microbiota dysbiosis in MASLD rats, especially reducing beneficial bacteria including s_roseburia hominis, s_Bacteroides vulgatus, and s_Akkermansia muciniphila. Interestingly, fecal microbiota transplantation (FMT) had demonstrated potential to restore gut microbiota dysbiosis induced by the synergism of high-fat diet (HFD) and sleep deprivation. After partially counteracting the impact of the synergistic effects on gut microbial homeostasis by FMT, hepatic steatosis, hepatic inflammation, and oxidative stress damage in rats of the HFD&#xa0;+&#xa0;SD group were substantially improved.<br><br>CONCLUSIONS: These results reveal that sleep deprivation exacerbates hepatic steatosis in MASLD by disrupting gut microbial homeostasis, thereby aggravating hepatic inflammation and oxidative stress, providing novel insights into the potential therapeutic strategies for MASLD and other sleep deprivation-related disorders.}, }
@article {pmid41844930, year = {2026}, author = {Kumari, N and Pal, G and Chawak, K and Arbi, SH and Anand, S}, title = {Current trends and updates on the emerging role of fecal microbiota transplantation in the treatment of neurodegenerative diseases.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {4}, pages = {}, pmid = {41844930}, issn = {1572-9699}, mesh = {*Fecal Microbiota Transplantation/trends/methods ; Humans ; *Neurodegenerative Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Animals ; Dysbiosis/therapy ; }, abstract = {Fecal microbiota consists of a consortium of bacterial populations that reside in the human body, particularly in the gastrointestinal system, and are crucial to numerous physiological processes. Due to its promising clinical potential and acceptable safety profile, FMT has been the subject of numerous investigations as a possible therapeutic method for curing diverse disorders. Neurodegenerative diseases (NDs) are one among them and warrant immediate attention. There is a lack of efficient treatments for many ailments, and despite decades of research, we still don't fully understand their mechanisms and causes. The lack of advancement has prompted the research community to focus more on investigating novel or different elements that may impact the etiology or management of these disorders. The gut-brain axis, which embraces the two-way communication between the gut and brain via immunological, neurological, endocrine, and metabolic pathways, is one such element. Since NDs are frequently linked to aberrant gut microbiome compositions, it is not surprising that altering the gut microbiome can be a promising strategy in the treatment and management of neurological disorders. Fecal microbiota transplantation (FMT) is a technique employed for modulating microbiome composition and is becoming more and more common. FMT or recolonizing the ''diseased'' gut with a normal microbiome is one way to restore a dysbiotic gut. Traditionally used to treat Clostridium difficile-linked infections, FMT has lately been investigated as a probable treatment strategy for NDs. This review aims to systematically tap the current trends and updates on the employment of FMT in neurodegenerative research, whether as a treatment regimen or to look into the role of the microbiota in pathogenesis.}, }
@article {pmid41844942, year = {2026}, author = {Thu, MS and Le, HBC and Duc, NP and Mai, VH and Walker, N and Hirankarn, N}, title = {Impact of microbiome-modulating strategies in cancer patients receiving immunotherapy (MSIT): A systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41844942}, issn = {2045-2322}, support = {N42A680423//National Research Council of Thailand/ ; }, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome/drug effects/immunology ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Synbiotics/administration &amp; dosage ; }, abstract = {The gut microbiota influences immune checkpoint inhibitors (ICIs) efficacy. Microbiome-modulating strategies (MMSs), including probiotics, synbiotics, and faecal microbiota transplantation (FMT), have emerged as promising adjuncts, but their clinical impact remains uncertain. We systematically reviewed PubMed, Embase, and CENTRAL to February 2025 for clinical cohorts evaluating MMS in cancer patients receiving ICIs. Thirty-six studies (25 trials/cohorts; n = 2,746) were included. Meta-analyses, and subgroup analyses were performed for efficacy along with microbiome shifts and safety. MMS plus ICIs achieved a pooled objective response rate (ORR) of 40% (95% CI: 31%-49%; I[2] = 63.4%; p = 0.0003; 95% PI: 15%-72%). Descriptive proportions showed ORR of 45% (95% CI: 32%-58%; I[2] = 72.5%; p = 0.0058) for probiotics and 33% (95% CI: 22%-48%; I[2] = 60.7%; p = 0.0064) for FMT; however, these findings are non-comparative and confounded by study differences. Exploratory subgroup signals were noted for probiotics in NSCLC (ORR 55%; 95%CI: 45%-64%; I[2] = 0%; p = 0.3683) and FMT in melanoma (ORR 39%; 95% CI: 15%-69%; I[2] = 72.5%; p = 0.0262). Dual ICI regimens showed the highest point estimate for ORR (43%; 95% CI: 17%-73%; I[2] = 68.5%; p = 0.0747) but increased toxicity. Microbiome analyses revealed enrichment of short-chain fatty acid-producing taxa and Bifidobacterium spp. among responders. Based on a limited pooled sample size (n = 143), MMS-related adverse events were mostly grade 1-2 (42%; 95% CI: 14%-77%, I[2] = 53.8%, p = 0.0210), with rare severe events (1%). Overall, MMS show promising, though preliminary, hypothesis-generating signals for modulating ICI response. Given high heterogeneity and reliance on early-phase, single-arm trials, the findings underscore urgent need for large, biomarker-driven randomized controlled trials to define optimal interventions and cautiously integrate microbiome modulation into immuno-oncology care.}, }
@article {pmid41845903, year = {2026}, author = {Cao, H and Sun, J and Lv, Y and Ye, J and Wang, Y and Jiang, H}, title = {Targeting the gut-kidney axis to improve kidney transplantation prognosis: from mechanisms to clinical intervention strategies.}, journal = {Renal failure}, volume = {48}, number = {1}, pages = {2642487}, pmid = {41845903}, issn = {1525-6049}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Graft Rejection/prevention &amp; control/immunology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Prognosis ; *Kidney Failure, Chronic/surgery ; *Kidney/immunology ; Immunosuppressive Agents/therapeutic use ; Graft Survival/immunology ; Intestinal Mucosa/immunology ; Animals ; Immune Tolerance ; }, abstract = {Kidney transplantation is an important treatment for end-stage renal disease, but lifelong immunosuppression is needed to prevent immune rejection, but the immunosuppressive therapy increases the risk of post-transplant complications. Therefore, how to improve the long-term survival of transplanted kidneys and reduce rejection has become a hot spot in current research. Recently, the 'gut-kidney axis' has received widespread attention as an important pathway for immune regulation. It refers to the fact that changes in either side of the gastrointestinal tract and kidney will affect the other side through energy metabolism, immuno-inflammation, intestinal mucosa, intestinal flora, among others, up and including to adverse consequences, which can be mutually causative. With the theory of 'gut-kidney axis', more and more studies have found that intestinal immune cells and microbiota play an important role in maintaining immune homeostasis and regulating the immune microenvironment of renal transplant recipients. Some studies have found that intestinal immune cells and microbiota not only influence the systemic immune status, but also may regulate the immune response of transplanted kidneys through metabolites and inflammatory mediators. In this review, we summarize the potential mechanisms of intestinal immune cells and microbiota in immune tolerance and rejection after renal transplantation based on the theory of 'gut-kidney axis'. In addition, we highlight microbiome modulation strategies, particularly dietary interventions and fecal microbiota transplantation, as emerging approaches with potential to improve transplant outcomes. A deeper understanding of the mechanism of action of the gut-kidney axis will provide new ideas and therapeutic targets for immunomodulation after renal transplantation.}, }
@article {pmid41846062, year = {2026}, author = {Zhu, Q and Gao, M and Yan, M and Ma, Z and Li, X and Yu, M and Niu, X and Wang, J}, title = {Naringin alleviates autoimmune hepatitis in mice via the gut-liver Axis through modulation of microbiota, metabolites, and immune responses.}, journal = {International immunopharmacology}, volume = {177}, number = {}, pages = {116498}, doi = {10.1016/j.intimp.2026.116498}, pmid = {41846062}, issn = {1878-1705}, mesh = {Animals ; *Flavanones/therapeutic use/pharmacology ; *Hepatitis, Autoimmune/immunology/drug therapy/metabolism/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects/immunology ; *Liver/drug effects/metabolism/immunology/pathology ; Mice ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Male ; Dysbiosis ; Humans ; Cytokines/metabolism ; }, abstract = {Autoimmune hepatitis (AIH) is an immune-mediated liver disease that could be impacted by gut microbiota dysbiosis. Naringin, a flavonoid derived from citrus fruits, has been reported to modulate gut microbial composition and alleviate liver diseases, but its role in AIH remains incompletely understood. In this study, we used multi-omics analysis and fecal microbiota transplantation (FMT) to examine the protective benefits of naringin in a ConA-induced AIH mouse model. To strengthen mechanistic conclusions, histopathological scoring, liver function indices, and immune cell profiling were determined. Naringin reduced IFN-γ and IL-17A, improved oxidative balance, remodeled hepatic transcriptome, and corrected microbial dysbiosis. Integrated multi-omics analysis revealed associations with altered MAPK, NF-κB, JAK-STAT, and autophagy pathways. Additional investigations revealed that naringin increased the expression of the tight junction proteins ZO-1 and occludin, improved intestinal barrier integrity, and decreased Th1/Th17 cell proportions without significantly altering Th2 cells, as validated by flow cytometry and immunohistochemistry. Importantly, FMT from naringin-treated donors provided hepatoprotective benefits in recipient mice. These findings shed fresh information on the gut-liver axis in AIH, highlighting naringin as a potential therapeutic agent through coordinated regulation of oxidative stress, immune responses, and gut microbiota-associated metabolic profiles.}, }
@article {pmid41846401, year = {2026}, author = {Bogatic, D and Costello, SP and Bryant, RV}, title = {Letter: Dose and Donor Matter-Determining the Optimal Strategy for Faecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.70625}, pmid = {41846401}, issn = {1365-2036}, }
@article {pmid41847216, year = {2026}, author = {Shi, H and Huang, L and Zhang, JH and Shen, C and Zhang, N and Lv, C and Shao, L and Li, M and Sun, Z and Shi, L and Yu, G and Chen, Y}, title = {Gut Microbiota Regulates Brain-Bone Axis to Influence Osteoporosis Pathogenesis and Treatment.}, journal = {Research (Washington, D.C.)}, volume = {9}, number = {}, pages = {1178}, pmid = {41847216}, issn = {2639-5274}, abstract = {Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, impaired microarchitecture, and increased fracture risk, primarily resulting from dysregulated bone remodeling. Increasing evidence highlights a close interaction between bone metabolism and the gut microbiota. Alterations in bone mineral density can influence gut microbial composition. Conversely, microbial dysbiosis disrupts bone homeostasis through multiple pathways, including microbial metabolites, immune regulation, and neuroendocrine signaling. Short-chain fatty acids suppress osteoclast differentiation and enhance intestinal calcium absorption, while gut dysbiosis promotes bone loss by impairing intestinal barrier integrity and increasing proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The gut-brain-bone axis represents an important regulatory network linking the central nervous system, gut-derived signals, and skeletal remodeling. Chronic stress and neurodegenerative conditions activate the hypothalamic-pituitary-adrenal axis and bone-derived extracellular vesicle signaling, thereby favoring bone resorption. Estrogen deficiency further disrupts the receptor activator of nuclear factor κΒ ligand/osteoprotegerin signaling pathway and alters gut microbial composition, contributing to postmenopausal bone loss. Therapeutic strategies targeting this axis, including probiotics, prebiotics, fecal microbiota transplantation, dietary fiber supplementation, and pharmacological or natural compounds, show potential in restoring microbial balance and improving bone metabolism. Future studies integrating multiomics approaches and well-designed clinical trials are needed to clarify microbiome-bone interactions and support the development of targeted interventions for osteoporosis.}, }
@article {pmid41849251, year = {2026}, author = {Chen, J and Shen, X and Chen, Y and Liang, J and Liu, Y and Cao, J and Wang, LS and Lu, B and Sun, C and Wang, Y}, title = {Finger Citron (Citrus medica L. var. sarcodactylis Swingle) and Its Characteristic Component Limettin Alleviated Diet-Induced Obesity via Modulating Gut Microbiota and Steroid Hormone Biosynthesis.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {12}, pages = {10232-10248}, doi = {10.1021/acs.jafc.5c15347}, pmid = {41849251}, issn = {1520-5118}, mesh = {Animals ; *Obesity/microbiology/metabolism/drug therapy/etiology ; Male ; *Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; Mice ; *Steroids/biosynthesis ; *Citrus/chemistry ; Mice, Inbred C57BL ; Humans ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; *Plant Extracts/administration &amp; dosage/chemistry ; *Anti-Obesity Agents/administration &amp; dosage ; }, abstract = {This study investigated the antiobesity effects and underlying mechanisms of finger citron extract (FC) and its characteristic compound limettin (LMT) in high-fat diet (HFD)-induced obese mice. FC and LMT significantly reduced body weight gain and improved glucose and lipid homeostasis in obese mice. Fecal 16S rRNA sequencing revealed that both treatments reversed HFD-induced gut dysbiosis, enriching norank_f__norank_o__Clostridia_UCG-014, while FC uniquely increased Akkermansia and decreased Rikenella. Serum metabolomics indicated that FC and LMT markedly activated the steroid hormone biosynthesis pathway, elevating 11β-hydroxyprogesterone, 17α-hydroxyprogesterone, and 11-deoxycorticosterone. Colon transcriptomics further confirmed altered local steroid synthesis and metabolism in the colon. Antibiotic depletion and fecal microbiota transplantation verified the indispensable role of gut microbiota in FC/LMT-mediated metabolic protection. Collectively, FC and LMT ameliorated diet-induced obesity by modulating steroid hormone biosynthesis through gut microbiota regulation, highlighting their potential as functional dietary supplements for obesity prevention.}, }
@article {pmid41850677, year = {2026}, author = {Mi, X and Liu, R and Jiang, Z and Tang, M and Yan, J and Liu, J and Li, Y and Zheng, J and Yang, W and Gong, L and Shi, J}, title = {Gut Microbiota-Derived Propionate Governs Hepatic N2 Neutrophils in Wilson's Disease.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {20}, number = {7}, pages = {101770}, pmid = {41850677}, issn = {2352-345X}, mesh = {Animals ; *Neutrophils/metabolism/immunology/drug effects ; *Hepatolenticular Degeneration/pathology/immunology/microbiology/metabolism ; *Propionates/metabolism/pharmacology ; Mice ; Mice, Knockout ; *Gastrointestinal Microbiome/immunology ; Transforming Growth Factor beta1/metabolism ; *Liver/pathology/immunology/metabolism ; Fecal Microbiota Transplantation ; Copper-Transporting ATPases/genetics ; Disease Models, Animal ; Male ; Humans ; Hydroxamic Acids ; }, abstract = {BACKGROUND &amp; AIMS: Neutrophil functions play a pivotal role in hepatic pathogenesis. Our previous work has established that N2-polarized neutrophils promote hepatic fibrogenesis in Wilson's disease depends on hepatic transforming growth factor-β1 (TGF-β1) production. However, the regulators governing TGF-β1 production in orchestrating disease-associated N2 neutrophils remain elusive. In this study, we investigated the immunomodulatory effects of gut microbiota-derived short-chain fatty acids (SCFAs) on neutrophil polarization.<br><br>METHODS: Fecal metagenomic sequencing and short-chain fatty acid (SCFA) profiling were performed on ATP7B-knockout (ATP7B-KO) mice and their wild-type (WT) littermate controls. Fecal microbiota transplantation (FMT) experiments were conducted by transferring feces from WT mice or Akkermansia muciniphila into recipient mice. Additionally, propionate or trichostatin A (TSA) was administered to both ATP7B-KO and WT groups. Mice were assessed using histological analyses, Sirius Red staining, flow cytometry, biochemical assays, immunohistochemistry, measurement of TGF-&#x3b2;1 levels, immunofluorescence, and quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression profiling. To elucidate the underlying molecular mechanisms, 4D label-free quantitative acetylated proteomics, site-directed mutagenesis, plasmid transfection, co-immunoprecipitation (IP), and luciferase reporter assays were employed.<br><br>RESULTS: We report that Akkermansia muciniphila was markedly reduced in the gut microbiota of mice with Wilson's disease, accompanied by decreased SCFA levels, especially propionate. Additionally, transplantation of fecal bacteria from wild-type mice or A muciniphila could promote an antifibrotic effect, elevate propionate levels, reduce TGF-&#x3b2;1 secretion, and decrease hepatic N2 neutrophils in mice with Wilson's disease. Moreover, administration of propionate also significantly enhanced antifibrotic immunity. Mechanistically, propionate reduced the production of TGF-&#x3b2;1 in hepatocytes by inhibiting histone deacetylase activity, increasing the acetylation of DNAJA3 at sites K134 and K385, thus decreasing expression of DNAJA3. Consistently, gut-derived propionate inversely correlated with hepatic injury severity in patients with Wilson's disease, which could be functionally mediated by TGF-&#x3b2;1.<br><br>CONCLUSIONS: Gut microbiota are pivotal for hepatic neutrophil polarization and liver fibrosis in Wilson's disease. Our findings suggest that therapeutic modulation of gut microbiota, SCFA profiles, and TGF-&#x3b2;1 production, particularly when combined with histone deacetylase inhibitors, may represent promising therapeutic approaches for Wilson's disease.}, }
@article {pmid41851729, year = {2026}, author = {Zhu, W and Han, L and He, L and Wei, S and Li, J and Xin, L and Zhang, H and Shen, J and Song, Y and Zhou, J and Chang, CJ and Zhou, J}, title = {Parabacteroides goldsteinii-derived outer membrane vesicles alleviate acute lung injury via modulation of bile acid metabolism.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {}, pmid = {41851729}, issn = {1477-3155}, support = {JSZK2019A01//Shanghai Jinshan Municipal Health Commission/ ; 20DZ2261200//Science and Technology Commission of Shanghai Municipality/ ; 20DZ2254400//Science and Technology Commission of Shanghai Municipality/ ; 82470069//National Natural Science Foundation of China/ ; 2022YFA0806200//National Key Research and Development Program of China/ ; ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; }, mesh = {Animals ; *Acute Lung Injury/metabolism/chemically induced/drug therapy ; Mice ; Male ; *Bile Acids and Salts/metabolism ; Mice, Inbred C57BL ; Bleomycin ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects ; *Bacterial Outer Membrane/metabolism ; Cytokines/metabolism ; Lung/metabolism/pathology ; }, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe clinical syndrome with limited therapeutic options. Acute lung injury (ALI) is widely used as an experimental animal model that recapitulates the key pathological features of human ARDS. Parabacteroides goldsteinii, a newly identified Gram-negative probiotic, exhibits anti-inflammatory effects in certain disease models. Gram-negative bacteria release nanoscale structures called outer membrane vesicles (OMVs), which show varying composition across species. The role of P. goldsteinii-derived OMVs (Pg-OMVs) in ALI or ARDS remains to be elucidated.<br><br>RESULT: In this study, we investigated the therapeutic potential of Pg-OMVs in a bleomycin (BLM)-induced ALI mouse model and explored their effects on pulmonary inflammation and gut microbiota composition. Compared to mice receiving BLM alone, Pg-OMV-treated mice exhibited significantly reduced inflammatory cell infiltration and lower levels of pro-inflammatory cytokines. Notably, Pg-OMV treatment significantly altered the gut microbiota composition, characterized by an increased abundance of Akkermansia muciniphila and a decreased abundance of Clostridia_bacterium. Fecal microbiota transplantation (FMT) experiments confirmed that the protective effects of Pg-OMVs were mediated via gut-lung axis. Further analysis revealed elevated cholic acid (CA) levels in the peripheral blood and bronchoalveolar lavage fluid following Pg-OMV treatment. CA was shown to suppress BLM-induced macrophage pyroptosis in the lung. Pharmacological inhibition of CA reversed the protective effects of Pg-OMVs, further confirming its pivotal role.<br><br>CONCLUSIONS: In summary, Pg-OMVs increased the abundance of Akkermansia muciniphila while decreasing the abundance of Clostridia_bacterium in the gut, elevated systemic CA levels, and suppressed macrophage pyroptosis via inhibition of the NF-&#x3ba;B pathway, thereby attenuating pulmonary inflammation and ultimately alleviating ALI. These findings highlight a novel therapeutic strategy for the treatment of ALI or ARDS by targeting the gut-lung axis.}, }
@article {pmid41852385, year = {2025}, author = {Ataei, P and Kalantari, H and Bodnar, TS and Turner, RJ}, title = {The gut-brain connection: microbes' influence on mental health and psychological disorders.}, journal = {Frontiers in microbiomes}, volume = {4}, number = {}, pages = {1701608}, pmid = {41852385}, issn = {2813-4338}, abstract = {The human gut microbiome has emerged as a pivotal modulator of brain function and mental health, acting through intricate bidirectional communication along the gut-brain axis. Mounting evidence suggests that microbial communities influence neurodevelopment, neurotransmission, and behavior via pathways involving the vagus nerve, immune signaling, and microbiota-derived metabolites such as short-chain fatty acids and neurotransmitter precursors. This review critically examines the mechanistic underpinnings of microbiota-brain communication and evaluates current findings linking dysbiosis to psychiatric conditions, including depression, anxiety, schizophrenia, autism spectrum disorder, and bipolar disorder. In addition, it assesses the therapeutic potential of microbiome-targeted interventions-such as probiotics, fecal microbiota transplantation (FMT), and precision dietary modulation-in ameliorating neuropsychiatric symptoms. While the field holds considerable promise, limitations, including correlational study designs, small sample sizes, and a lack of standardized methodologies, underscore the need for rigorous, large-scale clinical trials. A deeper understanding of host-microbe interactions may catalyze a paradigm shift in psychiatric treatment, paving the way for novel, personalized microbiome-based therapeutics.}, }
@article {pmid41852399, year = {2025}, author = {Tillotson, G}, title = {Editorial: Live Biotherapeutic Products: where are we?.}, journal = {Frontiers in microbiomes}, volume = {4}, number = {}, pages = {1664282}, pmid = {41852399}, issn = {2813-4338}, }
@article {pmid41852409, year = {2025}, author = {Bailey, A and Leuther, KK and Robinson, LA}, title = {The microbiome and lung cancer: microbial effects on host immune responses and treatment outcomes.}, journal = {Frontiers in microbiomes}, volume = {4}, number = {}, pages = {1606551}, pmid = {41852409}, issn = {2813-4338}, abstract = {The human microbiome plays a critical role in shaping physiological processes, immune system function, metabolism, and disease development. Recent research has highlighted the microbiome's profound cancer impact, particularly on lung cancer. This review explores how microbial communities in lung and gut influence tumor progression, immune responses, and treatment outcomes as well as describing the interactions between the microbiome and the host immune system in modulating the efficacy of cancer therapies. Emerging evidence from preclinical and clinical studies investigating the role of the lung and gut microbiome in lung cancer focus on alterations in the microbiota that influence the tumor microenvironment, modulate immune responses, and potentially enhance/hinder treatment effectiveness such as chemotherapy, targeted therapies, and immunotherapy. Microbial diversity plays a significant role in immune regulation, and specific microbial species may activate/suppress immune cells such as T-cells, dendritic cells, and macrophages. Furthermore, this review examines the therapeutic implications of microbiome modulation, including the use of probiotics, antibiotics, and fecal microbiota transplantation in enhancing cancer therapies. Alterations in the lung and gut microbiome and their interaction in the recently described gut-lung axis with its bidirectional communication significantly influence the tumor microenvironment and systemic immune responses. These findings suggest that microbial diversity can regulate immune functions, with specific species capable of activating or suppressing immune cell activity. Furthermore, microbiome-targeted interventions show potential in improving the effectiveness of treatments including chemotherapy, targeted therapies, and immunotherapy, underscoring the importance of the microbiome as a key factor in lung cancer pathogenesis and treatment.}, }
@article {pmid41852427, year = {2025}, author = {Al-Kuwari, A and Al-Karbi, H and Al-Khuzaei, A and Baroudi, D and Bendriss, G}, title = {Beyond antibiotics: leveraging microbiome diversity to combat antimicrobial resistance.}, journal = {Frontiers in microbiomes}, volume = {4}, number = {}, pages = {1618175}, pmid = {41852427}, issn = {2813-4338}, abstract = {The best way to fight harmful microbes may not lie in new antibiotics, but rather in leveraging the power of microbes themselves. Antimicrobial resistance (AMR) is a growing global concern, where the overuse of antibiotics has led to the emergence of resistant strains. This paper explores the potential of increasing diversity in gut microbiomes as natural approaches to fight AMR. The promotion microbial diversity is proposed as a promising strategy to reduce dependency on antibiotics by fostering a resilient microbial community. Strategies are discussed to address the loss of diversity caused by antibiotics including diet, probiotics, fecal transplants (FMT) and fermentation of animal/plant products. Preliminary findings from an experiment with camel milk fermentation suggest that fermentation can increase microbial diversity, potentially affecting resistance to common antibiotics such as tetracycline, streptomycin, penicillin, and chloramphenicol, and enhancing microbiome resilience, allowing it to naturally resist pathogens without additional antibiotic use. The results highlight both the benefits and potential risks fermented products. Additionally, FMT, naturally occurring in the animal world, is a promising method to restore microbiome balance and mitigating the impact of AMR. A mechanistic model is discussed to underscore the importance of maintaining microbial balance as an effective strategy for mitigating AMR and promoting long-term health. Further research are needed to better understand the mechanisms behind these changes and their implications for public health. This perspective paper calls for a shift in the approach to AMR, advocating for microbiome-based solutions as a sustainable alternative to traditional pharmaceutical interventions.}, }
@article {pmid41852522, year = {2026}, author = {Luo, Y and Cao, J and Li, B and Wang, J and Geng, T and Luo, Z and Xie, J}, title = {Global landscape analysis of clinical trials on gut microbiota modulation therapies for irritable bowel syndrome.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1737537}, pmid = {41852522}, issn = {2296-858X}, abstract = {OBJECTIVE: Systematically analyze the global landscape of interventional clinical trials on gut microbiota modulation (GMM) therapies for irritable bowel syndrome (IBS).<br><br>METHODS: Searched the Trialtrove database (1998-July 2025) with the key term combination "(Disease is Autoimmune/Inflammation: Irritable Bowel Syndrome) AND (Mechanism of Action: Microbiome modulator)", included 305 interventional trials (excluded 15 observational studies). Descriptive analysis was done via SPSS 26.0, adhering to TITAN Guidelines 2025.<br><br>RESULTS: Asia was the most active region; trials peaked in 2021, with Phase II (44.3%) and IV (33.3%) dominant. Probiotics led (single-strain: Lactobacillus/Bifidobacterium; multi-strain: Lactobacillus&#x202f;+&#x202f;Bifidobacterium), followed by fecal microbiota transplantation (FMT). IBS-D (49.6%) was the main subtype (IBS-C: 26.1%); probiotics were the most frequently studied for both, FMT for IBS-D, and prebiotics for IBS-C.<br><br>CONCLUSION: GMM therapies for IBS are relatively mature. Personalized therapies are necessary; multiomics and emerging therapies (e.g., Akkermansia muciniphila) will promote IBS precision medicine.}, }
@article {pmid41853345, year = {2023}, author = {Huang, Q and Yang, L and Cai, G and Huang, Y and Zhang, S and Ye, Z and Yang, J and Gao, C and Lai, J and Lin, L and Wang, J and Liu, T}, title = {Comparison of the gut microbiota of college students with the nine balanced and unbalanced traditional Chinese medicine constitutions and its potential application in fecal microbiota transplantation.}, journal = {Frontiers in microbiomes}, volume = {2}, number = {}, pages = {1292273}, pmid = {41853345}, issn = {2813-4338}, abstract = {Fecal microbiota transplantation (FMT) has been tested for the prevention and treatment of various intestinal and extra-intestinal diseases, but its efficacy is not stable, which may be due to the lack of an optimized method for screening high-quality donors. The low efficiency and high cost of donor screening are also obstacles to the clinical application of FMT. In this study, we tested the efficiency of the constitution theory of traditional Chinese medicine (TCM) in screening high-quality FMT donors. College student volunteers were sorted into either the balanced TCM constitution (BC) or unbalanced TCM constitution (UBC) groups, with the latter group comprising eight different constitution types, and the gut microbiota profiles of each UBC were compared with that of BC. Subsequently, the success rates of the qualified donors of BC and UBC volunteers were compared. Finally, the anti-obesity effect of FMT, obtained using the fecal microbiota of BC and UBC donors, was tested on mice with high fat diet-induced obesity. The results showed that the gut microbiota of BC and UBC volunteers were significantly different. There was a higher proportion of qualified FMT donors in the BC volunteer group than in the UBC volunteer group. Moreover, the experiment in mice showed that the fecal microbiota of BC and UBC volunteers conferred different anti-obesity effects. Overall, TCM constitution could be a reference for FMT practice. Our study presents a new idea, namely, using TCM constitution theory to efficiently screen high-quality FMT donors.}, }
@article {pmid41853353, year = {2023}, author = {Ortiz-Olvera, N and Fernández-Figueroa, EA and Argueta-Donohué, J and Miranda-Ortíz, H and Ruiz-García, E}, title = {Case Report: Oral and fecal microbiota in a super-donor: the healthy microbiota paradigm for fecal transplantation.}, journal = {Frontiers in microbiomes}, volume = {2}, number = {}, pages = {1219960}, pmid = {41853353}, issn = {2813-4338}, abstract = {Despite the numerous fecal microbiota transplantation trials that have been carried out, knowledge about the actual composition of a "healthy microbiota" remains scarce. The aim of this research was to describe the differences in the composition of oral and fecal microbiotas in a super-donor. The microbiota analysis was done using next-generation sequencing of the V3 and V4 regions of the bacterial 16S rRNA gene. The biodiversity found in the mouth was very rich, with 56 species identified, and there was a predominance of the genera Veillonella, Haemophilus, and Streptococcus. It is worth mentioning the presence (2.33%) of Fusobacterium nucleatum in the mouth. In feces, the genera Bacteroides and Faecalibacterium predominated, with the species F. prausnitzii being the most abundant. This analysis shows that the diversity of the microbiota of a super-donor plays a fundamental role in the effectiveness of its product in fecal matter transplantation. This suggests that transplanted gut microorganisms have the ability to maintain or recover health in a dynamic process between the microbiota and the host. Our findings encourage further research which will result in the development of bacterial therapies in infectious and inflammatory diseases.}, }
@article {pmid41853374, year = {2023}, author = {Gudka, R and Nyinoh, IW}, title = {Fecal microbial transplantation as a novel therapeutic for autism spectrum disorders: a review of the current literature.}, journal = {Frontiers in microbiomes}, volume = {2}, number = {}, pages = {1222089}, pmid = {41853374}, issn = {2813-4338}, abstract = {BACKGROUND: Autism spectrum disorders (ASDs) are complex neurobiological conditions with poor long-term outcomes and limited treatment options. The microbiota-gut-brain axis indicates a pathway by which the gut microbiota links to ASDs. Fecal microbial transplantation (FMT), whereby the gut microbiota is replaced with that of a healthy individual, shows promise for the treatment of neurobiological conditions. This review examines the current evidence for the use of FMT as a therapeutic for ASD.<br><br>DISCUSSION: ASDs and their associated gastrointestinal symptoms are improved with FMT, potentially due to the engraftment of features of a healthy gut. Longer treatment regimens that include daily maintenance doses appear to be the most effective long-term therapeutic option, with benefits persisting 2 years post-intervention. Evidence is mixed regarding the use of preparatory treatments. Considering the sex bias in ASD research, small sample sizes and the lack of placebo control arms, randomized controlled trials would be of benefit to the evidence base regarding the use of FMT as a therapeutic option for ASD.<br><br>CONCLUSION: FMT is a promising new therapeutic for ASD, but the evidence base is in its infancy.}, }
@article {pmid41853519, year = {2024}, author = {Li, Y and Yang, Y and Yang, N and Wu, Q and Yang, J and Guo, J and Zhang, H}, title = {Recent advances in fecal microbiota transplantation for Clostridium difficile infection-associated diarrhea after kidney transplantation.}, journal = {Frontiers in microbiomes}, volume = {3}, number = {}, pages = {1409967}, pmid = {41853519}, issn = {2813-4338}, abstract = {Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.}, }
@article {pmid41853530, year = {2024}, author = {Suo, Z and Yu, Y and Shi, F and Tian, J and Hao, Z and Zhang, J and Zou, J}, title = {Effects of oral liquiritigenin inoculation on gut microbiota and gene expression in intestinal and extraintestinal tissues of mice.}, journal = {Frontiers in microbiomes}, volume = {3}, number = {}, pages = {1380152}, pmid = {41853530}, issn = {2813-4338}, abstract = {INTRODUCTION: Liquiritigenin (LQ), a natural flavonoid found in traditional Chinese medicine and often administered orally, holds potential to affect both the gut and its microbiota, that potentially mediating or influencing its biological and pharmacological effects. However, the effects of LQ on gut microbiota composition and intestinal function remain poorly understood. In this study, we aimed to explore the impact of LQ on gut microbiota and gene expression in both intestinal and extraintestinal tissues.<br><br>METHODS: We orally inoculated six-week-old SPF C57BL/6 mice with either LQ (a concentration of 4 mg/ml diluted in dimethylsulfoxide, (DMSO)) or DMSO, and administered daily for a duration of 2 weeks. At the end of the experimental period, all mice were euthanized. Fresh fecal samples, as well as samples from the intestine, lung, and liver, were collected for subsequent microbiota analysis, RNA-seq, or histochemical and immunohistochemical (IHC) staining.<br><br>RESULTS: Findings show that LQ alters gut microbiota composition, enhancing microbial correlations in the colon but causing some dysbiosis, evidenced by increased pathobionts, decreased beneficial bifidobacteria, and reduced microbiota diversity. Gene expression analysis reveals LQ upregulates mucosal immune response genes and antiinfection genes in both the intestine and lung, with histology confirming increased Paneth cells and antimicrobial peptides in the intestine. Additionally, LQ affects tissue-specific gene expression, triggering hypersensitivity genes in the colon, downregulating metabolic genes in the small intestine, and reducing cell motility and adhesion genes in the lung.<br><br>DISCUSSION: These results suggest LQ's potential to modulate common mucosal immunity but also highlight possible risks of gut dysbiosis and hypersensitivity, particularly in vulnerable individuals. Our study, while informative about the effects of LQ on gut health, lacks direct evidence on whether changes in gut microbiota and gene expression caused by LQ impact inflammatory diseases or are causally linked. Future research should investigate this through fecal microbiota transplantation to explore the causal relationships and LQ's potential effects on immune responses and disease outcomes in relevant models.}, }
@article {pmid41853542, year = {2024}, author = {Daharsh, L and Lohani, SC and Ramer-Tait, AE and Li, Q}, title = {Characterization of double humanized BLT-mice with stable engraftment of a human gut bacterial microbiome.}, journal = {Frontiers in microbiomes}, volume = {3}, number = {}, pages = {1404353}, pmid = {41853542}, issn = {2813-4338}, abstract = {Humanized mice with human-like immune systems are commonly used to study immune responses to human-specific pathogens. However, one limitation of using humanized mice is their native murine gut microbiota, which significantly differs from that in humans. Given the importance of the gut microbiome to human health, these differences may profoundly impact the ability to translate results from humanized mouse studies to humans. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We previously created double humanized mice with a functional human immune system and a stable, human-like gut microbiome. Here, we characterized the engrafted human gut bacterial microbiome in our double humanized mouse model generated by transplanting fecal material from healthy human donors into the gut of humanized mice. Analysis of bacterial microbiomes in fecal samples from double humanized mice revealed they had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, extending up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors than humanized mice. In conclusion, our study highlights the successful engraftment of human fecal microbiota in BLT humanized mice and underscores the stability of this model, offering a valuable platform for investigating the intricate interplay among the human gut microbiome, immune system, and various diseases in vivo.}, }
@article {pmid41853554, year = {2024}, author = {Sehgal, K and Feuerstadt, P}, title = {Live biotherapeutic products: a capstone for prevention of recurrent Clostridiodes difficile infection.}, journal = {Frontiers in microbiomes}, volume = {3}, number = {}, pages = {1399440}, pmid = {41853554}, issn = {2813-4338}, abstract = {Clostridiodes difficile infection (CDI) continues to be one of the leading causes of healthcare-acquired diarrhea and infections, and recurrence is the biggest challenge in its management. As technology and research have led to a better understanding of the pathophysiology of C. difficile, we have come to appreciate the role that the gastrointestinal microbiota plays in infection onset and the prevention of recurrence. The gut microbiota is disrupted in those with CDI, which allows further propagation of the infection leading to recurrence, if the microbiota deficiency is unable to regrow itself. While antimicrobial therapy is necessary for treatment of any CDI, these therapeutics do not address the underlying disturbance of microbiota. Microbial remodulation therapies have been developed supplementing the microbiota deficiency that exists after the standard of care antimicrobial resulting in a reduction of recurrence. Fecal microbiota transplantation (FMT) was the initial attempt for this type of therapeutic and proved to be safe and effective, however never achieved FDA approval. In light of this, live biotherapeutic products (LBPs) were developed by pharmaceutical companies through a more standardized and regulated process. These products are safe and efficacious in reducing CDI recurrence when given after a standard of care antimicrobial, eventually leading to FDA approval of two products that can now be used widely in clinical practice.}, }
@article {pmid41854281, year = {2026}, author = {Masi, L and Troisi, S and Petito, V and Puca, P and Pane, C and Biamonte, F and Migliore, G and Emoli, V and Lopetuso, LR and Gasbarrini, A and Papa, A and Scaldaferri, F}, title = {Fecal microbiota transplantation in murine models of colitis and short bowel syndrome: lessons learned, limitations, and translational perspectives.}, journal = {Minerva gastroenterology}, volume = {72}, number = {1}, pages = {104-116}, doi = {10.23736/S2724-5985.26.04136-7}, pmid = {41854281}, issn = {2724-5365}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; *Short Bowel Syndrome/therapy/microbiology ; Mice ; *Colitis/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Humans ; Intestinal Barrier Function ; }, abstract = {Fecal microbiota transplantation (FMT) has become a powerful experimental tool for dissecting microbiota-driven mechanisms in murine models of gastrointestinal and systemic disease. This review provides a comprehensive methodological and translational overview of FMT in mice, focusing on lessons learned from inflammatory bowel disease (IBD) research and emerging perspectives in short bowel syndrome (SBS). We first outline the fundamental role of the gut microbiota in immune regulation, metabolic homeostasis, and maintenance of epithelial barrier integrity, establishing the rationale for modulating microbial communities through FMT. A detailed methodological analysis follows, highlighting how donor selection, recipient conditioning, sample handling, administration route, and environmental variables critically influence microbial engraftment and experimental reproducibility. The review then synthesizes current evidence from key murine IBD models, demonstrating that FMT can restore epithelial integrity, rebalance adaptive immunity, modulate cytokine networks, and enrich beneficial short-chain fatty-acid-producing taxa. Concepts such as functional engraftment, viability of transferred communities, and host-microbe metabolic interactions are discussed as central determinants of FMT efficacy. Finally, we address the emerging but challenging application of FMT in SBS. Profound alterations in intestinal anatomy, transit, oxygen tension, and substrate availability limit the integration of donor microbiota in SBS models, necessitating adapted strategies such as anaerobic handling, pre-conditioned consortia, synbiotics, and optimized delivery systems. Piglet models and computational approaches for donor-recipient matching are highlighted as promising translational tools. Overall, this review underscores the need for methodological standardization and physiologically tailored approaches to advance the reliability, mechanistic insight, and translational potential of FMT in both IBD and SBS.}, }
@article {pmid41854683, year = {2026}, author = {Wang, J and Shi, Y and Jia, Y and Peng, J}, title = {Effect of Diosmetin on Gut Microbiota and Serum Metabolites in Acute Pancreatitis Mice: A Metagenomic and Metabolomic Study.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {6}, pages = {e71679}, doi = {10.1096/fj.202503650RRR}, pmid = {41854683}, issn = {1530-6860}, support = {2023DK2002//Key Project of Research and Development Plan of Hunan Province/ ; 82170661//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; *Pancreatitis/drug therapy/metabolism/microbiology/chemically induced/blood ; Mice ; *Flavonoids/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Metabolomics/methods ; Mice, Inbred C57BL ; Metagenomics/methods ; Ceruletide/toxicity ; *Metabolome/drug effects ; Acute Disease ; Pancreas/drug effects/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Diosmetin is a bioactive flavonoid that exhibits well-documented antioxidant, anti-inflammatory, and anti-tumor properties. However, its potential to attenuate acute pancreatitis (AP) progression through gut microbiota modulation has not yet been elucidated. In this study, mice were pretreated with varying oral doses of diosmetin for 1 week before AP induction via intraperitoneal (i.p.) caerulein injections. The therapeutic efficacy and optimal dosage were determined through histopathological analysis of pancreatic tissue and serological biomarker assessment. Additionally, transcriptomic profiling and western blot were employed to elucidate the underlying signaling pathways. Furthermore, based on integrated metagenomic and metabolomic analyses, a core gut microbiota-metabolite-gene interaction network modulated by diosmetin was constructed. Finally, fecal microbiota transplantation (FMT) experiments validated the critical role of gut microbiota in the effects of diosmetin against AP. The results showed that medium-dose diosmetin treatment significantly attenuated pancreatic histopathological damage and acinar cell apoptosis in AP mice, while suppressing the activation of the MAPK inflammatory signaling pathway. Notably, diosmetin treatment was associated with restored microbial diversity, altered bacterial community structure, and changes in key metabolic pathways, reversing gut microbiota dysbiosis. Specifically, a diosmetin-responsive interaction network was constructed, highlighting associations between core bacterial taxa (Butyricimonas faecalis, Enterocloster bolteae, Roseburia intestinalis), key metabolites (3-indoleacrylic acid, 2-methoxy-4-vinylphenol, nitrite), and MAPK pathway-related genes. Finally, the protective effect of diosmetin was further substantiated by FMT, suggesting a potential role of the gut microbiota in this process. In conclusion, diosmetin ameliorated pancreatic injury in a murine model of caerulein-induced AP by modulating gut microbiota composition and associated metabolic profiles. These findings suggested that diosmetin represented a promising therapeutic option for AP, offering a scientific foundation for its clinical application and the underlying mechanisms involved.}, }
@article {pmid41856839, year = {2026}, author = {Suchodolski, JS and Toresson, L}, title = {Microbiome Modulation in Veterinary Medicine: From Diet to Fecal Microbiota Transplantation.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {56}, number = {3}, pages = {619-632}, doi = {10.1016/j.cvsm.2026.01.009}, pmid = {41856839}, issn = {1878-1306}, mesh = {Animals ; *Fecal Microbiota Transplantation/veterinary ; *Cat Diseases/therapy/microbiology ; Cats ; *Diet/veterinary ; Dogs ; *Dysbiosis/veterinary/therapy/microbiology ; *Dog Diseases/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; *Intestinal Diseases/veterinary/therapy/microbiology ; }, abstract = {The intestinal microbiome plays a crucial role in host health. As intestinal dysbiosis can have different underlying causes, multimodal therapeutic approaches are often necessary. Dietary modulation potentially combined with fibers should be the first-line approaches in all patients with acute or chronic enteropathy and help modulate the microbiome. A subset of animals with chronic intestinal disease have marked dysbiosis that results in abnormal microbial function and reflects underlying mucosal pathology, which often persists in chronic inflammatory enteropathy. Fecal microbiota transplantation can be a useful adjunct treatment of chronic disorders, but in patients with severe dysbiosis, repeated treatments are likely needed.}, }
@article {pmid41858792, year = {2026}, author = {Raber, J and Sharpton, TJ}, title = {Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.}, journal = {Frontiers in aging neuroscience}, volume = {18}, number = {}, pages = {1771904}, pmid = {41858792}, issn = {1663-4365}, support = {R01 ES030226/ES/NIEHS NIH HHS/United States ; }, abstract = {The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in germ-free mice demonstrate that microbiome alterations are sufficient to induce cognitive and neuropathological phenotypes, supporting causality in preclinical models. Genetic risk factors and environmental exposures affect both neurodegeneration risk and microbiome composition. In this review, we synthesize evidence from human cohorts and preclinical models on the gut-brain axis in cognitive health and disease. We then present a methodological framework for diet-microbiome-cognition research, addressing causal inference through mediation analysis, supervised approaches for deriving diet scores, validation strategies, and individual heterogeneity. This framework can guide development of microbiome-targeted dietary interventions to improve cognitive outcomes.}, }
@article {pmid41859112, year = {2026}, author = {Chen, H and Lou, G and Meng, F and Zhang, Y and Kuang, H and Yang, D}, title = {Critical role of reproductive tract microbiota and derived metabolites in inflammation, tumor immunity, and tumorigenesis of gynecological cancers: a narrative review.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1734792}, pmid = {41859112}, issn = {1664-3224}, mesh = {Humans ; Female ; *Genital Neoplasms, Female/immunology/microbiology/metabolism/therapy/etiology ; *Microbiota/immunology ; Animals ; *Genitalia, Female/microbiology/immunology/metabolism ; *Inflammation/immunology/metabolism/microbiology ; Carcinogenesis/immunology ; }, abstract = {Gynecological malignancies, including ovarian, cervical, and endometrial cancers, present significant clinical challenges due to the epidemiological complexity and limitations in current therapeutic strategies. Emerging evidence highlights the critical role of the microbiome and its metabolites in modulating tumor initiation, progression, and treatment responses. This review explores the intricate mechanisms through which gut and reproductive tract microbiota influence gynecological cancers via immune regulation, metabolic reprogramming, and epigenetic modifications. Key microbial metabolites, such as short-chain fatty acids, bile acids, and estrogen-metabolizing intermediates, serve as molecular bridges in host-microbe communication, impacting chemotherapy resistance and immunotherapy efficacy. Furthermore, we discuss the translational potential of microbiome-targeted interventions, including probiotics, fecal microbiota transplantation, and precision microbial therapies, as innovative approaches for diagnosis, prognosis, and treatment. Understanding the microbiota-reproductive axis offers novel insights into overcoming therapeutic resistance and improving patient outcomes in gynecologic oncology.}, }
@article {pmid41859191, year = {2026}, author = {Su, Y and Xia, Y}, title = {Gut microbiota dysbiosis and depression: Bidirectional interactions, mediating pathways, and microecological therapeutics.}, journal = {Current research in food science}, volume = {12}, number = {}, pages = {101372}, pmid = {41859191}, issn = {2665-9271}, abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a key target for ameliorating major depressive disorder (MDD). This review systematically synthesizes evidence on the bidirectional relationship between gut microbiota dysbiosis and MDD, and delineates the core mechanisms-such as neuroinflammation, neurotransmitter metabolism, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation-through which this axis influences depressive pathogenesis. Further, the intestinal microbiota characteristics related to MDD, the main regulatory pathways, and the potential efficacy of microbiome-targeted intervention measures-including psychobiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary strategies-were sorted out. In the clinical assessment and drug research of depression, the assessment tools are mainly divided into two categories: clinician-rated and self-reported. These two types are often used together to provide multi-dimensional evidence of therapeutic efficacy. Evidence suggests that stress-related intestinal permeability may initiate gut dysbiosis, which in turn can impair barrier function, promote neuroinflammation, disrupt neurotransmitter synthesis, and overactivate the HPA axis, potentially exacerbating depressive symptoms. Interventions targeting the gut microbiota may help reshape microbial communities, increase short-chain fatty acids (SCFAs) and 5-Hydroxytryptamine (5-HT), and dampen inflammatory and stress responses, thereby offering a promising, non-pharmacological avenue for alleviating MDD. This review not only offers a theoretical foundation for microbiota-based therapeutics in MDD but also highlights pathways toward developing safe, effective non-pharmacological strategies for depression management.}, }
@article {pmid41859453, year = {2026}, author = {Cao, L and Zhu, W}, title = {Insights from the high-altitude animal gut adaptation model: mechanisms of obesity regulation via microbiota-derived metabolite homeostasis and the gut-X axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1795452}, pmid = {41859453}, issn = {1664-302X}, abstract = {The unique environmental conditions at high altitudes drive the gut microbiota of resident animals to develop distinct structural and functional traits, thereby offering an ideal natural model for investigating the synergistic adaptation of hosts and microorganisms to extreme environmental stressors. This review systematically expounds the mechanism of metabolic adaptation of gut microbiota to high-altitude through the phenotypic characteristics of "high productivity and low inflammation," and understands the mediating effect of short-chain fatty acids and secondary bile acids, which are derived metabolites of flora. SCFAs can enhance the intestinal barrier, regulate the function of immune cells, act on the gut-brain axis, and then affect the feeding behavior. SBAs, as signal molecules, regulate the lipid and energy metabolism of the host through the gut-liver axis. This division of labor and coordination, driven by different metabolites and achieved through specific gut-X axis pathways, constitutes a microecological regulatory network that enables the host to maintain metabolic homeostasis in high-altitude areas. Understanding this natural model can reveal the role of "flora metabolite organ axis" in maintaining health. It can also provide reference direction for obesity intervention caused by high-fat diet (HFD) and other factors, such as regulating the function of gut microbiota through strategies such as dietary regulation, probiotics and prebiotics supplementation, and fecal microbiota transplantation (FMT), and regulating the specific gut-X axis pathway, so as to restore metabolic balance.}, }
@article {pmid41860558, year = {2026}, author = {Bloom, P and Khanna, S}, title = {Fecal microbiota transplantation in chronic liver disease: Current and future state of the art.}, journal = {Hepatology communications}, volume = {10}, number = {4}, pages = {}, pmid = {41860558}, issn = {2471-254X}, mesh = {*Fecal Microbiota Transplantation/methods/trends ; Humans ; *Liver Diseases/therapy/microbiology ; Chronic Disease ; Gastrointestinal Microbiome ; Animals ; Dysbiosis/therapy ; }, abstract = {Chronic liver diseases are associated with changes in gut microbiome composition and function. Early data suggest that fecal microbiota transplantation (FMT) may treat several chronic liver diseases, especially cirrhosis, hepatic encephalopathy, and alcohol-associated liver disease. Well-powered and multisite studies are needed to better understand which indications and subpopulations hold promise for FMT. At present, there is variability in the screening, processing, and administration of FMT. Some of this variability is inherent to the nature of FMT, but some of the variability could be standardized to optimize safety and efficacy. Ultimately, we may find that narrowed and donor-independent microbiome therapeutics are superior tools to provide a consistently effective result in chronic liver disease. Regulation of FMT for chronic liver disease indications in the United States will continue to require the rigid regulatory framework of other drugs, requiring an Investigational New Drug (IND) application.}, }
@article {pmid41861682, year = {2026}, author = {Ding, WL and Wang, L and Xu, BW and Lu, YN and Yue, TJ and Zhang, ZQ and Guo, FF and Han, RL and Huang, SC}, title = {Strontium chelate with Achyranthes bidentata polysaccharide as a carrier promotes bone regeneration through mediating the gut-liver-bone axis in TD chickens.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {155}, number = {}, pages = {158077}, doi = {10.1016/j.phymed.2026.158077}, pmid = {41861682}, issn = {1618-095X}, mesh = {Animals ; Chickens ; *Strontium/pharmacology/chemistry ; *Polysaccharides/pharmacology/chemistry ; *Achyranthes/chemistry ; *Bone Regeneration/drug effects ; *Osteochondrodysplasias/drug therapy/veterinary ; Liver/drug effects/metabolism ; Tibia/drug effects ; *Poultry Diseases/drug therapy ; Male ; Chelating Agents/pharmacology ; }, abstract = {BACKGROUND: Tibial dyschondroplasia (TD), characterized by impaired angiogenesis and abnormal chondrocyte maturation in the tibial growth plate (TGP), is a common bone disorder in commercial broilers. Strontium (Sr), a trace element with osteogenic and angiogenic properties that plays a crucial role in bone health, exhibits low bioavailability. Achyranthes bidentata polysaccharides, a major extract from Achyranthes bidentata with the function of "guiding the medicine downward", has been used to enhance drug delivery to the lower extremity meridians.<br><br>PURPOSE: This study aimed to prepare a novel Achyranthes bidentata polysaccharides-strontium (ABPS-Sr) chelate to enhance Sr bioavailability and investigate its therapeutic effects on tibial damage in TD broilers from the perspective of the gut-bone axis.<br><br>METHODS: The ABPS-Sr chelate was synthesized and optimized using response surface methodology, followed by structural characterization. A thiram-induced TD broiler model was established to evaluate the therapeutic efficacy of the ABPS-Sr chelate using qRT-PCR, Western blot, immunoprecipitation, micro-CT, histological staining, and biochemical assays. 16S rRNA sequencing and targeted and non-targeted metabolomics were employed to characterize alterations in gut microbiota, intestinal metabolites and plasma lipid metabolites. Experiments involving phosphatidylcholine (PC)-exposed broilers and fecal microbiota transplantation (FMT) in mice were performed to verify the mediate role of gut microbiota and tibia-damaging effects of PC.<br><br>RESULTS: The one-pot synthesis of ABPS-Sr chelate was optimized to achieve a yield of 27.7 %, with structural characterization confirming Sr[2+] coordination-induced conformational changes and porous architecture. Dietary supplementation with ABPS-Sr chelate significantly improved growth performance, restored tibial microstructure, and promoted vessel density in the TGP in TD broilers. Moreover, ABPS-Sr chelate promoted angiogenesis in the TGP by upregulating VEGF expression and restored osteogenic differentiation by activating the ITGB1/FAK/PI3K/AKT1 signaling pathway. Furthermore, ABPS-Sr chelate reshaped gut microbiota composition, restored intestinal barrier function, and corrected hepatic lipid metabolism disorders, particularly by reducing plasma glycerophospholipid (e.g., PC) accumulation that exerts negative effects on bone health.<br><br>CONCLUSION: This study demonstrated that ABPS-Sr chelate restores tibial injury in TD broilers by enhancing osteogenesis and angiogenesis via modulation of the gut-liver-bone axis, which provides a promising nutritional intervention strategy for improving poultry bone health.}, }
@article {pmid41861987, year = {2026}, author = {Ramírez-Amorós, C and Amesty, V and Martínez, L and Martínez Urrutia, MJ and Vilanova-Sánchez, A}, title = {Post-pubertal outcomes in patients with cloacal malformations: Colorectal, urological, and gynaecological function with patient-reported sexual outcomes.}, journal = {Journal of pediatric surgery}, volume = {61}, number = {7}, pages = {163087}, doi = {10.1016/j.jpedsurg.2026.163087}, pmid = {41861987}, issn = {1531-5037}, mesh = {Humans ; Female ; Retrospective Studies ; *Cloaca/abnormalities/surgery ; Follow-Up Studies ; Child ; Child, Preschool ; Treatment Outcome ; Patient Reported Outcome Measures ; Fecal Incontinence/etiology ; Young Adult ; Infant ; Abnormalities, Multiple/surgery ; Adolescent ; Urogenital Abnormalities/surgery ; Urinary Incontinence/etiology ; *Sexual Dysfunction, Physiological/etiology ; Colorectal Surgical Procedures ; Cloacal Exstrophy/surgery ; Adult ; Vagina/surgery/abnormalities ; }, abstract = {INTRODUCTION: Long-term functional outcomes in patients with cloacal malformations remain poorly described. This study reports long-term outcomes from a tertiary referral center.<br><br>METHODS: Retrospective review of female patients with cloacal malformations treated between 1980 and 2010. Colorectal, urological, and gynaecological outcomes were obtained from medical records. Sexual function was assessed using a validated female sexual health questionnaire and compared with 15 healthy controls.<br><br>RESULTS: Eleven women were included, with a mean age at follow-up of 24.77 &#xb1; 7.41 years. Associated anomalies were present in 73% of patients, including spinal anomalies in 27%. All patients underwent neonatal stoma creation and closure, the latter at a median age of 2.55 (1.61-3.72) years. Faecal continence was achieved in 73% of patients at a mean age of 10.4 &#xb1; 3.1 years; one patient required laxatives and five required enemas. All patients achieved urinary dryness. A Mitrofanoff procedure was required in 36%, and one patient underwent bladder augmentation. End-stage renal disease developed in 36%, with three patients undergoing renal transplantation and one awaiting transplant. Three patients (27%) required vaginoplasty, and four (36%) later underwent external genitoplasty. M&#xfc;llerian anomalies were present in 73%, and 91% menstruated. Sexual function assessment demonstrated increased fear of sexual activity, avoidance due to perineal appearance, reduced excitation, and greater difficulty with vaginal penetration compared with controls.<br><br>CONCLUSION: Most patients in our institution with cloacal malformations achieve satisfactory faecal and urinary continence following reconstruction. Renal dysfunction and impaired sexual function remain relevant long-term issues, supporting the need for lifelong multidisciplinary follow-up.}, }
@article {pmid41862794, year = {2026}, author = {Tian, M and Zeng, X and Zhong, Y and Ma, B and Feng, Y and Wu, X and Liao, Y and Xu, Y and Chen, T and Tan, B}, title = {Combination of Tripterygium glycosides and Lactobacillus paracasei sensitises epithelial ovarian cancer to cisplatin via downregulating Keap1-Nrf2-GPX4 signalling pathway.}, journal = {Cellular &amp; molecular biology letters}, volume = {31}, number = {1}, pages = {}, pmid = {41862794}, issn = {1689-1392}, support = {82160766//National Natural Science Foundation of China/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; 20242BAB20417//Youth Fund Project of Jiangxi Provincial Natural Science Foundation/ ; }, mesh = {Female ; Humans ; *Cisplatin/pharmacology/therapeutic use ; *Lacticaseibacillus paracasei/physiology ; NF-E2-Related Factor 2/metabolism ; Signal Transduction/drug effects ; Animals ; *Tripterygium/chemistry ; *Carcinoma, Ovarian Epithelial/drug therapy/metabolism/pathology ; Kelch-Like ECH-Associated Protein 1/metabolism ; *Glycosides/pharmacology/therapeutic use ; *Ovarian Neoplasms/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Down-Regulation/drug effects ; Fecal Microbiota Transplantation ; Mice ; Ferroptosis/drug effects ; Antineoplastic Agents/pharmacology ; }, abstract = {BACKGROUND: Epithelial ovarian cancer (EOC) is a highly heterogeneous malignancy with significant morbidity and mortality, and cisplatin (DDP) resistance remains a major obstacle in its treatment. Previous studies suggest that Tripterygium glycosides (TG), derived from Tripterygium wilfordii, may enhance EOC chemo-sensitivity to DDP, potentially involving gut microbiota, though the underlying mechanisms remain to be fully elucidated.<br><br>PURPOSE: This study sought to determine how TG enhanced chemotherapy sensitivity in EOC and to examine the involvement of gut microbiota in this process.<br><br>STUDY DESIGN: Experimental research in vivo models was conducted, including fecal microbiota transplantation (FMT) from healthy controls and validation assays with Lactobacillus paracasei.<br><br>METHODS: TG were administered alone or combined with FMT to evaluate their impact on DDP sensitivity in EOC. Mechanistic studies focused on the Keap1-Nrf2-GPX4 signalling pathway and ferroptosis induction. L. paracasei was co-administered with TG to assess synergistic effects, while Nrf2 pathway activation was tested to confirm its regulatory role.<br><br>RESULTS: TG significantly enhanced DDP sensitivity in EOC, either alone or synergistically with FMT. Mechanistically, TG inhibited the Keap1-Nrf2-GPX4 axis, inducing tumor ferroptosis. Gut microbiota, particularly the probiotic Lactobacillus, contributed to this effect: L. paracasei combined with TG amplified DDP cytotoxicity in EOC cells. Conversely, Nrf2 pathway activation attenuated the synergistic effect.<br><br>CONCLUSION: TG sensitises EOC to DDP by suppressing the Keap1-Nrf2-GPX4 pathway to trigger ferroptosis, with gut microbiota (e.g., L. paracasei) playing a synergistic role. Combining TG and probiotics may offer a promising and innovative method to improve chemotherapy efficacy in EOC, offering a foundation for future therapeutic development.}, }
@article {pmid41863247, year = {2026}, author = {Feng, S and Huang, Q}, title = {Microbiota-driven Immunopathogenesis in Systemic Lupus Erythematosus: Cross-site Mechanisms and Intervention Strategies.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240433654260209063544}, pmid = {41863247}, issn = {1875-5666}, abstract = {Systemic lupus erythematosus (SLE) is a complex autoimmune disease whose pathogenesis involves intricate interactions with the human microbiota. Accumulating evidence reveals significant compositional and functional dysbiosis in the gut, oral, skin, and vaginal microbiota of SLE patients compared to healthy individuals. These dysbioses actively contribute to disease development and progression through a multitude of mechanisms. These include impaired epithelial barrier integrity, exemplified by the "leaky gut" phenomenon, which facilitates the translocation of microbial antigens. Molecular mimicry, where microbial antigens share structural similarities with host self-antigens, triggers the production of cross-reactive autoantibodies. Furthermore, dysregulated production of microbial metabolites, such as short-chain fatty acids, tryptophan derivatives like tryptamine, and histamine, directly modulates host immune cell function, promotes inflammatory responses, and influences epigenetic regulation. The causal role of specific microbiota in SLE is substantiated by experimental models, including fecal microbiota transplantation studies where transfer of SLE-associated microbiota can recapitulate autoimmune features in recipient germ-free mice, and mono-colonization with pathobionts like Ruminococcus gnavus or Staphylococcus aureus can drive specific aspects of the disease. This growing understanding has paved the way for novel microbiota-targeting interventions. Strategies such as dietary modifications, probiotic and prebiotic supplementation, and fecal microbiota transplantation show considerable promise in preclinical and early clinical studies for restoring microbial homeostasis, rebalancing dysregulated immune responses, and alleviating disease activity. However, challenges in patient-specific variability, understanding precise mechanisms, and ensuring longterm safety remain. Future research must focus on delineating detailed causal pathways, validating efficacy in large-scale trials, and ultimately developing personalized microbiota-targeting interventions to improve SLE management and patient outcomes.}, }
@article {pmid41863409, year = {2026}, author = {Kaur, S and Bhandari, N and Mahajan, S and Mehta, D and Chauhan, S and Kumar, V and Rohilla, M and Mehta, S and Dhankhar, S}, title = {Molecular Pathways of Microbiota-derived Neuromodulation: An Integrative View.}, journal = {Current neurovascular research}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672026427392260131184931}, pmid = {41863409}, issn = {1875-5739}, abstract = {INTRODUCTION: The gut microbiota, also called "the forgotten organ", is a complex and dynamic ecosystem of microorganisms that is fundamental to human physiology, neurobiology, and disease. This review examines the intricate relationships between the gut microbiota and the nervous system via the microbiota-gut-brain (MGB) axis. It discusses their endocrine, immunological, and neural pathways.<br><br>METHODS: A thorough literature search was performed across databases including PubMed, Scopus, Web of Science, and Google Scholar, using keywords such as "gut microbiota," "microbiota- gut-brain axis," "neuromodulation," "serotonin," "dopamine," "GABA," "norepinephrine," "prebiotics," "probiotics," and "faecal microbiota transplantation"..<br><br>RESULTS: This article explains how the gut microbiota impacts significant body's chemical messengers such as serotonin, dopamine, GABA, and norepinephrine. These are essential for brain functioning. All of these diseases have evidence linking inflammation of the gut and the brain. Furthermore, gut dysbiosis has been responsible for some of the most serious disorders of mankind through pandemics and plagues.<br><br>DISCUSSION: Moreover, prebiotics, probiotics, faecal microbiota transplantation (FMT), synbiotics, diet, and bioactive substances such as curcumin and flavonoids are new treatment approaches. These strategies help bring back a normal balance of gut microbes for mental and neurological health. Even though preclinical studies have shown promise, bringing it to humans is not simple. Issues like the strain, the individual, and sustained use make it a substantial challenge.<br><br>CONCLUSION: Future directions of work should combine and focus human-based research efforts with precise and personalized microbiome modulation, allowing us to leverage the gut-brain axis therapeutically.}, }
@article {pmid41863784, year = {2025}, author = {Giannakogeorgou, A and van den Ende, T and Verhaar, BJH and de Clercq, N and van Laarhoven, HWM and Nieuwdorp, M}, title = {Targeting the gut microbiota as a treatment for obesity and cancer cachexia.}, journal = {Expert opinion on emerging drugs}, volume = {30}, number = {4}, pages = {225-240}, doi = {10.1080/14728214.2026.2650180}, pmid = {41863784}, issn = {1744-7623}, mesh = {Humans ; *Cachexia/therapy/physiopathology/microbiology/etiology ; *Obesity/therapy/physiopathology/microbiology ; Animals ; *Gastrointestinal Microbiome/physiology ; *Neoplasms/complications/therapy/physiopathology ; Fecal Microbiota Transplantation/methods ; Precision Medicine/methods ; }, abstract = {INTRODUCTION: Obesity and cancer cachexia represent two seemingly contrasting yet interrelated ends of the metabolic disorder spectrum, both characterized by disrupted energy homeostasis, inflammation and neuroendocrine dysfunction, and associated with increased morbidity and mortality. Existing treatments often fail to address the complex underlying pathophysiological mechanisms. Emerging research highlights the role of the gut microbiome in the pathophysiology of both conditions and how it can serve as a novel therapeutic target.<br><br>AREAS COVERED: This review explores shared and distinct pathways linking obesity and cancer cachexia. Key systems discussed include the gut-brain axis as well as skeletal muscle and adipose tissue metabolism. We discuss how the gut microbiota influences these processes through (diet-derived) gut microbial metabolites that affect specific signaling pathways. The review evaluates the efficacy and limitations of current anti-obesity and cachexia therapies and summarizes clinical and preclinical interventions targeting the gut microbiome, including pre-, pro-, postbiotics and fecal microbiota transplantation.<br><br>EXPERT OPINION: The gut microbiota holds potential as a therapeutic target in metabolic diseases, offering opportunities for precision medicine based on microbial and metabolic profiles. While early microbiota-based therapies show promise, further investigation into mechanistic pathways and novel engineered microbiota is essential to develop effective treatments for obesity and cachexia.}, }
@article {pmid41864031, year = {2026}, author = {Zhai, Z and Yang, Y and Xu, Y and Fu, Q and Chen, S and Wu, Z}, title = {Polydisperse polystyrene microplastics exacerbate colitis through gut microbiota-butyrate-PPARγ axis disruption in mice.}, journal = {Journal of hazardous materials}, volume = {507}, number = {}, pages = {141722}, doi = {10.1016/j.jhazmat.2026.141722}, pmid = {41864031}, issn = {1873-3336}, mesh = {Animals ; *PPAR gamma/metabolism ; *Colitis/chemically induced/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Microplastics/toxicity ; *Polystyrenes/toxicity ; Mice ; Mice, Inbred C57BL ; Male ; *Butyrates/metabolism ; Dextran Sulfate ; Signal Transduction/drug effects ; Microspheres ; }, abstract = {The escalating global prevalence of inflammatory bowel disease (IBD) parallels widespread dietary exposure to microplastics (MPs), yet causal mechanisms linking polydisperse MPs to colitis remain elusive. Here, we show that polydisperse polystyrene microspheres (PS-MS) exacerbate dextran sulfate sodium (DSS)-induced colitis in mice by disrupting a microbiota-butyrate-PPARγ signaling axis. Mechanistically, PS-MS treatment alone does not directly induce colon inflammation in healthy mice; however, it suppresses intestinal Muc2 protein expression and impairs the mucus barrier by reducing the abundance of Lachnospiraceae_NK4A136_group and butyrate levels, thereby inhibiting PPARγ signaling and aggravating colitis. An antibiotic cocktail (ABX)-mediated microbiota ablation abolishes PS-MS-induced colitis aggravation, whereas fecal microbiota transplantation (FMT) from PS-MS-exposed donors transmits susceptibility to antibiotic-treated mice, confirming microbiota-dependent pathogenesis. Exogenous sodium butyrate supplementation restores mucosal homeostasis via PPARγ activation, as evidenced by the abolition of protection following administration of the PPARγ antagonist GW9662, and by the comparable efficacy of the PPARγ agonist 5-ASA. Our findings establish the microbiota-butyrate-PPARγ axis as a critical target for counteracting the adverse effects of environmental MPs and propose butyrate-boosting therapies as a translatable strategy against IBD.}, }
@article {pmid41864264, year = {2026}, author = {Merrick, B and Mullish, BH and Goldenberg, SD and Khanna, S and Ahuja, V and Hvas, CL and Makharia, GK and Williams, HRT}, title = {A global evaluation of the use of faecal microbiota transplant (FMT).}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {167}, number = {}, pages = {108574}, doi = {10.1016/j.ijid.2026.108574}, pmid = {41864264}, issn = {1878-3511}, mesh = {*Fecal Microbiota Transplantation/statistics &amp; numerical data/methods/economics ; Humans ; *Clostridium Infections/therapy ; Clostridioides difficile ; Surveys and Questionnaires ; Global Health ; }, abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (CDI); its use is increasingly being investigated for other indications. Although regional surveys and national registries have provided insight into local practices, a comprehensive global overview of FMT access, implementation and governance is lacking.<br><br>METHODS: A survey regarding key aspects related to FMT use was disseminated electronically to members of the World Gastroenterology Organization, European FMT Network and International Society of Infectious Diseases. Responses were analysed both descriptively and using appropriate statistical methods.<br><br>FINDINGS: A total of 80 responses were obtained from 55 countries. FMT was available in significantly more Tier 1/2 than Tier 3/4 nations (24/28 vs 8/27; P < 0.001). In countries lacking access to FMT, reasons included: lack of expertise/infrastructure; financial constraints; regulatory uncertainty; and perceived lack of clinical need. Most countries using FMT employed both upper and lower gastrointestinal administration routes; 18/32 (56%) used capsulised FMT. Almost all countries with access to FMT used it to treat CDI, albeit with different thresholds for the number of CDI episodes prior to use. There were many non-CDI indications for FMT in current use. Payment for stool donation was reported by 10 countries.<br><br>INTERPRETATION: This is the first global overview of FMT availability and governance, highlighting substantial international inequities and considerable heterogeneity in regulation, clinical use, donor screening and cost. Standardization of practice and targeted support for lower-income countries is needed to ensure equitable access and to promote safe, high-quality delivery as FMT and microbiome-based therapeutics continue to evolve.}, }
@article {pmid41864269, year = {2026}, author = {Melchiorri, S and Besutti, VM and Castagliuolo, I}, title = {Blastocystis spp. in fecal microbiota transplantation: Evidence, policy, and the screening paradox.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {167}, number = {}, pages = {108548}, doi = {10.1016/j.ijid.2026.108548}, pmid = {41864269}, issn = {1878-3511}, mesh = {*Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Blastocystis/isolation &amp; purification ; Feces/parasitology/microbiology ; *Clostridium Infections/therapy ; *Blastocystis Infections/transmission ; Donor Selection ; Clostridioides difficile ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (rCDI). However, the detection of Blastocystis spp. in potential donors remains controversial and often leads to donor exclusion, despite uncertain pathogenicity. This review aims to critically evaluate the available evidence on Blastocystis spp. transmission through FMT, its clinical impact, and the implications of current donor screening strategies.<br><br>METHODS: A narrative review of the literature was performed using PubMed, Embase, and Web of Science. Studies reporting Blastocystis spp. detection in FMT donors or recipients, transmission events, clinical outcomes, diagnostic methods, and microbiome associations were included and analyzed.<br><br>RESULTS: Across published reports, 34 FMT recipients were exposed to Blastocystis spp.-positive donor material. Transmission was limited to common subtypes (ST1-ST3), was transient, and was not associated with adverse clinical outcomes or reduced efficacy of FMT for rCDI. No cases of symptomatic infection were reported. Frozen stool preparations appeared to abolish parasite viability. Molecular screening methods markedly increased detection rates compared with microscopy, frequently identifying low-burden colonization of uncertain clinical relevance. Available data suggest that Blastocystis spp. carriage may coexist with a healthy microbiome and does not negatively impact FMT outcomes.<br><br>CONCLUSION: Current evidence indicates that Blastocystis spp. transmission through FMT in immunocompetent adults is clinically benign. Routine donor exclusion based solely on Blastocystis spp. detection may therefore be overly restrictive. A risk-based approach incorporating parasite burden, subtype, host factors, and processing methods may better balance patient safety with donor availability, supporting more sustainable FMT programs.}, }
@article {pmid41867794, year = {2026}, author = {Alviter-Plata, A and Ahmari, N and Gadient, J and Brammer-Robbins, E and Martyniuk, CJ and Zubcevic, J}, title = {Loss of Bone Marrow β1/β2-Adrenergic Receptors Reprograms Host-Microbiota Interactions and Protects Against Diet-Induced Obesity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41867794}, issn = {2692-8205}, abstract = {The gut ecosystem is shaped by multiple factors with the immune system being one of the major determinants in shaping its composition in health and disease. On the other hand, the immune system regulates its responses through the action of the sympathetic nervous system (SNS) in part through beta-adrenergic receptors 1/2 (ADRB1/2). In the past years, a clear link has been established between the immune system, SNS, and the modification of nutrient absorption by the gut microbiota in the development of diet-induced obesity. We have previously shown in male mice transplanted with bone marrow cells ADRB1/2 knock-out mice (KD) showed mild immunosuppression and microbiota changes. Post-recovery, mice were challenged with high-fat diet (HFD) for two weeks ad libitum. Our findings show that KD mice are protected against diet-induced adiposity and weight gain. Additionally, these mice showed an increase in residual calorific values and a decreased expression of the fatty acid transporter FAT/CD36. Suggesting a decreased absorption of lipids in the KD mice. Gut microbiota analysis showed that KD microbiota composition on a HFD remained stable with a significant enrichment in the Bacteroidetes phylum, which is depleted in obesity. This was associated with a switch from triglycerides to diglyceride fecal profile. Moreover, microbiome culture showed a decrease in triglycerides after an incubation with 0.1% of HFD lipid extract. Suggesting a potential role of the Bacteroidetes phylum in the metabolism of these lipids. Our findings demonstrate not only that the gut microbiota can modify nutrient absorption and susceptibility to diet-induced obesity but also that the immune system contributes to selective depletion of microbial members that would otherwise thrive on dietary lipids. Revealing a novel mechanism by which host immunity sculpts the gut ecosystem in ways that influence metabolic outcomes.}, }
@article {pmid41868372, year = {2026}, author = {Wang, Y and Zhang, Y and Cui, Y and Zhu, J and Wang, C and Wang, S and Xiao, X and Yang, L}, title = {Gut microbiota-derived EPA alleviates neuroinflammation associated with white matter injury by influencing H3K9ac/BDNF/TrkB pathway.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1711114}, pmid = {41868372}, issn = {1664-302X}, abstract = {BACKGROUND: The objective of our investigation was to explore the features of gut microbiota dysbiosis and the concentrations of gut metabolites in relation to white matter injury (WMI). Furthermore, we sought to evaluate the influence of gut dysbiosis on neuroinflammation in WMI via intestinal metabolites, and its contribution to pathogenesis.<br><br>METHODS: A cerebral hypoxia-ischemia-induced WMI model was established in 3-day-old Sprague-Dawley rats. Liquid chromatography-mass spectrometry/gas chromatography-mass spectrometry analyses and 16S rRNA gene sequencing were undertaken to ascertain WMI biomarkers. Mechanistic experiments were used to analyse activation of the H3K9ac/BDNF/TrkB pathway and neuroinflammation.<br><br>RESULTS: The analysis of 16S rRNA sequencing disclosed gut microbiota dysbiosis in WMI rats, quantified using linear discriminant analysis effect size. Overall, 341 differentially expressed metabolic markers between the WMI and Sham groups were discovered. The Kyoto Encyclopedia of Genes and Genomes network enhancement evaluation revealed significant downregulation of 20 metabolic processes in the WMI group, which is strongly related to changes in fecal microbial metabolites, and the synthesis process of unsaturated fatty acids was the most significant. Gut microbiota dysbiosis may influence WMI by downregulating metabolites such as eicosapentaenoic acid (EPA). Fecal microbiota transplantation increased EPA concentration in the brain tissue of WMI rats. Gut microbiota-derived EPA promoted H3K9ac and BDNF/TrkB expression and inhibited the transcription of pro-inflammatory TNF-&#x3b1; and IL-1&#x3b2; molecules. These EPA-mediated effects were reversed by TrkB inhibition.<br><br>CONCLUSION: WMI induces gut dysbiosis involving down-regulation of unsaturated fatty acid synthesis. Fecal microbiota transplantation leads to increased levels of EPA. Gut microbiota-derived EPA increases levels of acetylated histone H3K9ac, causes activation of the BDNF/TrkB pathway, reduces neuroinflammation, and improves WMI-associated myelination disorders. It provides a basis for targeted treatment of white matter injury in the future.}, }
@article {pmid41869071, year = {2026}, author = {Schotz, KM and Alizadeh, M and Rapoport, AP and Ravel, J and Von Rosenvinge, EC}, title = {Faecal microbiota transplant for chronic norovirus infection: a case report of donor microbiota engraftment without clinical success.}, journal = {Gastroenterology report}, volume = {14}, number = {}, pages = {goag015}, pmid = {41869071}, issn = {2052-0034}, }
@article {pmid41870087, year = {2026}, author = {Wang, X and Wu, W and Yang, B and Liu, Y and Xu, Y and Wang, L and Lv, X and Gao, J and Lu, M and Yu, A and Li, N and Chen, Q and Lu, L and Zhao, D}, title = {Additive effects of fecal microbiota transplantation and infliximab on gut microbiome and metabolome in refractory inflammatory bowel disease patients.}, journal = {mSystems}, volume = {11}, number = {4}, pages = {e0077425}, pmid = {41870087}, issn = {2379-5077}, support = {82300753//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Infliximab/therapeutic use/pharmacology ; *Fecal Microbiota Transplantation/methods ; Female ; *Gastrointestinal Microbiome/drug effects ; Male ; *Metabolome/drug effects ; Adult ; *Inflammatory Bowel Diseases/therapy/microbiology/metabolism ; Middle Aged ; Treatment Outcome ; Combined Modality Therapy ; Young Adult ; }, abstract = {UNLABELLED: Fecal microbiota transplantation (FMT) is an emerging therapy for inflammatory bowel disease (IBD), yet its efficacy in patients refractory to conventional treatments and its underlying mechanisms require further elucidation. We studied 37 IBD patients (15 ulcerative colitis [UC], 22 Crohn's disease [CD]) refractory to conventional therapies and 16 healthy donors. FMT monotherapy from a single donor induced week-4 clinical response in 12 UC and 9 biologic-naïve CD patients, with all responders sustaining remission and most achieving endoscopic remission by week 14. Integrated multi-omics revealed FMT restored microbial diversity and profoundly reorganized host-microbiota-metabolite networks. In nine refractory CD patients (7 infliximab [IFX] non-responders, 2 FMT non-responders), IFX-FMT combination led to week-4 response in 6 patients, all of whom attained clinical and endoscopic remission by week 14, with more complete microbial-metabolic restoration than monotherapy. Our findings establish that FMT induces remission in refractory IBD via ecosystem network rewiring, and that IFX-FMT exhibits additive effects, supporting further trials of microbiome-directed adjunctive strategies.<br><br>IMPORTANCE: This study provides mechanistic and clinical insights into the therapeutic effects of fecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD), particularly when combined with the anti-tumor necrosis factor (anti-TNF) biologic infliximab (IFX). While both FMT and IFX achieve response in approximately 60% of IBD patients, their combined influence on the gut microbial and metabolic landscape in refractory disease has been poorly understood. Here, we demonstrate that FMT monotherapy restores gut microbial diversity and reconfigures host-microbiota-metabolite networks, correlating with clinical and endoscopic remission in patients refractory to conventional treatments. Furthermore, in Crohn's disease patients unresponsive to either therapy alone, combined IFX-FMT induced more complete microbial and metabolic normalization and achieved remission where monotherapy had failed. These findings reveal ecosystem-level network rewiring as a central mechanism of FMT efficacy and establish the additive potential of combining microbiome-targeted and immunomodulatory therapies. This work supports the development of microbiome-informed adjunctive strategies for severe or refractory IBD, highlighting an actionable path toward personalized, mechanism-based treatment regimens.<br><br>CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT07149441.}, }
@article {pmid41870947, year = {2026}, author = {Zhang, L and Zeng, X and Ma, C and Wei, Y and Wang, W and Liu, T and Li, W}, title = {Acupoint catgut embedding ameliorates laparotomy-induced cognitive decline in aged mice by restoring gut microbiota.}, journal = {Neuroreport}, volume = {37}, number = {6}, pages = {222-235}, doi = {10.1097/WNR.0000000000002255}, pmid = {41870947}, issn = {1473-558X}, support = {YQJH2023028//Program for Young Talents of Basic Research in Universities of Heilongjiang Province (YQJH2023028)/ ; }, mesh = {Animals ; Male ; *Laparotomy/adverse effects ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/physiology ; Mice ; *Postoperative Cognitive Complications/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation ; *Catgut ; *Acupuncture Points ; Hippocampus/metabolism ; *Cognitive Dysfunction/etiology ; }, abstract = {BACKGROUND: Postoperative cognitive dysfunction (POCD), a common neurological complication in elderly patients, significantly impairs recovery. Emerging evidence suggests the gut microbiota is involved in its pathogenesis. This study aimed to determine whether acupoint catgut embedding (ACE) could alleviate POCD by modulating the gut microbiota in aged mice after laparotomy.<br><br>METHODS: Eighteen-month-old male C57BL/6J mice underwent laparotomy on day 8 (excluding the Sham group). The ACE group received ACE treatment, while the anesthesia and surgery group served as surgical controls. The fecal microbiota transplantation (FMT)-ACE and FMT-AS groups received FMT from corresponding donors. Additional groups received oral indole-3-propionic acid (IPA) or vehicle-treated surgery. Hippocampal inflammation and blood-brain barrier proteins were assessed on day 9; cognitive function and intestinal markers on day 15.<br><br>RESULTS: Cognitive function was significantly improved in the ACE, FMT-ACE, and IPA groups. ACE and FMT-ACE treatments specifically elevated fecal g-Clostridia_UCG-014 abundance and serum IPA levels. These changes were accompanied by suppressed hippocampal toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-&#x3ba;B) signaling and proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1&#x3b2;], together with elevated tight junction proteins (occludin, claudin-5). Furthermore, colonic aryl hydrocarbon receptor (AhR) and IL-22 were upregulated, while serum lipopolysaccharide and diamine oxidase were reduced. Accordingly, IPA treatment mirrored the key anti-inflammatory and barrier-protective effects.<br><br>CONCLUSION: ACE alleviates POCD probably by modulating gut microbiota, specifically increasing g-Clostridia_UCG-014 abundance and metabolite IPA. These effects are potentially mediated by dual pathways: (a) suppression of neuroinflammation via TLR4/NF-&#x3ba;B signaling, and (b) enhancement of gut barrier integrity via AhR/IL-22 axis. Our findings highlight the therapeutic potential of ACE in targeting the gut-brain axis for POCD management.}, }
@article {pmid41871875, year = {2026}, author = {Zhang, Y and Xu, X and Wang, S and Yin, X and Zhang, B and Zhu, Z and Ji, R and Zhu, J and He, H and Cheng, S and Han, Z and Xie, T and Zhang, X and Wang, Y and Shen, S and Kou, Y and Bao, S and Liu, Y and Cao, B and Bonny, C and Guo, X and Segal, E and Tan, Y and Shen, L and Peng, Z}, title = {Fecal microbiota transplantation combined with anti-PD-1 therapy in refractory microsatellite-stable gastric cancer: a phase I feasibility and safety study.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {3}, pages = {}, pmid = {41871875}, issn = {2051-1426}, mesh = {Humans ; *Stomach Neoplasms/therapy/drug therapy ; Male ; Female ; *Fecal Microbiota Transplantation/methods ; Middle Aged ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology/adverse effects ; Aged ; Feasibility Studies ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Combined Modality Therapy ; Adult ; Treatment Outcome ; }, abstract = {BACKGROUND: The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome's impact on immune modulation is a promising area for overcoming resistance to immunotherapy.<br><br>METHODS: This study (NCT04130763) is an open-label, single-arm, single-center, phase I study assessing the safety and efficacy of fecal microbiota transplantation (FMT) from healthy donors in 10 patients with advanced GI cancer resistant to anti-programmed death-ligand 1 (PD-(L)1) treatment. 10 patients with histologically confirmed, unresectable, or metastatic GI cancers (8 gastric, 2 colorectal) who were refractory to anti-PD-(L)1 treatment were enrolled. Patients received initial FMT treatment via oral capsules (60 capsules), followed by a combination therapy phase, where maintenance FMT (10 capsules per treatment) was paired with nivolumab at 3&#x2009;mg/kg every 2&#x2009;weeks for six cycles. Serial biomarker assessments were conducted through both fecal and blood sampling.<br><br>RESULTS: The combination of FMT and anti-PD-1 treatment was well tolerated with no serious adverse events. The objective response rate was 20% and the disease control rate was 40%. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Moreover, microbial signatures were identified for anti-programmed cell death protein-1 (PD-1) responsiveness and validated in an independent cohort.<br><br>CONCLUSIONS: This phase I study demonstrates the feasibility and safety of combining FMT with anti-PD-1 therapy in patients with ICI-refractory gastric cancer. The observed preliminary efficacy signals and identified microbial signatures generate hypotheses for future trials to investigate microbiome-based approaches to enhance immunotherapy efficacy.<br><br>TRIAL REGISTRATION NUMBER: NCT04130763.}, }
@article {pmid41871943, year = {2026}, author = {Awoniyi, M and El Hag, M and Hernandez, J and Yang, Q and Evans, N and Nemet, I and Ngo, B and Coskuner, D and Zhou, J and Farmer, M and Su, L and Zhou, H and Roach, J and Stappenbeck, T and Sartor, RB}, title = {Dysbiotic microbiota trigger colitis-associated colorectal cancer and imprint a distinctive bile acid profile in a PSC-IBD model.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336675}, pmid = {41871943}, issn = {1468-3288}, abstract = {BACKGROUND: Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction.<br><br>OBJECTIVE: To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss.<br><br>DESIGN: Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)[-/-] &#xd7; interleukin (IL)-10[-/-] double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling.<br><br>RESULTS: PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7&#x3b1;-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10[-/-] donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2[-/-] donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity.<br><br>CONCLUSION: PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction.}, }
@article {pmid41872963, year = {2026}, author = {Kim, B and Kim, HN and Cheong, HS and Jeong, S and Kim, J and Park, DI and Joo, EJ}, title = {Fecal microbiota from hepatitis B-infected individuals alters triglyceride metabolism and microbial pathways in mice.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {}, pmid = {41872963}, issn = {1757-4749}, support = {RS-2023-KH135855//Korea Health Industry Development Institute/Republic of Korea ; NRF-2021R1A2C4002454//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: This study investigates the impact of chronic hepatitis B virus infection on triglyceride metabolism through alterations in the gut microbiome, using a faecal microbiota transplantation (FMT) mouse model. METHODS: This shotgun metagenomic analysis was conducted using stored samples from a previously published FMT experiment. Nineteen mice with sufficient faecal DNA for sequencing were included, comprising ten mice transplanted with microbiota from two hepatitis B virus (HBV)-infected donors and nine mice transplanted with microbiota from two non-infected donors. Shotgun metagenomic sequencing was performed on stool collected two weeks post-FMT, and metabolic parameters were compared between two and five weeks post-transplantation. RESULTS: Mice receiving microbiota from HBV-infected individuals exhibited lower triglyceride levels (100.05 ± 10.82 vs. 111.69 ± 12.27 mg/dL, p = 0.04) at five weeks post-FMT compared with those receiving microbiota from non-infected individuals. HBV-positive mice also showed higher microbial diversity and an increased abundance of short-chain fatty acid–producing bacterial species, including Anaerofustis stercorihominis, Bacteroides cellulosilyticus, and Butyricimonas virosa. Shotgun analysis revealed reduced activity in the pentose phosphate pathway and galactitol degradation pathways, both involved in carbohydrate and fatty acid metabolism, alongside unique bile acid dihydroxylation pathways. CONCLUSIONS: These findings indicate that gut microbiota with chronic HBV infection modulate host lipid metabolism, particularly triglyceride levels, through distinct microbial species and metabolic pathways.}, }
@article {pmid41873114, year = {2026}, author = {Wang, D and Cui, R and You, C and Zheng, W and Wang, L and Yang, Y and Yu, H and Cui, B}, title = {Relationship Between Gut Microbiota and Cancer Neuro-Immunity.}, journal = {Microbial biotechnology}, volume = {19}, number = {3}, pages = {e70336}, pmid = {41873114}, issn = {1751-7915}, support = {K2023011//Medical research key project of Jiangsu Commission of Health/ ; }, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Tumor Microenvironment/immunology ; Immunotherapy ; *Neuroimmunomodulation ; Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {The nervous system and the immune system are integral components of the tumour microenvironment, and neuroimmune mechanisms play critical roles in tumour metastasis, immune evasion and metabolic reprogramming. However, the relationship between the gut microbiota and cancer neuro-immunity remains poorly understood. This knowledge gap hampers our understanding of how these systems contribute to tumour progression and therapeutic resistance. This article systematically explores the interactions among the gut microbiota, the nervous system and the immune system in the regulation of tumour progression, with a particular focus on elucidating the pathways by which the gut microbiota and its metabolites modulate tumour phenotypes via neuroimmune mechanisms, and summarises the regulatory mechanisms through which cancer neuro-immunity shapes gut microbiota composition. Additionally, this article summarises the interplay between immunotherapy and cancer neuro-immunity, and explores the potential of microbiota-based interventions, such as faecal microbiota transplantation, probiotics, prebiotics and synbiotics, to enhance the efficacy of immunotherapy through neuroimmune mechanisms.}, }
@article {pmid41873461, year = {2026}, author = {Mattavelli, E and Da Prat, V and Corallo, S and Tartara, A and Figini, S and De Simeis, F and Marino, S and Uggè, A and Caccialanza, R and Pedrazzoli, P and Lasagna, A}, title = {Harnessing the gut microbiota in extra-intestinal cancers: from causal evidence to immunotherapy strategies.}, journal = {Immunotherapy}, volume = {18}, number = {3}, pages = {223-235}, pmid = {41873461}, issn = {1750-7448}, mesh = {Humans ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; *Neoplasms/therapy/immunology/microbiology ; Probiotics/therapeutic use ; Animals ; Dysbiosis/immunology ; *Immune Checkpoint Inhibitors/therapeutic use ; Prebiotics ; }, abstract = {The gut microbiota (GM) has emerged as a key modulator of cancer development and therapeutic response beyond the gastrointestinal tract. In extra-intestinal cancers, GM composition influences oncogenesis, with specific microbial taxa and their metabolites linked to either increased or decreased cancer risk, as highlighted by Mendelian Randomization studies. Beyond cancer initiation, GM plays a critical role in shaping the efficacy and toxicity of anticancer therapies, particularly immunotherapy. We searched PubMed and ClinicalTrials.gov using the terms"gut microbiota," "immune checkpoint inhibitors," "faecal microbiota transplantation," "solid tumor" in oncology patients. Evidence indicates that SCFA-producing bacteria, Akkermansia muciniphila, and members of Lachnospiraceae and Ruminococcaceae families enhance responses to immune checkpoint inhibitors (ICIs), whereas dysbiosis and immunosuppressive bacteria are associated with poor outcomes and immune-related adverse events. Therapeutic modulation of the GM through probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions shows promise in optimizing immunotherapy efficacy, yet standardized clinical protocols remain lacking. Integrating GM profiling with multi-omics and artificial intelligence approaches offers a path toward personalized microbiota-targeted interventions to improve patient outcomes. This review critically summarizes current evidence linking GM to cancer immunotherapy, discusses mechanistic insights, and outlines future perspectives for translating microbiota modulation into clinical practice.}, }
@article {pmid41873680, year = {2026}, author = {Zhang, S and Li, P and Dai, M and Wu, X and Lu, C and Lu, G and Ren, Q and Wang, X and Si, Y and Chang, L and Tang, S and Wu, J and Yuan, L and Lyu, L and Wang, H and He, F and Ding, J and Huang, G and Pan, X and Mei, Y and Li, L and Hu, S and Huang, X and Cui, B and Zhang, F and Wen, Q}, title = {Washed Microbiota Transplantation as a Rescue Therapy for Refractory Unidentified Pathogen Intestinal Infections: Findings From a National Multi-Centre, Real-World Study.}, journal = {Microbial biotechnology}, volume = {19}, number = {3}, pages = {e70335}, pmid = {41873680}, issn = {1751-7915}, support = {82400648//National Natural Science Foundation of China/ ; 82170563//National Natural Science Foundation of China/ ; 2021YFA0717004//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; Female ; *Intestinal Diseases/therapy/microbiology ; China ; Male ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; Adult ; Prospective Studies ; }, abstract = {Unidentified pathogen intestinal infections (UPIIs) represent a severe clinical dilemma, characterised by clear signs of intestinal infection yet no identifiable causative pathogen, often leading to prolonged, antibiotic-refractory illness. A nationwide retrospective study based on the prospective cohorts from September 2015 to February 2025 was conducted in China to evaluate washed microbiota transplantation (WMT) on this challenging condition. Patients diagnosed with UPIIs and then underwent WMT were included. The primary outcome was the clinical response rate one month post-WMT. Finally, among the 81 included patients, 71.6% were bedridden, 46.9% required ICU admission and 51.9% developed multiple organ dysfunction syndrome. Diarrhoea was the primary symptom, and over half received ≥ 3 empirical antibiotics. Despite the challenges, WMT achieved a one-month clinical response rate of 63.0% and a cure rate of 43.2%. Multivariate analysis identified several baseline risk factors affecting WMT efficacy, including adverse events (AEs) related to WMT (β = 1.545, p = 0.026, OR = 4.690, 95% CI 1.208-18.206), total abdominal symptom scores (TASS) before WMT (β = 0.292, p = 0.047, OR = 1.340, 95% CI 1.004-1.788) and WHO performance status score ≥ 4 (β = 1.583, p = 0.031, OR = 4.867, 95% CI 1.160-20.423). The overall AEs rate was only 8.3% (18/216). A nomogram based on logistic regression [akaike information criterion (AIC) = 93.75] was developed to predict the clinical non-response at one month after WMT. The favourable clinical outcomes observed in this study provide cohort-based evidence on using WMT for treating refractory UPIIs. These findings implied that if WMT is available, earlier WMT may be beneficial for UPIIs.}, }
@article {pmid41874370, year = {2026}, author = {Liu, C and Dan, L and Wang, X and Chen, L and Yuan, X}, title = {Gut microbiota impact on lung diseases: a mini review of clinical evidence.}, journal = {Infection and immunity}, volume = {94}, number = {4}, pages = {e0043025}, pmid = {41874370}, issn = {1098-5522}, support = {202557-011//Youth Talent Cultivation Program of the China Association of Chinese Medicine/ ; 2023SJZC040//Science and Technology Project of Lishui/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Lung Diseases/microbiology/therapy ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; COVID-19/microbiology ; Prebiotics ; SARS-CoV-2 ; }, abstract = {The gut-lung axis represents a bidirectional communication network through which the gut microbiota (GM) influences respiratory health. This mini-review synthesizes clinical evidence on the role of the GM in lung diseases. We focused exclusively on human clinical trials, randomized controlled trials, meta-analyses, and systematic reviews, sourced from major databases after duplicate removal. The evidence indicates that GM dysbiosis is a significant risk factor for the susceptibility and severity of various respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and infections, such as COVID-19 and pneumonia. Specific microbial signatures and metabolic profiles, particularly involving short-chain fatty acids (SCFAs), are associated with disease states and outcomes. Interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) show promise in modulating the GM and improving clinical parameters, though their efficacy can be inconsistent and influenced by confounding factors. In conclusion, the GM is a promising therapeutic target for lung diseases. However, future research must prioritize large-scale, longitudinal clinical trials and deeper mechanistic investigations to establish causality and develop effective, personalized microbiome-based therapies.}, }
@article {pmid41874416, year = {2026}, author = {Koseli, E and Tyc, KM and Buzzi, B and Akbarali, HI and Damaj, MI}, title = {The Role of the Gut Microbiome in Nicotine Withdrawal and Dependence.}, journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {}, number = {}, pages = {}, doi = {10.1093/ntr/ntag057}, pmid = {41874416}, issn = {1469-994X}, abstract = {INTRODUCTION: Smoking is considered a global pandemic with more than 1.3 billion people being active smokers. Increasing evidence suggests that nicotine exposure can lead to changes in the gut microbiome, increases in permeability, and impaired mucosal immune responses in the gastrointestinal tract. However, the literature on behavioral aspects of nicotine-microbiome interaction, such as dependence and withdrawal, is limited. In this study, we used homologous fecal material transplants (FMT) to modify the gut microbiome and its impact on the intensity of nicotine withdrawal in mice.<br><br>METHODS: We used osmotic minipumps as an application of chronic nicotine for 15&#xa0;days and orally gavaged FMT 2x a day to the mice. We assessed the nicotine withdrawal by measuring the number of somatic signs and anxiety-like behaviors at 24&#xa0;h and 1&#xa0;week after the mini pump removal. Fecal samples were also collected points to identify the gut microbiome changes.<br><br>RESULTS: Fecal transplants reduced the number of somatic signs and anxiety-like behaviors in nicotine-treated mice up to a week after the removal of minipumps. The shotgun metagenomic results of the fecal samples from 24&#xa0;h after minipumps removal time point show altered gut microbiome with a significant shift in the species composition between the nicotine treated and its homologous FMT treatment.<br><br>CONCLUSIONS: Our results indicate that under our experimental conditions fecal transplant can reduce the severity of nicotine withdrawal. This suggests that interactions along the gut-brain axis are important for the development of nicotine dependence and might help lower the risk of cancer and other serious health problems in humans.}, }
@article {pmid41875216, year = {2026}, author = {Castillo-Moral, &#xc1; and Toda-Ferran, C and Bulló, M and Teichenné, J and Escoté, X}, title = {Nutraceuticals and the Microbiota-Gut-Brain Axis: A Pathway for Preventing Cognitive Decline.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuag017}, pmid = {41875216}, issn = {1753-4887}, support = {//Vicente Lopez Program (Eurecat)/ ; //Autonomous Government of Catalonia/ ; 2021 SGR 00213//Departament de Recerca i Universitats de la Generalitat de Catalunya to the Nutrition and Metabolic Health Research Group/ ; 2021 SGR 01556//Precision Nutrition, Wellness and Prevention of Metabolic Diseases/ ; }, abstract = {With the global rise in aging populations, cognitive impairment and neurodegenerative diseases, such as Alzheimer's disease (AD), present a growing public health issue. Current pharmacological treatments primarily target symptoms rather than underlying causes, necessitating the exploration of alternative preventive strategies. Nutraceuticals have emerged as promising candidates for neuroprotection due to their ability to modulate oxidative stress, neuroinflammation, and mitochondrial function. This narrative review aimed to evaluate the neuroprotective potential of nutraceuticals and their interactions with the microbiota-gut-brain axis in preventing age-related cognitive decline. A comprehensive search of the scientific literature using the PubMed, Scopus, and Web of Science databases was undertaken, focusing on publications during the period 2010-2025. Nutraceuticals, including vitamins, omega-3 fatty acids, coenzyme Q10, polyphenols, and isothiocyanates, exhibit neuroprotective properties through antioxidant, anti-inflammatory, and mitochondrial-support mechanisms. The gut microbiota plays a crucial role in regulating the bioavailability and efficacy of these compounds. Microbiome-based interventions, such as prebiotics, probiotics, and fecal microbiota transplantation demonstrate potential in modulating neuroinflammatory responses and supporting cognitive function. Nutraceutical and microbiome-targeted interventions represent promising, low-risk strategies for preventing cognitive decline. Their ability to modulate neuroinflammation and oxidative stress underscores their potential for future clinical applications. Further large-scale studies are needed to validate their efficacy and explore personalized approaches adapted to individual microbiome profiles.}, }
@article {pmid41875611, year = {2026}, author = {Yang, Z and Zhang, F and Yang, S and Anayyat, U and Mo, Y and Ying, Y and Wang, X}, title = {Orally deliverable Perilla frutescens-derived nanovesicles as natural bioactive nanocarriers for colon-targeted colitis therapy via microenvironment reprogramming.}, journal = {Biomaterials advances}, volume = {184}, number = {}, pages = {214832}, doi = {10.1016/j.bioadv.2026.214832}, pmid = {41875611}, issn = {2772-9508}, mesh = {*Perilla frutescens/chemistry ; Animals ; *Colitis/drug therapy/therapy/pathology ; Administration, Oral ; Fecal Microbiota Transplantation ; Mice ; *Colon/drug effects/pathology ; Humans ; *Nanoparticles/chemistry ; Gastrointestinal Microbiome/drug effects ; }, abstract = {Effective oral therapy for inflammatory bowel disease (IBD) requires overcoming gastrointestinal barriers to modulate the dysregulated mucosal niche. Here, we present edible nanovesicles derived from Perilla frutescens (PLENs) as an intrinsically stable, bioactive nanotherapeutic. Multi-omics profiling defined a robust lipid-bilayer architecture encapsulating a synergistic cargo of proteins, miRNAs, and antioxidant metabolites. This structural integrity enabled PLENs to survive gastrointestinal transit and exhibit preferential fluorescence localization with prolonged retention in the inflamed colonic region, as indicated by in vivo imaging. Upon localization, PLENs executed a "dual-hit" therapeutic strategy: they reprogrammed the immune microenvironment, accompanied by reduced activation of the TLR4/MyD88-NF-κB axis and a phenotypic shift from pro-inflammatory M1 to reparative M2 macrophages. Concurrently, PLENs fundamentally restructured the gut ecosystem, accompanied by enrichment of taxa linked to saccharolytic fermentation and recovery of cecal short-chain fatty acids. Notably, fecal microbiota transplantation (FMT) further supported that this microbial remodeling contributed to the protective phenotype, highlighting the microbiome as an important component of efficacy.}, }
@article {pmid41875758, year = {2026}, author = {Cui, H and Liu, Q and Leung, PSC and Chow, MW and Liu, SJ and Liu, B}, title = {Gut microbiota in pathogenesis and therapeutic potentials in rheumatoid arthritis.}, journal = {Current opinion in immunology}, volume = {100}, number = {}, pages = {102760}, doi = {10.1016/j.coi.2026.102760}, pmid = {41875758}, issn = {1879-0372}, mesh = {Humans ; *Arthritis, Rheumatoid/therapy/etiology/immunology/microbiology ; Animals ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; *Dysbiosis/immunology ; Probiotics/therapeutic use ; }, abstract = {This review comprehensively explores the emerging roles of gut microbiota in the pathogenesis and therapeutic implications of rheumatoid arthritis (RA). Clinically, RA is a challenging autoimmune disease due to unclear pathology and limitations of conventional therapies. Recent studies highlight that gut dysbiosis - characterized by reduced microbial diversity, enrichment of proinflammatory taxa, and depletion of anti-inflammatory species - is an important contributor to RA. Mechanistically, gut microbiota dysregulation drives RA through molecular mimicry, metabolite-mediated inflammation, and immune cell migration. Therapeutic strategies targeting the gut-joint axis, including probiotics, high-fiber diets, Mediterranean dietary patterns, and fecal microbiota transplantation (FMT), demonstrate promise in restoring microbial homeostasis, enhancing intestinal barrier integrity, and suppressing proinflammatory cytokines. While preclinical and clinical studies underscore the potential of microbiota-based interventions, challenges such as standardization of FMT protocols and long-term safety require further investigation.}, }
@article {pmid41876026, year = {2026}, author = {Celis, A and Quera, R and Núñez, P and von Muhlenbrock, C and Espinoza, R and Concha, A and Mendoza, C and Marcet, F and Araya, D and Fuentes, J and Riesco, F and Correa, P}, title = {Long-term effectiveness and safety of colonoscopy-guided Fecal Microbiota Transplantation in recurrent Clostridiodes difficile infection: a prospective case series.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {502719}, doi = {10.1016/j.gastrohep.2026.502719}, pmid = {41876026}, issn = {0210-5705}, }
@article {pmid41877779, year = {2026}, author = {Sun, S and Long, F and Su, B and Chen, J and Luo, Y and Zhong, Y and Zhang, G}, title = {The gut microbiome in colorectal anastomotic leakage: from mechanisms to precision.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1781458}, pmid = {41877779}, issn = {2296-858X}, abstract = {Anastomotic leakage after curative colorectal cancer resection remains a frequent and severe complication that increases short-term mortality, worsens long-term oncologic outcomes, and places substantial burdens on individuals and health systems despite advances in surgical technique and perioperative care. Emerging evidence redefines anastomotic failure as not only a technical event but also a biologically driven process in which the gut microbiome regulates inflammation, epithelial repair, and barrier integrity at the healing interface. This review summarizes current data on the dual role of the intestinal microbiome in promoting physiological anastomotic healing and driving pathological leakage when perioperative stressors cause dysbiosis. Mechanistic sections describe how a diverse, metabolically active community supports collagen stability through short-chain fatty acid production, immune regulation, and maintenance of mucus and tight junction architecture. In contrast, the enrichment of microbial groups such as Enterococcus faecalis, Fusobacterium nucleatum, and Alistipes onderdonkii together with fungal and viral shifts, has been associated with extracellular matrix degradation and excessive inflammation. Furthermore, the review examines microbiome-related biomarkers for risk assessment, including DNA-based microbial signatures, metabolite profiles, and host immune markers. It also discusses how integrated multi-omics models combined with machine learning may outperform traditional clinical scores for preoperative and early postoperative prediction. Finally, the article critically evaluates perioperative microbiome-directed strategies ranging from dietary prehabilitation and microbial supplementation to selective decontamination and fecal microbiota transplantation, highlighting promising signals, variability of effect, safety considerations, and key methodological limitations that currently prevent routine implementation. In summary, this review addresses three interconnected domains-mechanisms of microbiome-driven anastomotic failure, microbiome-derived biomarkers for risk stratification, and perioperative intervention strategies-underscoring that AL is best understood as a host-microbiome interaction rather than a purely technical failure. This framing offers surgeons and perioperative teams a biologically rational basis for prevention, yet clinical translation will require causal validation, standardized intervention algorithms, and interpretable computational tools embedded into real-world perioperative practice.}, }
@article {pmid41878444, year = {2026}, author = {Chen, Y and Wang, Z and Zeng, Y and Xie, X and Liu, L and Qian, Y}, title = {Research progress on the role of gut microbiota dysbiosis in the pathogenesis of immune-mediated liver diseases.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1708826}, pmid = {41878444}, issn = {1664-3224}, mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Liver Diseases/immunology/etiology/therapy/microbiology ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; Liver/immunology ; Hepatitis, Autoimmune/immunology/microbiology ; }, abstract = {Gut microbiota dysbiosis plays a significant role in the pathogenesis of immune-mediated liver diseases (IMLDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), through multiple gut-liver axis mechanisms. Microbial metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids regulate hepatic immune homeostasis by activating G protein-coupled receptors (GPRs) and the farnesoid X receptor (FXR). Concurrently, disruption of the intestinal barrier integrity allows endotoxins (e.g., lipopolysaccharide) to activate hepatic macrophages via the TLR4/NF-κB pathway, triggering a pro-inflammatory cytokine cascade. Studies indicate an enrichment of Veillonella in AIH patients, while PBC patients display elevated Enterobacteriaceae and reduced Oscillospira spp. PSC is characterized by Klebsiella pneumoniae translocation and Candida albicans toxin-mediated injury. Therapeutic strategies such as fecal microbiota transplantation (FMT), probiotics, prebiotics, and bacteriophages therapy have shown efficacy in clinical settings, underscoring the potential of targeting the gut microbiota for managing IMLDs. Future research should integrate immune cell regulation by gut-derived factors and develop precision therapies based on the gut-liver axis.}, }
@article {pmid41878631, year = {2026}, author = {MacDonald, KV and Pai, N and Burow, C and deBruyn, JC and Huynh, HQ and Otley, A and Rozario, S and Marshall, DA}, title = {Balancing safety and effectiveness: parent preferences for fecal microbiota transplant and established therapies in pediatric inflammatory bowel disease-results of a multicenter Canadian study.}, journal = {Crohn's &amp; colitis 360}, volume = {8}, number = {1}, pages = {otag016}, pmid = {41878631}, issn = {2631-827X}, abstract = {BACKGROUND AND AIMS: Treatment decision-making in pediatric inflammatory bowel disease (IBD) is complex, with many existing and emerging options. However, little is known about parent preferences for these therapies. This multi-center Canadian study provides the first quantitative data on parent preferences for pediatric IBD treatments and explores characteristics associated with differing preferences.<br><br>METHODS: We conducted a cross-sectional survey including a discrete choice experiment (DCE) with Canadian parents (n&#x2009;=&#x2009;159) of children diagnosed with UC/IBD-U, recruited from four pediatric IBD clinics. The DCE assessed preferences across four treatment attributes: chance of clinical remission, severity and chance of known side effects, severity of rare unknown side effects, and mode of treatment delivery. Latent class modeling was used to explore preference heterogeneity.<br><br>RESULTS: Parents prioritized safety, particularly the risk of rare unknown side effects, followed by likelihood of remission. Latent class analysis identified two distinct groups: one most concerned about rare unknown side effects, and another prioritizing treatment effectiveness. Thirty-eight percent of parents were open to fecal microbiota transplant (FMT), an emerging therapy that uses donor stool to help restore gut microbiome health. Younger parents and those with children experiencing more severe disease and on multiple medications were more likely to accept FMT. Across the cohort, many parents were willing to trade off less desirable delivery modes or increased risk in exchange for better treatment outcomes.<br><br>CONCLUSIONS: Parents value both safety and effectiveness in IBD treatment decisions. Recognizing these preferences may support shared decision-making, particularly when discussing novel therapies like FMT.}, }
@article {pmid41878811, year = {2026}, author = {Chen, Y and Li, B and Lin, Y and Sha, W and Shi, C and Wang, M and Wang, S and Wang, J and Ma, Y and Wu, M and Fan, Z and Chen, Y and Zhou, Y and Fu, D and Li, J and Zheng, Y and Hu, L}, title = {Hypertension-Associated Acetate Deficiency Enhances Platelet Activation and Thrombosis Via Olfr78.}, journal = {Circulation research}, volume = {138}, number = {9}, pages = {e327498}, doi = {10.1161/CIRCRESAHA.125.327498}, pmid = {41878811}, issn = {1524-4571}, mesh = {Animals ; *Thrombosis/blood/metabolism/etiology ; Humans ; *Platelet Activation ; *Hypertension/blood/metabolism/microbiology/complications ; Male ; Mice ; *Acetates/metabolism/blood ; Mice, Inbred C57BL ; Mice, Knockout ; *Blood Platelets/metabolism ; Gastrointestinal Microbiome ; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; Female ; }, abstract = {BACKGROUND: Arterial thrombotic events constitute the leading cause of mortality in hypertension. Gut dysbiosis induces endothelial dysfunction and systemic inflammation, contributing to hypertension and its associated cardiovascular complications. Whether these dysbiotic microbiota metabolites in hypertension directly regulate platelet hyperactivation and thrombosis remains unclear.<br><br>METHODS: Fecal microbiota transplantation, 16S rRNA sequencing, and untargeted metabolomics were performed using samples from patients with hypertension. In vivo FeCl3-induced mesenteric arteriole thrombosis model, ex vivo microfluidic whole-blood perfusion assay, and in vitro platelet functional studies defined the functional effects of acetate on platelet activation. Moreover, platelet-specific Olfr78 (olfactory receptor 78)-deficient mice were employed to explore the underlying mechanisms of acetate on platelet activation.<br><br>RESULTS: Transplantation with fecal microbiota from patients with hypertension enhanced in vivo FeCl3-injured mesenteric arteriole thrombosis and ex vivo whole blood thrombus formation compared with fecal microbiota from healthy normotensive subjects. Untargeted metabolomics revealed that gut microbiota-derived acetate was decreased in patients with hypertension, and plasma acetate concentration negatively correlated with integrin &#x3b1;IIb&#x3b2;3 activation and P-selectin exposure. Acetate demonstrated superior antiplatelet efficacy against ADP-induced aggregation, dense-granule secretion, &#x3b1;-granule secretion, and integrin &#x3b1;IIb&#x3b2;3 activation than collagen or thrombin-induced platelet activation. Mechanistic studies using platelet-specific Olfr78[-/-] mice revealed that acetate bound to and activated Olfr78, a receptor not previously reported to be expressed in platelets, to elevate cAMP level and activate PKA, thereby increasing p-VASP and decreasing Ca[2+] mobilization as well as inactivating RhoA/ROCK2/MLC (myosin light chain) signaling to inhibit platelet activation. A high-fiber diet upregulated acetate/Olfr78 signaling in platelets to suppress microvascular thrombosis and protect against myocardial injury during myocardial infarction in mice.<br><br>CONCLUSIONS: Acetate is a negative regulator of platelet hyperreactivity and thrombus formation via the Olfr78 receptor, and acetate deficiency contributes to platelet hyperreactivity in hypertension. Lifestyle modifications, particularly high-fiber dietary intervention and acetate supplementation, exhibit potent antithrombotic effects in hypertension.}, }
@article {pmid41880488, year = {2026}, author = {Kim, SG and Ott, R and Bretin, A and Abo, H and Wang, Y and Wang, Y and Winer, S and Winer, DA and Reddivari, L and Heaver, SL and Ley, RE and Pellizzon, M and Ngo, VL and Gewirtz, AT}, title = {Wheat fiber mitigates colitis via non-SCFA microbial metabolite-trained intestinal macrophages.}, journal = {Science advances}, volume = {12}, number = {13}, pages = {eaec5757}, pmid = {41880488}, issn = {2375-2548}, mesh = {Animals ; *Macrophages/metabolism/immunology ; *Dietary Fiber/pharmacology ; *Colitis/metabolism/pathology/diet therapy/etiology/microbiology/prevention &amp; control ; Mice ; *Triticum/chemistry ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Intestines ; }, abstract = {The advent of highly refined wheat products has reduced fiber consumption, which is associated with increased risk for inflammatory bowel disease (IBD). We found that enriching diets with wheat fiber (WF) protected mice against colitis, especially relative to a low-fiber diet, as assessed by clinical, histopathologic, morphologic, and immunologic parameters. WF's protection against colitis was independent of short-chain fatty acids (SCFAs) yet associated with preservation of microbiota diversity, including maintenance of Bacteroides thetaiotaomicron (B. theta), which was necessary and sufficient for WF's colitis protection. B. theta's presence in gnotobiotic mice resulted in WF-induced fecal metabolites that reprogrammed macrophages toward an M2-like phenotype. Metabolic and phenotypic reprogramming of macrophages ex vivo via WF-induced metabolites, followed by their transplantation into mice, recapitulated WF's protection against colitis. Thus, microbiota-mediated metabolism of WF promotes macrophages that reduce proneness to intestinal inflammation, suggesting a mechanism by which WF consumption may curb development of IBD.}, }
@article {pmid41880553, year = {2026}, author = {Liao, Y and Jiang, R and Zhang, H and Zhang, W}, title = {The dual roles of microorganisms in inflammatory diseases: initiators and regulators.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {}, number = {}, pages = {1-33}, doi = {10.1080/10408363.2026.2637106}, pmid = {41880553}, issn = {1549-781X}, abstract = {Research on the microbiome is reshaping the conceptual foundations of inflammatory diseases. As a dynamic component of the host ecosystem, microbial communities collectively influence inflammatory responses and homeostatic balance through their metabolites, structural signals, and interactions with immune pathways. Dysbiosis can amplify immune activation and metabolic disturbances, leading to persistent inflammation, whereas specific commensal taxa and their metabolites possess the capacity to suppress excessive immune responses and restore homeostasis. This bidirectional regulatory capacity positions the microbiome as a central node that both drives and modulates inflammatory networks. Multi-omics investigations have delineated the systemic architecture of microbe-host interactions, revealing cross-system axes such as the gut-brain, gut-liver, and skin-gut pathways that constitute a signaling framework integrating inflammation and immunity, thereby reshaping our understanding of disease pathogenesis. Within this framework, inflammation is redefined as an adaptive strategy for maintaining systemic stability rather than merely a singular pathological reaction. Therapeutic approaches including fecal microbiota transplantation (FMT), engineered microbial strains, and interventions targeting metabolic signaling are propelling microecological medicine into an era of precision modulation. As systems biology converges with spatial omics, research on the microbiome is shifting from descriptive pathology toward mechanistic control, establishing it as a critical nexus linking immunity, metabolism, and disease evolution. This transformation heralds a paradigm shift in medicine from merely "suppressing inflammation" to actively "reconstructing ecological order."}, }
@article {pmid41883804, year = {2026}, author = {Han, Y and Wang, Z and Xie, J and Yang, G and Su, M and Wang, S and Yang, M and Yu, H and Li, M and Wang, L and Zhang, Y and Hou, B}, title = {Host-gut microbiota interactions in health and disease: mechanisms and intervention strategies.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1785607}, pmid = {41883804}, issn = {1664-302X}, abstract = {The mammalian gut microbiota is a complex and dynamic "microbial organ" that interacts with its host. The gut microbiota contains a vast gene pool and metabolic capacity, producing key metabolites such as short-chain fatty acids (SCFAs), bile acids, vitamins, and other compounds. These metabolites regulate core physiological functions like energy metabolism, immune homeostasis, and neural behavior via the gut-brain axis (GBA), immune signaling networks, and other pathways. This review explores the bidirectional regulatory role of the gut microbiota. The gut microbiota influences the host's metabolism and immune functions through its metabolites and structural components, while the host's physiological state, internal environment, and lifestyle can alter the microbiota's composition and function, creating a complex feedback network. Furthermore, the main mechanisms of dysbiosis in diseases are also explored. Dysregulation of the gut microbiota can damage the intestinal mucosal barrier, induce chronic inflammation, disrupt metabolic and immune signaling, and contribute to diseases such as type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders. Microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), can be promising in disease management, but their clinical applications face challenges, including individual genetic backgrounds, lifestyles, and environmental factors, as well as difficulties in achieving long-term colonization of specific strains. Future research needs to uncover precise causal mechanisms in host-microbe interactions, as well as develop individualized microbiota intervention strategies to provide new theoretical bases and practical tools for the prevention, diagnosis, and treatment of major diseases.}, }
@article {pmid41884305, year = {2023}, author = {Ito, K and Haraguchi, A and Sato, S and Sekiguchi, M and Sasaki, H and Ryan, C and Lyu, Y and Shibata, S}, title = {Feeding with resistant maltodextrin suppresses excessive calorie intake in a high-fat diet, mediated by changes in mouse gut microbiota composition, appetite-related gut hormone secretion, and neuropeptide transcriptional levels.}, journal = {Frontiers in microbiomes}, volume = {2}, number = {}, pages = {1149808}, pmid = {41884305}, issn = {2813-4338}, abstract = {Consuming resistant maltodextrin (RMD) decreases food intake and increase appetite-related gut hormones, but the underlying mechanisms have remained unknown. Therefore, we aimed to elucidate the mechanisms underlying the effects of RMD feeding on food intake (appetite) using Institute of Cancer Research male mice fed with a high-fat diet (HFD-cellulose group) or HFD in which cellulose was replaced with RMD (HFD-RMD group). Feeding mice with an HFD-RMD for approximately 8 weeks inhibited excessive calorie intake and altered the gut microbiota composition. Excessive calorie intake was inhibited for several days in mice fed only with an HFD-cellulose and transplanted with fecal microbiota from the HFD-RMD group (FMT-HFD-RMD group). Moreover, in the HFD-RMD and FMT-HFD-RMD groups, serum active glucagon-like peptide (GLP)-1 and peptide tyrosine tyrosine (PYY) levels were significantly higher, and appetite-related neuropeptide gene transcription in the hypothalamus were significantly altered, compared with the HFD-cellulose and FMT-HFD-cellulose groups. These results suggested that the long-term RMD intake changed the gut microbiota composition, increased the GLP-1 and PYY secretion, and altered the appetite-related neuropeptide gene transcription in the hypothalamus, leading to suppressed excessive calorie intake in an HFD.}, }
@article {pmid41886797, year = {2026}, author = {Misra, J and Bhargav Shreevatsa, KS and Ravi, K and Abomughaid, MM and Lakhanpal, S and Gupta, R and Jha, NK and Kumar, N}, title = {Microbiota-driven neuroimmune mechanisms in brain disorders: Microglial activation, cytokine signaling, and translational implications.}, journal = {Journal of neuroimmunology}, volume = {416}, number = {}, pages = {578913}, doi = {10.1016/j.jneuroim.2026.578913}, pmid = {41886797}, issn = {1872-8421}, mesh = {Humans ; Animals ; *Microglia/immunology/metabolism ; *Cytokines/immunology/metabolism ; *Brain Diseases/immunology/microbiology/metabolism ; Signal Transduction/immunology/physiology ; *Neuroimmunomodulation/immunology/physiology ; *Gastrointestinal Microbiome/immunology/physiology ; *Translational Research, Biomedical/trends/methods ; Neuroinflammatory Diseases/immunology ; Blood-Brain Barrier/immunology ; *Brain-Gut Axis/immunology ; }, abstract = {Neuroinflammation is increasingly recognized as a central driver of diverse neurological and neuropsychiatric disorders. Within this framework, the microbiota-gut-brain axis (MGBA) has emerged as a critical modulator of neuroimmune signaling rather than a broad systemic regulator. Microbial-derived metabolites and immune mediators influence central nervous system (CNS) homeostasis by shaping microglial maturation and activation, regulating cytokine signaling networks, including IL-1β, IL-6, and TNF-α and modulating inflammasome pathways, such as NLRP3. These immune mechanisms intersect with blood-brain barrier (BBB) integrity, where dysbiosis-associated inflammation and altered short-chain fatty acid (SCFA) production may compromise tight junction stability and promote peripheral immune infiltration. Through immune-glial crosstalk, microbial signals can amplify or attenuate neuroinflammatory cascades, thereby influencing vulnerability to autoimmune, neurodegenerative, and neurodevelopmental disorders. This review synthesizes current mechanistic evidence linking gut microbial perturbations to CNS immune regulation, emphasizing microglial activation, cytokine-mediated signaling, and BBB immunomodulation as core pathways. By reframing the MGBA through a neuroimmune lens, we highlight emerging therapeutic strategies targeting microbiota-driven inflammatory circuits to advance precision interventions for inflammatory brain disorders.}, }
@article {pmid41886951, year = {2026}, author = {Zuo, G and Shen, Y and Wang, L and Gao, Y and Luo, C and Wen, J and Li, J and Huang, JA and Liu, Z and Lin, Y}, title = {Low-dose epigallocatechin gallate combined with L-theanine effectively alleviate obesity and metabolic dysfunction-associated steatotic liver disease by remodeling gut homeostasis and avoiding its hepatotoxicity.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {155}, number = {}, pages = {158078}, doi = {10.1016/j.phymed.2026.158078}, pmid = {41886951}, issn = {1618-095X}, mesh = {Animals ; *Catechin/analogs &amp; derivatives/pharmacology/administration &amp; dosage/adverse effects ; *Glutamates/pharmacology/administration &amp; dosage ; Mice, Inbred C57BL ; *Obesity/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Liver/drug effects ; Oxidative Stress/drug effects ; *Fatty Liver/drug therapy ; Fecal Microbiota Transplantation ; Homeostasis/drug effects ; Dysbiosis ; }, abstract = {BACKGROUND: High-dose epigallocatechin gallate (EGCG) treats obesity and metabolic dysfunction-associated steatotic liver disease but causes hepatotoxicity, limiting its application.<br><br>OBJECTIVE: To determine whether low-dose EGCG combined with L-theanine (LTA) can reproduce the metabolic benefits of high-dose EGCG without hepatotoxicity, and to clarify the role of the gut microbiota.<br><br>METHODS: Diet-induced obese C57BL/6J mice were treated with L-EGCG (80 mg/kg/d), H-EGCG (160 mg/kg/d), LTA (80 mg/kg/d), or L-EGCG+LTA for 12 weeks. Metabolic parameters, liver function, oxidative stress, and gut barrier integrity, were evaluated. 16S rRNA sequencing and fecal microbiota transplantation (FMT) confirmed the causal role of microbiota remodeling in the observed therapeutic effects.<br><br>RESULTS: Although H-EGCG effectively reduced body weight and adiposity, it induced liver injury and gut dysbiosis with depletion of commensal butyrate producers and enrichment of polyphenol-metabolizing taxa, collectively exacerbating hepatic oxidative stress and mitochondrial injury. In contrast, L-EGCG+LTA achieved weight- and lipid-lowering effects comparable to H-EGCG while significantly attenuating hepatic oxidative stress and conferring hepatoprotective effects. Two-way ANOVA confirmed that the combined effects were predominantly additive, with both agents contributing independently. The combination additively remodeled the gut microbiota, markedly enriching beneficial taxa such as Bacteroides uniformis and Oscillospiraceae. FMT from combination-treated donors recapitulated metabolic benefits to HFD-fed recipient mice.<br><br>CONCLUSIONS: Co-administration of low-dose EGCG and L-theanine additively improves metabolic health by remodeling the gut microbiota, offering a promising strategy to enhance the safety and translational potential of EGCG-based interventions.}, }
@article {pmid41888318, year = {2026}, author = {Huang, W and Zhang, J and Shan, J and Shen, W and Du, P and Liu, J and Guo, X and Chen, Z and Zeng, W and Lin, Q and Fan, H}, title = {Lactobacillus paragasseri LPG-9 reduces placental inflammation in intrahepatic cholestasis of pregnancy by regulating TGR5 in mice.}, journal = {Communications biology}, volume = {9}, number = {1}, pages = {}, pmid = {41888318}, issn = {2399-3642}, support = {32370139//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32300085//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Female ; Pregnancy ; *Cholestasis, Intrahepatic/metabolism/microbiology/therapy ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Placenta/metabolism/pathology ; Mice ; Humans ; Mice, Inbred C57BL ; Bile Acids and Salts/metabolism ; *Pregnancy Complications/metabolism/microbiology/therapy ; *Probiotics/pharmacology ; *Inflammation ; Gastrointestinal Microbiome ; *Lactobacillus ; }, abstract = {Intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with adverse fetal outcomes, is characterized by elevated bile acid levels and placental inflammation by the TGR5. However, the interplay among the gut microbiome, bile acid metabolism, and ICP-associated placental inflammation remains unexplored. We aimed to investigate the role of the gut microbiota in regulating bile acid metabolism and placental inflammation, and to identify potential probiotic-based therapies for ICP in C57BL/6 mice. Immunohistochemical analysis of human placentas revealed significantly higher inflammation and decreased TGR5 expression in ICP compared with controls. In vivo and in vitro assays confirmed the anti-inflammatory effects of TGR5 activation. Using 16S rRNA sequencing and metabolomics, ICP mice exhibited a distinct gut microbiota composition and reduced abundance of bile salt hydrolase (BSH)-producing bacteria (e.g., Lactobacillus), accompanied by a significant decrease in the proportion of secondary bile acids. Transplanting fecal microbiota from ICP donors into healthy mice reproduced the disease phenotype of ICP, confirming the pathogenic role of gut microbiota dysbiosis. Supplementation with BSH-enriched Lactobacillus paragasseri LPG-9 remodeled the bile acid profile, thereby activating placental TGR5 to inhibit TLR4-NF-κB signaling and promoting hepatic bile acid excretion via BSEP.}, }
@article {pmid41889026, year = {2026}, author = {Shi, Y and Li, H}, title = {Microecological Interventions against Antibiotic-Induced Dysbiosis and Related Resistome Expansion.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2601009}, pmid = {41889026}, issn = {1738-8872}, mesh = {*Dysbiosis/chemically induced/therapy/microbiology ; Humans ; *Anti-Bacterial Agents/adverse effects ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Animals ; Intestinal Barrier Function ; Bacteria/drug effects/metabolism ; Drug Resistance, Bacterial ; Drug Resistance, Microbial/genetics ; Biofilms/drug effects/growth &amp; development ; Host Microbial Interactions ; Synbiotics ; }, abstract = {Antibiotic exposure and the emergence of antimicrobial resistance are critical global health threats, with antibiotic-induced gut dysbiosis contributing to increased mortality, prolonged illness, and significant economic burden. This review introduces the complex interplay between antibiotic exposure, gut microbiota dysbiosis, and the dissemination of antimicrobial resistance genes, which collectively undermine intestinal barrier function and promote systemic inflammation. It also explores how microbial metabolites influence resistance mechanisms through metabolic regulation, alteration of bacterial communities, antibiotic biotransformation, biofilm formation, and host-microbe interactions. Microecological interventions-including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary modifications, and emerging strategies-have the potential to restore microbial homeostasis, enhance colonization resistance to invading pathogens, and mitigate the spread of resistant pathogens. By integrating ecological and therapeutic perspectives, these approaches offer a sustainable framework for combating antibiotic resistance and improving clinical outcomes.}, }
@article {pmid41889649, year = {2026}, author = {Su, R and Ma, J and Li, J and Liu, Y and Ma, T and Wang, J and Mai, Q and Ma, Q and Wang, J and Wang, H and Yang, S and Zhang, X}, title = {Fecal microbiota transplantation ameliorates alcohol-associated liver disease through coordinated restoration of short-chain fatty acid and α-linolenic acid signaling.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1744446}, pmid = {41889649}, issn = {1664-302X}, abstract = {BACKGROUND: Alcohol-associated liver disease (ALD) is closely linked to gut microbiota dysbiosis. However, the specific microbial metabolic functions that drive the transition from microbial imbalance to hepatic inflammation and metabolic injury remain unclear, limiting the development of mechanism-based therapeutic strategies.<br><br>METHODS: This study integrated human microbiome analysis with fecal microbiota transplantation (FMT) experiments in an ALD mouse model. Multi-omics approaches, including 16S rRNA gene sequencing, untargeted metabolomics, and immunological profiling, were employed to systematically characterize the interactions among gut microbiota composition, microbial-derived metabolites, and host immune responses.<br><br>RESULTS: We observed that ALD progression was characterized by an early shift in microbial composition followed by a marked decline in microbial diversity, culminating in an ecological collapse of the gut microbiota. FMT from healthy donors significantly improved liver histopathology and serum biochemical parameters, accompanied by restoration of gut microbial diversity and key metabolic functions. Metabolomic analyses revealed enhanced short-chain fatty acid (SCFA) production and activation of &#x3b1;-linolenic acid (ALA)-related metabolic pathways following FMT. These metabolic improvements were associated with reduced inflammatory responses and improved immune homeostasis.<br><br>CONCLUSION: Our findings demonstrate that FMT from healthy donors ameliorates ALD by restoring critical microbial metabolic functions, particularly SCFA production and ALA-related pathways. These results highlight microbial metabolic function as a promising therapeutic target for microbiome-based interventions in ALD.}, }
@article {pmid41890300, year = {2026}, author = {Shirotani, M and Shimizu, S and Kitamura, K and Mikawa, Y and Haruna, R and Kawai, Y and Koide, S and Mohri, I and Matsuzaki, H and Tsuchiya, KJ and Tanaka, Y and Katayama, T}, title = {Safety and efficacy of a novel fecal microbiota transplantation method using hydrogen nanobubble water without antibiotics or bowel cleansing in children with autism spectrum disorder: an open-label, single-arm study demonstrating improvements in core and comorbidity symptoms.}, journal = {Frontiers in pediatrics}, volume = {14}, number = {}, pages = {1767346}, pmid = {41890300}, issn = {2296-2360}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is rising in prevalence, but effective treatments for its core symptoms remain limited. Fecal microbiota transplantation (FMT) has shown promise; however, conventional methods often require antibiotics and bowel cleansing, raising concerns regarding safety and sustainability. We developed a novel FMT method using hydrogen nanobubble water and investigated its efficacy and safety.<br><br>METHODS: This prospective, single-arm, before-and-after comparative study enrolled 30 children aged 5-12 years with ASD, selected according to inclusion and exclusion criteria. SHIN-1, a Good Manufacturing Practice (GMP)-grade prepared fecal microbial solution from a healthy screened donor, was suspended in hydrogen nanobubble water and administered via enema. Primary outcome was the Social Responsiveness Scale-2 (SRS-2), with objectivity confirmed using Gazefinder as an eye-tracking system. Secondary outcomes included sensory profile [Short Sensory Profile (SSP)], gastrointestinal symptoms [Gastrointestinal Symptom Rating Scale [GSRS], Bristol Stool Form Scale [BSFS]] and Patient Health Questionnaire-4 items (PHQ-4). Statistical analyses employed paired t-tests or Wilcoxon signed-rank tests (&#x3b1;&#x2009;=&#x2009;0.05).<br><br>RESULTS: At 30 weeks, fecal microbiota reconstitution was observed, with increases in short-chain fatty acid-producing and typically taxa abundant in developing children. SRS-2 scores decreased 29% (p&#x2009;<&#x2009;0.001), sustained at one year. The classification is as follows; 19 severe cases improved to mild and 6 to normal. Improvements were greater in children without gastrointestinal disorders (45% vs. 24%). Social Communication and Interaction (SCI), Restricted Interests and Repetitive Behavior (RRB), and subscales improved uniformly; sensory, gastrointestinal, and emotional symptoms improved by 30%-61%. No adverse events occurred.<br><br>CONCLUSION: This novel hydrogen nanobubble water-based FMT method was safe and effective, reducing both core and peripheral symptoms of ASD and suggesting broad benefits via the gut microbiota-brain axis.Clinical Trial Registration: https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031230041.}, }
@article {pmid41890703, year = {2026}, author = {Li, X and Liu, F and Zhu, Y and Shi, H}, title = {Gut Microbiota, Insulin Resistance, and Alzheimer's Disease: A Narrative Review of Mechanistic Links and Therapeutic Perspectives.}, journal = {International journal of general medicine}, volume = {19}, number = {}, pages = {593664}, pmid = {41890703}, issn = {1178-7074}, abstract = {Alzheimer's disease (AD) is increasingly regarded as a "neurometabolic syndrome" wherein systemic insulin resistance exacerbates cerebral glucose hypometabolism, tau hyperphosphorylation, and neuroinflammation. We hypothesize that gut microbiota dysbiosis produces metabolites that are associated with peripheral insulin sensitivity, potentially contributing to disruptions in cerebral insulin signaling and an increased risk of AD. We conducted integrated search of PubMed, Web of Science, and Scopus to synthesize evidence showing: (i) consistent taxonomic shifts in AD, highlighting reduced Firmicutes and increased Proteobacteria and Bacteroidetes, depletion of Ruminococcaceae and enrichment of Blautia and Bilophila; (ii) functional consequences of dysbiosis, leading to lower short-chain fatty acids, altered secondary bile‑acid signaling, elevated lipopolysaccharide and trimethylamine‑N‑oxide, and perturbed tryptophan catabolism; (iii) these microbial metabolites compromising gut and blood-brain barrier integrity, thereby triggering chronic inflammation, potentially modulating the PI3K‑Akt‑GSK‑3β pathway, and linking peripheral insulin resistance to cerebral dysfunction; and (iv) a translational discussion of therapeutic strategies that target both microbiota and insulin pathways, including dietary modulation, probiotics and prebiotics, fecal microbiota transplantation, intranasal insulin, metformin, and metabolite-based agents, show promise. This review uniquely integrates taxonomic, functional, and therapeutic literature to propose a mechanistic microbiota-insulin resistance-AD axis and highlights the need for longitudinal and interventional trials.}, }
@article {pmid41890764, year = {2026}, author = {Lai, J and Wang, Y and Zeng, L and Deng, Q and Qiao, Y and Liao, J and Sun, C and Geng, Y and Wu, H and Huang, D and Zhao, X and Wu, D}, title = {Melatonin alleviates airway inflammation and anxiety-depression in asthma via gut microbiota-SCFA axis-mediated inhibition of microglial activation.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1763305}, pmid = {41890764}, issn = {1664-3224}, mesh = {Animals ; *Melatonin/pharmacology ; *Asthma/drug therapy/psychology/metabolism/immunology ; *Microglia/drug effects/metabolism/immunology ; Mice ; *Depression/drug therapy/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Anxiety/drug therapy/metabolism ; *Fatty Acids, Volatile/metabolism ; Disease Models, Animal ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Asthma frequently co-occurs with anxiety and depression, yet the mechanisms underlying this lung-brain comorbidity remain elusive. The gut-lung-brain axis has emerged as a potential key mediator.<br><br>METHODS: Using an ovalbumin (OVA)-induced murine asthma model, we administered melatonin or sodium butyrate via drinking water. We assessed airway inflammation, lung function, anxiety- and depression-like behaviors, gut microbiota composition, short-chain fatty acid (SCFA) levels, and the MAPK/P65/NLRP3 signaling pathway in the hippocampus and BV2 microglial cells. Fecal microbiota transplantation (FMT) and antibiotic depletion experiments were conducted to establish causality.<br><br>RESULTS: Both melatonin and sodium butyrate significantly alleviated airway inflammation, improved lung function, and ameliorated anxiety- and depression-like behaviors in asthmatic mice. Melatonin increased gut-derived butyrate levels and restored gut microbiota balance. FMT from melatonin-treated donors replicated the therapeutic benefits, whereas antibiotic-mediated microbiota depletion abrogated the effects of melatonin. Mechanistically, both treatments inhibited the activation of the MAPK/P65/NLRP3 pathway in hippocampal microglia and LPS-stimulated BV2 cells.<br><br>CONCLUSION: Our findings demonstrate that melatonin mitigates asthma-related airway inflammation and neuropsychiatric comorbidity by modulating the gut microbiota-SCFA axis and suppressing microglial activation via the MAPK/P65/NLRP3 pathway. This study highlights a novel systemic mechanism and potential therapeutic strategy for asthma and its comorbidities.}, }
@article {pmid41890815, year = {2026}, author = {Xiong, Z and Dong, X and Yuan, Y and Lu, L and Deng, X}, title = {Gut Microbiota Mitigates Chronic Itch and Cutaneous Inflammation in DNFB-Induced Atopic Dermatitis Mice.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {573709}, pmid = {41890815}, issn = {1178-7031}, abstract = {BACKGROUND: Chronic itch is the most prominent symptom of atopic dermatitis (AD), which severely impacts the quality of life of patients and persists even after medication. Gut microbiota dysbiosis is considered to contribute to AD, however, the roles of gut microbiota in the modulation of chronic pruriceptive processing currently remain unclear. The present study aimed to elucidate the potential regulatory role of the gut microbiota in AD-associated chronic itch.<br><br>METHODS: In this study, the 1-fluoro-2,4-dinitrobenzene (DNFB)-induced mouse model of AD-associated chronic itch was established. Differences in gut microbiota composition between model and healthy controls were analyzed using high-throughput 16S rRNA gene sequencing. In addition, we performed oral fecal microbiota transplantation (FMT) from model mice to antibiotic cocktail-treated healthy mice and observed whether they could induce itch behavior. Furthermore, feces from healthy mice were transplanted into model mice to evaluate their effects on itch symptoms and skin inflammation.<br><br>RESULTS: The DNFB induced significantly itch behaviors and an altered gut microbiota composition. The gut microbiota from chronic itch mice through oral administration could induce itch behaviors in antibiotic cocktail-treated healthy mice. While, oral FMT from healthy mice to chronic itch mice not only significantly alleviated scratching behavior but also ameliorated skin damage and inflammation. Following FMT administration from healthy donors, remarkable alterations were observed in the metabolomic profiles of mice with DNFB-induced chronic itch.<br><br>CONCLUSION: These findings highlight the potential link between gut microbiota dysbiosis and chronic itching in AD, suggesting that targeting the gut microbiota may be a therapeutic strategy for chronic itch.}, }
@article {pmid41891399, year = {2026}, author = {Elsheikh, M and Ibrahim, MA and Fares, S and Bhongade, M and Adhem, K and Ramirez-Morales, XI and Kaseb, AO and Petrosino, J and Hassan, MM and Jalal, PK}, title = {Influence of Gut Microbiota on Response to Immune Check Point Inhibitors in MASLD Patients With HCC: Unraveling the Connection.}, journal = {Cancer medicine}, volume = {15}, number = {4}, pages = {e71738}, pmid = {41891399}, issn = {2045-7634}, support = {R21CA293626/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Carcinoma, Hepatocellular/drug therapy/immunology/microbiology/complications ; *Liver Neoplasms/drug therapy/microbiology/immunology/complications ; *Gastrointestinal Microbiome/immunology/drug effects ; Fecal Microbiota Transplantation ; Dysbiosis/immunology/microbiology ; *Liver Diseases/microbiology ; }, abstract = {Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment for various cancers, including advanced hepatocellular carcinoma (HCC). However, a significant proportion of patients with HCC, particularly those with metabolic dysfunction-associated liver disease (MASLD), exhibit resistance to ICI therapy. Studies have revealed that the presence of specific gut bacteria, such as Akkermansia, Bifidobacterium, and Lachnoclostridium, is associated with improved outcomes with ICI-treated HCC patients. Conversely, the overgrowth of bacteria like Enterobacteriaceae is linked to resistance to therapy. This review investigates the role of gut microbiota in shaping immune checkpoint inhibitor responses in MASLD-related hepatocellular carcinoma, focusing on how dysbiosis may contribute to ICI resistance and exploring microbiome modulation strategies, such as fecal microbiota transplantation and probiotics, aiming to optimize therapeutic outcomes.}, }
@article {pmid41892839, year = {2026}, author = {Lista, AR and Ayala Mosqueda, CV and Palacios, R and García Mansilla, MJ and Rodríguez Sojo, MJ and Ho Plágaro, A and Garcia Garcia, J and Gálvez, J and Rodríguez Nogales, A and Ruiz Malagón, AJ and Rodríguez Sánchez, MJ}, title = {Modulation of Microbiome-Mitochondria Axis as a Novel Approach for Treatment of Obesity: A Scoping Review.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {41892839}, issn = {2076-3271}, support = {PI18/00826, PY20-01157, PI20/01447, B-CTS-664-UGR20, PI19/01058, PI24/02089 and JDC2022-049478-I, CD23/00117, IFI21/00030//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Obesity/therapy/microbiology/metabolism ; *Mitochondria/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Energy Metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Background: Obesity is a multifactorial, chronic disease characterised by excessive fat accumulation, low-grade inflammation, and metabolic dysfunction. Emerging evidence suggests that the gut microbiome-mitochondria axis may play a significant role in the pathophysiology of obesity, particularly in regulating energy metabolism, inflammatory responses, and mitochondrial function. However, most mechanistic insights into this axis derive from preclinical animal studies, while human evidence remains limited and largely associative. Mitochondrial dysfunction disrupts cellular energy balance, increases reactive oxygen species production, and may exacerbate gut dysbiosis, further contributing to metabolic disturbances. In addition, factors such as micronutrient deficiencies also play a relevant role in obesity development and progression. Objectives: This review aims to examine the bidirectional interactions between the gut microbiome and mitochondrial systems in obesity, with a focus on the underlying molecular mechanisms and their potential as therapeutic targets. Methods: Evidence from experimental models and clinical studies was analysed to evaluate how modulation of the microbiome-mitochondria axis through probiotics, prebiotics, dietary strategies, and faecal microbiota transplantation influences mitochondrial function, inflammation, and metabolic regulation. Results: Preclinical studies indicate that the gut microbiome modulates mitochondrial activity through the production of bioactive metabolites, including short-chain fatty acids, secondary bile acids, and tryptophan-derived compounds, which influence mitochondrial efficiency, lipid metabolism, and glucose regulation. Dysbiosis reduces these beneficial metabolites, impairing mitochondrial signalling and promoting adiposity and insulin resistance. Interventions targeting this axis have shown potential in restoring metabolic balance, improving mitochondrial function, and mitigating obesity-related complications such as hyperlipidaemia and glucose intolerance. Conclusions: Targeting the microbiome-mitochondria axis represents a promising therapeutic strategy for obesity, with the evidence based largely on preclinical findings. However, further well-designed human studies are required to clarify causality, optimise interventions, assess long-term safety and efficacy, and establish standardised clinical protocols for implementation.}, }
@article {pmid41894083, year = {2026}, author = {Li, Y and Jiang, M and Pang, J and Ma, C and Zhang, H and Yin, F and Jia, Y and Zou, X and Zuo, T and Zhang, H}, title = {High-altitude exposure remodels the gut microbiota: health and disease.}, journal = {MedScience}, volume = {20}, number = {1}, pages = {120-146}, pmid = {41894083}, issn = {3091-4981}, mesh = {Humans ; *Altitude ; *Altitude Sickness/microbiology ; *Gastrointestinal Microbiome/physiology ; Acclimatization/physiology ; Animals ; Hypoxia/microbiology ; }, abstract = {With the increasing number of individuals travelling to or residing in high-altitude regions, understanding the physiological and pathological consequences of such environments has become increasingly important. High-altitude exposure poses significant challenges to human health, primarily due to hypobaric hypoxia, which triggers a cascade of responses, including energy deficiency, oxidative stress, and inflammation. One of the critical consequences is the disruption of the gut barrier, which facilitates the translocation of the gut microbiota and further exacerbates local and systemic inflammation. Notably, the gut microbiota, a dynamic environmental sensor, undergoes significant remodelling in high-altitude environments. The modified production of microbial metabolites such as bile acids influences gut homeostasis as well as glucose and lipid metabolism, and ultimately contributes to individual variability in high-altitude acclimatization. These changes have been implicated in the pathogenesis of altitude-related illnesses such as acute and chronic mountain sickness, as well as in metabolic and gastrointestinal disorders such as diabetes, obesity, irritable bowel syndrome, colorectal cancer, cholelithiasis, and osteoporosis. Preliminary explorations have demonstrated the therapeutic potential of microbiome-based interventions such as faecal microbiota transplantation in acute and chronic mountain sickness. Further research into gut microbiota modulation may provide applicable options for promoting high-altitude acclimatization and preventing high-altitude illness.}, }
@article {pmid41894953, year = {2026}, author = {Zhang, Y and Chen, Y and Huang, X and Gao, W and Eom, K and Dong, J and Li, L}, title = {Pterostilbene protects against doxorubicin-induced cardiotoxicity in canines via a gut microbiota-6AN-NOX2 axis.}, journal = {Pathology, research and practice}, volume = {282}, number = {}, pages = {156454}, doi = {10.1016/j.prp.2026.156454}, pmid = {41894953}, issn = {1618-0631}, mesh = {Animals ; Dogs ; *Gastrointestinal Microbiome/drug effects ; *Doxorubicin/toxicity ; *Cardiotoxicity/prevention &amp; control ; *Stilbenes/pharmacology ; Oxidative Stress/drug effects ; Male ; Antibiotics, Antineoplastic/toxicity ; Rats ; }, abstract = {BACKGROUND: Doxorubicin (DOX) is a powerful chemotherapeutic agent, but its clinical use is restricted by cumulative and irreversible cardiotoxicity. Intestinal dysbiosis has been linked to DOX-induced cardiac injury, yet the underlying mechanisms and therapeutic targets remain elusive. This study aimed to investigate whether pterostilbene (PTE), a natural prebiotic plant extract, alleviates DOX cardiotoxicity by regulating gut microbiota and their metabolites.<br><br>RESEARCH DESIGN AND METHODS: Eighteen beagles were randomized into control, DOX (30&#x202f;mg/m&#xb2; weekly for 7 weeks), and PTE (50&#x202f;mg/kg daily for 9 weeks) +&#x202f;DOX groups. Fecal microbiota transplantation (FMT) from canine donors to microbiota-depleted rats, 16S rRNA sequencing, metabolome analysis, and in vitro H9C2 cell experiments were conducted. Main outcomes included survival rate, cardiac function parameters, cardiac injury biomarkers, microbial diversity, and oxidative stress-related indicators.<br><br>RESULTS: In beagles receiving cumulative DOX (30&#x202f;mg/m[2] weekly for 7 weeks), PTE cotreatment (50&#x202f;mg/kg daily for 9 weeks) significantly improved survival (83.3% vs. 50.0%, n&#x202f;=&#x202f;6/group) and attenuated myocardial injury, evidenced by reduced plasma CK and LDH activities (both p&#x202f;<&#x202f;0.01 vs. DOX). Echocardiography revealed PTE restored LVEF and LVFS while reducing EPSS and LVIDd (p&#x202f;<&#x202f;0.05). 16S rRNA sequencing demonstrated PTE reversed DOX induced loss of &#x3b1;-diversity (ACE, Shannon, Chao indices, p&#x202f;<&#x202f;0.05) and enriched beneficial Faecalibacterium while suppressing proinflammatory Corynebacterium and Allobaculum (q<0.05). Fecal microbiota transplantation confirmed microbiota dependent cardioprotection. Metabolomics identified 6-aminonicotinamide (6AN) as a key microbial metabolite inversely correlated with cardiac damage. In H9C2 cells, 6AN (1&#x202f;&#xb5;M) replicated PTE's protection by restoring antioxidant enzyme activities, reducing ROS and MDA, and attenuating apoptosis (all p&#x202f;<&#x202f;0.01), effects abolished by NOX2 overexpression.<br><br>CONCLUSIONS: PTE mitigates DOX cardiotoxicity via restructuring gut microbiota, increasing microbial metabolite 6AN, and suppressing NOX2-mediated oxidative stress. Targeting the microbiota-6AN-NOX2 axis represents a promising strategy to preserve cardiac function during anthracycline chemotherapy. These findings establish a mechanistic basis for PTE as a safe, natural adjunctive therapy in cancer patients receiving DOX.<br><br>TRIAL REGISTRATION: Not applicable.}, }
@article {pmid41895369, year = {2026}, author = {Lin, F and Zhang, D and Liu, S and Wu, B and Wang, J and Yan, T and Jia, Y}, title = {Isoalantolactone ameliorates ulcerative colitis via gut microbiota-mediated modulation of intestinal barrier, T cell homeostasis, and metabolite reprogramming.}, journal = {European journal of pharmacology}, volume = {1020}, number = {}, pages = {178798}, doi = {10.1016/j.ejphar.2026.178798}, pmid = {41895369}, issn = {1879-0712}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/immunology/microbiology/metabolism/chemically induced/pathology ; *Sesquiterpenes/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Intestinal Barrier Function/drug effects ; Homeostasis/drug effects ; Male ; *T-Lymphocytes/drug effects/immunology/metabolism ; Mice ; Colon/drug effects/metabolism/immunology/pathology/microbiology ; Intestinal Mucosa/drug effects/metabolism/immunology/microbiology ; Dextran Sulfate ; Mice, Inbred C57BL ; Cytokines/metabolism ; Disease Models, Animal ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation, epithelial barrier dysfunction, and gut microbiota imbalance. This study examined the therapeutic potential of isoalantolactone (IAL), a bioactive sesquiterpene lactone naturally occurring in Inula helenium L., using a dextran sulfate sodium-induced murine colitis model. Treatment with IAL significantly mitigated weight loss, improved the disease activity index, preserved colon length, and alleviated goblet cell depletion. Mechanistically, IAL enhanced intestinal barrier integrity by upregulating tight-junction proteins zonula occludens-1, occludin, and mucin 2 and suppressing proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α, and IL-1β. Moreover, IAL rebalanced CD4[+]/CD8[+] T cell ratios in the colon, mesenteric lymph nodes, and spleen. Gut microbiota analysis revealed increased diversity, enrichment of beneficial taxa (Muribaculaceae, Prevotellaceae_UCG-001), and a reduced Firmicutes-to-Bacteroidetes ratio. Metabolomic profiling identified 130 differentially abundant metabolites, including increased levels of anti-inflammatory compounds (e.g., hydroferulic acid) and decreased levels of proinflammatory lipids (e.g., linoleoylcarnitine). Correlation analysis demonstrated an association between gut microbiota and faecal metabolites. In addition, faecal microbiota transplantation confirmed that IAL-modulated microbiota ameliorated colitis, with pseudo-germ-free recipients exhibiting improved barrier function and immune homeostasis. These findings highlight the importance of IAL as a novel therapeutic candidate for UC by modulating host-microbiota interactions; however, clinical validation is warranted.}, }
@article {pmid41896437, year = {2026}, author = {Jin, H and Zhou, W and Ying, R}, title = {Impact of ileostomy reversal on gut microbiome and metabolome in rectal cancer: a review of mechanisms and clinical consequences.}, journal = {Langenbeck's archives of surgery}, volume = {411}, number = {1}, pages = {}, pmid = {41896437}, issn = {1435-2451}, support = {2024S00023//the Social Development Science and Technology Project of Wenling City, Zhejiang Province/ ; }, abstract = {Prophylactic ileostomy is a critical measure for preventing anastomotic leakage after low rectal cancer surgery; however, the incidence of diarrhea following stoma reversal remains high, posing a major clinical challenge. Recent studies have revealed that the underlying pathophysiology involves not only anal sphincter dysfunction but also a comprehensive imbalance in the gut microbiota–metabolite–immune axis. This review systematically elucidates the dynamic evolution of the gut microbiome after stoma reversal and its interplay with host metabolism. It further delves into multidimensional pathophysiological mechanisms, including gut dysbiosis, reduced production of short-chain fatty acids, dysregulated bile acid metabolism, and impaired intestinal barrier integrity. In light of recent advances, this article analyzes the clinical characteristics and subtypes of postoperative diarrhea, summarizes precision diagnostic strategies based on multi-omics technologies, and provides an objective assessment of emerging therapies such as probiotics, fecal microbiota transplantation, metabolic interventions, and nutritional support. Finally, the necessity of establishing an integrated multidisciplinary management model is discussed, with the aim of offering new perspectives and a theoretical foundation for improving the quality of life in rectal cancer patients after surgery.}, }
@article {pmid41897337, year = {2026}, author = {Nawaz, S and Sugiura, T and Yusuf, I and Sultany, A}, title = {Gut-Heart Axis in HFpEF: The Emerging Role of Microbiome-Driven Inflammation and Endothelial Dysfunction.}, journal = {Biomolecules}, volume = {16}, number = {3}, pages = {}, pmid = {41897337}, issn = {2218-273X}, mesh = {Humans ; *Heart Failure/microbiology/physiopathology/metabolism ; *Inflammation/microbiology/metabolism ; *Gastrointestinal Microbiome ; Animals ; Stroke Volume ; Dysbiosis ; *Endothelium, Vascular/physiopathology ; Fatty Acids, Volatile/metabolism ; }, abstract = {Heart failure with preserved ejection fraction (HFpEF) represents the predominant form of heart failure, affecting over 50% of all heart failure patients with increasing prevalence in aging populations. Despite significant advances in cardiovascular medicine, HFpEF remains a complex clinical syndrome with poorly understood pathophysiology and limited treatment options. While most studies have traditionally focused on the renin-angiotensin-aldosterone system (RAAS) and other related mechanisms, emerging evidence has unveiled a critical bidirectional relationship between dysregulation of gut microbiota and HFpEF development. This phenomenon, mediated through microbiome-driven inflammation and endothelial dysfunction, introduces a novel concept and potential emerging conceptual framework in understanding HFpEF. This comprehensive review explores this novel gut-heart axis by synthesizing the latest evidence from original studies and clinical trials. We discuss novel mechanisms involving bacterial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, and amino acid derivatives. We also examine how gut dysbiosis may contribute to systemic inflammation through lipopolysaccharide translocation, NLRP3 inflammasome activation, and endothelial dysfunction. Furthermore, clinical trials investigating microbiome-targeted interventions, including probiotics, fecal microbiota transplantation, metabolite supplementation, and precision medicine approaches, are critically evaluated for their therapeutic potential. This review provides a framework for hypothesis generation and future research directions about therapeutic strategies targeting the gut-heart axis in HFpEF management.}, }
@article {pmid41897439, year = {2026}, author = {Xu, S and Li, X and Wu, X and Zheng, K and Yi, Y and Lin, Y and Tian, C and Zhu, Y and Tang, C and Hu, S and Zhang, S and He, Y and Chen, M and Feng, R}, title = {DUOX2-Driven Oxidative Stress Alters the Gut Redox Niche and Promotes Microbial Dysbiosis in Crohn's Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, pmid = {41897439}, issn = {2076-3921}, support = {82341217//National Natural Science Foundation of China/ ; 82370551//National Natural Science Foundation of China/ ; 82270579//National Natural Science Foundation of China/ ; 2025YFC3408601//National Key Research and Development Program of China/ ; 2024GXNSFFA010009//Guangxi Natural Science Foundation/ ; }, abstract = {Crohn's disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe-host crosstalk. DUOX2 expression was upregulated in human intestinal samples and was positively associated with inflammatory readouts, oxidative stress indices, and dysbiosis. Intestinal epithelial cell-specific Duox2 knockout (KO) mice exhibited reduced mucosal ROS, preserved barrier integrity, and attenuated dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Cohousing and fecal microbiota transplantation demonstrated that this protective phenotype was microbiota-dependent. Multi-omics profiling identified enrichment of Parabacteroides, particularly P. distasonis, in Duox2 KO mice, and oral supplementation with P. distasonis enhanced resistance to colitis. Mechanistically, DUOX2-derived oxidative stress constrained Parabacteroides growth, as P. distasonis displayed marked susceptibility to hydrogen peroxide, with excessive intracellular ROS accumulation and an absence of key antioxidant defenses-including peroxide reductase C (AhpC) and superoxide dismutase B (SodB)-indicating that epithelial DUOX2 shapes a hostile luminal redox niche unfavorable to these beneficial microbes. Pharmacological inhibition of DUOX2 with Compound 521 reduced oxidative stress, ameliorated colitis, and partially restored microbial balance. These findings establish a DUOX2-ROS-microbiota axis in which epithelial DUOX2 amplifies oxidative stress, remodels the gut ecosystem, and promotes inflammation, and highlights DUOX2 suppression or ROS-sensitive Parabacteroides as potential redox-centric therapeutic strategies for CD.}, }
@article {pmid41897579, year = {2026}, author = {Ichim, C and Boicean, A and Todor, SB and Boeras, I and Anderco, P and Birlutiu, V}, title = {Clinical and MicroRNA Responses to Fecal Microbiota Transplantation in Patients with Alcohol-Related Cirrhosis: A Pilot Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {6}, pages = {}, pmid = {41897579}, issn = {2075-4418}, abstract = {Background/Objectives: Alcohol-related liver cirrhosis is a systemic disorder characterized by profound immune, metabolic and gut-liver axis dysregulation. Emerging evidence highlights a bidirectional interaction between the intestinal microbiota and host microRNAs (miRNAs), positioning this axis as a potential regulator of systemic homeostasis. However, human data exploring the impact of microbiota modulation on miRNA expression in advanced liver disease remain limited. Methods: Six patients with alcohol-induced liver cirrhosis underwent fecal microbiota transplantation (FMT). Safety was assessed through clinical and paraclinical monitoring at predefined intervals. Quality of life was evaluated pre- and post-intervention using a validated liver-specific questionnaire. Fecal expression of miR-21-5p, miR-122-5p, miR-125-5p, miR-146-5p and miR-155-5p was analyzed and correlations with clinical domains, demographic variables and hepatic encephalopathy severity were explored. Results: FMT was well tolerated, with no severe adverse events reported. Preliminary improvements were observed in total clinical score (3.22 [3.06-3.57] vs. 4.25 [4.20-4.26], p = 0.001) and in several quality-of-life domains, including abdominal symptoms, fatigue, systemic manifestations, activity and emotional function (p < 0.05), while worry/concern scores remained unchanged. miR-125 and miR-146 demonstrated consistent associations with clinical status both before and after FMT, whereas miR-21 correlated mainly with age and body mass index. Notably, miR-125 and miR-146 were also associated with post-FMT hepatic encephalopathy severity, supporting their potential value as molecular correlates of clinical response in this exploratory study. Conclusions: In this pilot study, FMT appeared safe and was temporally associated with improvements in clinical parameters in alcohol-related cirrhosis, alongside dynamic changes in fecal miRNA expression. These preliminary findings support a potential microbiota-miRNA interaction and warrant validation in larger, controlled longitudinal studies.}, }
@article {pmid41898327, year = {2026}, author = {Belosic Halle, Z and Tomasic, V and Biscanin, A and Cacic, P and Saric, I and Mustapic, S and Stojic, J and Luetic, K and Bekic, D and Paic, M and Micetic, D and Krznaric Zrnic, I and Olic, I and Razov Radas, M and Skocilic, I and Golčic, M and Rados, L and Radic, J and Prejac, J and Mikolasevic, I}, title = {Immune-Mediated Colitis Induced by Immune Checkpoint Inhibitors: Pathophysiology, Clinical Management, and the Emerging Role of Fecal Microbiota Transplantation.}, journal = {Biomedicines}, volume = {14}, number = {3}, pages = {}, pmid = {41898327}, issn = {2227-9059}, abstract = {BACKGROUND/OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT).<br><br>METHODS: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach.<br><br>RESULTS: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease.<br><br>CONCLUSIONS: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice.}, }
@article {pmid41898402, year = {2026}, author = {Antohi, AL and Gheorghiță, AD and Andronic, O and Gradisteanu Pircalabioru, G and Treteanu, AR}, title = {Across the Social Network of the Gut: Bacterial, Fungal, and Viral Determinants of Checkpoint Inhibitor Efficacy and Toxicity.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, pmid = {41898402}, issn = {1422-0067}, support = {PN-IV-P8-8.1-PRE-HE-ORG-2023-0054 - Contract no 17PHE/2023//Unitatea Executiva Pentru Finantarea Invatamantului Superior Si A Cercetarii Stiintifice Universitare/ ; grant agreement - 101087007 - eBio-hub//HORIZON-WIDERA-2022-TALENTS-01/ ; ROGEN 324809//Development of genomic research in Romania-ROGEN/ ; }, mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects/immunology ; Animals ; *Neoplasms/immunology/drug therapy/microbiology ; *Fungi ; Bacteria ; Dysbiosis ; Fecal Microbiota Transplantation ; Viruses ; }, abstract = {Recent findings suggest that the gut microbiome significantly influences cancer outcomes, including responses to immune checkpoint inhibitor (ICI) treatments. Although early research focused on gut bacteria, it is now understood that the microbiome includes a bacteriome, virome, and mycobiome, all of which can modulate host immunity. Some commensal bacteria enhance anti-tumor immune responses and improve ICI efficacy, as demonstrated in both mice and patients. Fecal microbiota transplants (FMT) from patients responding to ICI have successfully reversed resistance in certain non-responders. In addition to bacteria, gut fungi and viruses are gaining attention as further factors influencing ICI effectiveness and toxicity. Recent multi-omics studies across cancer cohorts show that fungal and viral populations in the gut vary between ICI responders and non-responders. Commensal fungi may shape anti-cancer immunity by inducing inflammatory or tolerogenic pathways, while viral components can stimulate innate immune sensors that promote tumor surveillance. On the other hand, gut dysbiosis marked by expansion of pathobionts (including opportunistic fungi) and reduction in beneficial microbes is linked to serious immune-related adverse events (irAEs) such as ICI-induced colitis. This review discusses the multi-kingdom gut microbiome-bacteria, fungi, and viruses-and their interactions with the immune system in cancer therapy. We emphasize known mechanisms linking these microbes to anti-tumor immunity, overview human studies associating gut microbiome profiles with ICI outcomes and explore strategies to modulate the microbiome to enhance ICI efficacy while reducing toxicity. Understanding and utilizing the gut mycobiome and virome in conjunction with the bacteriome could pave the way for new biomarkers and therapeutic adjuvants in cancer immunotherapy.}, }
@article {pmid41898651, year = {2026}, author = {Lei, D and Zhou, C and Zheng, H and Kang, Y and Yan, Z}, title = {Fecal Microbiota Transplantation from APP/PS1 Mice Induces Th17-Related Inflammatory Parameters and Pathological Changes in the Gut-Brain Axis of Healthy C57BL/6J Mice.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, pmid = {41898651}, issn = {1422-0067}, support = {No. 2024YFHZ0334//Sichuan Provincial Science and Technology Support Program/ ; }, mesh = {Animals ; *Th17 Cells/immunology/metabolism ; Mice ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Alzheimer Disease/microbiology/pathology/therapy/metabolism ; Disease Models, Animal ; *Inflammation/pathology/microbiology ; Amyloid beta-Protein Precursor/genetics ; Male ; *Brain/pathology/metabolism ; *Brain-Gut Axis ; Mice, Transgenic ; }, abstract = {The gut-brain axis is increasingly implicated in Alzheimer's disease (AD) pathogenesis, but the potential correlation between AD-associated gut microbiota and central inflammation remains largely unclear. This study aimed to explore their correlative link, with a focus on changes and involvement of Th17 cell-related factors in the gut-brain axis. Healthy C57BL/6J mice were pretreated with antibiotics for 1 week to deplete the indigenous gut microbiota, followed by 2 weeks of fecal microbiota transplantation (FMT) using feces from APP/PS1 AD model mice. Hematoxylin-eosin (H&amp;E) staining, ELISA, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 16S rDNA sequencing, and correlation analysis were performed to evaluate ileal and central pathological changes, Th17 cell-related inflammatory mediators, ileal microbiota composition, and their potential correlations. The results demonstrated that AD-FMT significantly induced ileal inflammatory infiltration and central inflammation in recipient mice, which was accompanied by abnormal expression of Th17 cell-related indicators, elevated levels of Th17-associated inflammatory factors, upregulated RORγt mRNA expression, and perturbed ileal microbiota composition. Correlation analysis further suggested that specific ileal bacterial taxa were closely correlated with Th17 cell-related inflammatory factors. These findings suggest a potential correlation between AD-associated microbiota and central inflammation, possibly by regulating intestinal Th17 cell-related indicators and altering gut microbial composition. This study provides correlative evidence supporting the involvement of the gut-brain axis in AD-related pathogenesis, highlighting the link between gut microbiota, central inflammation and Th17-related factors.}, }
@article {pmid41899599, year = {2026}, author = {Huang, J and Zhu, XH and Trotman, LC and Tsao, CK}, title = {The Role of Gut Microbiome in Prostate Cancer: Current Evidence and Emerging Opportunities.}, journal = {Cancers}, volume = {18}, number = {6}, pages = {}, pmid = {41899599}, issn = {2072-6694}, abstract = {Prostate cancer (PCa) is one of the most common malignancies in men, and growing evidence implicates the gut microbiome as a significant, modifiable contributor to disease evolution and management. Dysbiosis influences PCa biology through effects on inflammation, immune regulation, metabolism, and hormone signaling. Microbial imbalance can promote systemic inflammation and increase intestinal permeability, activating immune signaling pathways such as NF-κB-IL-6-STAT3. In parallel, microbiome-driven metabolic effects, including IGF-1 signaling and microbial androgen synthesis or recycling, may contribute to resistance to androgen deprivation therapy (ADT). Microbial metabolites, notably short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), exert context-dependent effects on tumor growth, treatment resistance, and progression. Conversely, beneficial microbes have been associated with improved treatment sensitivity and immune regulation. Together, these insights support the gut microbiome as a potential biomarker and emerging therapeutic target in PCa. Modulation strategies, including diet, probiotics, antibiotics, and fecal microbiota transplantation (FMT), are being explored to improve treatment response and address resistance. As mechanistic evidence continues to grow, ongoing monitoring of the gut microbiome may help inform risk stratification and treatment optimization in prostate cancer.}, }
@article {pmid41900935, year = {2026}, author = {Santaniello, U and Mastorino, L and Pala, V and Rosset, F and Crespi, O and Quaglino, P and Ribero, S}, title = {Pharmacomicrobiomics in Psoriasis: Microbiome-Drug Interactions Across Systemic Treatments.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41900935}, issn = {2075-1729}, abstract = {Psoriasis is a chronic immune-mediated skin disease with highly variable responses to systemic therapies. Emerging evidence highlights the microbiome as a potential modulator of drug efficacy and toxicity. Gut bacteria can enzymatically metabolize drugs, such as methotrexate, altering bioavailability and therapeutic outcomes, while microbial metabolites-including short-chain fatty acids, branched-chain amino acids, and tryptophan derivatives-shape host immunity and barrier integrity, influencing drug action. Baseline microbial signatures have been linked to treatment response, potentially predicting anti-TNF or IL-17 inhibitor efficacy. Systemic therapies themselves reshape microbial communities: IL-17 blockade induces broad shifts in gut and skin microbiota, whereas cyclosporine and anti-TNF agents exert subtler effects. Small molecules such as apremilast and fumarates may reduce fungal overgrowth and influence microbial composition, whereas data on JAK/TYK2 inhibitors remain limited. Notably, current evidence exhibits a literature bias toward the gut microbiota, while the roles of the oral and skin axes remain understudied. Adjunctive microbiome-directed interventions, including probiotics and fecal microbiota transplantation, have demonstrated potential to enhance treatment outcomes by promoting anti-inflammatory taxa and restoring barrier function. Despite these promising findings, current evidence is heterogeneous, often limited by small sample sizes, short follow-up, and variable methodology. Integrating pharmacomicrobiomics data with clinical, genetic, and multi-omics profiling could enable precision medicine approaches in psoriasis, allowing therapy selection tailored to individual microbial and metabolic signatures. Future research should focus on longitudinal, multicenter studies to identify actionable microbial biomarkers, clarify mechanistic interactions between drugs, microbes, and host immunity, and evaluate microbiome-targeted adjuncts in randomized trials. Understanding the bidirectional crosstalk between systemic therapies and the microbiome may transform psoriasis management, improving efficacy, reducing adverse events, and enabling durable, personalized responses.}, }
@article {pmid41901063, year = {2026}, author = {Nunna Sai Venkata, L and Mishra, AK and Mohanta, YK and Rustagi, S and Bahuguna, A and Tomar, A and Baek, KH and Mishra, B}, title = {The Gut Gambit: A Review of How Microbial Imbalance Fuels Metabolic Mayhem.}, journal = {Nutrients}, volume = {18}, number = {6}, pages = {}, pmid = {41901063}, issn = {2072-6643}, mesh = {Humans ; *Dysbiosis/microbiology/metabolism/complications ; *Gastrointestinal Microbiome/physiology ; Oxidative Stress ; Epigenesis, Genetic ; *Metabolic Diseases/microbiology/genetics/metabolism ; Animals ; Insulin Resistance ; Probiotics ; }, abstract = {BACKGROUND/OBJECTIVES: An imbalance in gut microbiota, known as gut dysbiosis, results in reactive oxygen species overproduction, which can cause inflammatory conditions, damage DNA, trigger immunity, and induce epigenetic modifications of crucial genes that regulate metabolic pathways. Such a condition can also weaken the resilience of the protective gut wall and elevate colon permeability, allowing toxins from the gut to reach the liver and bloodstream, contributing to oxidative damage, autoimmune diseases, and epigenetic changes linked to metabolic disorders.<br><br>METHODS: The Scopus database was exclusively searched for the literature. Relevant articles were identified using predefined keywords, including gut dysbiosis, microbiota, microbiome, oxidative stress, metabolic disorders, inflammation, and epigenetics or combinations. Gut microbiota- and diet-induced metabolic disorders, particularly obesity, insulin resistance, dyslipidemia, and hypertension, may be inherited through epigenetic pathways.<br><br>RESULTS: The evidence analyzed suggests that the gut microbiota serves as a diverse metabolic and immunological organ. Its disruption affects the production of short-chain fatty acids, bile acid metabolism, immune signaling, and the redox balance, which contributes to the development of obesity, insulin resistance, and metabolic syndrome.<br><br>CONCLUSIONS: This review highlights key epigenetic mechanisms underlying metabolic disorders and oxidative stress in the context of gut dysbiosis. Furthermore, therapeutic strategies targeting the gut microbiota, such as dietary interventions, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, hold promise for mitigating oxidative stress and inflammation associated with metabolic syndrome.}, }
@article {pmid41901284, year = {2026}, author = {Bieganska, EA and Wolski, M and Zarlenga, M and Bilinski, J and Kosinski, P}, title = {Fecal Microbiota Transplantation (FMT) as a Prophylaxis of Necrotizing Enterocolitis (NEC)-Protocol for a Safety Study.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {3}, pages = {}, pmid = {41901284}, issn = {1424-8247}, support = {NA//This research is funded by statutory funds of Pediatric Surgery Clinic of the Medical University of Warsaw/ ; }, abstract = {Background/Objectives: Necrotizing enterocolitis (NEC) is an inflammatory disease with an incidence of about one in 1000 live births, much higher in premature and low birth weight newborns. Intestinal dysbiosis is an important element in the pathogenesis of NEC, and for this reason, experimental models have been used to administer fecal microbiota transplants (FMTs) for prophylaxis and treatment of NEC with very satisfactory results. The primary endpoint of the study is safety, defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) occurring from the time of intervention until hospital discharge, classified according to severity and assessed for relatedness to the intervention. Methods: This prospective, single-arm, open-label clinical study will include 20 infants born between 24 0/7 and 36 6/7 weeks of gestation. FMTs will be administered twice as a deep rectal infusion via a Foley catheter. The donors of the material from which the FMT will be prepared will be women in the third trimester of pregnancy. The safety of the therapy will be assessed by comparison with a control group, i.e., 20 patients who will meet the same inclusion criteria and will not meet any of the exclusion criteria, subject to the same hospital observation but without undergoing any medical/therapeutic intervention other than the collection of biological material. Discussion: The study will provide data on the safety and initial efficacy of FMT in this group of patients, which will allow for further research into the use of this method in the prevention of infections and NEC. Ethics: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland (KB/52/2025). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: The study is registered at ClinicalTrials.gov: ID: NCT06333405.}, }
@article {pmid41902480, year = {2026}, author = {Chugh, RM and Bhanja, P and Schueddig, E and Setianegara, J and Lin, Y and Guida, K and Rehman, S and Krepel, S and Koestler, D and Chen, RC and Cook, KL and Saha, S}, title = {Proton FLASH Exposure Preserves Gut Commensal Microbiomes and Spares Intestinal Stem Cells.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {31}, pages = {e19249}, doi = {10.1002/advs.202519249}, pmid = {41902480}, issn = {2198-3844}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; //This work was supported by a sponsored Research Agreement from IBA to perform preclinical research on FLASH Proton Radiotherapy (KUMC-IBA collaborative fund) and KUCC CCSG (P30 CA168524)./ ; }, mesh = {Animals ; Mice ; *Stem Cells/radiation effects ; *Gastrointestinal Microbiome/radiation effects/physiology ; *Intestinal Mucosa/radiation effects ; *Protons ; *Intestines/radiation effects ; Mice, Inbred C57BL ; }, abstract = {Emerging evidence shows that Proton FLASH radiotherapy can spare normal tissues while maintaining anti-tumor efficacy. However, its impact on intestinal stem cells (ISCs) and the gut microbiome remains unclear. Gut microbiome influences ISC's radiosensitivity. In a mouse model of abdominal irradiation, Proton FLASH exposure exhibited improved survival and less crypt-villus damage compared to Proton Conventional dose rate. Using scRNA-sequencing, we demonstrated that Proton FLASH exposure using pulsed pencil beam scanning spares two distinct ISC populations, Lgr5+ Crypt-based columnar cells (CBCs) and a Ly6a+, Clu+, Areg+, Anxa2+ revival stem cell (revSC) population-by modulating oxidative stress and cell cycle progression. Analysis of α and β-diversity demonstrated that Proton FLASH modulates gut microbiota composition without compromising overall species richness. Notably, Proton FLASH-irradiated mice had higher abundances of Alistipes sp. and Akkermensia sp., both known for protective effects on ISCs and the intestinal mucosa. The role of microbiome in Proton FLASH-mediated sparing effect was further confirmed by fecal microbiota transplantation, where Proton FLASH-donor microbiota demonstrated reduced lethality with protection of crypt villus morphology in recipient mice exposed to Proton Conventional dose rate. Our findings highlight the crucial role of the microbiome in the Proton FLASH-mediated sparing of the mucosal epithelium.}, }
@article {pmid41902532, year = {2026}, author = {Belančić, A and Fajkić, A and Sener, YZ and Jelaković, A and Alić, L and Gkrinia, EMM and Verbanac, D and Jelaković, B}, title = {Gut Dysbiosis as a Shared Mechanism in Obesity and Hypertension: Exploring a Promising Therapeutic Avenue.}, journal = {Endocrinology, diabetes &amp; metabolism}, volume = {9}, number = {3}, pages = {e70159}, doi = {10.1002/edm2.70159}, pmid = {41902532}, issn = {2398-9238}, mesh = {Humans ; *Dysbiosis/therapy/complications/microbiology ; *Hypertension/therapy/microbiology/etiology ; *Obesity/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; Prebiotics ; Probiotics/therapeutic use ; Intestinal Barrier Function ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Obesity and hypertension are interrelated global health challenges sharing common pathophysiological mechanisms, including insulin resistance, chronic inflammation and neurohormonal dysregulation. Emerging evidence highlights the gut microbiome as a crucial mediator in this interplay, influencing intestinal barrier integrity, systemic inflammation and metabolic homeostasis.<br><br>METHODS: In this narrative review, we critically examine the interplay between obesity-induced hypertension and the gut microbiome, evaluating current evidence, therapeutic implications and future research priorities.<br><br>RESULTS: Obesity-associated gut dysbiosis disrupts the intestinal epithelial barrier, increasing translocation of bacterial products like lipopolysaccharides into circulation, promoting systemic inflammation that exacerbates insulin resistance, adipose dysfunction and hypertension. Current treatments targeting obesity, from lifestyle modification to bariatric surgery, show beneficial effects on blood pressure, but microbiome-targeted interventions are an evolving therapeutic frontier. Prebiotics, probiotics, synbiotics and faecal microbiota transplantation have demonstrated potential antihypertensive effects in preclinical and clinical studies, although findings are heterogeneous and require confirmation in larger randomised trials. Methodological challenges remain, including the need for advanced microbial sampling techniques beyond faecal analysis to fully capture disease-relevant microbiota alterations.<br><br>CONCLUSION: This review synthesises current knowledge on gut microbiome involvement in obesity-induced hypertension, evaluates microbiome-based therapeutic strategies and identifies critical research gaps to guide future investigations aimed at mitigating the dual pandemics of obesity and hypertension.}, }
@article {pmid41902697, year = {2026}, author = {Tan, W and Fu, Y and Hu, W and Lin, Y and Cai, J and Huang, X and OuYang, Y and Lin, S and Ye, L}, title = {Loganic Acid Ameliorates Rheumatoid Arthritis via the Lactobacillus murinus-Inodole-3-Acetic Acid-AhR-IL-10 Axis.}, journal = {Phytotherapy research : PTR}, volume = {40}, number = {6}, pages = {3336-3353}, doi = {10.1002/ptr.70316}, pmid = {41902697}, issn = {1099-1573}, support = {2022-SF-141//the Science and technology Plan of Qinghai Province (key Research and Development and Transformation Plan)/ ; 82274193//National Natural Science Foundation of China/ ; 82422077//National Natural Science Foundation of China/ ; 2024B1515020093//Basic and Applied Basic Research Foundation of Guangdong Province/ ; }, mesh = {Animals ; *Arthritis, Rheumatoid/drug therapy/metabolism ; *Indoleacetic Acids/metabolism ; *Interleukin-10/metabolism ; Humans ; Mice ; Arthritis, Experimental/drug therapy ; *Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction/drug effects ; Male ; Gastrointestinal Microbiome/drug effects ; *Lactobacillus ; Tumor Necrosis Factor-alpha/metabolism ; *Lacticaseibacillus ; }, abstract = {Loganic acid (LA), a major iridoid glycoside from Gentiana macrophylla Pall., possesses anti-inflammatory and immunomodulatory properties, but its therapeutic potential in rheumatoid arthritis (RA) and its interaction with the gut microbiota remain poorly defined. Here, we show that LA markedly and dose-dependently attenuates disease severity in collagen-induced arthritis mice, as evidenced by reduced clinical arthritis scores, systemic inflammatory cytokines, and synovial tissue damage. LA reshaped the gut microbiota, and fecal microbiota transplantation from LA-treated donors partially reproduced its protective effects, indicating a causal contribution of the altered microbial community. In particular, LA selectively enriched OTUs annotated as Lactobacillus murinus (L. murinus) and increased levels of the microbial tryptophan metabolite indole-3-acetic acid (IAA). Both LA and IAA activated aryl hydrocarbon receptor (AhR) signaling, suppressed tumor necrosis factor-α-induced inflammatory responses in human synoviocytes, and, in vivo, enhanced IAA-AhR-interleukin-10 (IL-10) signaling in arthritic joints. Pharmacological inhibition of AhR with CH223191 substantially reversed LA's therapeutic effects, demonstrating that AhR signaling plays a critical role in its anti-arthritic activity. Collectively, these findings demonstrate that LA protects against RA through a dual mechanism: direct activation of AhR in joint tissues and indirect reinforcement of AhR signaling through an L. murinus-associated microbial IAA axis. This study highlights a gut microbiota-metabolite-AhR pathway as a key mediator of LA's anti-arthritic effects and supports LA as a promising microbiota-informed therapeutic candidate for RA.}, }
@article {pmid41902828, year = {2026}, author = {Zhong, XS and Lopez, KM and Liu, M and Xiao, Y and Ou, R and Kochkarian, T and Powell, DW and Fujise, K and Li, Q}, title = {Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {330}, number = {5}, pages = {G565-G580}, doi = {10.1152/ajpgi.00324.2025}, pmid = {41902828}, issn = {1522-1547}, support = {R01HL152683//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Colitis/chemically induced/physiopathology/therapy/microbiology/metabolism/complications ; *Ventricular Remodeling ; Interleukin-10/genetics/metabolism ; Mice ; Mice, Knockout ; *Gastrointestinal Microbiome ; Chronic Disease ; Mice, Inbred C57BL ; Disease Models, Animal ; Dextran Sulfate ; Male ; Myocardium/metabolism/pathology ; Fibrosis ; Inflammatory Bowel Diseases ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestines accompanied by profound extraintestinal manifestations. Although IBD shows a clear clinical association with cardiovascular derangements, whether and how chronic colitis impairs heart function remains unclear. To address this gap, we investigated the impact of chronic colitis on cardiac performance and the cardiac transcriptome using two mouse models: dextran sodium sulfate (DSS)-treated and Il10[-/-] mice. Heart function was assessed by echocardiography and molecular characterization was performed using RNA-sequencing (RNA-Seq), reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot. Both models exhibited significant functional cardiac impairment, characterized by reduced ejection fraction and fractional shortening along with histologically evident increase in collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed a profibrotic cardiac environment. RNA sequencing unveiled a shared upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1, Map3k6, Pck1, and Cfd) across both models, alongside model-specific alterations in pathways governing cAMP and cGMP signaling, arachidonic and linoleic acid metabolism, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, whereas Il10[-/-] colitis yielded 105 dysregulated genes. Notably, reconstitution of a healthy balance of gut microbiota by therapeutic fecal microbiota transplantation (FMT), validated using quantitative polymerase chain reaction (qPCR), successfully rescued heart function and mitigated fibrosis in both models. However, Il10[-/-] mice demonstrated relatively less cardiac recovery following FMT, highlighting interleukin-10 (IL-10)'s cardioprotective and anti-inflammatory contribution. Collectively, these findings provide evidence that chronic colitis impairs heart function, offer novel insights into colitis-induced cardiac remodeling, and suggest that FMT mitigates cardiac dysfunction by correcting gut dysbiosis, attenuating systemic inflammation, and reestablishing homeostasis along the gut-heart axis.NEW &amp; NOTEWORTHY Inflammatory bowel disease (IBD) extends beyond the gut, as chronic inflammation and microbiota dysbiosis contribute to serious extraintestinal complications. This study demonstrates that chronic colitis induces cardiac remodeling and dysfunction in two mouse models, marked by reduced cardiac performance, fibrosis, and upregulated fibrotic and inflammatory genes. Importantly, fecal microbiota transplantation (FMT) alleviated cardiac injury, highlighting its therapeutic potential. These findings reveal FMT as a promising therapy against chronic inflammation contributing to cardiovascular complications in IBD.}, }
@article {pmid41903098, year = {2026}, author = {Alwashmi, ASS and Khan, NU and Unar, A}, title = {Decoding Microbiota-Immune Interplay in Viral Pathogenesis: Toward Next-Generation Antiviral Therapies.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41903098}, issn = {1867-1314}, abstract = {Emerging viral threats, including COVID-19, influenza, and hepatitis B, underscore the urgent need for innovative antiviral strategies. Traditional antiviral drugs and vaccines are often limited by viral mutations, drug resistance, and inter-individual variability. The human microbiota has emerged as an active regulator of viral pathogenesis, influencing host susceptibility, immune responses, and therapeutic outcomes. This review comprehensively explores microbiota–virus interactions, including direct viral modulation by commensal bacteria and bacteriophages, metabolic reprogramming of host cells, and immunomodulation by microbial metabolites such as short-chain fatty acids (SCFAs) through the GPR43–NLRP3–MAVS axis. The gut–lung–immune axis and systemic consequences of virus-induced dysbiosis, including “leaky gut” and amplified cytokine responses (TNF-α, IL-6), are highlighted. Translational applications discussed include probiotics, prebiotics, postbiotics, fecal microbiota transplantation (FMT), and next-generation engineered microbial consortia. Evidence from clinical FMT trials in chronic hepatitis B, liver cirrhosis, and COVID-19 recovery, along with FDA-approved oral microbiota therapies, suggests therapeutic promise. The integration of AI-guided multi-omics approaches enables patient stratification and personalized interventions while addressing safety, strain specificity, and regulatory challenges. This review integrates mechanistic insights and clinical evidence to guide the development of next-generation microbiota-based precision antiviral therapies with improved efficacy and durability.}, }
@article {pmid41903138, year = {2026}, author = {Zheng, W and Wu, C and Wang, Y and Yan, X and Han, W and Liu, X and He, C and Chen, X and Zhou, X and Zhang, L and Liu, C and Xu, J and Wang, J and Yuan, X and Song, W and Wang, X and Liang, S and Huang, J and Zhang, Y and Yang, R and Zhang, L and Qin, N and Ma, X and Xu, Q and Li, G}, title = {Mutation elevation and functional alterations in Escherichia coli are pertinent to the onset of gestational diabetes mellitus.}, journal = {Cell reports}, volume = {45}, number = {4}, pages = {117143}, doi = {10.1016/j.celrep.2026.117143}, pmid = {41903138}, issn = {2211-1247}, abstract = {In the gut microbiome, purifying selection clears deleterious mutations. However, it is unknown whether this selection pressure is modifiable or what its health implications are. Here, we studied metagenomic and metabolic changes linked to gestational diabetes mellitus (GDM), and observed an increase in Escherichia coli (E. coli) mutations during host pregnancy, linking these genetic changes to host physiology. Severe depletion of bacterial genes before GDM onset was mostly traced to E. coli despite its stable abundance-indicating that functional genetic signals outweigh taxonomic shifts. E. coli and related microbes displayed pregnancy-linked single nucleotide polymorphism elevation, enriched at GDM onset in loci encoding membrane and biofilm components. These pangenomic alterations correlated with handicapped intermicrobial interactions of E. coli and with host serum metabolic abnormalities. We propose that pregnancy relaxes purifying selection, permitting mutation elevation in certain gut bacteria. Resulting functional deficits, potentially through altered ecology and metabolism, may subsequently impact host glucose regulation.}, }
@article {pmid41903570, year = {2026}, author = {Wang, X and Jia, Y and Wang, C and Li, D and Guo, X and Jiang, S and Zhou, Z and Gao, C and Wang, F}, title = {Decoding serotonin in endometriosis: unveiling its role in disease pathogenesis via the gut-reproductive microbiota axis.}, journal = {Human reproduction (Oxford, England)}, volume = {41}, number = {6}, pages = {940-958}, doi = {10.1093/humrep/deag047}, pmid = {41903570}, issn = {1460-2350}, support = {20200601011JC//Jilin Provincial Key Laboratory of Precision Infectious Diseases/ ; 3D5200117426//Key Laboratory of Health and Family Planning Commission of Jilin Province/ ; }, mesh = {Humans ; Female ; *Endometriosis/microbiology/metabolism/pathology ; *Serotonin/metabolism/blood ; Animals ; Adult ; *Gastrointestinal Microbiome/physiology ; Mice ; Cross-Sectional Studies ; Endometrium/metabolism/microbiology/pathology ; Case-Control Studies ; Vagina/microbiology ; }, abstract = {STUDY QUESTION: How can the potential mechanisms and targets of endometriosis be explored through multi-omics and multi-location approaches?<br><br>SUMMARY ANSWER: This exploration of the gut-reproductive axis in patients with endometriosis found that serotonin is elevated in endometriosis and promotes disease progression through enhanced cell proliferation and inflammation.<br><br>WHAT IS KNOWN ALREADY: Endometriosis is a common inflammatory disease. Recent studies indicate that peripheral serotonin, which is regulated by the gut microbiota, can promote the progression of irritable bowel syndrome and various cancers.<br><br>STUDY DESIGN, SIZE, DURATION: This cross-sectional study enrolled 22 endometriosis patients and 22 control patients with uterine fibroids (surgical cases, October 2022-June 2023). Samples of vaginal secretions, endometrial tissue, peritoneal lavage fluid, feces, and ectopic lesions were collected from both groups. For validation, serum samples were added from 20 additional endometriosis patients and 20 healthy reproductive-age volunteers.<br><br>This study employed 16S rRNA gene sequencing to analyze the microbiota in the vagina, endometrial tissue, peritoneal fluid, and feces of patients with endometriosis and control groups, complemented by untargeted metabolomic analysis of peritoneal fluid. The results identified serotonin as a key metabolite and revealed specific bacterial species, shared between the reproductive and gastrointestinal tracts of endometriosis patients, which were significantly correlated with serotonin levels. Mendelian randomization analysis was conducted to explore the relationship between serotonin, these bacterial species, and endometriosis. Serum serotonin levels in endometriosis patients, BALB/C mouse models, and their respective controls were measured using ELISA. Immunohistochemistry and fluorescence staining were used to detect the expression of serotonin and its receptors in both ectopic and normal endometrium. The effects of serotonin on the biological behavior of various endometriosis cell models, including proliferation, migration, invasion, and apoptosis, were investigated using CCK8 assay, wound healing test, Transwell assay, apoptosis detection, ELISA, transcriptomics, and qPCR. The impact of serotonin on BALB/C mouse models was evaluated using H&amp;E staining, flow cytometry, and ELISA.<br><br>We identified a significant enrichment of Akkermansia muciniphila (a bacterium shared by the gut and reproductive tract) in endometriosis patients, which positively correlated with peritoneal serotonin levels; Mendelian randomization analysis linked both to elevated endometriosis risk. Serotonin levels were elevated in patients' serum (using mouse models) and in ectopic endometrium, in comparison to those of controls. In vitro, serotonin boosted endometriosis cell proliferation, migration, invasion, and inflammation, with upregulated IL-17/NF-&#x3ba;B pathways. In mice, serotonin treatment increased lesion growth, cell proliferation, and inflammation.<br><br>LARGE SCALE DATA: N/A.<br><br>(a) The relatively limited sample size, together with potential imbalance in endometriosis ASRM stage distribution and cesarean section rates, may restrict the generalizability of our findings. In addition, due to the requirement for peritoneal lavage fluid collection, the control group could not consist of entirely healthy women, which may have resulted in a more conservative estimation of group differences. Serum sex hormone levels were not assessed; however, strict inclusion criteria and uniform surgical timing were applied to minimize hormonal confounding. Future studies incorporating cycle-phase-standardized hormone measurements may provide additional insights. (b) Dietary information was not collected in this study, despite the known influence of diet on gut microbiota composition and serotonin metabolism. (c) The direct causal relationship between Akkermansia muciniphila and elevated serotonin levels remains to be established and warrants further validation using germ-free mouse models or fecal microbiota transplantation approaches. (d) The precise mechanisms by which the gut-reproductive tract microbiota axis regulates local and systemic serotonin synthesis remain unclear and require further investigation.<br><br>Our study is the first to utilize a multi-omics approach combined with a joint analysis of the female gut-reproductive tract axis across multiple loci, revealing and validating a significant increase in serotonin levels in patients with endometriosis. This change may be regulated by the gut-reproductive microbiota axis. These findings provide new insights into the pathogenesis of endometriosis and identify potential targets for prevention and treatment.<br><br>This study was funded by the Jilin Provincial Key Laboratory of Precision Infectious Diseases (Grant No. 20200601011JC), Key Laboratory of Health and Family Planning Commission of Jilin Province (Grant No. 3D5200117426). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2300077490.}, }
@article {pmid41903849, year = {2026}, author = {Ekhlas, D and Verbiest, A and Stas, M and De Meyere, L and Vandermeulen, G and Tóth, J and Geboers, K and Timmermans, L and Verspecht, C and Wauters, L and Vermeersch, P and Jeppesen, PB and Verbeke, K and Joly, F and Derrien, M and Raes, J and Vanuytsel, T}, title = {Early ecological changes in intestinal microbiota with the long-acting GLP-2 analog apraglutide in short bowel syndrome.}, journal = {Clinical nutrition ESPEN}, volume = {73}, number = {}, pages = {103138}, doi = {10.1016/j.clnesp.2026.103138}, pmid = {41903849}, issn = {2405-4577}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Colon/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Glucagon-Like Peptide 2/agonists/therapeutic use ; *Short Bowel Syndrome/drug therapy/microbiology ; }, abstract = {BACKGROUND AND AIMS: Short bowel syndrome with intestinal failure (SBS-IF) is a rare, severe organ failure condition requiring long-term parenteral support. In SBS with colon-in-continuity (CiC), rapid transit and increased oxygen reshape gut and microbiota. We aimed to elucidate the effects of apraglutide, a novel long-acting glucagon-like peptide-2 (GLP-2) analog, on the gut microbiome in SBS-IF-CiC.<br><br>METHODS: We performed a 52-week multicenter, open-label, phase 2 study in adults with SBS-IF-CiC (Leuven n = 7, Paris n = 2) receiving weekly subcutaneous apraglutide. Duodenal, distal small bowel and sigmoid colon biopsies, fecal- and plasma samples were collected over time. Analyses included mucosa-associated and fecal microbiota, fecal parameters, and fermentation metabolites. For baseline comparison, duodenal and sigmoid colonic biopsies from 20 controls (10 per region) were collected.<br><br>RESULTS: Patients exhibited an altered ecosystem characterized by reduced richness, loss of colonic anaerobes and dominance of Lactobacillus and Bifidobacterium with larger inter-subject variability, lower pH, higher moisture, and lower microbial load compared to controls. Apraglutide did not change overall diversity or stool parameters, but reduced inter-subject variability in stool and sigmoid colon. Notably, Bifidobacterium decreased in both stool and sigmoid colon, whereas Prevotella increased in stool from some patients. Still, Lactobacillus remained dominant. Specific taxa correlated with fecal butyrate, propionate, and reduced distal colonic motility, indicating microbial metabolism may support boosted adaptation.<br><br>CONCLUSIONS: This study emphasizes that SBS-IF-CiC features an immature distal gut microbiota and apraglutide promotes early ecological maturation, suggesting that combining GLP-2 analog therapy with microbiome-targeted strategies may further enhance intestinal and ecosystem adaptation; ClinicalTrials.gov, Number NCT04964986https://www.<br><br>CLINICALTRIALS: gov/study/NCT04964986?term=NCT04964986&amp;rank=1.}, }
@article {pmid41903990, year = {2026}, author = {Gorji, L and Seldomridge, AN and Holder, AM}, title = {Leveraging the Human Microbiome to Improve Immunotherapy Sensitivity.}, journal = {Surgical oncology clinics of North America}, volume = {35}, number = {2}, pages = {285-298}, doi = {10.1016/j.soc.2025.10.007}, pmid = {41903990}, issn = {1558-5042}, support = {T32 CA009599/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; //Department of Defense CDMRP Melanoma Academy Scholar Program (AMH)/ ; }, mesh = {Humans ; *Immunotherapy/methods ; *Microbiota/immunology ; *Neoplasms/therapy/microbiology/immunology ; Fecal Microbiota Transplantation ; Precision Medicine ; Tumor Microenvironment/immunology ; }, abstract = {The human microbiome is composed of distinct microbial communities or ecosystems found throughout the human body, including within unique tumor microenvironments. In this review, we discuss the microbiome's influence on solid tumors, how the microbiome can be modulated to improve response to immunotherapy, and how emerging evidence suggests that microbiome modulation can add to the repertoire of personalized medicine.}, }
@article {pmid41904644, year = {2026}, author = {Wang, W and Wen, Y}, title = {The role of systemic inflammation in hepatic encephalopathy: advances in inflammatory mechanisms, prevention and treatment research.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2650232}, pmid = {41904644}, issn = {1365-2060}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/prevention &amp; control/immunology/etiology ; *Inflammation/complications/immunology/therapy ; Animals ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/immunology ; Ammonia/metabolism ; Rifaximin/therapeutic use ; Dysbiosis/immunology ; Liver Cirrhosis/complications/immunology ; Hyperammonemia ; Blood-Brain Barrier ; }, abstract = {OBJECTIVES: This review synthesizes current evidence establishing systemic inflammation as a key pathogenic driver in hepatic encephalopathy (HE) beyond hyperammonemia. It does not replace the ammonia hypothesis but rather acts as a critical synergistic factor, modulating and amplifying ammonia neurotoxicity. It further evaluates the mechanisms linking inflammation to HE and the therapeutic advances in inflammation-targeted prevention and treatment strategies.<br><br>METHODS: A comprehensive narrative literature review was conducted, analyzing relevant preclinical models and clinical studies. The search and synthesis focused on inflammatory mechanisms in chronic liver disease, gut-liver-brain axis dysfunction, cirrhosis-associated immune dysfunction (CAID), and resulting neuroinflammatory pathways.<br><br>RESULTS: Systemic inflammation, driven by gut dysbiosis, barrier failure, and CAID, amplifies ammonia neurotoxicity and independently contributes to neuroinflammation, blood-brain barrier disruption, and cerebral metabolic dysfunction in HE. Key inflammatory markers, such as IL-6, correlate with disease severity. Therapies targeting inflammation - particularly gut microbiota modulation with rifaximin and fecal microbiota transplantation (FMT) - demonstrate significant efficacy in reducing HE recurrence, lowering systemic inflammation, and improving cognitive outcomes. Other approaches, including albumin infusion, also show promise.<br><br>CONCLUSIONS: Systemic inflammation is a pivotal and synergistic factor in HE pathogenesis. Combining anti-inflammatory strategies that target the gut-liver-brain axis with traditional ammonia-lowering therapies offers a more comprehensive and effective treatment paradigm. Future research should prioritize protocol optimization, long-term safety assessment, and the development of personalized treatment approaches.}, }
@article {pmid41907211, year = {2026}, author = {Li, H and Shen, X and Lu, H}, title = {The Evolving Research Landscape of Radiation Enteritis Prevention and Management: A Data-Driven Analysis.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {581527}, pmid = {41907211}, issn = {1178-7031}, abstract = {OBJECTIVE: Radiation enteritis (RE) is a common complication following radiotherapy, adversely affecting patient prognosis and quality of life. This study aims to analyze the evolving research landscape of RE prevention and management through a data-driven approach, aiming to delineate the developmental trajectory, identify research hotspots and emerging frontiers, and forecast future trends in RE prevention and management.<br><br>METHODS: We conducted a data-driven analysis of relevant publications retrieved from the Web of Science Core Collection (2005-2024). Visualization tool was employed to examine collaboration networks, research hotspots, and trends. A supplementary search in PubMed was conducted to identify related clinical trials.<br><br>RESULTS: A total of 594 publications indexed in the Web of Science Core Collection were subjected to a data-driven visual analysis, while a supplementary search in PubMed identified 51 clinical trials to further clarify clinical research status. In this field, the main research topics include prostate cancer, rectal cancer, and cervical cancer, and the main research hotspots include studies on the pathological mechanism of RE, as well as research on the application of conformal radiotherapy, argon plasma coagulation, hyperbaric oxygen therapy, and microbiota transplantation in the prevention and management of RE. Early burst keywords mainly include "conformal radiotherapy", "sucralfate", "home parenteral nutrition", "intensity modulated radiotherapy", and "hyperbaric oxygen therapy". In the past three years, the burst keywords in the outbreak period mainly include "efficacy", "chemoradiation", "stem cells", and "transplantation".<br><br>CONCLUSION: This study reveals that the field has gradually shifted over the past two decades from an initial focus on pathological mechanisms and symptom management toward etiological therapy, with current research frontiers centered on therapies such as mesenchymal stem cell therapy and fecal microbiota transplantation. Future efforts should be guided by this paradigm shift, prioritizing the resolution of specific translational challenges inherent to these emerging treatments, fostering the multidisciplinary collaboration essential in clinical practice, and advancing toward more predictive, preventive, and personalized management strategies for RE. These findings provide valuable insights and guidance for future clinical research and innovation in this field.}, }
@article {pmid41907468, year = {2026}, author = {Gao, Y and Yang, D and Wang, D and Maimaiti, R}, title = {Behavioral and biological alterations following transplantation of ASD-associated gut microbiota in mice.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20951}, pmid = {41907468}, issn = {2167-8359}, mesh = {Animals ; *Autism Spectrum Disorder/microbiology/therapy/psychology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Mice ; Male ; *Behavior, Animal ; Humans ; Hippocampus/pathology/metabolism ; RNA, Ribosomal, 16S/genetics ; Cytokines/blood ; Mice, Inbred C57BL ; Child ; Disease Models, Animal ; T-Lymphocytes, Regulatory ; Female ; }, abstract = {BACKGROUND: Alterations in the gut microbiota have been increasingly reported in individuals with autism spectrum disorder (ASD). However, the extent to which ASD-associated microbial communities are linked to behavioral and host biological changes remains to be clarified.<br><br>METHODS: Fecal microbiota transplantation (FMT) was performed using samples from children with ASD or typically developing (TD) controls into antibiotic-pretreated mice. Behavioral performance was evaluated using open field, social interaction, and spatial learning paradigms. Gut microbial composition was assessed by 16S rRNA gene sequencing. Peripheral immune-related parameters were assessed, including circulating regulatory T cells and serum cytokine profiles. Histological and molecular analyses were conducted in the terminal ileum and hippocampus, including immunohistochemistry, Western blotting, exploratory brain proteomics, and targeted qRT-PCR validation.<br><br>RESULTS: Mice receiving ASD-associated microbiota displayed altered behavioral performance, including reduced sociability and impaired spatial learning. 16S rRNA sequencing revealed distinct gut microbial profiles between ASD-FMT and TD-FMT groups, with increased abundance of Enterobacteriaceae and related taxa in ASD-FMT mice. Peripheral analysis showed reduced regulatory T cell levels and altered serum cytokine profiles. Histological examination identified changes in intestinal architecture and increased expression of glial markers in the hippocampus. Proteomic analysis indicated differential expression of proteins enriched in pathways related to neural structural organization and metabolic processes.<br><br>CONCLUSIONS: These findings indicate that gut microbiota derived from children with ASD is associated with coordinated behavioral, peripheral immune-related, and brain histological changes in mice. This study provides integrative evidence supporting associations between ASD-associated microbial features and coordinated behavioral and biological alterations in the host.}, }
@article {pmid41907523, year = {2026}, author = {Fernanda Ricci, M and Cruz, CS and de Almeida, VM and d' Auriol, M and Rocha, VM and Machado, EC and Gallotti, B and Garbazza, I and Faria, AMC and Cassali, GD and Garcia, CC and André, LC and Martins, FS and Abreu, V and Almeida, S and Vieira, AT}, title = {Fiber-deprived diet weakens lung defense against antimicrobial-resistant Klebsiella pneumoniae and facilitates resistance phenotype in the gut microbiota.}, journal = {Gut microbes reports}, volume = {3}, number = {1}, pages = {2625617}, pmid = {41907523}, issn = {2993-3935}, abstract = {The rapid spread of antimicrobial-resistant (AMR) bacteria is a major global health challenge. The misuse of antibiotics and infections by resistant pathogens drive the dissemination of resistance genes, the human microbiota of which serve as reservoirs. Disruptions in the host-microbiota balance, which are influenced by diet, can increase resistance genes. Low-fiber diets are linked to gut dysbiosis, infection susceptibility, and weakened defenses. Here, we report that dietary fiber deprivation induced significant alterations in the gut microbiota of C57BL/6 mice, leading to reduced host tolerance to lung infection by the AMR strain Klebsiella pneumoniae B31 (KP 31) with higher levels of ampicillin-resistant Enterobacteriaceae and marked shifts in the gut microbial composition. Germ-free mice that received fecal transplants from fiber-deprived donors also displayed exacerbated inflammatory pathology following KP 31 infection. Infection further increased the abundance of cultivable resistant Enterobacteriaceae in the gut and was associated with the modulation of short-chain fatty acid (SCFA) levels, particularly propionate. Propionate appears to support antimicrobial activity, and its decrease in vitro promotes bacterial growth. Our findings highlight that the gut microbiota is a crucial reservoir for resistance genes. Low-fiber diets impair lung defenses and promote resistome expansion after AMR infection. Understanding these dynamics and their influencing factors is essential for strategies to combat antimicrobial resistance (AMR).}, }
@article {pmid41908202, year = {2026}, author = {Awashra, A and Neiroukh, H and AbuBaha, M and Shehadeh, W and Jallad, H and Emara, A and Abu-Khazneh, O and Zahran, A and Elgendy, MS and Fkheideh, T and Sawaftah, Z and Milhem, F and Hajjeh, O and Shubietah, A}, title = {The gut-heart axis in atrial fibrillation: Pathophysiology, evidence, and therapeutic potential.}, journal = {Heart rhythm O2}, volume = {7}, number = {3}, pages = {581-597}, pmid = {41908202}, issn = {2666-5018}, abstract = {BACKGROUND: Recent advances in microbiome research highlight a bidirectional relationship between gut microbiota and atrial fibrillation (AF), the most common sustained arrhythmia worldwide. Gut dysbiosis has been implicated in systemic inflammation, metabolite imbalance, bile acid signaling, and autonomic dysfunction, whereas AF itself alters microbial homeostasis through hemodynamic and neurohormonal changes.<br><br>OBJECTIVE: This review aimed to synthesize current evidence linking gut dysbiosis to AF pathogenesis, identify mechanisms underlying this interaction, and explore the therapeutic potential of microbiota-targeted interventions.<br><br>METHODS: We conducted a narrative review of preclinical, clinical, and epidemiologic studies examining the gut-heart axis in AF. Particular emphasis was placed on microbial metabolites (eg, trimethylamine N-oxide, short-chain fatty acids, indoxyl sulfate), bile acid modulation, and inflammatory signaling. Data on interventions, including diet, probiotics, pharmacologic approaches, and fecal microbiota transplantation, were integrated to assess translational potential.<br><br>RESULTS: Evidence suggests that gut-derived signals contribute to atrial remodeling through activation of the NLRP3 inflammasome, altered calcium handling, and impaired gap junction integrity. Conversely, AF promotes dysbiosis by reducing gut perfusion, altering motility, and exposing patients to polypharmacy. Microbiota-directed strategies, particularly dietary modification and probiotics, demonstrate promise in reducing arrhythmic risk, whereas early data indicate potential biomarker roles for gut microbial signatures in AF stratification. However, causality remains uncertain, given that most studies are observational with limited sample sizes.<br><br>CONCLUSION: The gut-heart axis represents a novel paradigm in AF research. Although preliminary findings support its mechanistic and therapeutic relevance, interventional studies are needed to establish causality and guide clinical application.}, }
@article {pmid41908827, year = {2026}, author = {Yang, X and Niu, R and Lan, T and Ren, S and Liang, H and Ma, Y and Liu, C}, title = {Traditional Chinese medicine and plant metabolites for rheumatoid arthritis via modulating gut microbiota: a scoping review evaluating the transition from correlation to causality.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1790536}, pmid = {41908827}, issn = {1663-9812}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis. The "gut-joint axis" proposes gut microbiota and metabolites modulate RA inflammation via mucosal and systemic immune responses. Botanical drugs (Traditional Chinese Medicine, TCM) and plant metabolites offer multi-target potential. However, most studies remain descriptive, demonstrating concurrent microbial shifts but lacking causal designs to verify mechanistic necessity.<br><br>OBJECTIVES: This scoping review examines TCM and plant metabolite interventions on RA gut microecology (2015-2025), focusing on the "microbiota-metabolite-immune" axis. It aims to classify evidence based on causal design rigor and identify steps to advance research from correlation to causality.<br><br>METHODS: We searched PubMed, Embase, and Web of Science (2015-2025). Studies reporting RA outcomes and gut microbiota changes following TCM interventions were included. We established a hierarchical classification system based on design rigor: antibiotic depletion (ABX), fecal microbiota transplantation (FMT), metabolite rescue, and blocking. Evidence was stratified: Level A (Closed-loop: ABX + FMT + rescue/blocking), Level A+ (plus in vitro blocking), Level B (Partial: ABX/FMT alone), and Level C (Correlational).<br><br>RESULTS: Of 25 included studies (24 animal, 1 clinical), only 2 were Level A, 1 Level A+, 3 Level B, and 19 Level C. While TCM improved RA phenotypes and altered microbiota, complete closed-loop verification remains rare. Short-chain fatty acids (SCFAs) show promise but inconsistent trends due to heterogeneity. Bile acids and tryptophan metabolites correlate with reduced inflammation, yet their mechanistic necessity remains largely untested.<br><br>CONCLUSION: Botanical drugs and plant metabolites demonstrate potential in modulating gut microbiota to improve RA. However, definitive causal links remain underexplored. Future research should prioritize "shortest closed-loop" strategies, including targeted quantification, rescue, and necessity validations. Longitudinal designs and systemic immune metrics are essential to transition from correlations to translatable mechanisms.}, }
@article {pmid41908832, year = {2026}, author = {Zhao, S and Tan, Z and Suo, J and Bu, Y}, title = {Lycium barbarum polysaccharides as prebiotics prevent colorectal cancer liver metastasis in non-alcoholic fatty liver disease by modulating gut microbiota-FGF21-PI3K-AKT axis.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1735434}, pmid = {41908832}, issn = {1663-9812}, abstract = {INTRODUCTION: Colorectal cancer liver metastasis (CRLM) is the leading cause of death in colorectal cancer, and nonalcoholic fatty liver disease (NAFLD) promotes CRLM. Lycium barbarum polysaccharides (LBPs), bioactive metabolites of the traditional medicinal plant Lycium barbarum L, inhibit the progression of colorectal cancer and NAFLD by regulating gut microbiota composition. However, their roles in preventing CRLM under NAFLD conditions remain unclear. This study aimed to investigate the preventive effect of LBPs on liver metastasis of colorectal cancer in the context of NAFLD and explore its potential mechanisms.<br><br>METHODS: An NAFLD mouse model was established, followed by prophylactic oral administration of LBPs by gavage for 28&#xa0;days before splenic injection of MC38 colorectal cancer cells to establish liver metastasis. Pseudo-germ-free mice combined with fecal microbiota transplantation were constructed to explore the role of the gut microbiota in the preventive effect of LBPs on CRLM. Gut microbiota and fecal short-chain fatty acids were analyzed by 16S rRNA sequencing and liquid chromatography-mass spectrometry. Spearman's correlation analysis was used to explore the correlation between bacterial genera and liver lipid metabolism indicators. Serum non-targeted metabolomic profiling and transcriptomic analysis of CRLM cells were performed to elucidate metabolic and molecular mechanisms.<br><br>RESULTS: Under NAFLD conditions, LBPs markedly reduced hepatic metastatic burden, liver weight, and liver-to-body weight ratio. LBPs ameliorated hepatic lipid metabolism and restored colonic barrier integrity in NAFLD mice. The gut microbiota was identified as a critical mediator of LBPs-induced protection against CRLM, and depletion of the microbiota completely abrogated the anti-metastatic effects of LBPs. LBPs enhanced microbial diversity and richness, enriched of short-chain fatty acid-producing bacterial genera, such as Cryptobacteroides, Evtepia, and Bacteroides-H, and elevated colonic butyrate levels. Metabolomic profiling revealed reduced serum acylcarnitines and increased organic acids. Transcriptomic profiling showed upregulation of fibroblast growth factor 21, activation of the PI3K-AKT signaling pathway, and promotion of epithelial-mesenchymal transition in colorectal cancer cells, while LBPs reverse these changes.<br><br>DISCUSSION: LBPs prevent CRLM associated with NAFLD by modulating the gut microbiota, enhancing butyrate production, improving hepatic metabolic homeostasis, and suppressing prometastatic signaling pathways. These findings highlight LBPs as promising preventive agents against CRLM in the setting of metabolic liver disease.}, }
@article {pmid41909032, year = {2026}, author = {Yu, Z and Ma, H and Zhang, H and Gao, L and Fu, X and Wang, H and Xiao, Y and Wu, X and Zhang, A and Kang, Y and Cui, G and Chen, Z and Wu, D}, title = {Gut microbiota mediates the anti-obesity effects of Gnaphalium affine methanol extract in HFD-induced obesity.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1779459}, pmid = {41909032}, issn = {2296-861X}, abstract = {BACKGROUND: Obesity constitutes a pressing global public health challenge, characterized by intricate associations with metabolic dysregulation and gut microbiota dysbiosis.<br><br>METHODS: This study systematically evaluated the anti-obesity efficacy and underlying mechanisms of Gnaphalium affine methanol extract (GAE) in high-fat diet (HFD)-induced obese mice, with integrated fecal microbiota transplantation (FMT) experiments to establish causal relationships between GAE-modulated gut microbiota and metabolic improvements.<br><br>RESULTS: GAE intervention significantly ameliorated HFD-induced metabolic disorders, as evidenced by reduced oxidative stress, enhanced glucose tolerance, suppressed visceral adiposity, and attenuated chronic low-grade inflammation. Mechanistically, GAE preserved intestinal barrier integrity through upregulation of tight junction protein expression. Multi-omics integration of 16S rRNA gene sequencing and untargeted metabolomics revealed that GAE substantially rectified gut microbiota dysbiosis and lipid metabolic disturbances, mediated by specific bioactive metabolites-including lysophosphatidylcholine 22:6 and N-oleoyl glycine-and enrichment of beneficial bacterial genera (Phascolarctobacterium and Lactobacillus). Critically, FMT experiments demonstrated that the gut microbiota remodeled by GAE administration was sufficient to transfer obesity-alleviating phenotypes to recipient mice.<br><br>CONCLUSION: Collectively, these findings establish that GAE exerts multi-target anti-obesity effects through modulation of the "microbiota-gut-metabolism" axis, providing compelling preclinical evidence supporting the development of GAE as a functional food ingredient for weight management applications.}, }
@article {pmid41909046, year = {2026}, author = {Song, Y and Liu, G and Yang, J and Wang, J and Feng, S and Lu, S and Qin, Z and He, X and Wu, L}, title = {The impact of washed microbiota transplantation on serum gastric function markers: pepsinogen I, pepsinogen II, and Gastrin-17.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1715003}, pmid = {41909046}, issn = {2296-861X}, abstract = {BACKGROUND AND AIMS: Conventional treatment methods for gastric diseases have problems such as drug resistance and recurrence. This study aims to explore whether a new treatment method-Washed Microbiota Transplantation (WMT)-can improve gastric mucosal health.<br><br>METHODS: The clinical data of patients before and after WMT treatment were collected and analyzed, including serum gastric function markers: gastrin-17 (G-17), pepsinogen I (PGI), pepsinogen II (PGII), and the PGI/PGII ratio (PGR). Inflammatory biomarkers: C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Fresh fecal samples were collected at baseline and after WMT treatment and stored at -80&#x202f;&#xb0;C until analysis. Gut microbiota profiling was performed using 16S rRNA genes sequencing. Gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale (GSRS), and health-related quality of life assessed by the SF-36 physical and mental component summaries (PCS and MCS). The safety and tolerability of WMT were also assessed.<br><br>RESULTS: After WMT treatment, serum G-17 and PGI levels decreased significantly within the WMT group (both p <&#x202f;0.05), while PGII demonstrated a downward trend. Notably, in between-group comparisons, only the change in G-17 showed a statistically significant advantage over the control group (p =&#x202f;0.032), whereas differences in PGI, PGII, and PGR were not significant. Inflammatory markers CRP and PCT likewise declined within the WMT group; notably, the magnitude of CRP reduction positively correlated with changes in PGI (r&#x202f;>&#x202f;0.5, p&#x202f;<&#x202f;0.01). Furthermore, 16S rRNA sequencing revealed a significant increase in gut microbial &#x3b1;-diversity following WMT, with Chao1, Shannon, and Simpson indices all significantly elevated after the second treatment course compared with baseline (p&#x202f;<&#x202f;0.05); the relative abundances of several key genera were significantly altered. In addition, patients exhibited significant improvement in GSRS scores (p&#x202f;<&#x202f;0.01), and both SF-36 PCS and MCS scores increased markedly compared to baseline (p&#x202f;<&#x202f;0.01). No serious adverse events were observed during the study period; a minority of patients reported mild, transient bloating or diarrhea.<br><br>CONCLUSION: WMT was associated with improvements in gastric mucosal health, gut microbial abundance and diversity, accompanied by reduced inflammation, alleviated gastrointestinal symptoms, improved quality of life, and a favorable safety profile.}, }
@article {pmid41909260, year = {2026}, author = {Wang, XL and Zhang, C and Lu, DS and Dong, ZY and Jin, BM and Wan, SY and Zhang, ZW and Zhang, CJ and Li, L}, title = {Paeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1766068}, pmid = {41909260}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, inflammation and gut dysbiosis. Paeoniflorin (PAF) exhibits potential against NAFLD, yet its antioxidant mechanism via the gut-liver axis remains unclear. In a high-fat/sucrose (HFS) diet-induced NAFLD mouse model, C57BL/6 mice received PAF (50 or 100 mg/kg/day) for 10 weeks. Oxidative stress markers, histopathology, gut microbiota, and serum metabolomics were conducted, with fecal microbiota transplantation (FMT) applied for causal validation. PAF ameliorated metabolic disorders by suppressing hepatic lipogenesis and promoting cholesterol excretion. PAF significantly ameliorated oxidative stress by enhancing hepatic and colonic anti-oxidant capacity, evidenced by increased SOD activity and decreased MDA levels. It concurrently reduced systemic inflammation and enhanced intestinal barrier integrity via upregulation of tight junction proteins. Furthermore, PAF reshaped the gut microbiota, elevating beneficial Akkermansia and microbial-derived SCFAs, while suppressing pro-oxidant and pro-inflammatory pathogens like Desulfovibrio and Helicobacter. FMT confirmed that these antioxidant and metabolic benefits were mediated by the gut microbiota. In conclusion, PAF alleviates NAFLD primarily through potent antioxidant actions and anti-inflammatory, achieved via remodeling gut microbial ecology and reinforcing intestinal barrier.}, }
@article {pmid41909883, year = {2025}, author = {Abubakar, D and Abdullahi, H and Ibrahim, I}, title = {Bridging Microbiomes: Exploring Oral and Gut Microbiomes in Autoimmune Thyroid Diseases- New Insights and Therapeutic Frontiers.}, journal = {Gut microbes reports}, volume = {2}, number = {1}, pages = {2452471}, pmid = {41909883}, issn = {2993-3935}, abstract = {Autoimmune thyroid diseases (AITDs) are the most common organ-specific autoimmune disorders characterized by thyroid dysfunction and immune system deficiencies. In recent decades, the role of the microbiome in autoimmune diseases has gained increasing attention, with emerging research linking gut microbiome alterations to the development of AITDs. This review summarizes current knowledge on the relationship between AITDs and the gut microbiome. Additionally, it emphasizes the role of the oral microbiome in AITDs, an area often overlooked in autoimmune research. Beyond the microbiome, the virome and mycobiome have been recognized as critical but underexplored components of the human microbiome, potentially contributing to immune dysregulation and the pathogenesis of AITDs. The review also explores modulating the microbiome for managing AITDs, including diet adjustment, the potential use of probiotics, postbiotics, symbiotics, and even fecal microbiota transplantation (FMT) to restore a balanced microbiome that may positively influence the immune system and, by extension, the course of AITDs. This review thoroughly explores the intricate relationship between AITDs, the gut, and oral microbiomes, paving the way for precision medicine applications in AITDs. Examining microbiota-thyroid interactions highlights the potential for targeted, personalized treatments and novel therapeutic therapies, guiding future therapeutic strategies for more effective and precisely tailored AITD management approaches.}, }
@article {pmid41909892, year = {2025}, author = {Montenegro-Borbolla, E and Wakim El-Khoury, J and Bertelli, C and Schoepfer, A and Guery, B and Galperine, T}, title = {Resolution of long-term severe irritable bowel syndrome following fecal microbiota transplantation: A case report and microbiota analysis.}, journal = {Gut microbes reports}, volume = {2}, number = {1}, pages = {2487905}, pmid = {41909892}, issn = {2993-3935}, abstract = {The diagnosis and management of irritable bowel syndrome (IBS) is challenging due to its complex symptoms and inconsistent treatment responses. Given the important role of gut microbiota in gastrointestinal health, fecal microbiota transplantation (FMT) is a promising intervention. We describe the case of a 55-y-old woman without prior gastrointestinal issues who, following severe depression, developed multiple gastrointestinal symptoms, including abdominal pain, fluctuating bowel habits, and a persistent burning sensation in her mouth and upper gastrointestinal tract. At Lausanne University Hospital, she was diagnosed with IBS resistant to multiple lines of treatment and a multidisciplinary team proposed multiple oral FMTs. One-month post-FMT, her gastrointestinal symptoms significantly improved and remained better after a year, with only the burning sensation persisting. Analysis of pre- and post-FMT samples and donor material, using 16S rRNA amplicon metagenomics, revealed a 90% genus-level taxonomic overlap between the patient and the donor. The observed changes in the relative abundance of these genera, including the enrichment of beneficial gut commensals, as well as the elimination of IBS-associated genera likely supported her recovery. Overall, FMT led to substantial improvement in her long-standing gastrointestinal symptoms.}, }
@article {pmid41910195, year = {2026}, author = {Jia, PP and Li, Y and Yang, HY and Ding, Y and Guo, FY and Wu, MF and Jia, JQ and Pei, DS}, title = {Fecal microbiota transplantation and Akkermansia muciniphila restore neurodevelopment and behavior via the gut-brain axis in autism-like zebrafish.}, journal = {The ISME journal}, volume = {20}, number = {1}, pages = {}, pmid = {41910195}, issn = {1751-7370}, support = {22576022//National Natural Science Foundation of China/ ; 32200386//National Natural Science Foundation of China/ ; CSTB2024TIAD-CYKJCXX0017//Chongqing Technology Innovation and Application Development Sichuan-Chongqing Special Key Project/ ; KJQN202400430//Science and Technology Research Program of Chongqing Municipal Education Commission/ ; R4014//Chongqing Medical University Talent Project/ ; J0325017//Chongqing Medical University Talent Project/ ; R4020//Chongqing Medical University Talent Project/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Zebrafish ; *Brain/growth &amp; development ; Disease Models, Animal ; *Probiotics/administration &amp; dosage ; *Gastrointestinal Microbiome ; Neurodevelopment ; *Autism Spectrum Disorder/therapy ; Behavior, Animal ; *Autistic Disorder/therapy ; Verrucomicrobia ; Akkermansia ; *Brain-Gut Axis ; }, abstract = {Effective therapies for Autism Spectrum Disorder (ASD) are currently limited, and the functional connections between gut microbiota and brain development are not fully elucidated. Using the Katnal2 mutant zebrafish as an ASD-like model, we evaluated whether fecal microbiota transplantation (FMT) from wild-type donors or supplementation with the probiotic Akkermansia muciniphila (A. muciniphila) could ameliorate neurodevelopmental deficits. Assessments included developmental phenotypes, behavior, microbial profiling, neurotransmitter-related gene expression, and short-chain fatty acid (SCFA) signaling in conventionally reared (CR) and germ-free (GF) fish. FMT from wild-type donors and A. muciniphila supplementation significantly improved hatching rates, growth parameters, heart rate, and locomotor activity in Katnal2 mutants, whereas microbiota from Katnal2 mutants induced analogous deficits in wild-type recipients. A. muciniphila successfully colonized the gut, reshaped microbial communities, and reduced anxiety-like behaviors. Mechanistically, A. muciniphila upregulates genes involved in dopamine (th), serotonin (tph1a), and gamma-aminobutyric acid (GABA) synthesis, downregulates the serotonin receptor htr3a, and enhances expression of the SCFA receptor ffar2, independently of total SCFA levels. Correlation analyses linked key developmental, behavioral, and transcriptional changes to altered microbial genera in a sample-specific manner, highlighting compositionally driven neuromodulatory effects of genetic and probiotic interventions. Thus, microbiota-targeted intervention with A. muciniphila rescues neurodevelopmental impairments in ASD models by remodeling the gut-brain axis, supporting its translational potential.}, }
@article {pmid41910214, year = {2026}, author = {Zhang, F and Xu, W and Zeng, R and Chen, J and Huang, J}, title = {Limosilactobacillus reuteri normalizes gut microbiota dysfunction and social deficits of rat offspring associated with prenatal exposure to stress.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2649440}, pmid = {41910214}, issn = {1949-0984}, mesh = {Animals ; Female ; Pregnancy ; *Limosilactobacillus reuteri/physiology ; *Prenatal Exposure Delayed Effects/microbiology/psychology ; Rats ; Oxytocin/metabolism ; *Gastrointestinal Microbiome ; *Social Behavior ; Fecal Microbiota Transplantation ; Male ; Paraventricular Hypothalamic Nucleus/metabolism ; *Stress, Psychological ; Rats, Sprague-Dawley ; }, abstract = {Prenatal stress (PS) is a potential risk factor for social behavior impairment in offspring. Here, we demonstrate that PS induces gut microbiota alterations that are associated with impaired sociability and social novelty preference in rat offspring. In addition, we found that these behavioral deficits could be partially rescued through either cohousing with normal offspring or fecal microbiota transplantation from control donors. Metagenomic analysis identified Limosilactobacillus reuteri (L. reuteri) as a key species based on the considerable difference in its abundance between the PS and control offspring. Subsequent investigations revealed that supplementing L. reuteri during critical neurodevelopmental windows restored oxytocin levels in the paraventricular nucleus (PVN) and rescued dopamine reward pathway function, thereby ameliorating PS-induced social deficits. Notably, these beneficial effects were completely abolished by either treatment with an oxytocin receptor antagonist or subdiaphragmatic vagotomy. Thus, both oxytocin signaling and vagal afferent pathways play essential roles in the observed benefits of L. reuteri. Our findings indicate that social behavior impairments in offspring exposed to prenatal maternal stress can be explained by a novel mechanism involving the gut microbiota-brain axis: whereby PS-induced depletion of specific commensal bacteria (particularly L. reuteri) disrupts vagus nerve-mediated oxytocinergic modulation of PVN-to-VTA dopaminergic circuits, ultimately leading to social behavior impairments in offspring.}, }
@article {pmid41911988, year = {2026}, author = {Zhang, XY and Liu, XX and Justine, EE and Xi, ZH and Li, ML and Wang, TS and Jin, CS and Zhang, W and Mi, XJ}, title = {Vinegar-processed Paeonia lactiflora Pall. ameliorates alcoholic liver disease through the modulation of gut microbiota and FXR-FGF15 gut-liver axis.}, journal = {Journal of ethnopharmacology}, volume = {365}, number = {}, pages = {121593}, doi = {10.1016/j.jep.2026.121593}, pmid = {41911988}, issn = {1872-7573}, mesh = {Animals ; *Paeonia/chemistry ; *Fibroblast Growth Factors/metabolism/genetics ; *Liver Diseases, Alcoholic/drug therapy/metabolism/pathology/microbiology ; *Acetic Acid/chemistry ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Male ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Liver/drug effects/metabolism/pathology ; Receptor, Farnesoid X-Activated ; Mice ; *Plant Extracts/pharmacology/chemistry ; Ethanol ; Disease Models, Animal ; Food, Processed ; }, abstract = {Paeonia lactiflora Pall. (PR) is a traditional Chinese medicine (TCM) renowned for its actions in nourishing blood and soothing liver. Guided by the theory of "vinegar processing into the liver meridian", vinegar-processed PR (PRV) is clinically preferred for liver diseases owing to its enhanced properties in soothing liver and ameliorating liver injury. Nevertheless, the efficacy differences and underlying mechanisms of PR and PRV against alcoholic liver disease (ALD) remain unclear.<br><br>AIM OF THE STUDY: This study aimed to systematically evaluate the efficacy of PR and PRV against ALD, and to elucidate the underlying mechanism of enhanced hepatoprotective effects of PRV from the perspective of the gut-liver axis by multi-omics approaches.<br><br>MATERIALS AND METHODS: UHPLC-Q-Exactive Orbitrap mass spectrometry combined with multivariate data analysis was employed to identify the chemical composition of PR and PRV. A Lieber-DeCarli liquid ethanol diet-induced ALD mice model was established in C57BL/6 mice, and the effects of PR and PRV on ALD-related liver injury and steatosis were evaluated using biochemical and histopathological analyses. Alterations of gut microbiota composition and bile acid (BA) profiles were assessed by 16S rRNA gene sequencing and LC-MS/MS, respectively. Furthermore, we conducted quantitative Real Time-PCR and western blotting to determine the mRNA and protein expression levels of Farnesoid X Receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway, respectively, which are involved in BAs metabolism and enterohepatic circulation. Fecal microbiota transplantation (FMT) was utilized to validate the mechanism underlying the enhanced therapeutic efficacy of PRV against ALD.<br><br>RESULTS: Vinegar processing significantly altered the phytochemical profile of PR, increasing phenolic acids and specific monoterpene glycosides components. PRV demonstrated superior efficacy over PR in alleviating dyslipidemia, hepatic steatosis, and inflammatory damage, while effectively restoring intestinal barrier integrity and reducing endotoxin translocation. Moreover, PRV modulated the composition of gut microbiota associated with ALD risk, such as Parasutterella, Allobaculum, Paramuribac ulum, and CAG_485. Mechanistically, this microbial restructuring was associated with BA metabolism normalization and intestinal FXR-FGF15 axis activation, which in turn suppressed hepatic Cyp7A1 expression, thereby reducing hepatic cholesterol accumulation and lipogenesis in the ALD model.<br><br>CONCLUSION: Our findings indicate that PRV alleviates ALD by restoring BA metabolism and activating the FXR/FGF15 pathway by regulating gut microbiota balance. These findings provide valuable data supporting the vinegar processing efficacy enhancement theory of TCM, thereby facilitating the clinical application of PRV and guiding future drug and dietary supplement development efforts.}, }
@article {pmid41912086, year = {2026}, author = {Wu, Y and Li, N and Bai, Y and Wang, L and Zhang, Y and Wang, J and Liu, X and Ni, X}, title = {Altered microbiota drive prelimbic cortex suppression and lower pain thresholds after sleep deprivation.}, journal = {Neurochemistry international}, volume = {196}, number = {}, pages = {106151}, doi = {10.1016/j.neuint.2026.106151}, pmid = {41912086}, issn = {1872-9754}, mesh = {Animals ; *Sleep Deprivation/metabolism/physiopathology/microbiology ; Mice ; Male ; *Pain Threshold/physiology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation/methods ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {Sleep disturbances are increasingly recognized as a lifestyle factor for abnormal pain perception. Recent studies highlight the critical role of gut microbiota in maintaining physiological balance and reveal a bidirectional relationship between microbiota alterations, sleep disorders, and pathological pain. This study investigates the potential role of microbiota in linking sleep deprivation to abnormal pain. Using a chronic sleep deprivation (CSD) model in mice, we observed significantly lower pain thresholds compared to controls. Brain-wide functional ultrasound imaging revealed reduced cerebral blood volume responses to pinprick stimulation in the prelimbic cortex (PrL) of CSD mice, indicating decreased neuronal activity during pain processing. This finding was confirmed by fiber photometry of calcium influx and c-Fos staining in the PrL. Importantly, chemogenetic activation of PrL neurons effectively reversed CSD-induced pain hypersensitivity. CSD also caused significant microbiota alterations, including increased diversity and changes in specific genera associated with brain function-related metabolic pathways. Fecal microbiota transplantation (FMT) demonstrated a causal relationship, as control mice that received microbiota from CSD mice developed pain hypersensitivity, whereas CSD mice that received control microbiota exhibited restored pain thresholds Notably, FMT-induced pain behavior changes correlated with PrL activity alterations. Our study indicates that CSD suppresses PrL activity and causes pain hypersensitivity through alterations in gut microbiota. This study emphasizes the gut-brain axis as a critical pathway in the interplay between sleep deprivation and pain regulation.}, }
@article {pmid41914284, year = {2026}, author = {Wang, P and Ding, L and Lang, Z and Zhang, Y and Yu, Y}, title = {Therapeutic Modulation of the Gut Microbiome in Coronary Artery Disease: Current Evidence and Future Directions.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {3}, pages = {45081}, doi = {10.31083/FBL45081}, pmid = {41914284}, issn = {2768-6698}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Coronary Artery Disease/microbiology/therapy/metabolism ; Probiotics/therapeutic use/administration &amp; dosage ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; Prebiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; Animals ; Methylamines/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {The gut microbiome is increasingly recognized as a modifiable contributor to coronary artery disease (CAD). This narrative review integrates mechanistic and clinical evidence regarding short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and bile acids, and appraises therapeutic modulation via diet; probiotics, prebiotics, and synbiotics; fecal microbiota transplantation (FMT); and drug-microbiome interactions. SCFAs generally confer anti-inflammatory and lipid-regulatory effects, whereas bile acid signaling exhibits context-dependent metabolic actions. Findings regarding TMAO are inconsistent; in several cohorts, associations with cardiovascular risk become null or attenuated after adjustment for renal function (estimated glomerular filtration rate [eGFR]) and dietary patterns. Most interventional studies are small, use surrogate endpoints, and vary in strains and dosing, limiting certainty. Microbiome profiles differ across geographic regions, racial and ethnic groups, and dietary patterns, underscoring the need for stratified approaches. Routine FMT in CAD remains constrained by safety, feasibility, and ethical and logistical considerations. Overall, the microbiome represents a promising yet unproven therapeutic target in CAD. Future trials should standardize interventions, rigorously control for confounders, evaluate drug-microbiome interactions, and be adequately powered to detect clinical events to enable precision medicine.}, }
@article {pmid41914747, year = {2026}, author = {Franklin, S and Sahasrabhojane, P and Hayase, T and Hayase, E and Chang, C-C and Senapati, J and Desikan, SP and Kadia, T and Lorenzi, PL and Jenq, RR and Shelburne, SA and Galloway-Peña, J}, title = {Short-chain fatty acid-producing microbes differentiate non-infectious and infectious neutropenic fever in leukemia.}, journal = {mSystems}, volume = {11}, number = {4}, pages = {e0134325}, pmid = {41914747}, issn = {2379-5077}, support = {K01 AI143881/AI/NIAID NIH HHS/United States ; K01AI143881//National Institute of Allergy and Infectious Diseases/ ; P30CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Leukemia, Myeloid, Acute/microbiology/complications ; *Gastrointestinal Microbiome ; Female ; Male ; Middle Aged ; Machine Learning ; Feces/microbiology ; *Fever/microbiology ; *Neutropenia/microbiology ; Adult ; *Bacteria/metabolism/classification ; Aged ; }, abstract = {UNLABELLED: Neutropenic fever (NF) is often the first sign of infection in patients with hematologic malignancies, but its cause is frequently unknown, leading to broad-spectrum antibiotic use without confirmed infections. Although research links gut microbiome disruptions to treatment-related infections, it typically examines NF as the outcome, leaving a gap in understanding how the microbiome and metabolic factors distinguish infectious from non-infectious cases. Stool samples from acute myeloid leukemia patients were analyzed to characterize gut microbiome composition and fecal metabolites at baseline and at fever onset. Machine learning models, network analyses, and functional profiling were used to differentiate infectious NF vs non-infectious NF at baseline and at fever onset. The baseline model (area under the receiver operating characteristic [AUROC] = 0.769) identified higher levels of Akkermansia, Enterobacter, Escherichia-Shigella, and Flavonifractor as predictors of infectious NF, while Collinsella, Lachnospiraceae, Coprococcus, and acetic acid were linked to non-infectious cases. At fever onset, Enterococcus was enriched in infectious NF, whereas Gemella, Butyrate, Lachnospiraceae, Ruminococcaceae, and Eisenbergiella abundances favored non-infectious NF outcomes (AUROC = 0.752). Network analyses also revealed greater functional diversity and microbiome-metabolome connectivity in non-infectious cases at fever onset. This study suggests that gut microbiota and metabolites may serve as biomarkers for distinguishing infectious from non-infectious neutropenic fever, warranting further validation in larger cohorts.<br><br>IMPORTANCE: Our study tackles the challenge of managing neutropenic fever (NF) in immunocompromised patients whose numbers have increased due to various immunodeficiencies and treatments that suppress immune function. Fever is often the only sign of a serious infection in these patients, yet there are neither clear patterns linking risk factors to infection nor biomarkers reliable for ruling out non-infectious causes. As a result, febrile patients are typically empirically treated for major pathogens, even in the absence of confirmed infections, which propagates antimicrobial resistance and gut dysbiosis. Our research utilizes gut microbiome and targeted metabolomic profiling from two cohorts of patients with acute myeloid leukemia undergoing chemotherapy and employs a machine learning framework to distinguish between infectious and non-infectious NFs at baseline and upon fever onset.}, }
@article {pmid41917988, year = {2026}, author = {Liu, M and Li, S and Cui, Y and Zhu, X and Wang, Z and Sun, H and Li, D and Liu, B and Shi, Y}, title = {Tryptophan metabolism mediated by the gut microbiota inhibits pyroptosis via the AhR signaling pathway to maintain intestinal epithelial homeostasis.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {41917988}, issn = {2049-2618}, support = {CARS-34//Modern Agro-industry Technology Research System of China/ ; No. 244200510010//Science and Technology Innovation Leading Talent in Central Plains/ ; }, mesh = {*Receptors, Aryl Hydrocarbon/metabolism ; *Tryptophan/metabolism ; Animals ; Fecal Microbiota Transplantation ; Homeostasis ; *Gastrointestinal Microbiome/physiology ; Signal Transduction ; *Pyroptosis ; *Intestinal Mucosa/metabolism/microbiology ; Intestinal Barrier Function ; Humans ; Mice ; Mice, Inbred C57BL ; *Basic Helix-Loop-Helix Proteins/metabolism ; }, abstract = {BACKGROUND: The intestinal epithelial barrier protects the gut from pathogen invasion as well as exposure to food antigens and toxins. Increasing evidence has linked the gut microbiota to the function of the intestinal epithelial barrier. Fecal microbiota transplantation (FMT) can treat various intestinal diseases by reshaping the gut microbiota. However, the mechanisms by which FMT exerts its effects across different gastrointestinal conditions remain unclear. Moreover, its limitations are significant, including issues related to donor selection, the complexity of the microbiome, potential infection risks, inconsistent clinical responses, and ethical and legal considerations. Therefore, exploring the microbes and metabolites that mediate the effects of FMT as a replacement for traditional FMT is of great importance. In this study, we aim to investigate the gut microbiota and its metabolites to support the therapeutic role of FMT in intestinal barrier damage and elucidate its potential molecular mechanisms.<br><br>RESULTS: Our findings indicate that FMT prevents Lipopolysaccharide (LPS)-induced pyroptosis and damage to the colonic epithelial barrier. Mechanistically, FMT treatment reprograms the composition of gut microbiota, increasing the relative abundance of Lactobacillus reuteri and the levels of tryptophan metabolites (ILA, IAld, and IAA) in the colon, thereby inhibiting pyroptosis and protecting the intestinal epithelial barrier. Importantly, the AhR/NLRP3 axis is essential for the pyroptosis-inhibitory effects of Lactobacillus reuteri and its tryptophan metabolites.<br><br>CONCLUSIONS: Our results provide the first evidence that targeting the regulation of Lactobacillus reuteri and tryptophan metabolism is a promising strategy for inhibiting pyroptosis and improving intestinal epithelial homeostasis. Video Abstract.}, }
@article {pmid41917993, year = {2026}, author = {Hu, R and Zhao, W and Fan, W and Li, R and Zhang, L and Qin, L and Zhu, H and Zhu, X and Sun, Q and Qiang, G and Liu, C}, title = {Maternal PM2.5 exposure induces insulin resistance in adult male mouse offspring via gut-liver axis.}, journal = {Particle and fibre toxicology}, volume = {23}, number = {1}, pages = {}, pmid = {41917993}, issn = {1743-8977}, support = {82173480//National Natural Science Foundation of China/ ; 82273590//National Natural Science Foundation of China/ ; 2025JKZDZC03//Key Foundation of Zhejiang Chinese Medical University/ ; }, mesh = {Animals ; Female ; Male ; *Particulate Matter/toxicity ; *Insulin Resistance ; Pregnancy ; *Liver/drug effects/metabolism ; Mice, Inbred C57BL ; *Maternal Exposure/adverse effects ; *Prenatal Exposure Delayed Effects/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Mice ; Fecal Microbiota Transplantation ; *Air Pollutants/toxicity ; Dysbiosis/chemically induced ; }, abstract = {BACKGROUND: The rising prevalence of metabolic diseases represents a global health challenge, with metabolically unhealthy normal-weight (MUHNW) individuals remaining largely overlooked. In addition to direct fine particulate matter (PM2.5) inhalation, there is growing recognition that maternal PM2.5 exposure may be a contributing environmental factor for metabolic disorders. However, the mechanisms by which maternal PM2.5 exposure induced metabolic disorders in the offspring remain unknown.<br><br>METHODS: Eight-week-old pregnant C57BL/6N mice were exposed to either filtered air (FA) or ambient PM2.5 throughout gestation, from gestational day 0 to 18, using a whole-body inhalation exposure system. Eight-week-old male C57BL/6N mice were treated once daily for three consecutive days with an antibiotic cocktail containing 1&#xa0;g/L ampicillin, 0.5&#xa0;g/L neomycin, 0.5&#xa0;g/L vancomycin, and 1&#xa0;g/L metronidazole to generate pseudo-germ-free mice. Subsequently, fecal microbiota from maternal PM2.5-exposed three-week-old male mouse offspring (donor) were transplanted to pseudo-germ-free mice (recipient) via oral gavage twice weekly for five weeks. After fecal microbiota transplantation (FMT), fecal samples from donor and recipient mice were collected for full-length 16S rRNA sequencing. Liver tissue from donor mice was analyzed by 5R 16S rRNA sequencing.<br><br>RESULTS: Maternal PM2.5 exposure induced non-obese insulin resistance in adult male mouse offspring, with the liver identified as a susceptible organ characterized by suppressed AKT phosphorylation. Subsequently, systemic and hepatic insulin resistance were recapitulated in pseudo-germ-free mice, which received gut microbiota from maternal PM2.5-exposed mouse offspring via FMT. Mechanistically, the increased abundance of Helicobacter hepaticus contributed to DNA damage-mediated colonic barrier injury. This impaired colonic barrier facilitated gut-to-liver translocation of bacteria and lipopolysaccharide (LPS), which triggered hepatic inflammation via activation of TLR4 signaling pathway, ultimately leading to insulin resistance.<br><br>CONCLUSIONS: These findings indicated a causal role for gut microbiota dysbiosis in maternal PM2.5 exposure-induced non-obese insulin resistance in the offspring, providing potential insights into the developmental origins of MUHNW from the perspective of maternal exposure to air pollution.}, }
@article {pmid41918524, year = {2026}, author = {Chen, Y and Chen, T and Tian, S and Tao, L and Fan, F and Yang, Y and Shen, X}, title = {Berberine-gut microbiota interactions based on CiteSpace: current research status and hotspots.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1751887}, pmid = {41918524}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiota modulates host metabolic and immune homeostasis through host-microbiota interactions and microbial metabolites. Berberine (BBR), the primary active constituent of Coptis chinensis, has been shown to ameliorate host metabolic disorders by remodeling the gut microbial community. However, systematic reviews remain relatively scarce regarding the mechanisms underlying BBR-gut microbiota interactions.<br><br>METHODS: Therefore, we conducted a bibliometric analysis of 426 articles retrieved from the Web of Science Core Collection (WOSCC) and the China National Knowledge Infrastructure (CNKI) database (January 1, 2005-January 31, 2025) using CiteSpace. Analyses included publication trends, country/author collaboration networks, keyword co-occurrence and burst detection, and document co-citation analysis.<br><br>RESULTS: The results revealed a steady increase in annual publications, with China contributing the majority of studies. Author collaboration networks indicated limited integration among research groups. Keyword analysis identified key research clusters such as diabetes, inflammation, bile acid metabolism, and colorectal cancer. Chinese studies placed greater emphasis on disease applications, whereas English-language articles tended to focus on mechanistic insights. Emerging research hotspots include depression, fecal microbiota transplantation, bile acids, and ulcerative colitis. Co-citation analysis highlighted two foundational themes: microbial metabolites and metabolic-immune crosstalk.<br><br>DISCUSSION: This bibliometric study systematically outlines the research landscape of berberine-gut microbiota interactions, highlighting emerging frontiers such as neuro-microbial crosstalk, fecal microbiota transplantation (FMT) -based combination therapies, and metabolic-immune mechanisms. The findings provide valuable references for identifying research trends, fostering collaboration, and guiding future investigations in this field.}, }
@article {pmid41918843, year = {2026}, author = {Huang, Q and Liang, Z and Cui, Y and Diao, J and Zhou, T and Shi, L and Deng, Z and Wang, R and Yuan, H and Chen, K and Du, Y and Chen, A and Chen, J and Xiao, W}, title = {Uremic Clearance Granules Regulate Immune Equilibrium via Gut Microbiome to Alleviate Chronic Renal Failure.}, journal = {Biomaterials research}, volume = {30}, number = {}, pages = {0342}, pmid = {41918843}, issn = {1226-4601}, abstract = {Chronic renal failure (CRF) is the common end point of various chronic kidney diseases, and there is currently no specific drug for CRF. Effectively halting its progression remains a clinical challenge. Gut microbiota disorders are a key factor influencing immune dysfunction in chronic kidney disease patients. Intervening in gut microbiota to improve immune regulatory function in patients could serve as a new strategy for treating CRF with Traditional Chinese Medicine. Uremic Clearance Granules (UCG), a Traditional Chinese Medicine formulation, effectively attenuate CRF progression, but their active components and mechanisms remain undefined. This study investigates how UCG mitigate CRF via coordinated regulation of gut microbiota, metabolites, and the T helper 17 cells / regulatory T cell axis. Using an adenine-induced CRF mouse model, we combined gut microbiota depletion, fecal microbiota transplantation, 16S rRNA sequencing, and metabolomics to delineate the gut-kidney interactions underlying UCG efficacy. Flow cytometry quantified immune cell profiles in blood, and microbial intervention experiments verified the therapeutic role of Bifidobacterium animalis (B. animalis). In this study, we found that UCG treatment alleviated renal injury, reduced intestinal permeability, and up-regulated intestinal barrier markers. Microbiota depletion and fecal microbiota transplantation demonstrated that UCG's renoprotective effects depend on gut microbial modulation. Specifically, UCG ameliorates CRF through gut-kidney axis remodeling by enhancing B. animalis abundance and sophocarpine, thereby rebalancing T helper 17/regulatory T immunity and preserving renal function. These findings identify a microbiota-dependent immunometabolic mechanism for UCG and highlight a potential therapeutic strategy for CRF via the drug-microbiota axis.}, }
@article {pmid41918984, year = {2026}, author = {Gancz, A and Zhang, G and McMillan, A and Dougherty, M and McGill, S and Gulati, A and Baker, E and Theriot, C}, title = {Successful fecal microbiota transplants in post-antibiotic treated recurrent Clostridioides difficile patients induce acylcarnitine and sphingolipid lipidomic shifts.}, journal = {Gut microbes reports}, volume = {3}, number = {1}, pages = {2648346}, pmid = {41918984}, issn = {2993-3935}, abstract = {Clostridioides difficile infection (CDI) is an urgent public health threat in the United States, causing over 500,000 cases, 29,000 deaths, and $4.8 billion in healthcare costs annually. Although fecal microbiota transplants (FMTs) are more effective than antibiotics for recurrent CDI (rCDI), their risks highlight the need for regulated alternatives such as live biotherapeutic products (LBPs). The development of effective LBPs requires understanding the biological mechanisms underlying FMT success. Building on our prior metabolomic study identifying lipids as key factors in FMT efficacy, we used liquid chromatography, ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (LC-IMS-CID-MS) to profile >850 lipid species across 26 classes. In stool samples from 15 rCDI patients collected pre- and post-FMT (2 weeks, 2 months, and 6 months), 397 lipids were confidently identified. FMT significantly altered the lipidome (adonis R[2] = 0.12, p < 0.001), with 96 lipid species across 18 classes showing differential abundance (mixed effects modeling, BH correction, p < 0.05). Medium and long-chain acylcarnitines decreased post-FMT, while very long-chain acylcarnitines and trihydroxy ceramides increased. Sphingolipids were elevated pre-FMT. Medium and long-chain acylcarnitines correlated with Enterobacteriaceae, known to utilize carnitine. These results implicate lipid-microbiota interactions in rCDI susceptibility and recovery, offering targets for next-generation LBPs.}, }
@article {pmid41919078, year = {2026}, author = {Fan, Y and Qin, H and Liu, J and Abbas, M and Yang, C and Cheng, H and Dong, X}, title = {Lactobacillus acidophilus alleviates slow transit constipation by modulating 5-HT pathway and gut microbial composition.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1775405}, pmid = {41919078}, issn = {2296-861X}, abstract = {INTRODUCTION: Slow transit constipation (STC) is a chronic disease characterized by delayed intestinal transit and weakened spontaneous contractions of colonic smooth muscle. Current pharmacological treatments are often associated with adverse effects, highlighting the need for safe and more effective therapeutic strategies. This study investigated the potential role of Lactobacillus acidophilus (L. acidophilus) in regulating intestinal motility and alleviating STC, as well as the underlying mechanism.<br><br>METHODS: A humanized mouse model was established by intragastric administration of fecal bacterial suspension from STC patients on alternate days, in order to evaluate the effect of L. acidophilus on constipation. The regulatory effect of L. acidophilus on intestinal motility was evaluated using defecation parameters. Colon histopathology was assessed by hematoxylin-eosin (H&amp;E) staining. Immunohistochemistry (IHC), RT-qPCR, ELISA, and in vitro cell experiments were performed to examine the inflammatory cytokine levels and changes in the 5-hydroxytryptamine (5-HT) signaling pathway. In addition, metagenomic sequencing was used to analyze changes in the intestinal microbial community.<br><br>RESULTS: The results showed L. acidophilus treatment significantly enhanced intestinal peristalsis and maintained the intestinal barrier by up-regulating Occludin expression and down-regulating inflammatory cytokines, including TNF-&#x3b1; and IL-1&#x3b2;, thereby suppressing inflammatory responses. Both in vivo and in vitro experiments showed that L. acidophilus affected the synthesis and release of 5-HT by regulating the expression of TPH1 and the mechanosensitive ion channel Piezo1. Additionally, L. acidophilus reshaped the intestinal microbial community structure and altered the inter-bacterial interaction network, which was closely associated with improved intestinal motility.<br><br>CONCLUSION: Our current research reveals that constipation symptoms by L. acidophilus through the gut microbiota composition, intestinal barrier, and the 5-HT signaling pathway. These findings provide a strong theoretical basis for the development of L. acidophilus as a potential therapeutic strategy for the treatment of STC.}, }
@article {pmid41921871, year = {2026}, author = {Li, B and Fu, J and Wang, S and Bi, X and Xu, D and Wang, L and Qiao, D}, title = {Efficacy and safety of fecal microbiota transplantation on depressive and anxiety symptoms: A systematic review and meta-analysis.}, journal = {Journal of affective disorders}, volume = {406}, number = {}, pages = {121717}, doi = {10.1016/j.jad.2026.121717}, pmid = {41921871}, issn = {1573-2517}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Depression/therapy ; *Anxiety/therapy ; Treatment Outcome ; *Anxiety Disorders/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {This study aimed to systematically evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in relieving depressive and anxiety symptoms through a systematic review and meta-analysis of clinical studies. We conducted a comprehensive search of the MEDLINE, EMBASE, Cochrane Library, and Web of Science databases for relevant literature published up to February 28th, 2026. Randomized controlled trials (RCTs) and prospective cohort studies that used standardized scales to assess the effects of FMT on depressive or anxiety symptoms were included. Data were pooled using a random-effects model to calculate standardized mean differences (SMDs) and the 95% confidence intervals (CIs). Subgroup analysis, meta-regression, publication bias assessment, and sensitivity analysis were performed. Eight studies involving 532 participants were included in the analysis. FMT demonstrated significant improvements in both depressive symptoms and anxiety symptoms, with effect sizes of Hedges' g = -0.81 and Hedges' g = -1.05, respectively. However, substantial heterogeneity was observed for both outcomes, and the small number of included studies imposed certain limitations on the conclusions. Subgroup analysis suggested that the type of control groups in RCTs might partially explain the heterogeneity in both depressive and anxiety symptom outcomes. Furthermore, FMT exhibited a favorable safety profile, with no serious adverse events reported. In conclusion, these findings suggest that FMT is a potentially effective and safe intervention for improving depressive and anxiety symptoms. Large-scale, high-quality, and standardized RCTs are required to verify these results and promote the clinical translation of this therapy.}, }
@article {pmid41922969, year = {2026}, author = {Wei, C and Zhou, X and Xia, X and Feng, W and Wang, L and Li, X}, title = {Cold environment is associated with worse outcomes in ischemic stroke patients and the underlying gut microbial mechanism.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41922969}, issn = {1471-2180}, support = {42275197//National Natural Science Foundation of China/ ; TJWJ2023XK007//Key Projects of Tianjin Municipal Health Commission/ ; TA-10207 PRC//Asian Development Bank Technical Assistance Project/ ; TJYXZDXK-3-017C//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, abstract = {BACKGROUND: Increasing evidence suggests that cold environment is a potential risk factor for acute ischemic stroke (AIS) and is associated with poor prognosis, however, its underlying mechanisms remain unclear. Since gut dysbiosis and AIS are causally related and cold environment can induce changes in the gut microbiota, we wondered whether cold-season-related gut dysbiosis aggravates stroke progression.<br><br>METHODS: In total, 101 patients with AIS were enrolled and divided into two groups: cold-season onset ischemic stroke (CIS) and non-cold-season onset ischemic stroke (NCIS). Gut microbiota composition was analyzed using 16&#xa0;S rRNA gene sequencing, and signature taxa were identified via linear discriminant analysis effect size (LEfSe). Correlations between key microbial taxa and clinical parameters were assessed using Spearman rank analysis. To evaluate the potential causal role of gut microbiota in cold season stroke, fecal microbiota transplantation (FMT) was performed in mice, followed by middle cerebral artery occlusion (MCAO).<br><br>RESULTS: The composition of gut microbiota in the CIS group significantly differed from the NCIS group. The characteristic microbiota of the CIS group was distinguished by an elevated relative abundance of Escherichia-Shigella and Enterococcus, coupled with a decreased percentage of Blautia, Eubacterium_hallii_group, Subdoligranulum, Dorea, Faecalibacterium, Ruminococcus, and Collinsella. Furthermore, Escherichia-Shigella, Enterococcus, Blautia, Eubacterium_hallii_group and Faecalibacterium showed predictive value for 3-month poor prognosis in patients. Compared with mice inoculated with the NCIS gut microbiota, mice inoculated with the CIS gut microbiota showed more severe brain damage, impaired intestinal barrier function, and higher levels of inflammatory factors after the stroke model was established.<br><br>CONCLUSIONS: Our study indicates that cold-season-related gut dysbiosis may be linked to stroke severity and poor prognosis in AIS patients, suggesting that modulation of gut microbiota could represent a potential avenue for therapeutic intervention.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-026-05013-8.}, }
@article {pmid41923637, year = {2026}, author = {Zhang, J and Liu, C and Wang, Y and Chen, Y and Shang, H and Zheng, W and Jin, L and Xie, P and Li, Y and Liu, Y and Zhang, Y and Wang, Y and Zhao, W and Xiao, H and Wang, G and Zhang, X and Yang, X and Dong, E and Zhang, Y}, title = {Bacteroides acidifaciens exacerbates cardiac ischemia/reperfusion injury via the microbial-host isozyme DPP4.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {5}, pages = {905-924.e8}, doi = {10.1016/j.chom.2026.03.012}, pmid = {41923637}, issn = {1934-6069}, mesh = {Animals ; *Bacteroides/enzymology/pathogenicity ; Mice ; *Myocardial Reperfusion Injury/microbiology ; *Dipeptidyl Peptidase 4/metabolism ; Gastrointestinal Microbiome/physiology ; Humans ; Glucagon-Like Peptide 1/metabolism/blood ; Disease Models, Animal ; Mice, Inbred C57BL ; Isoenzymes/metabolism ; Fecal Microbiota Transplantation ; Male ; Myocytes, Cardiac ; Myocardial Infarction ; }, abstract = {Ischemia/reperfusion (I/R) injury is a key driver in cardiomyocyte loss and cardiac dysfunction in ischemic heart disease. Here, we uncover a previously unrecognized gut microbiota-mediated mechanism that contributes to myocardial I/R injury. Using murine I/R models and fecal microbiota transplantation, we demonstrate that the gut microbiota mediates cardiac damage through selective enrichment of Bacteroides acidifaciens (B. acidifaciens) following I/R-induced intestinal hypoxia and elevated luminal lactate levels. B. acidifaciens produces dipeptidyl peptidase 4 (BaDPP4), which degrades cardioprotective peptides (e.g., glucagon-like peptide-1 [GLP-1]) in the plasma, amplifying myocardial injury. Pharmacological inhibition of BaDPP4 with daurisoline, a microbial DPP4-specific inhibitor, mitigates cardiac dysfunction. In acute myocardial infarction patients with I/R injury, B. acidifaciens abundance and BaDPP4 levels correlate with clinical markers of cardiac damage. Together, these findings reveal a gut-heart axis whereby microbial-derived DPP4 exacerbates cardiac I/R injury and highlight the hypoxia-lactate-BaDPP4 axis as a promising target for microbiota-based cardioprotection.}, }
@article {pmid41923890, year = {2026}, author = {Willis, DN and Dubberke, ER and Hayashi, RJ and Tarr, PI and Haslam, DB and Hink, T and Luo, J and Tao, Y and Padhye, A and Hall, EM and Storch, GA}, title = {Clostridioides difficile Colonization and Infection in Pediatric Oncology and Stem Cell Transplant Patients.}, journal = {Open forum infectious diseases}, volume = {13}, number = {4}, pages = {ofag149}, pmid = {41923890}, issn = {2328-8957}, abstract = {BACKGROUND: Pediatric oncology and hematopoietic stem cell transplant (HSCT) patients have elevated risk for Clostridioides difficile infection (CDI), which can prolong hospitalization and delay chemotherapy. Colonization is an important prelude to symptomatic CDI. We sought to characterize colonization status in these patients.<br><br>METHODS: We retrospectively studied 276 stools longitudinally collected over 34 months from 32 HSCT and 12 oncology patients treated at a single tertiary center. Specimens were cultured for C difficile and compared by whole genome sequencing. The fecal microbiome was characterized by 16S rRNA gene sequencing.<br><br>RESULTS: Baseline cultures were positive in 16 (50%) HSCT patients and 2 (12%) oncology. On subsequent samples, 64% of patients who were initially negative acquired colonization: 8 of 15 (53%) HSCT and 8 of 10 (80%) oncology. Nine clonal strains and 25 multilocus sequence types were identified by whole genome sequencing, with 4 clones found in both cohorts. Nine patients had different strains at different time points. Seven clonal strains were found in multiple patients. Seven (15.9%) patients had symptomatic CDI. C difficile-positive stools had greater microbial diversity than negative stools in both the oncology cohort (Simpson diversity index, 0.07; 95% CI, .01-.14; P = .03) and the HSCT cohort (0.15; 95% CI, .07-.24; P < .001).<br><br>CONCLUSIONS: C difficile acquisition and colonization are common in pediatric oncology and HSCT patients. The high prevalence of clonally related strains in multiple patients suggests that asymptomatic patients may be important reservoirs of this pathogen and lead to symptomatic CDI in some patients. Gut microbial composition may influence the risk of colonization.}, }
@article {pmid41924270, year = {2026}, author = {Hu, Y and Li, Y and Zhang, Q and Tan, Q and Liu, H and Yang, Y and Jin, C and Zhang, W and Jia, J and Wang, J}, title = {The AMP-antibiotic-microbiota triad in IBD: a mechanistic framework for dysregulated antimicrobial defense.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1779550}, pmid = {41924270}, issn = {1664-3224}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; *Inflammatory Bowel Diseases/immunology/microbiology/metabolism/drug therapy ; *Antimicrobial Peptides/immunology/metabolism ; Animals ; *Gastrointestinal Microbiome/immunology/drug effects ; Intestinal Mucosa/immunology/microbiology/metabolism ; Intestinal Barrier Function ; Paneth Cells/immunology ; Dysbiosis ; }, abstract = {Inflammatory bowel disease (IBD) represents a chronic relapsing disorder driven by a loss of homeostatic balance between the host immune system and the intestinal microbiota. Endogenous antimicrobial peptides (AMPs), produced primarily by epithelial and immune cells, function in concert with commensal microorganisms to preserve mucosal integrity and barrier function. Disruption of this antimicrobial equilibrium-through genetic susceptibility such as NOD2 mutations or environmental perturbations including antibiotic overuse-can impair antimicrobial defense, distort microbial composition, and initiate chronic inflammation. Recent investigations have revealed distinct alterations in AMP expression across IBD subtypes. In Crohn's disease, Paneth cell-derived α-defensins (HD5 and HD6) are markedly diminished in the ileal mucosa, whereas colonic, segmental IBD exhibits inadequate induction of β-defensins and LL-37. Conversely, in actively inflamed regions, certain AMPs such as human β-defensin-2 (HBD2) and lysozyme are strongly upregulated, reflecting a compensatory response to inflammatory cell infiltration and microbial invasion. Beyond host-derived peptides, broad-spectrum antibiotic exposure profoundly reshapes commensal communities, attenuates basal pattern-recognition receptor signaling, and secondarily perturbs AMP regulation-creating a feedback loop that amplifies dysbiosis. Here, we conceptualize these interactions as an integrated AMP-antibiotic-microbiota triad, in which endogenous antimicrobial regulation, exogenous antimicrobial pressure, and microbial ecological resilience dynamically co-determine mucosal stability. By positioning AMPs within this tripartite regulatory framework, this review delineates how antimicrobial imbalance arises across IBD subtypes, compares emerging therapeutic strategies-including AMP enhancement, microbiota-sparing antibiotic regimens, fecal microbiota transplantation, and metabolite-guided interventions-and highlights implications for precision recalibration of antimicrobial homeostasis in IBD.}, }
@article {pmid41924474, year = {2026}, author = {Li, M and Dai, L and Yang, Y and Chen, S and Ma, J and Feng, P}, title = {Jinzhi and fecal microbiota transplantation: a comparative review of historical and modern microbial therapeutics.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1700764}, pmid = {41924474}, issn = {1664-302X}, abstract = {Since its formal introduction in 1958, fecal microbiota transplantation (FMT) has gained prominence. However, challenges remain in standardizing protocols and optimizing efficacy. This review provides a systematic comparison between the historical practice of Jinzhi and modern FMT, focusing on their preparation methodologies. We hypothesize that specific, underexplored features of Jinzhi preparation could inform and refine current FMT practices. Specifically, we propose that the utilization of adolescent donors, underground low-temperature fermentation, and the careful consideration of seasonal timing, all integral to Jinzhi's traditional protocol, may offer novel insights and testable hypotheses for enhancing microbial diversity, functionality, and therapeutic stability in FMT. By bridging this ancient wisdom with modern microbiome science, we aim to outline a novel and actionable framework for developing the next generation of microbiota-based therapeutics, urging future research to empirically test these historically inspired hypotheses.}, }
@article {pmid41924481, year = {2026}, author = {Niu, C and Wang, J and Lu, X and Yu, Y}, title = {Probiotics for ulcerative colitis: mechanisms, therapeutic advances, and emerging strategies.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1787284}, pmid = {41924481}, issn = {1664-302X}, abstract = {Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with a rising global incidence. Existing therapies are often limited by suboptimal efficacy and frequent relapse. Gut microbiota dysbiosis is central to UC pathogenesis, providing a rationale for probiotic-based, microbiota-targeted interventions. This review synthesizes evidence that probiotics mitigate UC through multiple synergistic mechanisms: competitive exclusion to rebalance the microbiota, upregulation of tight junction proteins to restore the intestinal barrier, and bidirectional immunomodulation to restrain excessive inflammation. These mechanisms are supported by extensive preclinical and clinical data. Research is increasingly moving beyond conventional live formulations toward defined postbiotics, probiotic-traditional Chinese medicine combinations, targeted delivery systems engineered with smart materials, and fecal microbiota transplantation. These strategies seek to overcome limitations such as low bacterial viability and poor targeting, thereby improving therapeutic precision and efficacy. Collectively, probiotics and their derivative approaches offer promising adjunct or alternative options for the clinical management of UC via multitarget modulation of the intestinal microenvironment.}, }
@article {pmid41924769, year = {2026}, author = {Yan, F and Sui, M and Gao, H and Liu, Y and Yu, L}, title = {A distinct plasma lipidomic signature and multi-omics network in depression of polycystic ovary syndrome.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {276}, number = {}, pages = {117486}, doi = {10.1016/j.jpba.2026.117486}, pmid = {41924769}, issn = {1873-264X}, mesh = {Female ; *Polycystic Ovary Syndrome/blood/psychology/microbiology/complications ; Animals ; Multiomics ; Humans ; Mice ; *Depression/blood/microbiology ; Lipidomics/methods ; Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; *Lipids/blood ; Lipid Metabolism ; Mice, Inbred C57BL ; }, abstract = {Patients with polycystic ovary syndrome (PCOS) are at an elevated risk of depression, yet the underlying mechanisms remain elusive. Emerging evidence implicates the gut-brain axis and systemic lipid homeostasis alterations as potential key contributors. We profiled untargeted plasma lipidomes of PCOS patients with and without comorbid depression (PCOS-DP) and integrated these data with our prior gut microbial and host transcriptomic datasets to construct multi-omics interaction networks. The causal role of the candidate gut microbial was preliminary explored in a germ-free PCOS mouse model using fecal microbiota transplantation, followed by behavioral phenotyping and ELISA-based protein quantification. We identified a distinct plasma lipidomic signature differentiating PCOS-DP from PCOS alone, characterized primarily by the downregulation of 26 lipid species. Most of these altered lipids were triacylglycerols (TAGs) enriched with FA18:1 and FA18:2, whose levels correlated with coagulation dysfunction. Multi-omics network analysis revealed significant interconnections between depression-associated gut microbiota (including Bacteroides eggerthii), specific altered lipids such as TAG (60:12/FA22:6), and host genes involved in inflammation (e.g., IL22, NLRP7), metabolism, and neural processes. Animal validation demonstrated that B. eggerthii colonization in PCOS mice specifically exacerbated anhedonia and hyperlocomotion, alongside modulating plasma IL-22 expression, suggesting its context-dependent neurobehavioral effect role. This study delineates a TAG-downregulated lipid signature with diagnostic potential and reveals a novel "gut microbiota-lipid-host gene" interaction network underpinning PCOS-DP, with B. eggerthii as a key microbial modulator of neurobehavioral phenotypes in the context of PCOS. These findings provide new pathophysiological insights and highlights potential diagnostic biomarkers for PCOS-DP.}, }
@article {pmid41925105, year = {2026}, author = {Zu, S and Yu, X and Song, J and Xiao, Y and Yi, H and Li, H}, title = {The Role of Gut Microbiota and Their Derived Metabolites in Chemotherapy-Induced Nausea and Vomiting in Ovarian Cancer.}, journal = {Cancer medicine}, volume = {15}, number = {4}, pages = {e71752}, pmid = {41925105}, issn = {2045-7634}, support = {2023QH1193//Startup Fund for Scientific Research, Fujian Medical University/ ; YCXH 22-10//Nursing Research Special Fund of Fujian Maternal and Child Health Hospital/ ; }, mesh = {Female ; Animals ; Humans ; *Gastrointestinal Microbiome ; *Ovarian Neoplasms/drug therapy/microbiology ; Rats ; *Vomiting/chemically induced/microbiology/metabolism ; *Nausea/chemically induced/microbiology/metabolism ; Dysbiosis/microbiology ; Cisplatin/adverse effects/administration &amp; dosage ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Carboplatin/adverse effects/administration &amp; dosage ; Paclitaxel/adverse effects/administration &amp; dosage ; Metabolomics/methods ; Aged ; Feces/microbiology ; }, abstract = {OBJECTIVE: This study aimed to investigate the relationship between gut microbiota and chemotherapy-induced nausea and vomiting (CINV) in patients with ovarian cancer undergoing platinum-based chemotherapy (carboplatin or cisplatin combined with paclitaxel).<br><br>METHODS: Clinical data and fecal samples were collected from patients with ovarian cancer after admission but prior to the initiation of their first chemotherapy cycle. Patients were divided into the CINV (n&#x2009;=&#x2009;25) and non-CINV (n&#x2009;=&#x2009;25) groups on the basis of symptoms occurring after chemotherapy. No additional samples were collected during chemotherapy. Integrated metagenomic sequencing and untargeted metabolomic profiling identified CINV-associated microbial taxa and metabolites. Additionally, fecal microbiota transplantation (FMT) in SD rats validated causal links between gut dysbiosis and CINV pathogenesis.<br><br>RESULTS: Bacteroides caccae, Corynebacteriales, and Corynebacterium were significantly enriched in the CINV group. KEGG enrichment revealed upregulated pathways in CINV, including focal adhesion, lysosome function, and eukaryotic cellular communities. Metabolomic analysis identified 19 significantly increased metabolites in the fecal samples of CINV patients versus 10 in non-CINV controls. KEGG enrichment revealed that the pentose phosphate pathway, glutathione metabolism, and lipoic acid metabolism were significantly implicated in CINV pathogenesis. Multi-omics integration revealed Bacteroides sp. A1C1 strongly correlated with hesperetin, arbutin, orciprenaline, and myristolic acid. In rats, cisplatin-induced CINV models showed higher kaolin consumption versus controls (p&#x2009;<&#x2009;0.05). FMT from non-CINV donors reduced kaolin consumption in cisplatin-treated rats (p&#x2009;<&#x2009;0.05). The expression of 5-HT3R, NK1R, and NK2R in the medulla oblongata and colon was significantly increased in the cisplatin model group (p&#x2009;<&#x2009;0.05) and partially reversed by non-CINV FMT (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: Gut microbiota dysbiosis directly contributes to CINV pathogenesis. Bacteroides sp. A1C1 and its putatively identified metabolites (hesperetin, arbutin, orciprenaline, and myristolic acid) represent potential diagnostic biomarkers for CINV.}, }
@article {pmid41926238, year = {2026}, author = {Chen, J and Liang, S and Liu, D and Yang, S and Yan, Q and Jiang, Z}, title = {2'-Fucosyllactose Alleviates Metabolic Hypertension in Mice via Gut Microbiota Modulation and Involvement of the LPS/TLR4 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {14}, pages = {11513-11529}, doi = {10.1021/acs.jafc.5c12123}, pmid = {41926238}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Hypertension/metabolism/drug therapy/microbiology/genetics/physiopathology ; *Gastrointestinal Microbiome/drug effects ; Male ; *Toll-Like Receptor 4/metabolism/genetics ; Signal Transduction/drug effects ; *Lipopolysaccharides/metabolism ; *Trisaccharides/administration &amp; dosage ; Humans ; Mice, Inbred C57BL ; Bacteria/isolation &amp; purification/classification/genetics/metabolism ; Blood Pressure/drug effects ; Fatty Acids, Volatile/metabolism ; }, abstract = {2'-Fucosyllactose (2'-FL) shows promise in ameliorating metabolic disorders. However, the role of 2'-FL in metabolic hypertension (MH) remains unclear. This study aimed to evaluate the effects of 2'-FL on MH and explore its underlying mechanisms. 2'-FL treatment (1000 mg/kg) reduced systolic blood pressure (SBP) by 16.6% and alleviated dyslipidemia, microglial activation, and neuroinflammation in MH mice. 2'-FL markedly increased short-chain fatty acids (SCFAs)-producing beneficial bacteria, e.g., Akkermansia and Bifidobacterium by 3.9-fold and 19.5-fold, accompanied by increased fecal acetate and butyrate. Notably, the benefits of 2'-FL for MH were transferable via fecal microbiota transplantation (FMT). Particularly, 2'-FL-mediated attenuation of vascular dysfunction was associated with the inhibition of the lipopolysaccharide/toll-like receptor 4 (LPS/TLR4) signaling, a protective effect that could be transferred via FMT. The antihypertensive and metabolic benefits of 2'-FL in mice were accompanied by gut-brain axis modulation. These findings suggest that 2'-FL represents a promising dietary strategy for preventing hypertension-associated complications.}, }
@article {pmid41928077, year = {2026}, author = {Hao, X and Ma, C and Gao, X and Wang, F and Han, B and Bai, D and Ou, L and Zeng, Q}, title = {Effects of U62631.5 on short-chain fatty acid receptor 41(GPR41) and the related intestinal bacterium Butyricicoccus pullicaecorum after fecal bacterial transplantation in nonalcoholic fatty liver disease.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41928077}, issn = {1471-2180}, support = {2022ZXJ03C05//Heilongjiang Science and Technology Department Fund/ ; 82271770//National Natural Science Foundation of China/ ; NCRCG-PLAGH-2024002//Project of the National Clinical Research Center for Geriatric Diseases/ ; }, abstract = {BACKGROUND: LncRNAs exhibit diverse biological functions and may be crucial in nonalcoholic fatty liver disease (NAFLD) development. Our focus is on the mechanism of lncRNA U62631.5, regulating GPR41 and Butyricicoccus pullicaecorum (B. pullicaecorum), an intestinal bacterium producing butyric acid. Ensembl analysis suggests an interaction between U62631.5 and GPR41.<br><br>METHODS: 1. Male C57BL/6 mice were randomly divided into control group, model group, transplantation control group, transplantation model group by using the fecal microbiota transplantation (FMT) technique in this study. The liver tissue and small intestine tissue in each group were observed by hematoxylin-eosin (HE) staining, and liver histopathology was quantitatively assessed using the NAFLD Activity Score (NAS). The expression of U62631.5 and GPR41 in peripheral blood, liver tissue, and small intestine tissues were detected by PCR. Fecal samples were used by16S rRNA sequencing. The contents of short chain fatty acids in intestinal were detected by gas chromatography, and the expression of B. pullicaecorum was detected by PCR. 2.Hepatic lipid accumulation was observed in HepG2 cells. GPR41 promoter function analysis was detected. After siRNA and overexpression of U62631.5, the U62631.5 and GPR41 were further detected by PCR.<br><br>RESULTS: 1. Animal level: Compared with the model group, hepatic lipid accumulation and the injury of intestinal mucosal were improved, the expression of U62631.5 and GPR41 were increased, the content of butyric acid was increased, and B. pullicaecorum was increased in the transplantation model group. The results were contrary to the above results in the model group compared with the control group, the transplantation control group compared with the control group, and the transplantation model group compared with the transplantation control group. 2.Cell levels: It was found that the promoter activity of GPR41 gene was increased significantly by U62631.5. We interfered with U62631.5 by siRNA and found that GPR41 was almost undetectable by PCR. After overexpression of U62631.5, the expression of GPR41 was increased.<br><br>CONCLUSION: U62631.5 may play a role by regulating adjacent gene GPR41 related intestinal bacteria in NAFLD, and B.pullicaecorum may be one of the intestinal bacteria in this process.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-026-05014-7.}, }
@article {pmid41928384, year = {2026}, author = {Valdez-Palomares, F and Noriega, LG and Reyes-Romo, D and Canizales-Quinteros, S and Nambo-Venegas, R and Salinas-Lara, C and Tovar-Palacio, A and Menjivar, M and Peña-Espinoza, B and Ortiz, G and Palacios-González, B}, title = {Human fecal transplantation from stunted children promotes metabolic dysfunction in mice fed with a high-fat and high-fructose corn syrup diet.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2651984}, pmid = {41928384}, issn = {1949-0984}, mesh = {Animals ; Male ; Humans ; *Fecal Microbiota Transplantation/adverse effects ; Mice ; Mice, Inbred C57BL ; *High Fructose Corn Syrup/adverse effects/metabolism ; *Diet, High-Fat/adverse effects ; *Growth Disorders/metabolism/microbiology/therapy ; Child ; *Gastrointestinal Microbiome ; Feces/microbiology ; Obesity/etiology/metabolism ; Bacteria/classification/genetics/isolation &amp; purification ; Mexico ; }, abstract = {Stunting, or impaired child growth due to poor nutrition and infections, is characterized by a low height-for-age and affects 48%-56% of school-aged children worldwide. It is associated with later weight gain and chronic diseases. The gut microbiome in undernourished children may increase obesity risk if they are exposed to high-calorie environments. To investigate this, we assessed whether the intestinal microbiome of stunted children elevates obesity risk upon exposure to an obesogenic environment. Fecal microbiota transplantation (FMT) was performed using pooled stools from healthy (n = 6) or stunted (n = 6) school-aged children from a low-income cohort in Mexico. Eight-week-old male C57BL/6 mice underwent bowel cleansing with polyethylene glycol (PEG), followed by weekly intragastric FMT for 4 weeks. The mice were subsequently fed either a control diet (CT) or a high-fat, high-fructose corn syrup diet (HFFr, including 15% HFCS-55) for 15 weeks. Metabolic outcomes were assessed through body composition, indirect calorimetry, oral glucose tolerance test, insulin tolerance test, and histological analysis of visceral adipose tissue. The microbiota composition was evaluated by 16S rRNA V3-V4 hypervariable region sequencing, and the predicted functional capacity was analyzed using PICRUSt2. FMT from stunted children increased susceptibility to diet-induced obesity, visceral adipose tissue hypertrophy, and insulin resistance. In contrast, FMT from healthy children promoted energy expenditure and visceral adipose tissue hyperplasia, conferring a protective effect against diet-induced obesity and insulin resistance in the mice. Healthy-FMT led to sustained enrichment of Akkermansia and Parabacteroides, whereas stunting-FMT increased Proteobacteria, Veillonella, Desulfovibrionaceae, and Bifidobacterium. Microbial‒phenotypic correlations showed that Akkermansia and Parabacteroides were negatively correlated with fasting glucose, body weight, and fat mass, and positively correlated with postprandial RER, VO2, and lean mass. In conclusion, stunting-FMT recipient mice showed a higher risk of obesity and metabolic issues in an obesogenic environment. Healthy-FMT confers metabolic resilience, characterized by increased abundance of taxa such as Akkermansia and Parabacteroides, which are linked to enhanced energy expenditure, improved glucose metabolism, and favorable adipose tissue structure.}, }
@article {pmid41928387, year = {2026}, author = {Houshyar, Y and Zhang, F and Tavakoli, P and Grimm, MC and Hold, GL}, title = {Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2653288}, pmid = {41928387}, issn = {1949-0984}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/virology ; *Virome ; *Mycobiome ; Dysbiosis/microbiology/virology ; *Gastrointestinal Microbiome ; *Fungi/classification/genetics/isolation &amp; purification ; Animals ; Bacteria/classification/genetics ; Fecal Microbiota Transplantation ; Viruses/classification/genetics/isolation &amp; purification ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing-remitting disorder of the gastrointestinal tract characterized by immune dysregulation, epithelial barrier dysfunction, and microbial imbalance. While bacterial dysbiosis, including depletion of short-chain fatty acid (SCFA) producers and enrichment of pathobionts, is well characterized, the gut virome and mycobiome remain comparatively neglected. Both exhibit high variability and are constrained by sequencing bias, contamination, and incomplete reference databases, leaving much of the viral and fungal diversity unresolved. Emerging evidence links fungal and viral dysbiosis to IBD pathogenesis, including Candida overgrowth, loss of Saccharomyces, expansion of Caudoviricetes phages, and detection of eukaryotic viruses such as Cytomegalovirus and Epstein-Barr virus in inflamed mucosa. These alterations disrupt barrier integrity, modulate immune signaling, and interact with bacteria and archaea in cross-kingdom networks that amplify inflammation. Translationally, the virome and mycobiome are now recognized as therapeutic targets, inspiring interventions from pre/probiotics and synbiotics to precision phage therapy and microbiota-based transplantation, including fecal virome transplantation (FVT) and fecal microbiota transplantation (FMT). This review recognizes the challenges and opportunities of studying these neglected kingdoms, reframes IBD dysbiosis and highlights new directions for biomarker discovery and multikingdom microbiota-directed therapies.}, }
@article {pmid41929183, year = {2026}, author = {Dong, W and Yan, C and Korwin-Mihavics, B and Stack, K and Hughes, G and Schmidt, A and Schwartz, K and Caballero-Flores, G and Alexander, M}, title = {β-hydroxybutyrate modulates enteric pathogen susceptibility through regulation of commensal bacteria and intestinal Th17 responses.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41929183}, issn = {2692-8205}, abstract = {T helper 17 (Th17) cells are a critical T lymphocyte subset involved in mucosal immunity and host defense against enteric pathogens. Although ketogenic diets (KD) and the major ketone body β-hydroxybutyrate (BHB) reshape gut microbiota and suppress Th17 responses under defined diet conditions, it remains unclear whether elevation of BHB alone, independent of dietary macronutrient composition and systematic metabolic shift, is sufficient to remodel Th17-inducing commensals and alter host susceptibility to enteric infection. Here, we used 1,3-butanediol (BD), a precursor metabolized to BHB independently of KD, to elevate systemic BHB levels in mice. BD treatment significantly reduced the frequency of ileal Th17 cells, as assessed by flow cytometry for Th17 markers IL-17A and RORγt. 16S rRNA gene sequencing revealed that BD altered gut microbial community structure, as indicated by beta-diversity analysis based on Bray-Curtis dissimilarity, and reduced Shannon diversity and evenness. Linear discriminant analysis effect size identified segmented filamentous bacteria (SFB) as significantly decreased in the ileum following BD treatment, and SFB abundance positively correlated with Th17 markers. Microbiota transplantation demonstrated that BD-shaped microbiota was sufficient to suppress Th17 responses in recipient mice, accompanied by reduced SFB abundance. In a Citrobacter rodentium infection model, BD treatment was associated with increased pathogen burden, and fecal C. rodentium levels were negatively correlated with SFB abundance. Together, these results indicate that BD-induced elevation of BHB reshapes commensal microbiota, including decreasing SFB levels, resulting in dampened Th17 responses and increased susceptibility to enteric infection.}, }
@article {pmid41929479, year = {2026}, author = {Pan, Y and Li, B and Liu, L and Wang, Z and Liu, X}, title = {Gut dysbiosis induces the development of asthenozoospermia through butanoate metabolism.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1760881}, pmid = {41929479}, issn = {1664-3224}, mesh = {Male ; Humans ; *Asthenozoospermia/metabolism/etiology/microbiology ; *Dysbiosis/complications/metabolism/microbiology ; Animals ; Mice ; *Gastrointestinal Microbiome ; *Butyrates/metabolism ; Adult ; Fecal Microbiota Transplantation ; Case-Control Studies ; Sperm Motility ; Metabolomics ; Spermatozoa ; }, abstract = {BACKGROUND: Asthenozoospermia is a leading cause of male infertility with a rising incidence. While gut dysbiosis is implicated in metabolic disease, its role in asthenozoospermia pathogenesis remains unclear.<br><br>MATERIALS AND METHODS: We conducted a case-control study comparing the fecal microbiomes of men with isolated asthenozoospermia (n=60) and healthy controls (n=60) using shotgun metagenomic sequencing. Causality was assessed by fecal microbiota transplantation (FMT) from patients or controls into germ-free male mice. Metabolic perturbations were profiled by untargeted serum metabolomics and targeted short-chain fatty acid (SCFA) quantification in humans, alongside untargeted testicular metabolomics and serum SCFAs in recipient mice.<br><br>RESULTS: Metagenomic analysis (LEfSe) identified species-level differences, with marked depletion of butyrate-producing taxa in asthenozoospermia, most notably the prototypical butyrate producer Faecalibacterium prausnitzii. The relative abundance of F. prausnitzii was significantly positively correlated with sperm motility and progressive motility, linking gut composition to sperm quality in asthenozoospermia. Untargeted serum metabolomics identified 39 differential metabolites; KEGG enrichment prioritized butanoate metabolism. Targeted SCFA profiling confirmed significantly lower serum butyrate in asthenozoospermia versus controls. In germ-free males, FMT with patient-derived microbiota reduced sperm motility and progressive motility and induced histopathological abnormalities, including decreased interstitial Leydig cells, loss and atrophy of select intratubular cells, and an increased proportion of abnormal seminiferous tubules. Following patient FMT, recipient mice exhibited significantly reduced serum butyrate; testicular metabolomics revealed distinct profiles with 140 key differential metabolites, again implicating butanoate metabolism. Mechanistically, reduced F. prausnitzii-derived butyrate might impair Leydig cell steroidogenesis via disrupted PPAR signaling.<br><br>CONCLUSIONS: Asthenozoospermia is associated with gut dysbiosis characterized by loss of butyrate-producing bacteria, systemic and testicular disturbances in butyrate metabolism, and microbiota-mediated transmission of impaired sperm quality. These findings implicate the gut-testis axis in asthenozoospermia pathogenesis and nominate butyrate metabolism as a potential therapeutic target.}, }
@article {pmid41929953, year = {2026}, author = {Oso, TA and Okesanya, OJ and Adebayo, UO and Obadeyi, KB and Ayelaagbe, OB and Talabi, OA and Adewole, PD and Anorue, CO and Ahmed, MM and Talabi, OT and Ogaya, JB and Lucero-Prisno, DE}, title = {Microbiome alterations in Alzheimer's disease: A systematic review of current evidence and global perspectives.}, journal = {Journal of Alzheimer's disease reports}, volume = {10}, number = {}, pages = {25424823261436287}, pmid = {41929953}, issn = {2542-4823}, abstract = {BACKGROUND: Growing evidence implicates the gut-brain axis in Alzheimer's disease (AD), with gut microbiome dysbiosis proposed to modulate neuroinflammation, amyloid pathology, and cognitive decline.<br><br>OBJECTIVE: To systematically synthesize human studies (2021-2025) profiling gut microbiomes in AD; identify consistent taxonomic and functional signatures; map geographic study distribution; and highlight translational gaps.<br><br>METHODS: A PRISMA-compliant systematic review of human studies using 16S rRNA, metagenomics, metatranscriptomics, or fecal microbiota transplantation (FMT)/probiotic designs was conducted. Two reviewers screened studies and assessed quality using Joanna Briggs Institute tools. Owing to heterogeneity, findings were narratively synthesized across microbiome diversity, taxonomy, function, metabolism, oral-brain links, causality, interventions, and predictive analyses.<br><br>RESULTS: Thirty-seven studies, mainly from Asia with some from Europe, North America, and Africa, revealed consistent gut dysbiosis in AD. Findings show reduced alpha-diversity, loss of short-chain fatty acid-producing bacteria (e.g., Faecalibacterium prausnitzii, Bifidobacterium), and enrichment of pro-inflammatory taxa (Escherichia/Shigella, Proteobacteria). Functional analyses indicate reduced butyrate synthesis, disrupted lipid and tryptophan-kynurenine metabolism, and links with apolipoprotein epsilon (&#x3b5;4) gene and cognition. Limited causal evidence arises from Mendelian randomization and small FMT trials, with randomized, longitudinal confirmation still needed.<br><br>CONCLUSIONS: Current evidence suggests a biologically plausible association between gut microbiota and AD pathogenesis, positioning microbiome-derived biomarkers and interventions as promising but still exploratory avenues. Harmonized, longitudinal, multi-omic, and geographically inclusive studies are urgently needed to clarify causal mechanisms and translate these correlational findings into validated diagnostics and therapeutics.}, }
@article {pmid41931118, year = {2026}, author = {Ansari, S and Purohit, KJ and Shelke, AB and Shah, M and Nkhoma, IA and Navale, AM and Wakchaure, R}, title = {Microbiota-driven mechanisms in multisystem diseases: integrative evidence across cardiovascular, metabolic, neurological and autoimmune disorders.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {5}, pages = {}, pmid = {41931118}, issn = {1572-9699}, mesh = {Humans ; *Dysbiosis/microbiology ; *Autoimmune Diseases/microbiology ; *Cardiovascular Diseases/microbiology ; *Nervous System Diseases/microbiology ; *Gastrointestinal Microbiome ; *Metabolic Diseases/microbiology ; Animals ; }, abstract = {The human microbiota represents one of the body's most influential biological systems, engaging in constant metabolic, immunological, and neuroendocrine communication with the host. Disruption of this intricate ecosystem, or dysbiosis, has emerged as a fundamental determinant in the onset and progression of numerous chronic diseases. This review consolidates contemporary evidence on how alterations in microbial composition, metabolite production, and barrier integrity contribute to pathophysiological changes across multiple organ systems. Gut-derived metabolites-including short-chain fatty acids, bile acid derivatives, trimethylamine-N-oxide, and lipopolysaccharide-serve as key mediators linking microbial imbalance to systemic inflammation, metabolic dysfunction, autoimmunity, and neurodegeneration. We outline the mechanistic pathways through which dysbiosis promotes hypertension, atherosclerosis, obesity, type 2 diabetes, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, urinary tract infections, and chronic kidney disease. Particular emphasis is placed on the gut-brain, gut-lung, and gut-kidney axes, which facilitate bidirectional immune and metabolic signalling between the intestine and distant tissues. Additionally, the review highlights emerging therapeutic interventions aimed at restoring microbial homeostasis, including targeted dietary strategies, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbiome-directed pharmacological approaches. Collectively, the evidence positions the microbiota as a central regulator of human health and disease, offering a compelling platform for next-generation diagnostic and therapeutic innovation. Advancing mechanistic understanding of host-microbe interactions will be essential to developing personalized microbiome-based strategies capable of preventing, mitigating, or reversing disease across diverse clinical contexts.}, }
@article {pmid41931990, year = {2026}, author = {Gao, J and Yi, Y and Ran, W and Cheng, Y and Deng, W and Duan, S and Shi, F and Wei, Y and Zhang, Y and Gong, Q}, title = {Targeting astrocytic Nrf2 by Trilobatin alleviates lipopolysaccharide-induced depressive-like behaviors and cognitive impairment in mice: Mechanistic insights into gut microbiota and metabolites modulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {155}, number = {}, pages = {158118}, doi = {10.1016/j.phymed.2026.158118}, pmid = {41931990}, issn = {1618-095X}, mesh = {Animals ; *NF-E2-Related Factor 2/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Lipopolysaccharides ; Male ; *Cognitive Dysfunction/drug therapy/chemically induced ; Mice, Inbred C57BL ; *Astrocytes/drug effects/metabolism ; Neuroprotective Agents/pharmacology ; *Depression/drug therapy/chemically induced ; Disease Models, Animal ; Behavior, Animal/drug effects ; *Disulfides/pharmacology ; Alzheimer Disease/drug therapy ; Oxidative Stress/drug effects ; Major Depressive Disorder/drug therapy ; Flavonoids ; Polyphenols ; }, abstract = {BACKGROUND: Clinical and preclinical evidence links major depressive disorder (MDD) and Alzheimer's disease (AD), suggesting MDD treatment could prevent some AD. Dysfunction within the microbiota-gut-brain axis contributes to MDD and AD pathogenesis via dysregulated microbial metabolites. Trilobatin (TLB) functions as a neuroprotective agent modulating gut microbiota. However, its capacity to alleviate depressive-like behavior and cognitive deficits through restoration of gut microbial ecology and metabolite profiles requires clarification.<br><br>OBJECTIVE: The present research was designed to examine the impact of TLB on depressive-like behavior and cognitive impairments, and the role of the gut microbiota and metabolites.<br><br>METHODS: Neuroprotective effects of TLB on MDD and AD were evaluated using an LPS mouse model exhibiting depressive-like behavior and memory impairment. The principal molecular target of TLB was identified through a combination of single-cell sequencing, surface plasmon resonance, and gene knockout approaches. Mechanistic insights into gut microbiota and metabolites were gained through 16S rRNA sequencing and fecal microbiota transplantation (FMT).<br><br>RESULTS: TLB attenuated LPS-induced depressive-like behaviors manifested as lowered sucrose preference, extended immobility, and improved cognitive deficits as reflected by Y-maze and novel object recognition. Mechanistically, TLB directly bound Nrf2, enhanced Nrf2-ARE activity, and suppressed neuroinflammation and oxidative stress. TLB restored gut microbiota homeostasis, elevated Akkermansia muciniphila (AKK) abundance and short-chain fatty acids, and strengthened intestinal tight junction proteins. FMT from TLB-treated mice replicated these benefits in wild-type but not Nrf2-knockout mice. AKK supplementation similarly ameliorated behavioral and cognitive deficits via Nrf2 activation.<br><br>CONCLUSION: Our findings reveal that TLB mitigates neuropsychiatric deficits by activating Nrf2, remodeling restructuring gut microbiota and fortifying intestinal barrier function. The Nrf2-mediated microbiota-gut-brain axis is suggested as a potential therapeutic target for MDD and AD, positioning TLB as a promising natural Nrf2 activator.}, }
@article {pmid41932357, year = {2026}, author = {Winston, JA and Jennings, R and Randolph, NK and Welton, M and Partridge, E and Schreeg, M and Yaxley, PE and Rudinsky, AJ}, title = {Fecal microbiota transplantation dosing regimen accelerates clinical resolution in canine parvovirus infection: a novel spectrum-of-care approach.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-9}, doi = {10.2460/javma.25.11.0764}, pmid = {41932357}, issn = {1943-569X}, abstract = {OBJECTIVE: To evaluate the efficacy of a novel spectrum-of-care fecal microbiota transplant (FMT) dosing regimen as an adjunctive therapy for canine parvovirus (CPV).<br><br>METHODS: 27 client-owned dogs naturally infected with CPV were enrolled from March to November 2023 in a prospective, double-blinded, placebo-controlled clinical trial. Patients were randomized into FMT-treated (n = 19) or placebo-treated (8) groups. Along with conventional treatments, CPV-infected dogs were administered FMT (single FMT enema, then 14 days of oral lyophilized FMT capsules) or placebo (single saline enema, then 14 days of oral placebo capsules) at admission. During hospitalization, dogs were monitored daily including fecal, clinical severity, and medication scores. Feces and serum were collected at admission, day 4, day 7, day 14, and day 21 for quantification of CPV viral shedding and immune response (bead-based multiplex of cytokines/chemokines). The primary outcome variable was length of hospitalization.<br><br>RESULTS: Interim analysis revealed that placebo-treated dogs had excessive study withdrawals due to worsening clinical status when compared to FMT-treated dogs (37.5% compared to 0%, respectively), leading to ethical discontinuation of the placebo arm. Fecal microbiota transplant-treated dogs had significantly reduced hospitalization length and medications required for treatment (maximum medication score) compared to placebo-treated dogs. Fecal microbiota transplant did not reduce fecal viral shedding or elicit a host immune response.<br><br>CONCLUSIONS: This novel FMT dosing regimen (single enema FMT followed by oral capsular FMT), designed to be feasible for inpatients or outpatients, accelerated clinical recovery from CPV.<br><br>CLINICAL RELEVANCE: In-house and commercially available FMT products were effective in CPV-infected dogs, thus broadening the spectrum of care available to these patients.}, }
@article {pmid41932472, year = {2026}, author = {Yan, Q and Yang, F and Li, Q and Wang, J and Wang, Y and Zeng, X and Shen, R and Yang, J and Peng, Y and Si, D and Diao, Y and Wei, L}, title = {Atractylodes macrocephala polysaccharide AMP1-1 ameliorates weightless-induced cognitive dysfunction via the microbiota-gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {358}, number = {}, pages = {151754}, doi = {10.1016/j.ijbiomac.2026.151754}, pmid = {41932472}, issn = {1879-0003}, mesh = {Animals ; *Polysaccharides/pharmacology/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Cognitive Dysfunction/drug therapy/etiology/metabolism ; Rats ; *Atractylodes/chemistry ; Male ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Hippocampus/drug effects/metabolism ; Rats, Sprague-Dawley ; *Brain/drug effects/metabolism ; Signal Transduction/drug effects ; Myeloid Differentiation Factor 88/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Atractylodes macrocephala Koidz., a traditional Chinese medicine known for "strengthening the spleen and replenishing qi", has been recognized for its gastrointestinal protective and immunomodulatory properties, suggesting a potential role in gut-brain axis regulation. This study investigated the protective effect and underlying mechanism of a purified inulin-type polysaccharide from Atractylodes macrocephala, AMP1-1, against weightlessness-induced cognitive impairment via the microbiota-gut-brain axis. Using a tail-suspension rat model to simulate microgravity, we assessed: (i) cognitive function through behavioral tests; (ii) neuroinflammation and barrier integrity through histological staining, ELISA, and Western blot; and (iii) gut microbiota composition through 16S rDNA sequencing and metabolomics analysis. Fecal microbiota transplantation (FMT) and butyrate supplementation were employed to validate the causal contributions of gut microbiota and their metabolites. AMP1-1 administration significantly improved cognitive performance, inhibited hippocampal neuroinflammation via the TLR4/MyD88/NF-κB pathway, and enhanced the integrity of both intestinal and blood-brain barriers in suspended rats. It also reshaped the gut microbiota structure, elevated fecal butyrate levels, and reduced systemic lipopolysaccharide (LPS). FMT from AMP1-1-treated donors replicated the cognitive and barrier-protective effects in recipient rats, and butyrate supplementation similarly alleviated neuroinflammation and cognitive deficits. These findings demonstrate that AMP1-1 alleviates weightlessness-induced cognitive impairment by modulating the gut microbiota to promote butyrate production, thereby restoring gut and brain barriers, suppressing peripheral and central inflammation, and inhibiting the hippocampal TLR4/MyD88/NF-κB pathway. AMP1-1 emerges as a promising prebiotic-like agent for preventing neuroinflammation-related cognitive decline under microgravity conditions.}, }
@article {pmid41932647, year = {2026}, author = {Wang, DY and Wang, YW and Yu, KC and Yang, X and Ma, J and Li, BH and Peng, YL and Deng, XY and Chen, ZX and Wang, L}, title = {Probiotic potential of Parabacteroides johnsonii in mitigating age-related ovarian functional decline.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2026.03.023}, pmid = {41932647}, issn = {1673-8527}, abstract = {The gut microbiota is increasingly recognized as a regulator of reproductive health, yet its role in ovarian aging remains unclear. Here, we combine Mendelian randomization (MR) analysis with experimental validation to investigate the causal relationship between gut microbiota and ovarian aging. MR analysis identifies four microbial taxa significantly associated with age at natural menopause. In mouse models, germ-free mice exhibit accelerated ovarian functional decline, including reduced ovarian reserve and impaired folliculogenesis. Fecal microbiota transplantation (FMT) from young donors alleviates ovarian aging phenotypes, whereas FMT from aged donors exacerbates functional decline. Metagenomic analysis reveals species-level differences between young and ovarian-aging mice, with Parabacteroides johnsonii (P. johnsonii) enriched in young mice. Administration of P. johnsonii to middle-aged mice improves ovarian reserve, reduces follicular atresia, enhances granulosa cell proliferation, and decreases systemic inflammation. These findings highlight a causal role of the gut microbiota in ovarian aging and support microbiota-targeted interventions as a potential strategy to preserve ovarian function.}, }
@article {pmid41932663, year = {2026}, author = {Lu, S and Shengle, Q and Shiqing, L and Huihuang, D and Qiaolian, C and Ruifeng, C and Pei, F and Xiao, W and Conglin, L and Xiaoqian, S and Zhonghao, F and Xin, Z and Qian, G and Xiangying, A and Weiqi, P and Yutao, W and Luping, L and Zifeng, Y}, title = {Sheng Jiangsan alleviated influenza-induced acute lung injury by regulating Lactobacillus murinus.}, journal = {Journal of ethnopharmacology}, volume = {367}, number = {}, pages = {121524}, doi = {10.1016/j.jep.2026.121524}, pmid = {41932663}, issn = {1872-7573}, mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Acute Lung Injury/drug therapy/virology/microbiology ; Gastrointestinal Microbiome/drug effects ; *Orthomyxoviridae Infections/drug therapy/complications/microbiology ; Mice ; Male ; Lung/drug effects/pathology/virology ; *Antiviral Agents/pharmacology/therapeutic use ; Mice, Inbred BALB C ; *Anti-Inflammatory Agents/pharmacology ; RNA, Ribosomal, 16S/genetics ; *Lactobacillus/drug effects ; Dogs ; STAT1 Transcription Factor/metabolism ; }, abstract = {Sheng Jiangsan (SJS) authorized by the Chinese Food and Drug Administration for treating wind-heat common cold, exhibits broad-spectrum antiviral activity. However, its specific antiviral and anti-inflammatory mechanisms require clarification. Gut microbiota and their metabolites play significant roles in lung disease progression and intervention, yet no research has explored whether the anti-influenza effect of SJS-derived Qingjie-Tuire (QT) Granule involves these pathways.<br><br>AIM OF THE STUDY: This study aimed to determine whether QT Granule exerts its anti-influenza effects through modulation of gut microbiota and metabolites, specifically investigating associated antiviral and anti-inflammatory mechanisms. An experimental study employing influenza-infected mice. Mechanistic analysis integrated 16S rRNA full-length sequencing, UHPLC-MS/MS metabolomics, fecal microbiota transplantation (FMT), and targeted probiotic intervention.<br><br>MATERIALS AND METHODS: Influenza-infected mice received QT Granule treatment. Gut microbiota composition was analyzed via full-length 16S rRNA sequencing. Metabolite profiles were assessed using UHPLC-MS/MS. Functional validation involved QT-treated mice FMT into infected mice and supplementing infected mice with Lactobacillus murinus and Lactobacillus reuteri (species enriched by QT). Outcomes included lung pathology, viral titers, survival, and lung/intestinal inflammation, and intestinal barrier integrity.<br><br>RESULTS: QT treatment significantly reduced lung pathological damage, lowered viral titers, restored pulmonary macrophage and T-cell proportions, decreased p-STAT1/p-STAT3/p-ERK expression, maintained intestinal barrier function, attenuated lung and intestinal inflammation, and prolonged survival time/survival rate in infected mice. QT intervention restored influenza-depleted UFAs, including docosahexaenoic acid (DHA) and arachidonic acid (AA), and enriched L. murinus and L. reuteri. Crucially, both FMT using QT-treated mouse feces and direct supplementation with L.murinus/L. reuteri replicated QT's core therapeutic effects.<br><br>CONCLUSIONS: QT Granule exerts potent anti-influenza and anti-inflammatory effects by modulating gut microbiota (specifically enriching L.murinus and L.reuteri) and restoring UFA metabolites. This gut-lung axis mechanism provides novel insight into traditional Chinese medicine intervention in viral lung diseases.}, }
@article {pmid41933285, year = {2026}, author = {Yu, Q and Chen, A and Yi, J and Iqbal, M and Tang, Z and Ge, H and Hu, Y and Liu, W and Zheng, L and Tang, J and Xiang, J}, title = {Gut microbiota-associated nutritional-immune status predicts prognosis in postoperative NSCLC patients.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2652460}, pmid = {41933285}, issn = {1949-0984}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/surgery/immunology/microbiology/diagnosis ; *Gastrointestinal Microbiome ; Animals ; *Lung Neoplasms/surgery/immunology/microbiology ; Prognosis ; Male ; Female ; *Nutritional Status ; Mice ; Fecal Microbiota Transplantation ; Middle Aged ; Retrospective Studies ; Aged ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Fatty Acids, Volatile/metabolism ; Postoperative Period ; }, abstract = {BACKGROUND: Surgical resection is the primary treatment for non-small cell lung cancer (NSCLC) patients with stages I and II; however, the postoperative prognosis varies among individuals. The prognostic nutritional index (PNI) reflects the nutritional-immune status of patients, but its microbial determinants remain unclear.<br><br>METHODS: PNI was analyzed in a cohort of 372 retrospective and 139 prospective NSCLC patients. This analysis integrated gut microbiota signatures using 16S rRNA sequencing, fecal metabolomics, and murine fecal microbiota transplantation (FMT) models.<br><br>RESULTS: A PNI value of &#x2265;46.2 stratified postoperative NSCLC patients with improved 5-y survival (HR&#x2009;=&#x2009;0.3889, 95% CI 0.2840-0.5356, p&#x2009;<&#x2009;0.001). Patients with a high PNI showed enrichment of short-chain fatty acid (SCFA)-producing taxa, such as Akkermansia and Eubacterium hallii, and elevated butyrate/isovalerate levels, correlating with increased infiltration of CD8[+] T cells (Pearson r&#x2009;=&#x2009;0.51, p&#x2009;=&#x2009;0.02). FMT from high-PNI patients reduced lung tumor growth in mice compared with FMT from low-PNI patients (7.2 vs 18 nodules, p&#x2009;=&#x2009;0.01). Oral administration of A. muciniphila or/and E. hallii or butyrate suppressed tumor growth and enhanced CD8[+] tumor-infiltrating lymphocytes (TILs) (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: PNI and its linked gut microbiota&#x2012;SCFA axis are clinically prognostic biomarkers and potential immunomodulatory targets for early-stage NSCLC. Targeting this axis may serve as a promising coadjuvant strategy for NSCLC patients undergoing surgical resection.}, }
@article {pmid41938830, year = {2026}, author = {Wu, T and Xing, H and Wu, T and Xie, X and Ji, L and Wang, W and Zhang, X and Zhang, Y and Jiang, C and Bao, T}, title = {Imbalance of the Brain-Gut-Microbiota Axis in Major Depressive Disorder: From Pathogenesis to Clinical Translation.}, journal = {Neuropsychiatric disease and treatment}, volume = {22}, number = {}, pages = {591429}, pmid = {41938830}, issn = {1176-6328}, abstract = {Major depressive disorder (MDD) is one of the most common psychiatric conditions, characterized by complex pathogenesis and marked inter-individual variability in treatment response, leading to persistent impairment of physical and mental health as well as social functioning. In recent years, the brain-gut-microbiota axis (BGMA) has emerged as a key biological pathway linking the gut microbiota with the central nervous system, and its role in MDD has become a major research focus. Although substantial progress has been made in elucidating the association between MDD and the BGMA, the precise mechanisms, critical pathways, and their integrated clinical applications remain to be fully clarified. On the basis of a comprehensive overview of the physiological functions, structural components, and disease associations of the BGMA, this review systematically summarizes the bidirectional interactions between MDD and the BGMA. Integrating the latest findings from preclinical and clinical studies, we further dissect the key regulatory pathways of this axis in MDD and highlight the therapeutic potential of BGMA-based interventions, including pharmacotherapy, fecal microbiota transplantation, dietary modulation, and physical therapies. This work aims to provide a theoretical foundation for developing novel treatment strategies for patients with MDD and for improving their prognosis and quality of life.}, }
@article {pmid41939435, year = {2026}, author = {Yan, D and Li, Q and Wang, M and Nie, Y and Sun, X and Na, L and Wang, H}, title = {Platelet-Rich Plasma Attenuates Knee Osteoarthritis in Rats via Modulation of Gut Microbiota.}, journal = {Drug design, development and therapy}, volume = {20}, number = {}, pages = {574392}, pmid = {41939435}, issn = {1177-8881}, mesh = {Animals ; *Platelet-Rich Plasma ; Rats ; *Osteoarthritis, Knee/therapy/drug therapy/pathology ; Male ; *Gastrointestinal Microbiome/drug effects ; Rats, Sprague-Dawley ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Injections, Intra-Articular ; }, abstract = {BACKGROUND: Platelet-rich plasma (PRP), a platelet and plasma concentrate extracted from whole blood via centrifugation, has multiple bioactive properties. However, its role in the progression of knee osteoarthritis (KOA) and the underlying mechanisms of action remain unclear. In this study, we investigated the therapeutic effects of PRP extracted from rat whole blood on the progression of KOA and assessed whether its mechanism involves modulation of the gut microbiota (GM).<br><br>METHODS: Knee osteoarthritis (KOA) rat models were established by intra-articular injection of 1 mg of sodium monoiodoacetate (MIA) into the knee joints. The rats were administered intra-articular injections of 60&#xa0;&#x3bc;L of PRP on days 15, 17, and 19 post-modeling. Moreover, we established pseudo-germ-free (pGF) KOA rat models and performed fecal microbiota transplantation (FMT) experiments to investigate whether the GM mediates the therapeutic effects of PRP on KOA. Therapeutic efficacy was assessed by conducting gait analysis, joint swelling measurement, and micro-CT scanning. The pathological changes were evaluated via Safranin O-Fast Green and hematoxylin-eosin (HE) staining, as well as immunohistochemistry (IHC). The alterations in the GM were evaluated by 16S rRNA gene sequencing.<br><br>RESULTS: We found that PRP effectively improved abnormal gait patterns, reduced inflammation levels, alleviated subchondral bone loss, repaired the damaged articular surface, and mitigated cartilage destruction in KOA rats. Concurrently, PRP intervention restored intestinal barrier function and positively modulated the dysregulated composition of the GM. The pGF condition reversed the improvements induced by PRP in KOA rats, whereas transplanting GM from PRP-treated KOA rats to recipient KOA rats promoted recovery in the latter.<br><br>CONCLUSION: This study demonstrated that PRP ameliorates KOA progression, at least partially, by modulating GM diversity (notably Ligilactobacillus murinus), enhancing intestinal barrier integrity, and reducing systemic inflammation.}, }
@article {pmid41939708, year = {2026}, author = {Luo, X and Feng, J and Sun, Y and Tan, Z and Wang, L and Bao, Y and Lu, J and He, J and Lu, B}, title = {Synergistic effects of fecal microbiota transplantation and andrographolide on gut microbiota modulation in dextran sulfate sodium-induced colitis in mice.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1762107}, pmid = {41939708}, issn = {1664-302X}, abstract = {BACKGROUND: Andrographolide (Andro) and fecal microbiota transplantation (FMT) are emerging treatments for colitis. However, whether their combined administration provides superior efficacy has not been established.<br><br>METHODS: This study attempted to clarify the reparative effects of FMT, Andro, and their combination on colitis in mice. Research subjects were allocated to: (1) the Control (CTRL) group, (2) the dextran sulfate sodium (DSS) group, (3) the FMT group, (4) the Andro group, and (5) the Andro combined with FMT group. The experiment lasted 15&#x202f;days, during which weight, colon length, and hematochezia were monitored. Colon tissues were histologically analyzed via HE staining to assess inflammatory infiltration. The concentrations of key serum inflammatory factors were measured using ELISA. WB and IHC were employed to quantify inflammatory factor levels in intestinal tissues. Finally, the taxonomic composition of colonic microbiota was examined with 16S rRNA gene sequencing.<br><br>RESULTS: All three treatments mitigated colitis, as indicated by lowered pathological body weight wasting, colon shortening, hematochezia, and inflammation. Serum and intestinal cytokine levels were significantly decreased following treatment. Mechanistic analysis indicated that Andro attenuated inflammatory responses primarily through inhibition of NF-&#x3ba;B. Moreover, 16S rRNA sequencing revealed a beneficial modulation of the gut microbiota by all three treatments compared with the DSS group. Integrated analysis demonstrated that Andro combined with FMT therapy produced superior therapeutic outcomes relative to either intervention alone.<br><br>CONCLUSION: The combined administration of Andro and FMT provides enhanced protection against DSS-induced colitis in mice, highlighting a potential synergistic therapeutic strategy.}, }
@article {pmid41939897, year = {2026}, author = {Sun, X and Bai, X}, title = {Immune dysregulation in pediatric tic disorders: mechanisms, biomarkers, and therapeutic frontiers.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1708940}, pmid = {41939897}, issn = {1664-3224}, mesh = {Humans ; Biomarkers ; *Tic Disorders/immunology/therapy/etiology/diagnosis ; Child ; Animals ; Autoimmune Diseases/immunology/therapy ; Streptococcal Infections/immunology ; Gastrointestinal Microbiome/immunology ; Autoantibodies/immunology ; Cytokines/metabolism ; Obsessive-Compulsive Disorder ; }, abstract = {Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.}, }
@article {pmid41940048, year = {2026}, author = {Okita, A and Watanabe, T and Nakagawa, M and Ogino, K and Hashida, S and Tsukuda, K and Yokoyama, N}, title = {Full-Thickness Skin Transplantation Combined with Negative-Pressure Wound Therapy for a Refractory Peristomal Large Skin Ulcer Caused by Mucocutaneous Separation: A Case Report.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41940048}, issn = {2198-7793}, abstract = {INTRODUCTION: Stomal mucocutaneous separation is a frequent complication of colostomy, which may complicate wound care due to contamination from fecal leakage, resulting in delayed wound healing. In addition, systemic factors may further influence postoperative wound healing. We report successful combination treatment, involving full-thickness skin graft transplantation and negative-pressure wound therapy (NPWT) in a patient with a large peristomal ulcer that developed progressively in the postoperative course following complete circumferential mucocutaneous separation and infection, which occurred after neoadjuvant chemotherapy followed by laparoscopic abdominoperineal resection.<br><br>CASE PRESENTATION: A 75-year-old male, who had been diagnosed with advanced low rectal cancer, received 4 cycles of mFOLFOX6 chemotherapy (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab, followed by laparoscopic abdominoperineal resection with lymph node dissection. Approximately 4 weeks later, partial mucocutaneous separation developed, accompanied by subcutaneous abscess formation. Subsequently, this led to complete circumferential mucocutaneous separation, which evolved into a giant peristomal ulceration with a significant tissue loss. Conservative local wound care, including frequent debridement, was continued, and granulation tissue gradually filled the peristomal skin defect. Three months after the operation, full-thickness skin graft transplantation combined with NPWT was performed. At 6 years after the operation, the patient remained recurrence-free, and there were no postoperative complications or issues with the colostomy or skin graft.<br><br>CONCLUSIONS: This combination therapy successfully treated a giant peristomal ulcer that progressively developed after mucocutaneous separation with infection, which occurred later than typical postoperative wound complications following neoadjuvant chemotherapy (mFOLFOX6 + bevacizumab) and laparoscopic surgery. Delayed wound healing, potentially related to bevacizumab, may have contributed to both the late onset and unusually extensive progression of the ulcer. The therapy proved compatible with long-term stoma care.}, }
@article {pmid41940919, year = {2026}, author = {Lapauw, L and Vermeiren, L and Vercauteren, L and Amini, N and Peeters, L and Dalle, S and Koppo, K and Derrien, M and Dupont, J and Raes, J and Gielen, E}, title = {An exploratory multi-biomarker panel including fecal calprotectin, Brain-Derived Neurotrophic Factor, Fibroblast-Growth Factor-21 and irisin shows poor diagnostic accuracy for detecting probable sarcopenia in community-dwelling older persons.}, journal = {Aging clinical and experimental research}, volume = {38}, number = {1}, pages = {}, pmid = {41940919}, issn = {1720-8319}, support = {G099721N//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {BACKGROUNDS: Serum and fecal biological markers that reflect underlying drivers of sarcopenia, may aid in novel predictive or diagnostic tools for sarcopenia. AIMS: To explore the potential of five specific myokines and fecal calprotectin (fCPT) as biomarkers for diagnosing the presence of at least probable sarcopenia in community-dwelling individuals aged ≥ 65 years. METHODS: This cross-sectional, exploratory study included 156 participants (median age 73y), of whom 59 (20♂, 39♀) had at least probable sarcopenia per EWGSOP2 criteria, and 97 (33♂, 64♀) controls. Myostatin, irisin, Brain-Derived Neurotrophic Factor (BDNF), Insulin-like Growth Factor-1 (IGF-1), Fibroblast Growth Factor-21 (FGF-21), and fCPT were measured using Enzyme-Linked ImmunoSorbent Assay (ELISA). Muscle mass and function were assessed via appendicular lean mass (ALM), hand grip strength (HGS), 5-time chair stand test (CST), gait speed, and the Short Physical Performance Battery (SPPB). Linear and logistic regressions analyses were performed. Diagnostic accuracy was evaluated using Area’s Under the Curve (AUC). RESULTS: Participants with fCPT < 50 µg/g walked faster than those with fCPT ≥ 200 µg/g. Higher fCPT associated with slower gait speed (β: -0.003; 95% CI [-0.001; -0.00002]), while IGF-1 associated with higher HGS (β: 0.077; 95% CI [0.039; 0.116]). BDNF alone diagnosed at least having probable sarcopenia (AUC: 0.63; sensitivity 53%, specificity 71%). A multi-biomarker panel comprising BDNF, irisin, FGF-21 and fCPT modestly improved accuracy (AUC: 0.71; sensitivity 64%, specificity 77%), but this improvement was not statistically significant compared with the single biomarkers BDNF (p = 0.330) and fCPT (p = 0.180). DISCUSSION: The multi-biomarker panel significantly diagnosed at least having probable sarcopenia, but with high false negative (36%) and positive (23%) rates, respectively. CONCLUSION: The clinical relevance of this specific multi-biomarker panel may be limited due to moderate diagnostic accuracy. Validation in larger cohorts is needed.}, }
@article {pmid41942347, year = {2026}, author = {Joshi, M and Sharma, S and Thakur, B and Kaur, S and Mouafo, HT}, title = {Combatting multidrug resistance in Klebsiella pneumoniae: mechanisms, global trends, and innovative therapeutic strategies.}, journal = {Future microbiology}, volume = {21}, number = {3}, pages = {329-348}, pmid = {41942347}, issn = {1746-0921}, mesh = {Humans ; *Drug Resistance, Multiple, Bacterial/genetics ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Klebsiella pneumoniae/drug effects/genetics/pathogenicity ; *Klebsiella Infections/microbiology/epidemiology/drug therapy/therapy ; Cross Infection/microbiology/epidemiology ; beta-Lactamases/metabolism/genetics ; Virulence ; }, abstract = {Emergence of drug-resistant bacterial infections, particularly those caused by Klebsiella pneumoniae, represents a growing public health issue. K. pneumoniae is the leading cause of nosocomial infections, associated with diverse diseases and high mortality rates. Its ability to develop multiple resistance mechanisms, including biofilm formation, efflux pump activity, β-lactamase production, enzymatic modification, and porin loss, contributes to its resistance to conventional antibiotics. These challenges urge the ned for novel therapeutics and alternative therapies. While resistance rates remain lower in developed countries, regions in Africa, South Asia, and Middle East report rates exceeding 80%, often due to antibiotic misuse and inadequate regulations. Particularly concerning are novel hypervirulent carbapenem-resistant strains linked to bloodstream infections and high mortality, especially in low- and middle-income countries. Emerging approaches, including fecal microbiota transplantation, might help gut dysbiosis and enhance host immunity against carbapenemase-producing Enterobacterales. Additionally, molecular studies identified cytoplasmic response regulators that promote resistance gene expression and plasmid-mediated transfer, offering prospective therapeutic targets. This review summarizes current knowledge regarding the genetic, molecular, and epidemiological mechanisms of multidrug resistance and virulence in K. pneumoniae, and discusses emerging therapeutic strategies including new β-lactamase inhibitors, bacteriophage and host-directed therapies, in silico therapeutic strategies, and vaccine development.}, }
@article {pmid41943291, year = {2026}, author = {Yin, W and Yan, Z and Wang, Z and Zhou, Z}, title = {Structural characterization of a polysaccharide isolated from Allium macrostemon Bunge bulbus and its mechanism in ameliorating DSS-induced ulcerative colitis in mice.}, journal = {Carbohydrate polymers}, volume = {381}, number = {}, pages = {125174}, doi = {10.1016/j.carbpol.2026.125174}, pmid = {41943291}, issn = {1879-1344}, mesh = {Animals ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism/microbiology ; *Polysaccharides/chemistry/pharmacology/isolation &amp; purification/therapeutic use ; Mice ; Dextran Sulfate ; Gastrointestinal Microbiome/drug effects ; Male ; *Allium/chemistry ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Colon/drug effects/metabolism ; Mice, Inbred C57BL ; Chive ; }, abstract = {A polysaccharide (AMP) was isolated and purified from the bulbus of Allium macrostemon Bunge (AMB) and structurally characterized. AMP, with the weight-average molecular weight of 9.007 kDa, is a branched polysaccharide with a main chain composed of →1)-β-D-Fruf-(2→ and →1,6)-β-D-Fruf-(2→ linkages, with short side chains formed by β-D-Fruf-(2 → 6)-β-D-Fruf-(2→. AMP administration effectively mitigated DSS-induced ulcerative colitis (UC) in mice by reinforcing the integrity of the intestinal barrier, balancing gut microbiota, replenishing short-chain fatty acids (SCFAs) levels, and restoring normal metabolic activity in the colon. AMP treatment decreased the harmful bacterial, including Bacteroides, Escherichia-Shigella, Parabacteroides, and the Clostridia vadinBB60 cluster, while increasing beneficial SCFAs-producing such as Ruminococcus and the Christensenellaceae R-7 group. Fecal microbiota transplantation experiments further demonstrated that AMP exerted its anti-colitis effect through a microbiota-dependent manner. In addition, in vitro fermentation experiment showed that AMP can be translated to SCFAs by gut microbiota. Meanwhile, AMP regulated metabolic pathways such as the glycerophospholipid, arachidonic acid, and linoleic acid metabolism in colon tissue. The acute toxicity test showed AMP possesses a wide safety margin. Collectively, our data highlight AMP as a promising functional food component for the prevention of UC, and provide a scientific basis for developing AMP-derived bioactive products.}, }
@article {pmid41943367, year = {2026}, author = {Gao, X and Huang, H and Hu, L and Ding, W and Hou, Z and Xu, R and Du, G and Kang, Z}, title = {High-molecular weight hyaluronic acid protects against colitis by remodeling microbiota and restoring barrier function.}, journal = {Carbohydrate polymers}, volume = {381}, number = {}, pages = {125145}, doi = {10.1016/j.carbpol.2026.125145}, pmid = {41943367}, issn = {1879-1344}, mesh = {Animals ; *Hyaluronic Acid/pharmacology/chemistry/therapeutic use ; Molecular Weight ; Intestinal Barrier Function/drug effects ; Dextran Sulfate ; *Colitis/chemically induced/drug therapy/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; Male ; *Colitis, Ulcerative/drug therapy/chemically induced ; Mice, Inbred C57BL ; Colon/drug effects/pathology ; }, abstract = {Hyaluronic acid (HA) is a promising therapeutic candidate for ulcerative colitis (UC), yet how its molecular weight (Mw) governs efficacy and the associated microbiota-linked mechanisms remain insufficiently defined. Here, we systematically evaluated biotechnologically produced HA with distinct Mws (LHA, 2 kDa; MHA, 300 kDa; HHA, 3000 kDa) in a dextran sulfate sodium (DSS)-induced murine colitis model. A Mw-associated protective trend was observed, with HHA showing the most consistent beneficial profile in alleviating clinical manifestations, preserving colonic architecture, and restoring epithelial barrier integrity (Occludin, ZO-1, and mucin). Mechanistically, HHA attenuated systemic inflammation (TNF-α, IL-1β, and LPS) and was associated with modulation of the NF-κB/PPARγ signaling axis. Integrated 16S rRNA sequencing and untargeted metabolomics further revealed that HHA reshaped the gut ecosystem by enriching beneficial genera, including Bifidobacterium and Lactobacillus, and promoted metabolic homeostasis, characterized by increased vitamin B6-related metabolites (pyridoxal) and fatty acids, together with reduced purine metabolism. Molecular dynamics simulations suggested a putative interaction in which microbiota-associated pyridoxal may bind TNF-α, providing a structural hypothesis for the observed attenuation of inflammatory signaling. Moreover, fecal microbiota transplantation (FMT) demonstrated that the HHA-conditioned microbiota was sufficient to confer protection against DSS colitis. Collectively, these findings identify HHA as a bioactive polymer that ameliorates colitis via a coordinated microbiota-metabolism-immunity axis.}, }
@article {pmid41944837, year = {2026}, author = {Weirauch, T and Vehreschild, MJGT}, title = {[Modulation of the gut microbiome for the eradication of multidrug-resistant pathogens: current approaches and perspectives].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {69}, number = {5}, pages = {590-596}, pmid = {41944837}, issn = {1437-1588}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Anti-Bacterial Agents/therapeutic use/administration &amp; dosage ; *Drug Resistance, Multiple, Bacterial ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/therapeutic use ; Evidence-Based Medicine ; *Bacterial Infections/microbiology/therapy ; Treatment Outcome ; *Cross Infection/microbiology/prevention &amp; control ; }, abstract = {The global rise in antibiotic resistance represents one of the greatest threats facing modern medicine. Colonization of the gastrointestinal tract with multidrug-resistant organisms is considered a critical risk factor for nosocomial infections across various patient populations. In this context, targeted decolonization strategies are moving into the focus of clinical research. For a long time, non-absorbable antibiotics were considered a promising approach for local eradication; however, the evidence generated on this question does not suggest sufficient clinical efficacy of this approach. Alternative strategies, such as fecal microbiota transplantation, have shown encouraging results in case reports and small-scale studies for the decolonization of multidrug-resistant organisms. Live biotherapeutic products and certain probiotics are also being explored as potential options for microbiome modulation and reduction of antimicrobial resistance. However, the current evidence base remains heterogeneous, and robust randomized controlled trials are largely lacking. This article aims to provide an overview on the current understanding of gastrointestinal colonization with multidrug-resistant organisms and to discuss the clinical relevance of non-absorbable antibiotics as well as the potential role of microbiome-based therapies in the context of the global antibiotic resistance crisis.}, }
@article {pmid41945234, year = {2026}, author = {Huang, B and An, H and Qiu, Y and Ye, T and Huang, Y and Zheng, M and Shi, D and Su, Y and Wang, R}, title = {Comparative Effectiveness and Safety of Fecal Microbiota Transplantation in Ulcerative Colitis: An Updated Systematic Review and Meta-Analysis.}, journal = {Advances in therapy}, volume = {43}, number = {6}, pages = {2645-2667}, pmid = {41945234}, issn = {1865-8652}, support = {82204925//National Natural Science Foundation of China/ ; 82474290//National Natural Science Foundation of China/ ; CACM-2024-QNRC2-B39//Young Talent Supporting Program of the China Association of Chinese Medicine (CACM)/ ; X2024004//Financial Project of Fujian Province/ ; 2024J01782//Natural Science Foundation of Fujian Province, China/ ; 2025QNGGA002//Fujian Provincial Science and Technology Project in Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Colitis, Ulcerative/therapy ; Randomized Controlled Trials as Topic ; Enema ; Remission Induction ; Treatment Outcome ; Colonoscopy ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is a potential therapy for ulcerative colitis (UC). Evidence has expanded, but the impact of delivery route on efficacy and safety remains uncertain.<br><br>METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science and China National Knowledge Infrastructure (CNKI) from inception to October 2025 for randomized controlled trials (RCTs) comparing donor-derived FMT with placebo/sham or autologous FMT in patients with UC. Primary outcomes were clinical and endoscopic remission at induction (8-12&#xa0;weeks). Adverse events (AEs) were secondary. Random effect models generated risk ratios (RRs) with 95% CIs. Pre-specified subgroup analyses compared delivery routes (colonoscopy, rectal enema, combined colonoscopy&#x2009;+&#x2009;enema, nasoduodenal infusion, oral capsules).<br><br>RESULTS: Sixteen RCTs were included. Overall, FMT improved clinical remission (RR&#x2009;=&#x2009;1.81, 95% CI: 1.41-2.31; I[2]&#x2009;=&#x2009;0%) and endoscopic remission (RR&#x2009;=&#x2009;1.74, 95% CI: 1.00-3.01; I[2]&#x2009;=&#x2009;45.5%). By route, significant effects were seen for colonoscopy (RR&#x2009;=&#x2009;1.58, 95% CI 1.05-2.37), rectal enema (RR&#x2009;=&#x2009;1.62, 95% CI 1.04-2.54) and combined colonoscopy&#x2009;+&#x2009;enema (RR&#x2009;=&#x2009;2.39, 95% CI 1.47-3.89) for clinical remission; nasoduodenal and oral capsule results were imprecise. For endoscopic remission, the combined route showed the most consistent benefit (RR&#x2009;=&#x2009;2.19, 95% CI 1.04-4.62). AEs did not differ from control (RR&#x2009;=&#x2009;1.03, 95% CI 0.90-1.18; I[2]&#x2009;=&#x2009;11.2%).<br><br>CONCLUSIONS: FMT improves induction-phase clinical and endoscopic remission in patients with UC without increasing AEs. Efficacy appears route-dependent, with colonoscopy&#x2009;+&#x2009;enema demonstrating the largest effect. Head-to-head trials optimizing route and dosing with longer follow-up are warranted.}, }
@article {pmid41945453, year = {2026}, author = {Kraeuter, AK and Sarnyai, Z}, title = {Ketogenic diet-derived faecal microbiota transplantation improved sensorimotor gating deficits in an acute NMDA-receptor antagonist model of schizophrenia in mice.}, journal = {Food &amp; function}, volume = {17}, number = {8}, pages = {3529-3536}, doi = {10.1039/d6fo00213g}, pmid = {41945453}, issn = {2042-650X}, mesh = {Animals ; *Schizophrenia/therapy/chemically induced/physiopathology/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Sensory Gating ; *Receptors, N-Methyl-D-Aspartate/antagonists &amp; inhibitors ; *Diet, Ketogenic ; Disease Models, Animal ; Dizocilpine Maleate ; Gastrointestinal Microbiome ; Feces/microbiology ; }, abstract = {Ketogenic diets (KDs) show promise as a novel treatment for schizophrenia, although its mechanisms of action are still unclear. KDs have been shown to modify the gut microbiota and may exert some of their brain-directed effects through that. We hypothesised that KD-induced changes in the gut microbiota mediate some of the therapeutic effects of KDs in a preclinical model of schizophrenia. To test this hypothesis, we transplanted the gut microbiota through faecal matter obtained from mice maintained on a KD to standard diet-fed mice (faecal microbiota transplantation; FMT) and assessed its effect on a translationally validated endophenotype of psychotic disorders, the sensorimotor gating deficit induced by the NMDA-receptor antagonist MK-801, in mice. Faecal samples were collected from male C57BL/6 mice fed a KD for 4 months and prepared into a liquid for inoculation. Ten-week-old male C57BL/6 mice maintained on a standard diet (SD) received 3 inoculations every second day. One week after the last inoculation, animals received 0.2 mg kg[-1] MK-801 (dizocilpine) to induce a schizophrenia-like sensorimotor gating deficit as measured by the pre-pulse inhibition (PPI) of startle. MK-801 reduced PPI, which was attenuated by the faecal microbial transplant derived from mice fed with a KD. We showed for the first time that FMT through inoculation with KD faeces improved a highly translatable behavioural endophenotype of schizophrenia. Our novel findings confirm that some of the beneficial effects of KDs in schizophrenia are mediated by the gut microbiota.}, }
@article {pmid41945864, year = {2026}, author = {Jing, S and Lan, X and Liu, Y and Wang, J and Wang, Y and Guo, N}, title = {Rhodotorula dairenensis Affords Protection against Zearalenone-Induced Enterohepatic Toxicity by Regulating Gut Microbiota-Bile Acid-FXR Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {15}, pages = {12364-12383}, doi = {10.1021/acs.jafc.5c15173}, pmid = {41945864}, issn = {1520-5118}, mesh = {Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Zearalenone/toxicity/metabolism ; Mice ; Receptor, Farnesoid X-Activated ; Signal Transduction/drug effects ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Rhodotorula/metabolism ; *Bile Acids and Salts/metabolism ; Male ; Liver/metabolism/drug effects ; Mice, Inbred C57BL ; Bacteria/isolation &amp; purification/classification/genetics/metabolism ; Intestines/microbiology/drug effects ; Probiotics/administration &amp; dosage ; }, abstract = {Zearalenone (ZEN), a common mycotoxin contaminating crops, poses a threat to animal and human health, making efficient prevention and detoxification critical. A previous study from our group identified that Rhodotorula dairenensis ZDY342B (342B) removes ZEN via adsorption and degradation in vitro, but its in vivo protective effect and mechanism remain unclear. Using a mouse model, gavage with 342B and ZEN showed that 342B reduced ZEN accumulation in various organs, regulated gut microbiota composition and bile acid metabolism, and alleviated ZEN-induced intestinal barrier damage and hepatic inflammation. Antibiotic pretreatment and fecal microbiota transplantation confirmed gut microbiota-mediated 342B's protection, and 342B reduced ZEN's enterohepatic circulation. Inhibiting intestinal farnesoid X receptor (FXR) weakened 342B's protective effect, indicating FXR is the key target. In summary, 342B alleviates ZEN-induced intestinal and hepatic damage by regulating intestinal FXR signaling via the intestinal microbiota, providing a new approach for probiotic-based mycotoxin control.}, }
@article {pmid41946028, year = {2026}, author = {Niu, L and Tan, Y and Cao, W and Wang, E and Qi, F}, title = {Lactobacillus casei serves as a primary functional strain in fecal microbiota-mediated neuroprotection against cerebral ischemia/reperfusion injury.}, journal = {Pathology, research and practice}, volume = {282}, number = {}, pages = {156441}, doi = {10.1016/j.prp.2026.156441}, pmid = {41946028}, issn = {1618-0631}, mesh = {Animals ; *Lacticaseibacillus casei/physiology ; *Reperfusion Injury/microbiology/pathology/prevention &amp; control ; Mice ; Male ; *Brain Ischemia/microbiology/pathology ; *Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; *Neuroprotection/physiology ; *Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; }, abstract = {OBJECTIVE: Cerebral ischemia/reperfusion (I/R) injury leads to neurological impairment, neuroinflammation, and neuronal death. Emerging evidence suggests gut microbiota influence neural function. This study explores the function of fecal microbiota transplantation (FMT) in cerebral I/R injury and explores the primary functional microbiota strain.<br><br>METHODS: Mouse models of cerebral I/R injury were generated using middle cerebral artery occlusion and reperfusion. Mice received FMT or L. casei administration, with or without the acetylcholine (ACh) receptor antagonist Benzethonium Chloride (BenC). Neurological function was evaluated using Longa scores, and MWM. Brain injury, neuronal death, and apoptosis were assessed via histological assessments. Neuroinflammation and cholinergic anti-inflammatory pathway (CAIP) activation were examined through ELISA, flow cytometry, immunofluorescence, immunohistochemistry, and western blot analyses. Microbiota composition was determined by 16S rRNA sequencing.<br><br>RESULTS: FMT substantially enhanced neurological function, reduced infarct size, ameliorated neuronal death, and restricted pro-inflammatory cytokine concentration and microglial activation. Lactobacillus casei (L. casei) was identified as the predominant strain enriched by FMT, positively correlating with ACh and &#x3b1;7nAChR levels. Both FMT and L. casei treatments restored serum ACh levels, upregulated &#x3b1;7nAChR expression, and increased anti-inflammatory immune cell infiltration, indicating CAIP activation. However, these neuroprotective effects were diminished by BenC, confirming dependence on cholinergic signaling.<br><br>CONCLUSION: This study suggests that FMT and L. casei attenuates I/R-induced neurological injury by activating the CAIP, suppressing neuroinflammation, and promoting neuronal survival. These findings highlight L. casei as a key microbiota-derived mediator of gut-brain axis-dependent neuroprotection.}, }
@article {pmid41946054, year = {2026}, author = {Tang, S and Peng, Y and Li, Y and Li, Y and Sun, H and Piao, S and Liu, Z and Wu, Y and Hou, Z and Liu, Z and Liu, S and Wang, R}, title = {Congming decoction alleviates Alzheimer's Disease induced by Aβ25-35 in rats via the microbiota-metabolism-inflammation axis, demonstrating its formulation advantages.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {155}, number = {}, pages = {158139}, doi = {10.1016/j.phymed.2026.158139}, pmid = {41946054}, issn = {1618-095X}, mesh = {Animals ; *Alzheimer Disease/drug therapy/chemically induced/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Male ; Rats ; Amyloid beta-Peptides ; *Gastrointestinal Microbiome/drug effects ; Rats, Sprague-Dawley ; Peptide Fragments ; Inflammation/drug therapy/metabolism ; Feces/chemistry ; Brain/drug effects/metabolism/pathology ; Disease Models, Animal ; Chromatography, High Pressure Liquid ; }, abstract = {BACKGROUND: Congming decoction (CMD) is a traditional Chinese herbal formulation traditionally employed for enhancing memory. Despite its historical use, the specific mechanisms and advantages of CMD in the context of Alzheimer's disease (AD) remain inadequately understood.<br><br>PURPOSE: This study seeks to elucidate the therapeutic effects of CMD on AD in rats induced by A&#x3b2;25-35 and to clarify its underlying process through a multi-perspective approach.<br><br>STUDY DESIGN AND METHODS: Cognitive function and pathological alterations were assessed using behavioral tests, hematoxylin and eosin (HE) staining, and immunohistochemistry. Fecal metabolomics analysis, conducted via ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS), was utilized to investigate CMD's impact on metabolic disorders. The structure of the gut microbiota was analyzed through 16S rRNA sequencing. Short-chain fatty acids (SCFAs) and bile acids (BAs) in feces, serum, and brain tissue were quantified using gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-TQ-MS). To establish causal relationships, experiments involving antibiotic-induced microbiota depletion (ABX) and fecal microbiota transplantation (FMT) were performed. Network pharmacology and molecular docking techniques were also employed to identify potential active components and targets. Inflammatory markers were evaluated using enzyme-linked immunosorbent assay (ELISA) kits, immunohistochemistry, and immunofluorescence in brain tissue.<br><br>RESULTS: CMD markedly enhanced learning and memory, mitigated pathological changes in the brain and colon, and reestablished gut microbiota equilibrium. It regulated 45 endogenous metabolites involved in BAs, &#x3b1;-linolenic acid, and linoleic acid metabolism. CMD also modulated the levels of SCFAs and BAs in fecal matter, serum, and brain tissue. Strong correlations were identified among gut microbiota, metabolites, and AD-related indicators. Antibiotic treatment inhibited the neuroprotective benefits of CMD, whereas FMT from CMD-treated donors successfully replicated its therapeutic benefits. Network pharmacology analysis indicated that the active components of CMD might target inflammatory pathways. Additionally, CMD exhibited a significant restorative impact on markers associated with the AKT/NF-&#x3ba;B signaling pathway.<br><br>CONCLUSION: CMD exerts anti-AD effects by modulating the microbiota-gut-brain axis through remodeling gut microbiota, regulating metabolic homeostasis, and reducing brain inflammation. Notably, CMD demonstrated superior efficacy compared to single herbs or herb pairs.}, }
@article {pmid41947174, year = {2026}, author = {Wu, L and Zhang, Y and Zhang, G and Feng, X and Zhu, W and Yang, H and Ji, X and Yin, M and Li, S and Li, Y and Shi, W and Cong, B}, title = {Microbiota-associated metabolite pantothenic acid enhances skeletal muscle contusion repair via epigenetic regulation of macrophage M2 polarization.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41947174}, issn = {1479-5876}, support = {82293651//Major Projects of the National Natural Science Foundation of China/ ; 82130055//Key Projects of the National Natural Science Foundation of China/ ; 253A5601D//Hebei Province Innovation Capability Improvement Project/ ; }, abstract = {BACKGROUND: The quality of skeletal muscle contusion repair hinges on the timely resolution of inflammation and the initiation of regeneration, processes in which M2 macrophage polarization plays a critical role. Nevertheless, the upstream signals that regulate this polarization—particularly specific instructions mediated via the “gut-muscle axis”—remain poorly defined.<br><br>METHODS: The study was conducted as follows. First, intestinal barrier integrity following skeletal muscle contusion was assessed using histochemical staining and molecular assays. To elucidate the role of the gut microbiota in skeletal muscle repair, dysbiosis models and fecal microbiota transplantation (FMT) were established. Key gut microbiota and metabolites were subsequently identified through 16S rDNA sequencing and untargeted metabolomics analysis of fecal and serum samples. Based on these findings, targeted metabolite intervention experiments were conducted to evaluate their effects on the repair process of skeletal muscle contusion. To delineate the role of macrophages in this context, macrophage depletion was achieved via administration of clodronate liposomes. The impact of the key metabolites on macrophage polarization was then tested both in vivo and in vitro and the subsequent effect of polarized macrophages on C2C12 myoblast differentiation was examined in co-culture system. Finally, we explored the underlying epigenetic mechanisms through which the important metabolites regulates macrophage polarization.<br><br>RESULTS: Here, we identify a gut microbiota-dependent pathway that facilitates skeletal muscle injury repair. We observed that gut microbiota dysbiosis following skeletal muscle contusion was accompanied by a marked enrichment of the microbial metabolite pantothenic acid (vitamin B5). Functional assays demonstrated that depletion of the gut microbiota severely compromised muscle repair, whereas exogenous supplementation with pantothenic acid significantly enhanced regeneration and attenuated fibrosis. Mechanistically, pantothenic acid exerted its beneficial effects not by acting directly on myocytes, but through remodeling the immune microenvironment. In cultured macrophages, pantothenic acid elevated intracellular acetyl-CoA levels, promoted histone H3 lysine 27 acetylation (H3K27ac) at the promoter of the M2-associated gene Arg1, and acted synergistically with IL-4 to drive macrophage polarization toward the M2 phenotype. This epigenetic regulation was validated in vivo by ChIP-qPCR on macrophages sorted from contused muscles of pantothenic acid-treated mice, confirming that the modification occurs within the muscle microenvironment. This shift in macrophage polarization subsequently promoted myoblast differentiation and maturation.<br><br>CONCLUSION: Collectively, our findings delineate a comprehensive mechanism whereby a gut microbiota-associated metabolite, pantothenic acid, epigenetically programs macrophage M2 polarization via a &#x201c;metabolism-epigenetics&#x201d; axis to accelerate skeletal muscle repair. This work provides a novel conceptual framework for therapeutic interventions targeting the gut-muscle axis.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-08087-0.}, }
@article {pmid41947394, year = {2026}, author = {Li, H and Zhao, Y and Luo, Y and Bao, B and Hao, J and Duan, S and Liu, Z}, title = {Goat Milk Fat Globule Membrane Supplementation Ameliorates Alzheimer Disease Cognitive Impairment by Modulating the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {15}, pages = {12054-12068}, doi = {10.1021/acs.jafc.5c11966}, pmid = {41947394}, issn = {1520-5118}, mesh = {Animals ; *Glycolipids/administration &amp; dosage ; *Alzheimer Disease/microbiology/drug therapy/psychology/metabolism ; *Glycoproteins/administration &amp; dosage/metabolism ; *Gastrointestinal Microbiome/drug effects ; Humans ; Lipid Droplets ; Mice ; Male ; Goats ; Dietary Supplements/analysis ; Amyloid beta-Peptides/metabolism ; Bacteria/isolation &amp; purification/classification/genetics ; *Cognitive Dysfunction/drug therapy/microbiology/psychology/metabolism ; Milk/chemistry ; Brain/metabolism/drug effects ; Female ; }, abstract = {Research has found Alzheimer disease (AD) is accompanied by cognitive dysfunction and gut microbiota imbalance. Goat milk fat globule membrane (GMFGM) derived from goat milk, is a membrane primarily composed of proteins and polar lipids that regulates the gut microbiota. However, its role in AD remains unclear. Therefore, we examined the neuroprotective effects of GMFGM in 5xFAD mice. Supplementation with GMFGM (400 mg/kg bw, 8 weeks) improved cognitive performance, reduced brain Aβ deposition, alleviated neuroinflammation, and upregulated neurotrophic factors. Moreover, GMFGM preserved gut barrier integrity, lowered serum LPS levels, and reshaped gut microbiota composition, decreasing Alistipes, Dorea formicigenerans, and Duncaniella dubosii while increasing Stenotrophomonas. Further fecal microbiota transplantation validated the mechanism by which GMFGM ameliorates AD cognitive impairment by modulating the gut microbiota. These results indicate that GMFGM may rescue cognition by modulating the gut microbiota, alleviating gut damage, reducing LPS levels, and consequently inhibiting neuroinflammatory.}, }
@article {pmid41948377, year = {2026}, author = {Wang, L and Sha, YY and Hu, GY and Qian, YM and Guo, J}, title = {Da Yuan Yin Regulates Gut Microbiota and Improves Intestinal Injury in Sepsis.}, journal = {Food science &amp; nutrition}, volume = {14}, number = {4}, pages = {e71456}, pmid = {41948377}, issn = {2048-7177}, abstract = {Sepsis is a common disease, which is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Da Yuan Yin (DYY) is a traditional Chinese medicine that has anti-inflammatory and purgative effects. Sepsis mouse model was conducted by lipopolysaccharide induction to explore the effects of DYY in vivo. Hematoxylin-eosin staining was performed to observe mouse ileum tissue. ELISA and western blot were carried out to measure the levels of inflammatory factors and tight junction proteins. Moreover, proliferation and apoptosis were measured by immunohistochemistry (Ki67) and TUNEL staining. 16S rRNA sequencing was implemented to predict the effects of DYY on gut microbiota in sepsis. Metabolic function was predicted by PICRUSt2 and experimentally validated by measuring short-chain fatty acids (SCFAs) and β-glucuronidase activity. A fecal microbiota transplantation (FMT) experiment was performed to establish causality. In this study, DYY alleviated sepsis-induced intestinal injury. Additionally, DYY inhibited inflammation (TNF-α, IL-1β, and IL-6), cell apoptosis, and promoted proliferation in sepsis, as well as the promotion of tight junction proteins (claudin-1, occludin, and ZO-1). 16S rRNA sequencing revealed that DYY could regulate the alteration in the abundance of gut microbiota in sepsis and promote the growth of bacilli, such as Lactobacillales and Enterobacteriaceae. Functionally, DYY increased protective SCFA levels and suppressed β-glucuronidase activity. Crucially, FMT from DYY-treated donors replicated these protective effects in septic recipients, directly demonstrating the mediatory role of gut microbiota. Collectively, DYY can mitigate intestinal injury and modulates gut microbiota in sepsis; the protective role of DYY on sepsis was mediated through the regulation of gut microbiota, which may be a promising therapeutic strategy for sepsis.}, }
@article {pmid41948520, year = {2026}, author = {Rynikova, M and Bojcukova, V and Demeckova, V}, title = {One therapy, many targets: redefining ulcerative colitis treatment through fecal microbiota transplantation.}, journal = {Therapeutic advances in gastroenterology}, volume = {19}, number = {}, pages = {17562848261437918}, pmid = {41948520}, issn = {1756-283X}, abstract = {Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease driven by a multifactorial interplay between gut microbiota dysbiosis, immune dysregulation, and epithelial barrier dysfunction. Accurate diagnosis and a deeper understanding of UC pathogenesis are essential for developing durable and mechanism-based therapies. Despite major advances, conventional treatments such as immunosuppressants and biologics often fail to achieve sustained remission and carry significant adverse effects, underscoring the need for novel, multi-target interventions. This review synthesizes current insights into UC pathogenesis, diagnostic approaches, and therapeutic strategies, with a particular focus on fecal microbiota transplantation (FMT) as a single therapy acting on multiple disease axes. By restoring microbial equilibrium, FMT can modulate host immunity and reinforce epithelial integrity, collectively promoting mucosal healing. We summarize mechanistic evidence, findings from preclinical and clinical studies, and key variables influencing FMT efficacy, including donor selection, preparation, and delivery routes. While evidence supports the therapeutic promise of FMT, challenges remain regarding standardization, long-term engraftment, and sustained safety. Nonetheless, FMT represents a transformative therapeutic platform that redefines UC treatment by bridging microbial restoration, immune modulation, and barrier repair. Future research should aim to refine FMT protocols and develop next-generation microbiota-based therapeutics, such as defined microbial consortia and live biotherapeutic products, to enable safer, more consistent, and personalized modulation of the gut ecosystem in UC.}, }
@article {pmid41948584, year = {2026}, author = {Yu, J and Liu, X}, title = {Gut microbiota and sepsis: mechanisms, clinical correlations, and therapeutic prospects.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1793041}, pmid = {41948584}, issn = {2296-858X}, abstract = {Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host response to infection. According to the Global Burden of Disease Study, this condition affects over 50 million people annually and causes approximately 5.3 million deaths, with fatality rates varying significantly across populations and healthcare settings, ranging from about 20% to 50%, representing a major challenge in critical care medicine. In recent years, the gut microbiota, as the largest microbial ecosystem in the human body, has increasingly demonstrated a central role. It is not only essential for maintaining intestinal barrier integrity, immune homeostasis, and metabolic balance but also actively participates in the pathogenesis, progression, and outcomes of sepsis through modulating immune responses, influencing the production of key metabolites, and mediating gut-organ axes. This article systematically reviews the characteristics of sepsis-induced gut microbiota dysbiosis, delves into the molecular mechanisms by which dysbiosis drives immune disorders, metabolic disturbances, and multi-organ injury, evaluates the clinical potential and current limitations of microbiome-associated biomarkers, and summarizes recent advances and controversies in microbiota-targeted therapeutic strategies, including probiotics, fecal microbiota transplantation, precision nutrition, and antibiotic stewardship. This review aims to analyze the shortcomings and translational challenges in current research, providing a theoretical basis and forward-looking perspective for developing precise microbiome-based individualized management strategies for sepsis.}, }
@article {pmid41950979, year = {2026}, author = {Khoruts, A and Kuchma, N and Vaughn, BP}, title = {Fecal Microbiota Transplantation Rapidly Reduces Systemic Inflammation and Resolves Clostridioides difficile Pseudomembranous Colitis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2026.03.023}, pmid = {41950979}, issn = {1542-7714}, }
@article {pmid41951277, year = {2026}, author = {Bajer, L and Polakovicova, P and Heczkova, M and Holm, K and Hole, MJ and Hlavaty, M and Bohdanecka, A and Drastich, P and Tichanek, F and Meyer-Myklestad, MH and Medhus, AW and Reikvam, DH and Jørgensen, KK and Brezina, J and Macinga, P and Wohl, P and Fabian, O and Hov, JR and Cahova, M}, title = {Geography-independent mucosal microbiota alterations in primary sclerosing cholangitis persist after liver transplantation.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {4}, pages = {101716}, pmid = {41951277}, issn = {2589-5559}, abstract = {BACKGROUND &amp; AIMS: Primary sclerosing cholangitis (PSC)-associated alterations of fecal gut microbiota have already been described, but data on the mucosal microbiota are still limited. We aimed to further define disease-specific mucosal microbial patterns independent of geography and assess the relationship to liver transplantation (LTx), gut inflammation (inflammatory bowel disease), and PSC recurrence (rPSC).<br><br>METHODS: We performed 16S ribosomal RNA gene (V3-V4) sequencing of ileocolonic biopsies from 115 patients with PSC (pre-LTx), 159 liver-transplanted patients (post_LTx, recurrence occurred in 38), and 96 healthy controls (HC) from Norway and the Czech Republic.<br><br>RESULTS: Alpha diversity was lower in all PSC groups compared with HC. Elastic net models discriminated pre_LTx (AUC ileum 0.97; colon 0.93; p <0.001) and post_LTx PSC patients (AUC ileum 0.97; colon 0.97; p <0.001) from HC, and distinguished pre_LTx from post_LTx (AUC ileum 0.83; colon 0.83; p <0.001). The shared, cohort-independent PSC microbiota was dominated by Enterococcus, Pseudomonas, Veillonella, Klebsiella, and Streptococcus, while several common commensals were underrepresented. A microbial dysbiosis index calculated from PSC-associated genera correlated negatively with alpha diversity and serum albumin, while a positive correlation was observed with markers of cholestatic disease (ALP, GGT) and liver fibrosis (APRI). There were no associations with the presence of inflammatory bowel disease or fecal calprotectin. Differences between post-LTx patients with and without recurrence were limited, but several genera deregulated in pre-LTx PSC (Klebsiella, Bilophila, Coprococcus, Odoribacter) showed similar trends in rPSC.<br><br>CONCLUSIONS: Our findings in two European countries revealed a distinct mucosal microbiota composition associated with PSC that persists after LTx. These microbial patterns correlate with the severity of liver injury in PSC but not with markers of intestinal inflammation.<br><br>IMPACT AND IMPLICATIONS: This study provides an extensive evaluation of mucosa-associated microbiota in primary sclerosing cholangitis (PSC) before and after liver transplantation across two European cohorts. The persistence of PSC-related dysbiosis after transplantation highlights the importance of the gut-liver axis in PSC and supports further investigation into microbiota-driven mechanisms. Together with the strong association between microbiota composition and markers of cholestasis and fibrosis, this suggests potential clinical utility as an indicator of disease activity or even as a target for prevention or therapy.}, }
@article {pmid41951653, year = {2026}, author = {He, L and Yuan, D and Li, Q and Zhang, X and Niu, K and Li, X and Ou, Y and Du, H and Yuan, J and Duan, Y and Niu, H}, title = {Fecal virome transplantation attenuates arthritis in mice by remodeling gut ecology, systemic tryptophan metabolism, and innate immune responses.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {}, pmid = {41951653}, issn = {2055-5008}, support = {2024VPPC-S02//the Open Project of the Key Laboratory of Viral Pathogenesis and Infection Prevention and Control (Jinan University), Ministry of Education/ ; 2025A1515012786//the Natural Science Foundation of Guangdong Province/ ; 2022YFF0710702 and 2022YFF0710701//the National Key &amp;D Programs of China/ ; 202201020381//the Guangzhou Joint Fund for Key Laboratory/ ; YXJC2022004//the Medical Joint Fund of Jinan University/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Tryptophan/metabolism ; Mice ; *Immunity, Innate ; RNA, Ribosomal, 16S/genetics ; *Arthritis, Rheumatoid/therapy/immunology ; *Virome ; Disease Models, Animal ; Feces/microbiology/virology ; Cytokines/blood ; Metabolomics ; Bacteria/classification/genetics ; Male ; }, abstract = {Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and systemic immune dysregulation. Emerging evidence suggests that the gut microbiome plays an important role in immune modulation in RA, yet the role of the gut virome remains poorly understood. Here, using the K/BxN serum-transfer arthritis model, we systematically evaluated the potential role of fecal virome transplantation (FVT) in modulating gut ecology and innate inflammatory responses. Arthritic mice exhibited marked alterations in gut virome composition compared with healthy controls. Administration of purified virus-like particles (VLPs) from healthy donors correlated with reductions in paw swelling, histopathological inflammation, bone erosion, circulating proinflammatory cytokines, and myeloid cell infiltration in inflamed tissues. In parallel, 16S rRNA sequencing showed that FVT remodeled the gut bacterial community toward a composition more similar to that of healthy controls. Targeted serum metabolomics revealed increased levels of microbiota-derived tryptophan metabolites, including indole-3-lactic acid and related indole derivatives, suggesting a link between gut microbial remodeling and systemic immunometabolic regulation. Collectively, these findings indicate that FVT may attenuate inflammatory arthritis by remodeling gut microbial ecology, potentially involving virome-bacteriome interactions and immunometabolic pathways.}, }
@article {pmid41951771, year = {2026}, author = {Liu, LM and He, XF and Zhang, YL and Zhou, JT and Miao, H and Zhao, YY}, title = {Gut microbiota and renal fibrosis: novel mechanistic insights and therapeutic potential.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {41951771}, issn = {1745-7254}, abstract = {Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), are associated with changes in the composition and function of gut microbiota. Available evidence has delineated that both AKI and CKD were associated with microbial dysbiosis that led to impairment of the intestinal epithelial cell barrier, decreasing the abundance of beneficial bacteria (Lactobacillus reuteri and Bifidobacterium animalis), and increasing the abundance of pathogenic bacteria (Eggerthella lenta and Fusobacterium nucleatum). This was accompanied by the alteration in microbial-derived metabolites, including reducing short-chain fatty acid production and accumulating uremic toxins, such as indoxyl sulphate, indole-3-acetic acid (IAA), and trimethylamine-N-oxide (TMAO), thereby exacerbating renal inflammation and fibrosis. However, supplementation with probiotics, such as Parabacteroides goldsteinii, Lactobacillus johnsonii, Bacteroides ovatus and Bacteroides fragilis, attenuated renal fibrosis by the regulation of nuclear factor κB, NLR family pyrin domain containing 3 inflammasome, aryl hydrocarbon receptor, sodium-glucose transport 2, farnesoid X receptor, glucagon-like peptide-1 receptor, and nuclear factor erythroid 2-related factor 2 signalling pathways via microbial-derived metabolites, such as IAA, TMAO, indole-3-aldehyde, hyodeoxycholic acid and 1,5-anhydroglucitol. This review elaborates on the microbial dysbiosis-related renal pathogenesis and discusses therapeutic potential and targets of renal fibrosis. Further, targeting modulation of gut microbiota by several cardinal approaches, such as probiotics, natural products (neohesperidin, madecassoside, and polysaccharides), and fecal microbiota transplant, are also highlighted. However, these therapeutic approaches need to be further evaluated by large controlled trials. These findings expand the understanding of microbial dysbiosis-associated underlying molecular mechanisms of renal fibrosis in the host and elucidate a clear pathophysiological rationale for the intervention of renal fibrosis.}, }
@article {pmid41952403, year = {2026}, author = {El-Salhy, M and Corsetti, M and Gilja, OH and Gonlachanvit, S and Hatlebakk, JG and Hoff, DAL and Lahtinen, P and Lunding, JA and Mazzawi, T and Monaghan, TM and Ohlsson, B and Patcharatrakul, T and Kim, YS and Shin, CM}, title = {Towards a Standard Protocol for Fecal Microbiota Transplantation in Irritable Bowel Syndrome.}, journal = {Journal of neurogastroenterology and motility}, volume = {32}, number = {2}, pages = {185-197}, pmid = {41952403}, issn = {2093-0879}, abstract = {Randomized controlled trials (RCTs) of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) have produced outcomes varying from no effect at all to high efficacy and durable effects over time. This review analyzed differences in the protocols used in FMT RCTs for IBS in the recently published literature with the aim of identifying the factors responsible for the success or failure of these RCTs. The results of this analysis might be useful in formulating an effective standard protocol for FMT in IBS. A systematic search was conducted in the PubMed database of the literature published in English from January 2015 to December 2023 using several search phrases comprising MeSH expressions. Those RCTs that carefully selected donors based on environmental factors that are known to affect the gut microbiota positively and ensured bacterial diversity before and during FMT produced successful outcomes. Furthermore, direct freezing of the donor's fecal transplant, storing it at -80°C until the FMT is performed, and then thawing it at 4°C and mixing it manually appear to be factors associated with the success of FMT in IBS. Administering the donor's fecal transplant into the small intestine results in durable effects of FMT and long-term colonization of beneficial bacteria. A standard protocol for FMT with large and durable effects should include (1) careful donor selection, (2) handling the donor's fecal transplant in a way that preserves its microbiota contents, and (3) administering the transplant into the small intestine.}, }
@article {pmid41953022, year = {2026}, author = {Han, W and Li, Q and Yuan, G}, title = {The gut microbiome as an actionable drug-sensitivity modulator for immune checkpoint blockade: clinical evidence for FMT, live biotherapeutics, and defined consortia.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1802676}, pmid = {41953022}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; Animals ; }, abstract = {Immune checkpoint inhibitors (ICIs) deliver durable benefit to only a subset of patients and can be limited by immune-related adverse events (irAEs). The gut microbiome has emerged as an actionable, host-level modulator of ICI drug sensitivity and toxicity. This mini-review links microbial ecology to antigen presentation, T-cell priming and fitness, metabolite signaling, and barrier inflammation, and summarizes interventional evidence across three modalities. Responder-derived fecal microbiota transplantation (FMT) provides the strongest proof-of-concept for re-sensitization in anti-PD-1-refractory melanoma. Microbiome repair can also improve refractory ICI-associated colitis. Early trials of live biotherapeutics and defined consortia support scalability but highlight context dependence and design pitfalls, including antibiotic preconditioning. We discuss practical determinants of reproducibility, including co-medications, diet, engraftment and functional readouts, and conclude with safety, regulatory, and reporting priorities for clinically deployable microbiome engineering.}, }
@article {pmid41953448, year = {2026}, author = {Bautista, J and López-Cortés, A}, title = {Biohacking the human gut microbiome for precision health and therapeutic innovation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1776983}, pmid = {41953448}, issn = {1664-302X}, abstract = {Biohacking, the self-directed application of biotechnology, digital tools, and lifestyle interventions, has rapidly converged with gut microbiome science to create adaptive, individualized, and minimally invasive precision-health paradigms. This narrative review integrates current evidence on diet-based modulation, microbial therapeutics (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation), and synthetic-biology approaches (engineered strains and phage or synthetic consortia) within a multi-omics and continuous-phenotyping framework. Mechanistically, short-chain fatty acids (SCFAs), bile-acid derivatives, and tryptophan catabolites operate as endocrine-like mediators linking gut microbial ecology with host immunity, metabolism, and neuroendocrine signaling. Pathways mediated by microbial metabolites underpin translational applications that span metabolic optimization, through improved insulin sensitivity, reduced adiposity, and attenuation of inflammation, and neurocognitive enhancement via the microbiome-gut-brain axis. Evidence from oncology further indicates that microbial metabolites and engineered taxa remodel stromal and immune niches, shaping therapeutic response and disease progression. Concurrently, emerging digital infrastructures, wearables, biosensors, metabolic avatars, and AI-driven "health twins," enable real-time, closed-loop modulation of host-microbe dynamics. Persistent challenges include methodological heterogeneity, safety concerns regarding live biotherapeutics and unsupervised fecal microbiota transplantation (FMT), fragmented regulation, and vulnerabilities in cyberbiosecurity and data equity. We propose a translational roadmap emphasizing standardized metadata (STORMS), validated reference frameworks, longitudinal multi-omics for causal inference, strain-level safety genomics, and governance integrating ethical and cybersecurity oversight. Under these conditions, microbiome-focused biohacking may evolve from anecdotal experimentation into a more reproducible and scientifically grounded component of preventive and personalized medicine. This manuscript is presented as a narrative and conceptual review, integrating validated microbiome research with emerging biohacking frameworks while explicitly distinguishing evidence-based findings from exploratory or speculative concepts.}, }
@article {pmid41955275, year = {2026}, author = {Santens, P and Bruggeman, A and Laukens, D and Vandenbroucke, RE}, title = {Faecal microbiota transplant for Parkinson's disease.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awag123}, pmid = {41955275}, issn = {1460-2156}, }
@article {pmid41956787, year = {2026}, author = {Ye, JJ and Pan, YL and Wang, J and Lyu, Y}, title = {[Research advances on hepatic encephalopathy following transjugular intrahepatic portosystemic shunt].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {34}, number = {3}, pages = {249-255}, pmid = {41956787}, issn = {1007-3418}, support = {82370619//National Natural Science Foundation of China/ ; XJZT24LY33//Medical Staff Training Promotion Project of Xijing Hospital, Air Force Medical University/ ; }, mesh = {*Hepatic Encephalopathy/etiology/prevention &amp; control ; Humans ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; Hypertension, Portal/surgery ; *Postoperative Complications/prevention &amp; control/etiology ; Risk Factors ; }, abstract = {Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapeutic method for complications of portal hypertension in cirrhosis, but the high incidence rate of postoperative hepatic encephalopathy seriously affects patient prognosis. Current research focuses on the core mechanisms and intervention methods specific to or related to TIPS, clarifying that the risk factors for hepatic encephalopathy are centered on perioperative TIPS parameters (stent diameter, portosystemic venous pressure gradient, spontaneous portosystemic shunt). The pathogenesis is key to shunt-related ammonia metabolism imbalance, hemodynamic abnormalities, and gut-hepatic-brain axis abnormalities. Prevention and treatment strategies revolve around a comprehensive management system of "preoperative risk stratification-intraoperative precise shunt-postoperative targeted intervention," emphasizing TIPS-specific procedures such as stent optimization, spontaneous portosystemic shunt closure, and flow-limiting stents, as well as targeted technologies like fecal microbiota transplantation and artificial intelligence risk prediction, ultimately providing practical evidence for the precise prevention and treatment of hepatic encephalopathy following TIPS.}, }
@article {pmid41957048, year = {2026}, author = {Wang, X and Song, Y and Zhao, W and Liu, Y and Fu, Y and Zhang, Y and Zhao, Q and Miao, M and Zhao, W and Wang, X and Li, Z}, title = {Cinnamaldehyde mitigates MASLD through SIRT1/FOXO1-induced autophagy and synergistic gut microbiota modulation.}, journal = {NPJ science of food}, volume = {10}, number = {1}, pages = {}, pmid = {41957048}, issn = {2396-8370}, support = {ZYYZDXK-2023005//National Administration of Traditional Chinese Medicine Key Discipline Construction Project of High-Level TCM/ ; 82304831//National Natural Science Foundation of China/ ; 242300421090//Henan Science Fund for Excellent Young Scholars/ ; 2023TQ0109, GZB20230196//China Postdoctoral Science Foundation/ ; 232301420077//Associates Fund of Henan Province science and technology research and development program/ ; 2025HYTP092//Young Talent Support Program of Henan Association for Science and Technology/ ; NA (2024)//Central Plains Science and Technology Innovation Young Top Talent Project/ ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health burden with limited therapeutic options. Cinnamomum cassia, a medicinal-food homologous plant, contains principal bioactive cinnamaldehyde (CA), whose anti-MASLD mechanisms require clarification. ‌This study employed both a high-fat diet (HFD)-induced MASLD model and a free fatty acid (FFA)-stimulated cell model. CA administration attenuated intracellular lipid accumulation in vitro and ameliorated both hepatic steatosis and systemic hyperlipidemia in vivo, while inhibiting hepatic lipid peroxidation. Mechanistically, integrated RNA-seq, network pharmacology, siRNA, immunofluorescence, and transmission electron microscopy analyses identified the SIRT1/FOXO1-autophagy axis as CA's key regulatory pathway. Gut microbiome profiling revealed CA's capacity to ameliorate HFD-induced dysbiosis, particularly enriching Lachnospiraceae_NK4A136. Fecal microbiota transplantation (FMT) and Spearman correlations link serum lipids and hepatic injury factors to gut microbiota, indicating partially microbiota-mediated metabolic modulation by CA. Collectively, CA ameliorates MASLD through coordinated autophagy enhancement and microbial homeostasis restoration, holding promise as a functional food ingredient for ‌metabolic liver disease prevention.}, }
@article {pmid41957631, year = {2026}, author = {Cheng, J and Le, S and Wang, D and Liu, P and Liu, C and Shen, D and Wang, D}, title = {Gut microbiota dysfunction mediates stress-exacerbated aortic dissection via the bacteroides vulgatus-outer membrane vesicles-stearic acid-JNK/MAPK axis.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {}, pmid = {41957631}, issn = {1477-3155}, support = {LHGJ20230213//Joint Construction project of Henan Medical Science and Technology/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; Male ; *Aortic Dissection/metabolism/microbiology ; Mice, Inbred C57BL ; *Bacteroides/metabolism ; Disease Models, Animal ; MAP Kinase Signaling System ; Bacterial Outer Membrane/metabolism ; Fecal Microbiota Transplantation ; Myocytes, Smooth Muscle/metabolism ; Dissection, Thoracic Aorta ; Stearic Acids ; }, abstract = {BACKGROUND: Aortic dissection (AD) is a lethal condition involving vascular smooth muscle cell (VSMC) transformation and extracellular matrix degradation. While gut microbiota dysbiosis is implicated in cardiovascular diseases, its role in stress-exacerbated AD pathogenesis is unknown. This study investigates the mechanism linking chronic restraint stress (CRS) to AD progression via gut microbiota modulation.<br><br>METHODS: A &#x3b2;-aminopropionitrile (BAPN)-induced AD mouse model combined with CRS was utilized. Aortic dilation, mortality, and VSMC phenotype shift (assessed via &#x3b1;-SMA/SM22&#x3b1; and OPN/MMP2 expression) were evaluated. Gut microbiota composition was analyzed using 16&#xa0;S rRNA sequencing. Microbiota depletion was achieved via antibiotics, and fecal microbiota transplantation (FMT) from CRS-exposed mice was performed. Serum metabolomics analysis, incorporating liquid chromatography-mass spectrometry (LC-MS), has demonstrated that outer membrane vesicles (OMVs) derived from Bacteroides vulgatus (B. vulgatus) contain high levels of the key metabolite stearic acid (SA). In vitro effects of stearic acid (SA) on AngII-induced JNK phosphorylation in VSMCs were tested, with validation using the JNK agonist anisomycin. Statistical analyses included correlation tests and appropriate comparisons (e.g., t-tests, ANOVA).<br><br>RESULTS: CRS significantly accelerated aortic dilation, increased mortality, and promoted a synthetic VSMC phenotype (decreased &#x3b1;-SMA/SM22&#x3b1;, increased OPN/MMP2) in BAPN-treated mice. 16&#xa0;S sequencing revealed CRS reduced gut microbiota diversity, particularly depleting B. vulgatus, which correlated negatively with AD severity. Antibiotic-mediated microbiota ablation mitigated CRS-aggravated AD, while FMT from CRS mice exacerbated it. Metabolomics identified stearic acid (SA), a metabolite derived from OMVs of B. vulgatus, as negatively correlated with aortic diameter. SA supplementation inhibited VSMC synthetic transformation, reduced AD incidence, and suppressed JNK/MAPK pathway activation in vivo. Mechanistically, SA attenuated AngII-induced JNK phosphorylation in VSMCs in vitro, an effect reversed by the JNK agonist anisomycin.<br><br>CONCLUSIONS: CRS exacerbates the pathogenesis of AD by disrupting the gut microbiota, particularly by reducing the abundance of B. vulgatus and the levels of SA, which is a metabolite encapsulated in the OMVs of B. vulgatus. This leads to unchecked JNK/MAPK signaling, driving detrimental VSMC transformation. Restoration of SA inhibits this pathway and mitigates AD progression. Targeting the gut microbiota-B. vulgatus-SA axis presents a novel therapeutic strategy for stress-aggravated AD.}, }
@article {pmid41959053, year = {2026}, author = {Midani, FS and Lee, DH and Moon, Y and Seale, M and Horvath, TD and Ardis, AK and Cantú, J and Coles, E and Pizzini, JD and Zhu, D and Dooling, SW and Ahern, GJ and Ardis, CK and Beckford, A and Ruggiero, NM and Shin, J and Joos, R and Stanton, C and Ross, RP and Dai, DLY and Mandhane, PJ and Petersen, C and Turvey, SE and Kiely, ME and Murray, DM and Costa-Mattioli, M and Tolias, KF and Britton, RA and Danhof, HA}, title = {Infant gut microbiomes contribute to metabolic states that impact brain function.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41959053}, issn = {2692-8205}, abstract = {Alterations in the gut microbiome are associated with neurodevelopmental disorders, but causal mechanisms and therapeutic strategies remain undefined. Here, we demonstrate that human infant microbiomes isolated during the first six months of life drive behavioral impairments in mice and that microbiota-based interventions restore mice to normal behavior. Early-life microbiomes from twelve infants who later exhibited cognitive deficits at 2 years old (low-scoring) transferred adverse metabolic, brain, and behavioral phenotypes to mice, in contrast to microbiomes from twenty-three cognitively typical or high-scoring infants. Deficits in mice were rescued by fecal microbiota transplant from high-scoring infants or a rationally designed consortium that promoted amino acid levels. We confirmed lower fecal amino acid concentrations in low-scoring infants and replicated the association between early-life microbiome composition and cognitive outcomes in a second geographically independent infant cohort. Altogether, we discovered an early-life microbiome-mediated metabolic state causally linked to cognitive deficits and amenable to microbial intervention.}, }
@article {pmid41959551, year = {2026}, author = {Lv, W and Hu, H and Huang, Y and Yang, J and Li, Y and He, J and Wang, K and Liu, Y and Wang, Q}, title = {Microbial mechanisms and therapeutic interventions in the periodontitis-inflammatory bowel disease axis: a comprehensive review.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2656084}, pmid = {41959551}, issn = {2000-2297}, abstract = {BACKGROUND: Periodontitis and inflammatory bowel disease (IBD) are chronic inflammatory conditions of the oral and gastrointestinal tracts that exhibit bidirectional microbial and immunological crosstalk.<br><br>OBJECTIVE: Aimed at elucidating the bidirectional crosstalk between periodontitis and IBD at both microbiological and immunological levels and evaluate related therapeutic interventions, this review comprehensively summarizes recent evidence on their interaction via the oral-gut-bone axis, focusing on microbial ecology, host responses, and innovative therapies.<br><br>DESIGN: Distinct yet overlapping dysbiotic signatures are observed in both diseases, with periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum capable of translocating to the gut and perturbing intestinal homeostasis, while gut inflammation reciprocally reshapes the oral microbiome. Mechanistic links include a spectrum of convergent pathways: (i) microbial metabolites-short-chain fatty acids, choline metabolites, indole derivatives, polyamines, and bile acids-that modulate barrier integrity and immune responses; (ii) shared immune cells and inflammatory mediators driving mucosal damage at both sites; (iii) bacterial extracellular vesicles (BEVs) and lysine lactylation (Kla)-mediated signaling; and (iv) oxidative stress, iron metabolism dysregulation, and ferroptosis contributing to tissue destruction.<br><br>RESULTS: Therapeutic strategies targeting this axis encompass bidirectional interventions: periodontal and IBD treatments that mutually influence oral and gut health, natural anti-inflammatory and antimicrobial compounds, probiotics and prebiotics, oral and fecal microbiota transplantation, and emerging bacteriophage therapy. Critically, the clinical translation of collaborative dentistry-gastroenterology management is highlighted as a promising avenue for integrated care.<br><br>CONCLUSIONS: By integrating findings across microbial ecology, host response, and therapeutic innovation, this review provides a comprehensive framework for understanding and targeting the periodontitis-IBD axis.}, }
@article {pmid41960434, year = {2026}, author = {Yao, W and Yan, S and Du, R and Zhao, Y and Zhang, H and Wang, B and Cheng, X and Ma, Z and Bao, S and Li, X and Song, Y}, title = {Eucommia polysaccharides alleviate experimental colitis by reshaping colonic microbiota composition, metabolites, and modulating the IL-17 signaling pathway.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1769429}, pmid = {41960434}, issn = {1664-302X}, abstract = {Intake of plant polysaccharides are associated with a reduced risk of ulcerative colitis (UC). Eucommia polysaccharides (EUPs) are promising nutritional supplements with notable antibacterial, anticancer, and anti-inflammatory properties. They exhibit a moderate molecular weight and are resistant to gastric acid degradation. Yet, the action mechanisms of microorganisms and metabolites in EUPs for UC treatment remain incompletely elucidated. The current study was formulated to assess the therapeutic efficacy of EUPs against fecal microbiota transplantation (FMT)-induced colitis, focusing on comparing the effects of low-dose and high-dose EUPs. After East Frisian sheep received dextran sulfate sodium (DSS) intervention, their fecal microbiota was used to prepare fecal bacterial suspensions for mouse FMT. Administration of high-dose EUPs alleviated key colitis symptoms, improved colonic epithelial barrier, preserved microbial diversity, and significantly reduced harmful bacterial (e.g., g_Klebsiella and g_unidentified_Enterobacteriaceae). Furthermore, this treatment significantly enriched the bile secretion pathways, particularly those involving deoxycholic acid (DCA) and hyodeoxycholic acid (HDCA). Additionally, DCA and HDCA were significantly negatively correlated with g_unidentified_Enterobacteriaceae and g_Klebsiella, and these two bile acids were also negatively correlated with key genes associated with the IL-17 signaling pathway. Overall, this study elucidates that EUPs ameliorate FMT-induced colitis in a mouse model via restoring gut microbes and metabolites and modulating the IL-17 pathway, thereby providing novel insights into therapeutic strategies for UC.}, }
@article {pmid41960919, year = {2026}, author = {van Leeuwen, PT and Gadaleta, P and Brul, S and Seppen, J and Wortel, MT}, title = {Environmentally mediated interactions predict community assembly and invasion success in a gut microbiota synthetic community.}, journal = {mSystems}, volume = {11}, number = {5}, pages = {e0011326}, pmid = {41960919}, issn = {2379-5077}, mesh = {*Gastrointestinal Microbiome/physiology ; Coculture Techniques ; Bacteroides/growth &amp; development ; Escherichia coli/growth &amp; development ; Humans ; *Microbial Interactions ; Models, Biological ; }, abstract = {The gut microbiome plays a crucial role in host homeostasis, with implications for nutrition, immune development, metabolism, and protection against pathogens. Disturbance of the microbiome by microbial invasion can be negative or positive: invasions of opportunistic pathogens can cause disease while dysbiotic states need invasions to recover. However, the complexity of the microbiome challenges our understanding of what factors determine the ability of microbes to invade. In this study, we measure interactions between members of a synthetic community of prominent gut bacteria using supernatant assays, which quantify the growth of one species in the cell-free culture medium of another. We measure relative abundances of co-cultures of up to four species to validate a generalized Lotka-Volterra model parameterized with these supernatant assays. We predict differential invasion outcomes of the opportunistic pathogens Escherichia coli and Bacteroides ovatus based on their monoculture growth profiles and interactions with other species, and we experimentally confirm model predictions of invasion success. The predictive value of our model indicates that environmentally mediated interactions, e.g., through soluble chemicals, primarily determine co-culture abundances and invasion success. Furthermore, model analyses show that negative interactions within the resident community and neutral to positive interactions with the invading species promote invasion success, but the interactions toward the invading species dominate. Our validated approach opens the way for testing of interactions of human gut microbiome species, thereby developing interventions to avoid pathogenic overgrowth and therapies to enhance health-benefitting invasions.IMPORTANCEThe stability of the human gut microbiome is crucial for host health, with opportunistic pathogen invasions causing diseases and healthy strain replacements needed for recovery. The microbiota's complexity complicates the understanding of invasion outcomes. This study uses a 10-species synthetic community of common gut microbiota to predict stable communities and invasion success. We grow cells in the growth medium of other species with the cells removed to parameterize a computational model, accurately predicting community composition up to four species and invasion success of Escherichia coli and Bacteroides ovatus. Our findings show that interactions through soluble compounds in the environment dictate co-culture growth and invasions. Furthermore, model analysis shows that interactions within the resident community and toward the invader are both important, but the latter dominate. These results pave the way for larger-scale studies to characterize gut microbiome interactions and properties that resist invasions, potentially benefiting health through improved probiotics and fecal microbiota transplants.}, }
@article {pmid41963962, year = {2026}, author = {Li, Y and Wu, H and Yang, J and Weedor, JG and Ding, H and Cui, W and Cui, B and He, Z and Zhang, W and Xing, Y and Zeng, F and Huang, X and Zheng, K and Shen, Y and Yu, Y and Pan, W and Yang, X}, title = {Clostridium butyricum ameliorates Toxoplasma gondii-induced neuropsychiatric disorders by attenuating glial-mediated synaptic pruning via the gut-brain axis.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {}, pmid = {41963962}, issn = {1742-2094}, support = {Nos. 202310313083Y//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; Nos. X202510313020//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; Nos. X202510313017//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; No. JC20250007//the Faculty Development Grant of Basic Medical Sciences in Xuzhou Medical University/ ; Nos. 82372283//the National Natural Science Foundation of China/ ; No. QL-YB022//the XZHMU-QL Joint Research Fund/ ; No. 2022M710120//China Postdoctoral Science Foundation/ ; }, abstract = {UNLABELLED: Gut microbiota dysbiosis contributes to Toxoplasma gondii (T. gondii)-induced neuropsychiatric disorders (TNDs); however, the underlying mechanisms remain largely elusive. Here, we identified the critical role of butyrate-producing bacteria in TNDs in mice. Decreased abundance of butyrate-producing bacteria was consistently observed in patients with Alzheimer’s disease and T. gondii-infected mice. Dietary supplementation with Clostridium butyricum (C. butyricum), a gut commensal butyrate-producing bacterium, reversed gut microbiota dysbiosis, ameliorated intestinal barrier disruption and inflammation, and reduced endotoxemia. Coincidentally, C. butyricum administration suppressed microglial and astrocytic activation, rescued synaptic ultrastructure damage and synaptic loss, thus alleviating cognitive impairment and anxiety/depression-like behaviors. Mechanistically, C. butyricum treatment mitigated the abnormal synaptic pruning mediated by glial cells and C1q to prevent the neuropathology induced by T. gondii infection. Importantly, fecal microbiota transplantation from C. butyricum-supplemented mice into antibiotic-treated recipients recapitulated the therapeutic effects on gut and brain pathology observed in infected mice. Together, our findings suggest that C. butyricum ameliorates TNDs by modulating glial cell-mediated abnormal synaptic pruning via the gut-brain axis, highlighting the therapeutic potential efficacy of butyrate-producing bacteria against TNDs.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03761-y.}, }
@article {pmid41964110, year = {2026}, author = {Deng, L and Wang, X and Mebratie, DY and Tang, Y and Hu, J and Qi, J and Tian, M and Bao, Y and Zhu, L and Wang, S}, title = {Dietary conjugated linoleic acid enhances resistance to Salmonella infection by promoting PPARγ-mediated metabolic reprogramming and effector function in CD8[+] T cells.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2657625}, pmid = {41964110}, issn = {1949-0984}, mesh = {Animals ; *Linoleic Acids, Conjugated/administration &amp; dosage ; *PPAR gamma/metabolism/genetics/immunology ; *CD8-Positive T-Lymphocytes/immunology/metabolism/drug effects ; Salmonella typhimurium/immunology/physiology ; Mice ; *Salmonella Infections/immunology/microbiology/prevention &amp; control ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects ; Intestinal Mucosa/immunology/microbiology ; Female ; Immunity, Mucosal ; Dietary Supplements ; }, abstract = {Conjugated linoleic acid (CLA) is a dietary lipid that modulates host-microbiota-immune interactions, yet its mechanistic impact on mucosal defense remains unclear. Here, we show that oral CLA supplementation enhances resistance to Salmonella Typhimurium infection and is associated with coordinated changes in gut microbial composition and mucosal immune responses. CLA-enriched commensals, including Dubosiella and Lactobacillus, were associated with increased production of CLA-derived oxylipins and activation of immune surveillance genes. Functionally, CLA pretreatment reduced Salmonella colonization, preserved epithelial integrity, and decreased neutrophilic inflammation without direct antibacterial effects. Single-cell RNA sequencing of ileal intraepithelial lymphocytes revealed that CLA predominantly reprogrammed intestinal CD8[+] T cells toward an oxidative phenotype and enhanced effector activity. ATAC-seq revealed increased chromatin accessibility at loci associated with metabolic regulation, consistent with transcriptional reprogramming toward oxidative fitness. Mechanistically, CLA directly activated PPARγ signaling to promote mitochondrial biogenesis, oxidative phosphorylation, and the production of IFN-γ and granzyme B in CD8[+] T cells; pharmacologic inhibition of PPARγ attenuated these effects both in vitro and in vivo. Notably, depletion of CD8[+] T cells eliminated CLA-mediated protection and abolished early restriction of bacterial dissemination at Peyer's patches and mesenteric lymph nodes. Although CLA enhanced CD8[+] T-cell effector programs, antibiotic depletion and fecal microbiota transplantation experiments demonstrated that an intact gut microbiota is necessary for effective protection in vivo. Together, these findings identify CLA as a dietary modulator that strengthens mucosal resistance to Salmonella by promoting PPARγ-mediated metabolic reprogramming and enhanced effector fitness in intestinal CD8[+] T cells.}, }
@article {pmid41964572, year = {2026}, author = {Li, K and Ran, X and Ding, H and Han, J and Zhang, L and Wang, X and Guo, W and Li, Y and Fu, S and Bi, J}, title = {Lycium Barbarum Polysaccharide Attenuates Staphylococcus aureus-Induced Mastitis via the Gut Microbiota-Derived Indole-3-Propionic Acid/AhR-IL-22-STAT3 Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {15}, pages = {12038-12053}, doi = {10.1021/acs.jafc.5c06224}, pmid = {41964572}, issn = {1520-5118}, mesh = {Animals ; Female ; *Staphylococcus aureus/physiology/drug effects ; *STAT3 Transcription Factor/genetics/immunology/metabolism ; Mice ; *Indoles/metabolism/immunology ; *Mastitis/microbiology/drug therapy/metabolism/genetics/immunology ; *Staphylococcal Infections/microbiology/drug therapy/genetics/metabolism ; *Drugs, Chinese Herbal/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; *Receptors, Aryl Hydrocarbon/genetics/metabolism/immunology ; Interleukin-22 ; Humans ; Signal Transduction/drug effects ; }, abstract = {Mastitis caused by Staphylococcus aureus (S. aureus) is marked by inflammation and disruption of the blood-milk barrier (BMB), posing health risks to humans and animals. We investigated the therapeutic effects of Lycium barbarum polysaccharide (LBP) in lactating mice with S. aureus-induced mastitis. Oral LBP reduced bacterial colonization, inflammatory cytokines, oxidative stress, and BMB damage. 16S rRNA sequencing and fecal microbiota transplantation (FMT) confirmed that protective effects depended on gut microbiota modulation. Metabolomic analysis revealed that LBP promoted microbial tryptophan metabolism, elevating indole-3-propionic acid (IPA). Mechanistically, IPA activated the aryl hydrocarbon receptor (AhR) and upregulated IL-22-STAT3 signaling, thereby enhancing the epithelial integrity and suppressing inflammation. Pharmacological inhibition of AhR or STAT3 abolished these benefits. Collectively, our results demonstrate that LBP mitigates S. aureus-induced mastitis through a microbiota-dependent IPA-AhR-IL-22-STAT3 axis, providing new insights into microbiota-targeted strategies for infection-associated inflammation.}, }
@article {pmid41964647, year = {2026}, author = {Khanna, S and Bloom, PP}, title = {Difficile to treat: advanced management strategies in difficult to treat Clostridioides difficile infections.}, journal = {Expert review of anti-infective therapy}, volume = {24}, number = {4}, pages = {413-424}, doi = {10.1080/14787210.2026.2659725}, pmid = {41964647}, issn = {1744-8336}, mesh = {Humans ; *Anti-Bacterial Agents/administration &amp; dosage ; *Clostridium Infections/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Clostridioides difficile/isolation &amp; purification ; Fidaxomicin/administration &amp; dosage ; Recurrence ; Cross Infection/microbiology/therapy ; Animals ; Diarrhea/microbiology ; Practice Guidelines as Topic ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) remains a leading cause of healthcare-associated infectious diarrhea, with a major burden driven by recurrences and severe or even fulminant disease in vulnerable hosts. The therapeutic landscape has shifted toward fidaxomicin-based antibiotic regimens and microbiota restoration strategies, including standardized microbiota-based products.<br><br>AREAS COVERED: Recent international guidelines, outcome studies, and pivotal trials focused on difficult-to-treat phenotypes such as refractory or fulminant CDI, multiply recurrent CDI, and CDI in high-risk populations (immunocompromised, inflammatory bowel disease, critical illness) were reviewed. A PubMed search was supplemented by hand-searching additional references, guidelines and regulatory documents. Evidence is summarized for optimized antibiotic regimens, bezlotoxumab, conventional fecal microbiota transplantation (FMT), FDA-approved microbiota-based products, and salvage strategies including intracolonic therapy and surgery.<br><br>EXPERT OPINION: Advanced CDI management is moving from repeated antibiotic cycling toward individualized recurrence prevention and microbiota restoration strategies. Implementation requires diagnostic stewardship, early recognition of recurrences, clear pathways for microbiota-based therapy access, and multidisciplinary care for fulminant infection. Over the next five years, standardized microbiota therapeutics and better risk tools should shift care toward earlier, more durable recurrence prevention.}, }
@article {pmid41965671, year = {2026}, author = {Li, Z and Yang, M and Zhang, Y and He, J and Li, J}, title = {Cross-species fecal microbiota transplantation alters the carbohydrate metabolic phenotype: insights from Gansu zokor (Eospalax cansus).}, journal = {BMC veterinary research}, volume = {22}, number = {1}, pages = {}, pmid = {41965671}, issn = {1746-6148}, support = {No. 2024JC-ZDXM-14//Natural Science Basic Research Program of Shaanxi Province/ ; }, abstract = {The Gansu zokor (Eospalax cansus), a subterranean rodent endemic to China, exhibits remarkable adaptability to hypoxic conditions. Although it is known that the gut microbiota of Gansu zokor undergoes changes under hypoxia, thereby influencing carbohydrate metabolism, it remains unclear whether such a hypoxia adaptation mechanism can be simulated in surface-dwelling animals. In this study, we established a cross-species fecal microbiota transplantation model from Gansu zokor to SD rats to investigate carbohydrate metabolic adaptations under hypoxia. Using 16 S rRNA sequencing, we characterized the features of gut microbiota. Furthermore, we examined molecular markers associated with glycolysis and the tricarboxylic acid cycle in the liver and brain of SD rats exposed to prolonged hypoxia. The results demonstrated that fecal microbiota transplantation altered the composition of gut microbiota in SD rats, leading to modifications in carbohydrate metabolic networks in the liver and brain under prolonged hypoxia. This shift rendered their carbohydrate metabolic patterns more similar to those observed in Gansu zokor. In conclusion, this study provides new evidence supporting the role of gut microbiota in hypoxia adaptation in subterranean rodent and offers a valuable animal model reference for the treatment of hypoxia-induced injuries via fecal microbiota transplantation.}, }
@article {pmid41966031, year = {2026}, author = {Wu, J and Yang, Z and Chen, L and Xu, Q and Zhang, Y and Yang, Y and Beloved, M and Zhan, S and Cao, W and Li, Z and Wang, G and Lv, Q and Han, J}, title = {A polysaccharide from Pueraria lobata ameliorates hepatic fibrosis via gut microbiota-dependent suppression of ferroptosis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {155}, number = {}, pages = {158123}, doi = {10.1016/j.phymed.2026.158123}, pmid = {41966031}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Pueraria/chemistry ; *Polysaccharides/pharmacology/chemistry ; Mice ; *Liver Cirrhosis/drug therapy/chemically induced ; Male ; *Ferroptosis/drug effects ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism ; Carbon Tetrachloride ; Liver/drug effects/pathology ; Humans ; Disease Models, Animal ; }, abstract = {BACKGROUND: Hepatic fibrosis, driven by oxidative stress and subsequent hepatocellular injury, represents a major worldwide health challenge. Pueraria lobata Radix, a traditional Chinese herb, contains polysaccharides with demonstrated hepatoprotective properties, though their mechanisms remain incompletely defined.<br><br>PURPOSE: This study aims to characterize the structure of P. lobata polysaccharide (PLP2) and to decipher its protective mechanisms against hepatic fibrosis.<br><br>METHODS: PLP2, a homogeneous, water-soluble polysaccharide, was purified from P. lobata and structurally characterized. Subsequently, the hepatoprotective activity of PLP2 was investigated in a CCl&#x2084;-induced murine model of hepatic fibrosis.<br><br>RESULTS: Structural analysis indicated that PLP2 (Mw = 142.9 kDa) was mainly composed of (1&#x2192;4)-&#x3b1;-D-Glc and (1&#x2192;4)-&#x3b1;-D-GalA units, with a minor presence of &#x2192;4,6)-&#x3b1;-D-Glc-(1&#x2192; residues. In a CCl&#x2084;-induced murine model of hepatic fibrosis, PLP2 treatment effectively ameliorated liver injury, histopathological damage, and inflammatory responses. Mechanistically, PLP2 treatment restored mitochondrial ultrastructure and hepatic ATP levels, thereby suppressing hepatic ferroptosis through the activation of the Nrf2/HO-1/GPX4 axis. The indispensable role of Nrf2 was further validated using the inhibitor ML385, which abolished PLP2's protection. Notably, the hepatoprotective effects of PLP2 were predominantly dependent on gut microbiota integrity, as direct PLP2 treatment failed to protect hepatocytes in vitro. This role was further confirmed by the abolition of protection with antibiotic treatment and the transfer of benefits via fecal microbiota transplantation.<br><br>CONCLUSION: These findings provide evidence that PLP2 exerts its anti-fibrotic effects through the gut microbiota-dependent suppression of ferroptosis via the Nrf2/HO-1/GPX4 axis, providing a solid scientific foundation for the clinical application of P. lobata.}, }
@article {pmid41966334, year = {2026}, author = {Premikha, M and Rajendiran, U and Wahab, MT and Venkatachalam, I}, title = {Interventions targeting gut colonization by multi-drug-resistant organisms in healthcare settings: a systematic review and meta-analysis of randomized controlled trials.}, journal = {The Journal of hospital infection}, volume = {172}, number = {}, pages = {228-241}, doi = {10.1016/j.jhin.2026.03.035}, pmid = {41966334}, issn = {1532-2939}, mesh = {Humans ; Randomized Controlled Trials as Topic ; *Drug Resistance, Multiple, Bacterial ; Probiotics/therapeutic use ; *Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Cross Infection/prevention &amp; control/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Bacterial Infections/prevention &amp; control ; }, abstract = {Gut colonization with multi-drug-resistant organisms (MDROs) increases risks of infection, transmission and mortality in healthcare settings. Although decolonization strategies have been attempted to reduce the impact of gut MDROs, no consensus exists on their effectiveness. Our study evaluates the effectiveness of these strategies. We searched PubMed, Embase, CENTRAL, CINAHL and Web of Science for randomized controlled trials (RCTs) published from January 2005 to December 2024. Eligible studies included patients in healthcare settings with baseline MDRO colonization confirmed by rectal swab or stool sample. The primary outcome was reduction in colonization rates in the short term (<28 days) and long term (≥28 days). Two reviewers independently screened studies, extracted data and assessed bias using the Cochrane RoB 2 tool. A random-effects model was used for meta-analysis. This study was registered on PROSPERO (CRD42025625291). Of 900 studies screened, 14 RCTs were included. Interventions included probiotics (N = 7), oral non-absorbable antibiotics (N = 6) and fecal microbiota transplantation (FMT) with antibiotics (N = 1). No significant effect was observed for short-term (risk ratio [RR] = 1.18; 95% confidence interval [CI]: 0.81-1.71; P = 0.39) and long-term decolonization (RR = 1.12; 95% CI: 0.95-1.32; P = 0.16). Post-hoc subgroup analyses showed no significant differences across immune status, target organisms, intervention types and timing of outcome assessment. Risk of bias was low in four studies, with seven having some concerns and three at high risk. Certainty of evidence was low. Current evidence does not support routine use of interventions for gut MDRO decolonization. Well-powered RCTs focused on pathogen-specific interventions and clinically meaningful endpoints are needed to evaluate promising strategies for sustained decolonization (e.g. FMT) and emerging strategies (e.g. bacteriophages).}, }
@article {pmid41966656, year = {2026}, author = {Gavi, F and Bracco, M and Testori, N and Rossi, F and Fettucciari, D and Panio, E and Assumma, S and Russo, P and Gandi, C and Foschi, N and Ragonese, M and Turri, F and Bientinesi, R and Palermo, G and Ciccarese, C and Iacovelli, R and Kröner, PT and Gasbarrini, A and Sighinolfi, MC and Rocco, B}, title = {Gut microbiome impact on systemic therapy outcomes in metastatic renal cell carcinoma: a systematic review.}, journal = {World journal of urology}, volume = {44}, number = {1}, pages = {}, pmid = {41966656}, issn = {1433-8726}, abstract = {BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) treatment with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor–tyrosine kinase inhibitors (VEGF-TKIs) yields durable benefit in a subset of patients, yet primary resistance remains frequent. Emerging data implicate the gut microbiome as a determining factor of systemic therapy efficacy. This review systematically evaluates clinical evidence on antibiotics (ATBs), probiotics, dietary interventions, and fecal microbiota transplantation (FMT) in modulating the gut microbiome to influence outcomes in adult patients with mRCC.<br><br>METHODS: Eligible studies included adult (&#x2265;&#x2009;18&#xa0;year) RCC cohorts receiving microbiome interventions versus standard care, reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or immune-related adverse events (irAEs).<br><br>KEY FINDINGS AND LIMITATIONS: Six studies (N&#x2009;=&#x2009;4738) met criteria: three retrospective cohorts linking peri-ICI ATB exposure to inferior ORR (12.9&#x2013;34.8%), shorter PFS (hazard ratios [HR] 1.96&#x2013;3.10), and OS (HR 3.5); one prospective RCT (n&#x2009;=&#x2009;20) demonstrating engraftment of Bifidobacterium animalis yogurt during VEGF-TKI therapy with enrichment of Akkermansia muciniphila and trends to longer PFS; and one phase II RCT abstract (n&#x2009;=&#x2009;50) showing FMT from an ICI responder improved 1-year PFS (66.7% vs. 35.0%, p&#x2009;=&#x2009;0.036) and ORR (54% vs. 28%) in pembrolizumab&#x2009;+&#x2009;axitinib recipients.<br><br>ATB-induced dysbiosis compromises ICI efficacy in mRCC; probiotics and FMT exhibit promise to augment immunotherapy and targeted therapy. Prospective, biomarker-driven RCTs with standardized microbiome assays are needed before routine clinical implementation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-026-06386-1.}, }
@article {pmid41966990, year = {2026}, author = {Maseng, MG and Hansen, SH and Grännö, O and Bang, C and Lund, C and Huppertz-Hauss, G and Perminow, G and Valeur, J and Bengtson, MB and Opheim, R and Boyar, R and Frigstad, SO and Aabrekk, TB and Detlie, TE and Kristensen, VA and Strande, V and Hovde, &#xd8; and Asak, &#xd8; and Franke, A and Halfvarsson, J and Høivik, ML and Hov, JR}, title = {Disentangling the gut microbiome and inflammation in inflammatory bowel diseases: longitudinal observations from the IBSEN III study.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izag051}, pmid = {41966990}, issn = {1536-4844}, support = {//Takeda Pharmaceuticals, Pfizer, Ferring Pharmaceuticals, Tillotts Pharma, Foundation Dam, and the Norwegian South-Eastern Health Authorities/ ; 90569 to J.H.//NordForsk/ ; 2019-01185 to JH//Vinnova/ ; 2988039 to MLH//Research Council of Norway/ ; No: 2020066//Regional Health Authorities South-Eastern Norway/ ; //DFG Excellence Cluster 2167 "Precision Medicine in Chronic Inflammation" (PMI) and the DFG Research Unit 5042 "miTarget"/ ; no: 327634//Research Council of Norway/ ; }, abstract = {BACKGROUND AND AIM: Despite the well-established involvement of the gut microbiome in inflammatory bowel disease (IBD), less is known about how the gut microbiome changes over time and how it varies with clinical disease activity and fecal calprotectin (f-calprotectin). To address this gap, we utilized samples from the population-based inception cohort of the Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) study.<br><br>METHODS: Data and stool samples from study participants with IBD and symptomatic controls were collected at diagnosis and after 3, 6, and 12&#x2009;months. Microbiome profiling of stool samples was performed targeting the V3-V4 region of the 16S rRNA gene, and a consensus-based approach of mixed models was employed for the longitudinal microbiome analysis.<br><br>RESULTS: We included 1251 samples from 744 patients with ulcerative colitis, 618 samples from 356 patients with Crohn' s disease and 266 samples from 164 symptomatic non-IBD controls. In the IBD population, we observed that levels of f-calprotectin decreased over time, as did the patient-reported disease activity (P&#x2009;<&#x2009;.001). Distinct changes in the gut microbiome of IBD patients were observed throughout the first year, such as increased alpha diversity (P&#x2009;<&#x2009;.001) and significant taxonomic changes.Notably, there was no covariation between the changes in alpha diversity and f-calprotectin or symptom score.<br><br>CONCLUSION: The gut microbiome during the first year after IBD diagnosis showed changes that paralleled inflammation and clinical disease activity, albeit without covariation, suggesting that there may be a disease-driving impact of gut microbiome independent of inflammation and inflammation-driven symptoms.}, }
@article {pmid41967083, year = {2026}, author = {Pum, K and Lou, E and Goffredo, P and Jahansouz, C and Subramanian, S and Prakash, A}, title = {Immunotherapy with guts: a review of microbial therapeutic adjuncts for immunotherapy in solid tumors.}, journal = {The oncologist}, volume = {31}, number = {6}, pages = {}, pmid = {41967083}, issn = {1549-490X}, support = {R21 CA267707/CA/NCI NIH HHS/United States ; //Minnesota Colorectal Cancer Foundation and The Mezin-Koats Foundation/ ; }, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Probiotics/therapeutic use ; *Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Immunotherapy has transformed the management of some solid tumor types, but its impact has been limited to the subset of cancer patients who have "hot" or immunogenic tumors. Num2erous studies are based on strategies for turning "cold," or immune-unresponsive, tumors into a "hot" state. The gut microbiome has emerged as a potential co-therapy for standard immune checkpoint inhibitors (ICIs) to achieve this goal. Recent approaches have primarily focused on the use of probiotics, microbial consortia, or fecal microbiota transplantations in combination with anti-PD-1 and anti-CTLA-4 antibodies.<br><br>METHODS: This review highlights the current status of microbiome modulation and its potential impact on clinical practice. Probiotics, such as CMB588, and microbial consortia have been selected following successful preclinical studies. These taxa may initiate T cell infiltration and are commonly found in the microbial profiles of individuals who have previously responded to immunotherapy.<br><br>RESULTS: Several trials with these therapies have had success and noted minimal safety concerns compared to monotherapy treatments. Fecal microbiota transplantation (FMT), originally used to treat Clostridium difficile infections, has also demonstrated promising results in increasing immune checkpoint inhibitor (ICI) efficacy across various cancer types and is being utilized in multiple ongoing trials.<br><br>CONCLUSION: These therapeutics form the foundation for exciting possibilities in immunotherapy and improving patient outcomes.}, }
@article {pmid41967501, year = {2026}, author = {Deschamps, C and Tronel, A and Bailly, E and Sohnagou Tanfede, MR and Gilibert, S and Denis, S and Soranzo, T and Van De Wiele, T and Marinelli, L and Blanquet-Diot, S}, title = {Small intestinal microbiome, the underrated maestro of SIMO disease.}, journal = {FEMS microbiology reviews}, volume = {50}, number = {}, pages = {}, pmid = {41967501}, issn = {1574-6976}, support = {BOFGOA2022000803//Ghent University/ ; //FWO/ ; FWOEOS202200603//FNRS/ ; }, mesh = {Humans ; *Intestine, Small/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; *Blind Loop Syndrome/microbiology ; }, abstract = {Small intestinal microbial overgrowth (SIMO) results from a breakdown in the delicate equilibrium between luminal environment, gut motility, and microbial ecology. Despite extensive research, these factors have largely been investigated as separate entities, with limited integrative insights into their interplay. This review is the first comprehensive synthesis of physicochemical, mechanical, and microbial parameters shaping SIMO pathogenesis. By reviewing both clinical and experimental data, we reveal how alterations in pH, transit time, digestive secretion dynamics, bile acid composition and impaired intestinal absorption collectively reshape microbial load, diversity, and metabolic output, establishing a self-perpetuating loop of dysfunction. We further discuss the limitations of current diagnostic tools and the transformative potential of emerging approaches, from sampling capsules enabling molecular analyses, to in vitro models simulating human small intestinal ecosystem. This integrative perspective shifts the paradigm from a microbe-centered to an ecosystem-based understanding of SIMO, outlining key challenges and opportunities for personalized diagnostics, mechanistic research, and microbiota-targeted next-generation therapeutics including pre-, pro-, postbiotics and faecal transplantation.}, }
@article {pmid41968703, year = {2026}, author = {Si, Y and Hu, Y and Zhou, Y and Ju, H and Shi, Y and Fang, H}, title = {The Key Genus of Gut Microbiota in Cognition Improvement Following Metformin Treatment in T2DM: A Two-sample Mendelian Randomization Study Combined 16s Rrna Sequencing.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303475583260405213850}, pmid = {41968703}, issn = {2212-3873}, abstract = {INTRODUCTION: Diabetes increases the risk of cognitive impairment. Metformin, a standard treatment for type 2 diabetes mellitus (T2DM), may potentially improve cognitive dysfunction. This study aims to explore the role of metformin in the cognitive performance of diabetic mice.<br><br>METHODS: We divided experimental animals into five groups, including a control group, a diabetes group, a Metformin + Diabetes group, a Control + Fecal Microbiota Transplantation (FMT) group, and a Diabetes + FMT group. These groups assessed cognitive function and plasma longchain fatty acid levels. Gut microbiota composition and the relationship between diabetes and gut microbiota were analyzed using 16S rRNA sequencing of stool samples and Mendelian randomization analysis.<br><br>RESULTS: Compared to the Diabetes group and Control + FMT group, mice receiving metformin or FMT treatment showed improved long-term memory, short-term memory, and spatial cognition (P < 0.05), accompanied by increased phosphatidic acid and decreased phosphatidylcholine, phosphatidylethanolamine, and lysophosphatidylcholine (P < 0.05). Bioinformatics analysis of 16S rRNA sequencing (P < 0.01) and Mendelian Randomization analysis (OR: 1.071, 95% CI: 1.003-1.144, P = 0.040) showed changed gut microbial composition, and Lachnospiraceae_ NK4A136 was the common significantly differential genus.<br><br>DISCUSSION: Metformin appears to enhance cognitive function in diabetic mice through mechanisms independent of blood sugar control, likely involving the brain-gut axis. Metformin increased the abundance of Lachnospiraceae_NK4A136, a genus found at lower levels in T2DM patients compared to healthy individuals. Thus, supplementing Lachnospiraceae_NK4A136 might improve cognitive function in diabetics.<br><br>CONCLUSION: Metformin can improve cognitive function in diabetic mice by modulating the gutbrain axis and altering plasma long-chain fatty acids.}, }
@article {pmid41968757, year = {2026}, author = {Wu, M and Zhang, Y and Yu, J}, title = {How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma.}, journal = {Cancer biology &amp; medicine}, volume = {23}, number = {5}, pages = {561-579}, pmid = {41968757}, issn = {2095-3941}, support = {2023ZD0500200//Non-communicable Chronic Diseases-National Science and Technology Major Project/ ; 3133344//Strategic Seed Funding Collaboration Research Scheme CUHK/ ; 3135509//Strategic Impact Enhancement Fund CUHK/ ; 3134277//Impact Case for RAE CUHK/ ; }, mesh = {Humans ; *Liver Neoplasms/immunology/therapy/microbiology ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; Animals ; Dysbiosis/immunology ; Tumor Microenvironment/immunology ; Fecal Microbiota Transplantation ; }, abstract = {Hepatocellular carcinoma (HCC) remains a major global health challenge with limited long-term survival despite advances in surgical, locoregional, and systemic treatments. Although immune checkpoint blockade (ICB) has reshaped HCC therapy, only a subset of patients achieves durable responses, reflecting substantial heterogeneity in tumor biology and immune microenvironments. Dysbiosis, involving the loss of beneficial bacteria, like Lactobacillus reuteri and Akkermansia muciniphila, and the expansion of pathogens, such as Klebsiella pneumoniae and Catenibacterium mitsuokai, drives HCC by promoting microbial translocation and chronic inflammation. This process is mediated by microbiota-derived metabolites. Pro-carcinogenic agents, like deoxycholic acid (DCA) and quinolinic acid, induce inflammation and activate oncogenic pathways, while protective short-chain fatty acids (SCFAs), like acetate and butyrate, modulate T-cell and ILC3 responses to influence antitumor immunity. Tryptophan catabolites, acting via the aryl hydrocarbon receptor (AhR), further fine tune immune and barrier functions. In addition, emerging data implicate intratumoral microbiota as active modulators of immune suppression and metastatic behavior. These mechanistic insights have accelerated the development of microbiome-targeted interventions, such as probiotics, prebiotics, engineered bacterial strains, and fecal microbiota transplantation, to enhance ICB responsiveness. This review synthesizes current advances linking the gut microbiome to HCC immunobiology and highlights emerging therapeutic strategies aimed at optimizing immunotherapy through precise microbial modulation.}, }
@article {pmid41969116, year = {2026}, author = {Shakirov, R and Pankratova, Y and Shakurov, A and Senina, A and Boulygina, E and Grigoryeva, T and Yarullina, D and Karpukhin, O}, title = {Comparative characteristics of the microbiota of diverticula in complicated diverticulitis.}, journal = {The new microbiologica}, volume = {49}, number = {1}, pages = {65-70}, pmid = {41969116}, issn = {1121-7138}, mesh = {Humans ; *Diverticulitis/microbiology ; *Bacteria/classification/isolation &amp; purification/genetics ; Male ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; }, abstract = {We present a comparison of the mucosal microbiota within different diverticula in a patient with diverticular disease (DD) complicated by diverticulitis and pelvic abscess. The conventional culture method and the 16S rRNA-based sequencing approach were employed to characterize the microbiota of perforated diverticulum (PD) and adjacent visually intact diverticulum (ID) from the same surgically resected colonic segment. Compared to PD, the microbiota of ID demonstrated depletion in butyrate-producing genera and increased abundances of Proteobacteria, Enterobacteriaceae, and Bacteroides. The predominantly pro-inflammatory character of the microbiota in ID suggests its probable pathological role in the progression of DD towards more complicated forms, up to inflammatory destruction (perforation) of the diverticulum wall. The insights of this study pave the way for the development of forthcoming clinical trials focusing on microbiota-related therapies, including the use of antibiotics, probiotics, and fecal microbiota transplantation (FMT), to potentially treat or manage DD and its complications.}, }
@article {pmid41969207, year = {2026}, author = {Saha, P and Roy, S and More, M and Bose, D and Trivedi, A and Brooks, BW and Syn, WK and Diehl, AM and Chatterjee, S}, title = {Underlying MASLD-induced gut microbiome dysbiosis and intestinal inflammation are key to poor outcomes in vibriosis infections in a preclinical model.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2652474}, pmid = {41969207}, issn = {1949-0984}, mesh = {Animals ; *Vibrio Infections/microbiology/pathology ; *Dysbiosis/microbiology ; Mice ; *Gastrointestinal Microbiome ; Disease Models, Animal ; Mice, Inbred C57BL ; Vibrio vulnificus/physiology ; Inflammation/microbiology ; Male ; Liver/pathology ; Intestines/microbiology ; *Non-alcoholic Fatty Liver Disease/microbiology ; Intestinal Barrier Function ; Anti-Bacterial Agents ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally, especially in developed countries, including the United States. The etiology of MASLD is closely associated with several other cardiometabolic conditions and can further aggravate to more severe stages of liver disease, including steatohepatitis and cirrhosis. Moreover, patients with underlying MASLD conditions have altered gut microbiome signatures and intestinal homeostasis, leading to gut barrier dysfunction, thereby making them more vulnerable to acute gastrointestinal infections like non-cholera vibriosis. However, the exact role of the gut microbiome and intestinal pathophysiology in increasing susceptibility to infection in patients with MASLD remains poorly understood. In this study, we used oral inoculation of the bacterium Vibrio vulnificus to investigate the pathophysiological outcomes in both control and diet-induced MASLD mouse cohorts. Our results showed that non-cholera vibriosis in mice with underlying MASLD caused increased liver damage, an inflammatory surge, followed by the onset of fibrotic lesions compared to the chow-diet fed control mice, depicting a worsened outcome. Depletion of the gut bacteriome by antibiotic treatment and following fecal microbiota transplantation in these mouse cohorts showed decreased pathophysiology in the livers, indicating that an altered gut microbiome in MASLD could be a key factor in the increased likelihood of non-cholera vibriosis in patients with MASLD.}, }
@article {pmid41969481, year = {2026}, author = {Huang, M and Chen, Y and Cui, X}, title = {Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.}, journal = {Translational cancer research}, volume = {15}, number = {3}, pages = {214}, pmid = {41969481}, issn = {2219-6803}, abstract = {BACKGROUND AND OBJECTIVE: Microbiota and their metabolites form a dynamic regulatory network that modulates the tumor microenvironment (TME) and immune cell functionality, emerging as critical targets in cancer immunotherapy. Despite remarkable advances in immune checkpoint inhibitors (ICIs), clinical efficacy remains limited by primary or acquired resistance in a substantial proportion of patients. Accumulating evidence indicates that the gut microbiota-metabolite-immune axis is a critical determinant of ICI responsiveness, but the underlying molecular mechanisms and tumor-specific regulatory patterns remain incompletely elucidated. This narrative review aims to systematically dissect the mechanistic interplay of this axis across diverse cancer types and synthesize current microbiota-targeted therapeutic strategies for improved immunotherapy outcomes.<br><br>METHODS: We conducted a systematic literature search of PubMed for studies published between January 2019 and December 2025, with a particular focus on basic and translational research elucidating the roles of gut microbiota and their metabolites in cancer immunotherapy across various malignancies.<br><br>KEY CONTENT AND FINDINGS: This review elucidates the molecular mechanisms by which core metabolites regulate antitumor immunity, synthesizes characteristic microbial signatures across gastrointestinal and non-gastrointestinal cancers. Furthermore, we evaluate the translational potential of intervention strategies, including fecal microbiota transplantation, probiotic supplementation, and engineered microbes, as adjuvants to enhance ICI efficacy and overcome resistance.<br><br>CONCLUSIONS: Microbiota-based personalized therapeutic strategies are increasingly recognized as promising tools to modulate antitumor immunity and improve immunotherapy outcomes. Systematic profiling of the gut microbiota-metabolite-immune axis across cancer types will facilitate the development of precision interventions to overcome ICI resistance. Future research integrating multi-omics approaches and large-scale clinical trials is pivotal to translate mechanistic insights into clinically viable therapies, ultimately revolutionizing the landscape of cancer immuno-oncology.}, }
@article {pmid41970392, year = {2026}, author = {Peng, Y and Hu, Q and Gao, C}, title = {Fecal microbiota transplantation for intestinal rehabilitation after GI bleeding and perforation post-cardiac transplant: a case report.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1766362}, pmid = {41970392}, issn = {2296-858X}, abstract = {Gastrointestinal complications present a critical challenge following heart transplantation. These issues often stem from multifactorial mechanisms, including immunosuppressive therapy and physiological stress, which compromise mucosal defenses. We report a case of a 53-year-old heart transplant recipient who developed severe gastrointestinal bleeding and perforation due to stress ulcers. Following embolization therapy, the clinical course was further complicated by secondary intestinal cicatricial obstruction, necessitating effective intestinal rehabilitation. To address the resulting malabsorption and facilitate recovery while maintaining immunosuppressive stability, fecal microbiota transplantation (FMT) was employed to restore gut microbiota diversity. This intervention successfully promoted intestinal functional recovery. This case offers a practical reference for managing complex post-transplant gastrointestinal complications, highlighting the therapeutic potential of FMT.}, }
@article {pmid41971318, year = {2026}, author = {Jin, L and Bian, X and Zhang, G and Zhu, J and Li, X and Yang, D}, title = {Combined polysaccharides from Angelica sinensis, Crataegus pinnatifida, Prunus persica, and Carthamus tinctorius attenuate cold exposure-induced bone loss by modulating the gut microbiota and fecal metabolites.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1768890}, pmid = {41971318}, issn = {1664-302X}, abstract = {BACKGROUND: Chronic cold stress is a significant risk factor for skeletal deterioration; however, effective therapeutic strategies targeting the underlying environmental-metabolic interactions remain unclear. This study investigated the osteoprotective potential of Mixed Polysaccharides (MPs) and elucidated the mediating role of the gut microbiome.<br><br>METHODS: Cold exposure-induced bone loss was established in rats. Fecal microbiota transplantation (FMT), 16S rRNA gene sequencing, and untargeted metabolomics was employed to illustrate the positive effect of MPs on the improvement of cold-exposed bone loss.<br><br>RESULTS: MPs treatment effectively reversed cold-induced trabecular microarchitecture deterioration and bone mass loss. In femoral tissue, MPs rebalanced skeletal turnover by upregulating osteogenic markers (Runx2, Osterix) and suppressing osteoclastogenic factors (TRAP, c-fos), concurrent with a marked reduction in the levels of pro-inflammatory cytokines TNF-&#x3b1; and IL-1&#x3b2; in femur. Furthermore, MPs restored intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Occludin), thereby mitigating the intestinal barrier impairment driven by cold stress. FMT experiments demonstrated that the osteoprotective effects of MPs are microbiota-dependent, as the transplantation of MPs-modulated microbiota recapitulated the bone-preserving and barrier-restoring phenotypes in recipient mice. Multi-omics integration identified that MPs selectively promoted the expansion of Lactobacillus intestinalis and the accumulation of cholylhistidine. Correlation analysis further revealed a strong link between the enrichment of these microbial and metabolic signatures, reduced pro-inflammatory cytokine levels, and improved bone formation.<br><br>CONCLUSION: Our findings indicate that MPs alleviate cold-stress-induced bone loss by remodeling the gut microbiota and metabolic profile, fortifying the intestinal barrier and decreasing pro-inflammatory cytokine.}, }
@article {pmid41971324, year = {2026}, author = {Wang, B and Deng, F and Liu, Z and Tian, J and Li, Y and Mao, Y and Song, H}, title = {Clinical application of fecal microbiota transplantation and its influencing factors.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1807071}, pmid = {41971324}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapy that has received significant attention in recent years, although its origins can be traced back to 4th-century China. In modern medicine, FMT has been incorporated into clinical guidelines for the treatment of recurrent Clostridioides difficile infection. By re-establishing a healthy gut microbiota and regulating the immune system, FMT has potential therapeutic effects on various diseases, such as gastrointestinal diseases, diabetes, tumors, Alzheimer's disease, and liver disease. However, its efficacy varies based on the type of disease and individual differences. The clinical application of FMT is influenced by multiple factors, including fecal matter processing, administration route, dosage, donor screening, and recipient detection. Currently, FMT faces numerous challenges, including the need to verify the stability and durability of its efficacy, standardize donor screening criteria, and optimize fecal processing and administration. Future research is expected to reveal the mechanisms of action of FMT, optimize treatment protocols, and refine its safety, efficacy, and convenience, thereby bringing hope for patients with complex and challenging diseases.}, }
@article {pmid41974014, year = {2026}, author = {AlAwadhi, HK and Hyesoo Chang, N and Jogendran, M and Bretthauer, M}, title = {Gastroenterology/Hepatology: What You May Have Missed in 2025.}, journal = {Annals of internal medicine}, volume = {179}, number = {5_Supplement}, pages = {e2601058}, doi = {10.7326/ANNALS-26-01058}, pmid = {41974014}, issn = {1539-3704}, mesh = {Humans ; *Gastroenterology/trends ; *Gastrointestinal Diseases/therapy/diagnosis ; }, abstract = {During 2025, gastroenterology and hepatology experienced advances in treatment and surveillance of common diseases. Technological innovations have been reported that may positively affect patients worldwide. New drug options for treatment of metabolic dysfunction-associated steatohepatitis are emerging, and old drugs have new indications and patterns of use for common gastroenterologic diseases. The 9 articles featured here were selected because they represent important information for clinicians who are not gastroenterologists but who often diagnose, treat, and follow patients with gastroenterologic conditions. Two randomized trials address potential overtreatment of patients with Barrett esophagus without high-grade dysplasia and patients with severe alcohol-associated hepatitis. For clinicians who care for patients with malignant gastric outlet obstruction, 2 new randomized trials now provide evidence that a new endoscopic approach is a good alternative to traditional surgical gastroenterostomy or duodenal stenting. Aspirin is emerging as promising adjuvant therapy for patients with colorectal cancer that is positive for PI3K pathway alterations, and fecal microbiota transplantation has been shown to be noninferior to standard vancomycin for patients with a first episode of Clostridioides difficile infection. Finally, a randomized trial showed that structured exercise and training for patients with colon cancer after surgery and adjuvant oncologic treatment reduce recurrence and increase survival.}, }
@article {pmid41974041, year = {2026}, author = {Wu, S and Chew, NF and Ma, X and Situ, J and Shun, EH and Li, C and Ip, JD and Ho, SS and Zhang, AJ and Tsoi, JY and Chan, WM and Ma, W and Liang, Y and Mao, W and Chen, KWY and Yin, F and To, KK and Yuan, S and Chan, JF and Zhu, L and Huang, Y and Sridhar, S}, title = {Molnupiravir is effective against hepatitis E virus infection in an animal model.}, journal = {Hepatology communications}, volume = {10}, number = {5}, pages = {}, pmid = {41974041}, issn = {2471-254X}, mesh = {Animals ; *Hepatitis E/drug therapy/virology ; *Antiviral Agents/pharmacology/therapeutic use ; *Hepatitis E virus/drug effects/genetics ; Disease Models, Animal ; Rats ; Ribavirin/pharmacology/therapeutic use ; *Hydroxylamines/pharmacology/therapeutic use ; Male ; Sofosbuvir/pharmacology ; RNA, Viral ; Hepatocytes/virology ; Humans ; Cytidine/analogs &amp; derivatives ; }, abstract = {BACKGROUND: There are few treatment options for patients with chronic hepatitis E unresponsive to ribavirin. Drug repurposing is required to identify new treatments. Molnupiravir, a nucleoside analogue, is approved for the treatment of coronavirus disease 2019 (COVID-19). This study evaluated the activity of molnupiravir against hepatitis E virus (HEV) in cell culture and animal models.<br><br>METHODS: Cytotoxicity and antiviral efficacy of molnupiravir, ribavirin, and sofosbuvir were investigated using infectious cDNA clones and wild-type HEV isolates in PLC/PRF/5 cells and primary rat hepatocytes. Immunosuppressed rats were infected with HEV and treated with molnupiravir and ribavirin. The effectiveness of molnupiravir in clearing HEV in serum, feces, and liver tissue was compared with that of untreated and ribavirin-treated animals. Mutations arising in virus populations during treatment were assessed using next-generation sequencing.<br><br>RESULTS: The antiviral effect of molnupiravir was comparable to that of ribavirin and superior to that of sofosbuvir against HEV strains in vitro, with decreased HEV RNA in supernatant (p<0.05) and cytoplasmic viral protein expression. No additive effect with sofosbuvir was observed. Rats (n=14 per group) treated with 400&#xa0;mg/kg/d molnupiravir cleared viremia within 4 weeks of treatment, and 9/14 of these animals also cleared viral shedding in stool. Mean viremia and fecal viral loads were reduced compared with untreated and ribavirin-treated animals (p&#x2264;0.005). Partial effectiveness was apparent at the lower 250&#xa0;mg/kg/d molnupiravir dose. Molnupiravir-treated rats had improved liver histology compared with control animals. Frequent transition mutations were observed in HEV from molnupiravir-treated animals.<br><br>CONCLUSIONS: Molnupiravir limits HEV infection in cell culture and animal models. Molnupiravir could be an alternative for ribavirin-refractory chronic hepatitis E.}, }
@article {pmid41975112, year = {2026}, author = {Liu, J and Sun, X and Yuan, P and Qin, Y and Wu, W and Fan, Y and Zhang, Y and Zou, L and Ren, C and Li, S}, title = {Clinical response and risk factors of fecal microbiota transplantation in children: a systematic review and meta-analysis.}, journal = {European journal of pediatrics}, volume = {185}, number = {5}, pages = {}, pmid = {41975112}, issn = {1432-1076}, support = {No.ZF2025046//the Hebei Provincial Department of Finance/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; Child ; Risk Factors ; *Inflammatory Bowel Diseases/therapy ; Treatment Outcome ; *Clostridium Infections/therapy ; }, abstract = {UNLABELLED: The objective of this study is to investigate the clinical response and incidence of adverse events (AEs) following fecal microbiota transplantation (FMT) in children, across various diseases, populations, and treatment protocols. A systematic search was conducted across eight major Chinese and English databases, identifying 47 studies up to August 28, 2025, for inclusion. Study quality was assessed using the Quality Assessment with Diverse Studies (QuADS) tool. Single-arm rates were pooled via meta-analysis employing the Freeman-Tukey double arcsine transformation, followed by extensive subgroup comparisons to identify influencing factors. FMT demonstrated efficacy in pediatric recurrent Clostridium difficile infection (rCDI), inflammatory bowel disease (IBD), and autism spectrum disorder (ASD), although a higher incidence of AEs was observed in children with IBD. Subgroup analyses revealed that the use of donor feces from relatives or friends was associated with a higher clinical response rate in rCDI. The presence of comorbidities such as IBD diminished the response rate in rCDI patients. Younger age in rCDI and IBD patients showed a trend towards higher clinical response rates, though this did not reach statistical significance. No statistically or clinically significant differences were found in other subgroup comparisons. Meta-regression suggested IBD to be a risk factor for FMT-related AEs.<br><br>CONCLUSION: This study innovatively delineates the efficacy-safety profile of pediatric FMT and outlines a pathway for optimizing individualized treatment regimens, providing crucial evidence-based guidance for clinical practice.<br><br>TRIAL REGISTRATION: This study has been registered on the PROSPERO database (CRD42024614196).<br><br>WHAT IS KNOWN: &#x2022; Fecal Microbiota Transplantation (FMT) demonstrates preliminary therapeutic potential in several pediatric diseases. &#x2022; Existing evidence remains fragmented, with limited systematic data on factors modifying efficacy and safety in children.<br><br>WHAT IS NEW: &#x2022; The study revealed FMT's high efficacy across rCDI, IBD, and ASD, and identified IBD as a risk factor for elevated FMT-related adverse events in pediatric patients. &#x2022;&#xa0;Notably, related/friend donors improved rCDI response rates, while comorbidities like IBD reduced rCDI treatment efficacy.}, }
@article {pmid41975274, year = {2026}, author = {Nikolaidis, M and Hu, C and Juran, BD and McCauley, BM and Schlicht, EM and Bianchi, JK and Ali, AH and Tragaki, V and Atkinson, EJ and Johnson, S and Mars, RA and Eaton, JE and Carey, EJ and Franke, A and Schramm, C and Kashyap, PC and Go, YM and Tran, V and Teeny, S and Jones, DP and Grant, CW and Athreya, AP and Miller, GW and LaRusso, NF and Gores, GJ and Karlsen, TH and Hov, JR and Amoutzias, GD and Lazaridis, KN}, title = {Compositional and functional differences of gut microbiome and metabolome inform pathogenesis of cholestatic liver disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2655793}, pmid = {41975274}, issn = {1949-0984}, support = {RC2 DK118619/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Metabolome ; Female ; Male ; Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; Middle Aged ; *Liver Cirrhosis, Biliary/microbiology/metabolism ; *Cholangitis, Sclerosing/microbiology/metabolism ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Adult ; Metagenome ; Aged ; Metabolomics ; }, abstract = {Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are rare, idiopathic, chronic cholestatic liver diseases that respond differently to limited medical therapies and often lead to liver transplantation. We examined the compositional and functional differences in the gut microbiome, mycobiome, and metabolome of these diseases to better understand their impact on pathogenesis and outcomes. Stool sample metagenomes and metabolomes from patients with PSC (n = 245), PBC (n = 280) and matched controls (n = 245 and n = 278, respectively) were analyzed by shotgun sequencing and ultrahigh-resolution mass spectrometry. Comparisons were conducted with covariate-adjusted linear models. The gut microbiomes of patients with PSC and PBC were characterized by reduced diversity and increased abundance of pathobionts and virulence factors, coupled with altered microbial metabolism, including a reduction of short-chain fatty acids and B-vitamins. Untargeted stool metabolomics supported these results. Patients were stratified into groups using their microbial signatures, and each group had distinct patterns of microbiome-related changes. Cox regression analysis revealed that pathogenic microbial species were predictive of hepatic decompensation, whereas beneficial species had a protective effect. Based on previous groundwork and our new results, microbiome-based interventions such as probiotics, short-chain fatty acid supplementation, and phage therapy represent promising therapeutic options for cholestatic liver diseases.}, }
@article {pmid41976908, year = {2026}, author = {Oommen, TT and Philips, CA and Ahamed, R and Theruvath, AH and Tharakan, A and Rajesh, S and Augustine, P}, title = {Palliative Healthy Donor Stool Transplantation (pFMT) in Patients with End-Stage Alcohol-Related Cirrhosis and Severe Unstable Decompensations-A Cohort Study.}, journal = {Journal of clinical medicine}, volume = {15}, number = {7}, pages = {}, pmid = {41976908}, issn = {2077-0383}, abstract = {Background and Aims: Severe alcohol-associated hepatitis (SAH) can trigger unstable decompensations in cirrhosis patients. They experience high rates of emergency department visits and hospitalization. We evaluated real-world clinical outcomes following palliative-faecal microbiota transplantation (pFMT) compared to best supportive care (BSC) in this critically ill population. Patients and Methods: From July 2021 to April 2024, 28 patients on pFMT were compared with 37 on BSC. Patients on pFMT received nasoduodenal healthy donor stool infusion daily for 5-days. Patients were followed up for portal hypertension-related events, infections, hospitalizations, extrahepatic organ failure and 6- and 12-months survival. 16S rRNA sequencing on stool samples collected at baseline and on follow up were analysed for changes in relative abundance (RA) of bacterial communities. Results: Patients were matched for age, type of decompensation and liver disease severity at enrolment. Twelve-month survival was 64.3% in pFMT versus 51.4% in BSC groups. pFMT dramatically reduced hospital readmissions (mean 0.76 ± 0.76 vs. 2.29 ± 1.27, p < 0.001). Unstable decompensations beyond 3 months occurred in 14.3% of pFMT versus 64.9% of BSC (p < 0.001). Organ failures were lesser with pFMT: acute kidney injury 7.7% versus 93.8% (p < 0.001), hepatic encephalopathy 7.1% versus 68.2% (p < 0.001). Infection burden was significantly lower (53.6% vs. 83.8%, p = 0.008), particularly infections requiring admission (17.4% vs. 66.7%, p < 0.001) with pFMT. Microbiome analysis revealed progressive expansion of Gram-negative genera in BSC, and beneficial Actinobacteria in pFMT-treated patients at 3, 6, and 12 months. Conclusions: Palliative FMT represents a unique disease-modifying intervention in end-stage alcohol-related cirrhosis, preventing organ failure progression, reducing healthcare utilization, and improving survival trajectories.}, }
@article {pmid41979342, year = {2026}, author = {Cai, K and Chen, Z and Deng, S and Chen, J and Yu, J and Zhang, X and Jia, W and Huang, A and Chen, Y and Xie, Z and Li, P and Liao, Q}, title = {UPLC-Q-TOF/MS-Based Metabolomics and 16S rRNA Profiling Reveal that Corosolic Acid Ameliorates High-Fat Diet-Induced MASLD by Modulating the Gut-Liver Axis to Inhibit the cGAS-STING Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {16}, pages = {13282-13301}, doi = {10.1021/acs.jafc.5c13513}, pmid = {41979342}, issn = {1520-5118}, mesh = {Animals ; Gastrointestinal Microbiome/drug effects ; Mice ; Diet, High-Fat/adverse effects ; Male ; Mice, Inbred C57BL ; *Liver/metabolism/drug effects ; Metabolomics ; RNA, Ribosomal, 16S/genetics/metabolism ; Humans ; *Triterpenes/administration &amp; dosage ; *Nucleotidyltransferases/metabolism/genetics ; Bacteria/genetics/classification/isolation &amp; purification/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy/genetics/microbiology ; Chromatography, High Pressure Liquid ; *Membrane Proteins/metabolism/genetics ; Mass Spectrometry ; }, abstract = {Metabolic-associated steatohepatitis liver disease (MASLD) is characterized by abnormal hepatic fat accumulation and liver injury. Corosolic acid (CA) has proven lipid-lowering and hepatoprotective effects, yet the underlying mechanism by which CA mitigates MASLD remains unclear. In this study, mice were fed a high-fat diet for 8 weeks to induce MASLD, followed by 8 weeks of CA intervention. We found that CA significantly suppressed weight gain, reduced serum lipid levels, and improved liver function in the HFD-fed mice. Fecal metabolomic analysis showed that CA regulated multiple metabolic pathways including histidine metabolism and altered 10 shared metabolites between feces and serum, such as HAD-Car. 16S rRNA sequencing and fecal microbiota transplantation confirmed that CA reshaped gut microbiota, upregulating beneficial bacteria (e.g., Lachnospiraceae_NK4A136_group) and downregulating harmful strains (e.g., Blautia). Mechanistically, HAD-Car alleviated MASLD by inhibiting the cGAS-STING pathway. Collectively, CA exerts anti-MASLD effects via regulating gut microbiota and metabolites, offering new insights into MASLD treatment.}, }
@article {pmid41979409, year = {2026}, author = {Paaske, SE and Baunwall, SMD and Dahlerup, JF and Hvas, CL}, title = {Letter: Dose and Donor Matter-Determining the Optimal Strategy for Faecal Microbiota Transplantation in Clostridioides difficile Infection. Authors' Reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.70671}, pmid = {41979409}, issn = {1365-2036}, }
@article {pmid41979582, year = {2026}, author = {Smółka, L and Strugała, M and Kursa, K and Pomianowski, B and Blady, K and Bratek, K}, title = {The impact of the gut microbiome on the development of atherosclerosis and peripheral arterial disease: A narrative review.}, journal = {Przeglad epidemiologiczny}, volume = {79}, number = {4}, pages = {580-594}, doi = {10.32394/pe/214773}, pmid = {41979582}, issn = {0033-2100}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Atherosclerosis/microbiology ; *Peripheral Arterial Disease/microbiology ; *Dysbiosis ; }, abstract = {Atherosclerosis is a chronic, progressive process affecting medium and large arteries, while peripheral artery disease (PAD) represents one of its clinical manifestations in the limb arteries. Although classical risk factors such as poor diet, hypertension, diabetes, and smoking are well established, increasing evidence indicates that the gut microbiome is an important and modifiable contributor to vascular pathophysiology. This paper reviews current knowledge on the role of the gut microbiome in the initiation and progression of atherosclerosis and PAD, with emphasis on bacterial metabolites, proinflammatory mechanisms, and potential therapeutic interventions. Gut dysbiosis-an imbalance in the intestinal microbial community-has been associated with increased cardiovascular risk. Patients with vascular diseases show higher levels of pro-atherogenic taxa, including Enterobacteriaceae, Streptococcus spp., Lachnoclostridium, and Family XI, alongside a reduction of beneficial short-chain fatty acid (SCFA)-producing bacteria such as Roseburia, Faecalibacterium, Coprococcus2, and Ruminococcaceae. Two key microbial metabolites influence vascular health. Trimethylamine N-oxide (TMAO), formed from choline and L-carnitine via microbial and hepatic metabolism, promotes endothelial dysfunction, inflammation, and platelet reactivity, thereby accelerating atherosclerosis. Conversely, SCFAs-acetate, propionate, and butyrate-exert anti-inflammatory effects, improve insulin sensitivity, and enhance nitric oxide synthesis, resulting in vascular protection. Therapeutic strategies targeting the gut microbiota show promising potential. These include the use of probiotics and prebiotics (notably Lactobacillus rhamnosus GG), adherence to a Mediterranean diet, and fecal microbiota transplantation (FMT), all aimed at restoring eubiosis and a favorable intestinal metabolic profile. In summary, the gut microbiome appears to be a key modulator of the pathogenesis of atherosclerosis and PAD. Targeted modulation of gut microbial composition and activity may emerge as an innovative and effective strategy for the prevention and treatment of cardiovascular diseases.}, }
@article {pmid41980626, year = {2026}, author = {Li, K and Zhu, R and Chen, Y and Wang, X and Jiang, Y and Han, T and Yue, X and Xia, T and Xin, H}, title = {Portulaca oleracea L. polysaccharide alleviates colitis-associated bone loss through Muribaculaceae-enriched gut microbiota and elevated colonic melatonin.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.04.033}, pmid = {41980626}, issn = {2090-1224}, abstract = {AIMS: Colitis and its associated bone loss are major global health concerns with limited therapeutic options. Portulaca oleracea L. polysaccharide (POP) has been suggested to ameliorate both conditions via microbiota modulation. The study aimed to explore whether POP can alleviate colitis-associated bone loss and its underling mechanism.<br><br>METHODS: A murine model of dextran sodium sulfate (DSS)-induced colitis with bone loss was used to assess the effects of POP. The 16S rRNA sequencing and ex vivo fecal microbiota transplantation (ex-FMT) were employed to identify bacterial taxa potentially associated with POP's protective effects. The functional impact of microbial metabolites was evaluated by treating cells with fecal supernatants (FS), and their compositional profiles were analyzed using fecal metabolomics.<br><br>RESULTS: POP mitigated DSS-induced colitis and bone loss and reshaped gut microbial composition, featuring enrichment of Muribaculaceae. Transplantation of POP-modulated microbiota (POPFMT) replicated the therapeutic benefits, which were maintained following gentamicin treatment (GENFMT) but abolished by vancomycin (VANFMT). Compared with the DSSFMT group, Muribaculaceae abundance was significantly higher in the POPFMT group. This increase was maintained in the GENFMT group but markedly reduced in the VANFMT group. FS from POP group maintained gut barrier function by increasing ZO-1 and Occludin expression, while suppressing apoptosis in HT-29 cells. FS from POPFMT group suppressed inflammatory osteoclastogenesis of RAW 264.7 cells via the TRAF6/p65-NFATc1 signaling axis. Metabolomics revealed distinct tryptophan-related profiles, with POPFMT and GENFMT were characterized by elevated melatonin abundance, DSSFMT by increased indole, and VANFMT by increased indole derivatives. Colonic melatonin levels were consistently higher in the POP-treated, POPFMT, and GENFMT groups. Exogenous melatonin ameliorated DSS-induced colitis and bone loss, whereas the 4P-PDOT attenuated its protective effects.<br><br>CONCLUSION: POP ameliorates DSS-induced colitis and bone loss by modulating the gut microbiota. The POP-modulated gut microbiota is characterized by enrichment of Muribaculaceae and is associated with increased colonic melatonin levels, which contributes to the observed attenuation of colitis and bone loss.}, }
@article {pmid41981196, year = {2026}, author = {Hamdi, L and Agranyoni, O and Goldberg, Y and Zarka, N and Fainstein, N and Theotokis, P and Salamotas, I and Grigoriadis, N and Katz, A and Ben-Hur, T and Navon-Venezia, S and Einstein, O}, title = {High-intensity exercise training alters gut microbiota to mitigate the development of experimental autoimmune encephalomyelitis.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41981196}, issn = {2045-2322}, support = {0008147//Ministry of Innovation, Science and Technology/ ; }, mesh = {Animals ; *Encephalomyelitis, Autoimmune, Experimental/microbiology/therapy/pathology/immunology ; Mice ; *Gastrointestinal Microbiome ; *Physical Conditioning, Animal ; Fecal Microbiota Transplantation ; Female ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; Fatty Acids, Volatile/blood ; Disease Models, Animal ; }, abstract = {Exercise training (ET) has demonstrated beneficial effects in autoimmune and neurological disorders, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). ET modulates the gut microbiota, which influences neuroimmune interactions via the microbiota-gut-brain and microbiota-gut-immune system axes. However, the role of gut microbiota in mediating ET's protective effects in autoimmune neuroinflammation remains unclear. We investigated whether gut microbiota mediates the beneficial effects of ET on EAE development. Healthy mice underwent high-intensity continuous training (HICT). Fecal microbiota from HICT and sedentary mice were transplanted into naïve recipients, followed by proteolipid protein (PLP) immunization to induce EAE. Disease severity, gut microbial composition (16S rDNA sequencing), short-chain fatty acid (SCFA) levels (LC-MS), and autoreactive T-cell proliferation (flow cytometry) were assessed. Faecal microbiota transplantation (FMT) from HICT donors significantly reduced EAE severity, delaying onset and decreasing CNS inflammation, demyelination, and axonal damage. These effects correlated with distinct microbial signatures, including increased Faecalimonas and Escherichia genera, and decreased Mucispirillum genus. HICT-FMT mice exhibited higher Faecalimonas abundance and reduced serum SCFA levels. PLP-reactive T-cell proliferation was suppressed in HICT-FMT recipients. Gut microbiota from HICT mice confers protection against EAE development, associated with microbial-metabolic shifts and modulation of autoreactive T-cell responses.}, }
@article {pmid41981603, year = {2026}, author = {Liu, Y and Chen, C and Liu, H and Wang, W and Zhou, X and Guo, M and Zhao, J and Zeng, Z and Xu, L}, title = {Decoding the gut microbiota-immune dialogue: from bidirectional axis to therapeutic applications.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {}, pmid = {41981603}, issn = {1477-3155}, support = {82160503, 82272812//National Natural Science Foundation of China/ ; QKHZC-2020-4Y156, QKH-JC-2018-1428, QKHJC-ZK-2022-624//Project of the Guizhou Provincial Department of Science and Technology/ ; }, abstract = {UNLABELLED: The gut microbiota (GM), a highly complex micro-ecosystem residing within the host’s gastrointestinal tract, works in conjunction with the gut immune system to form a precise bidirectional regulatory network, that maintains symbiotic homeostasis and overall host health. Cumulative evidence has demonstrated that the critical impact of the bidirectional causal relationship between the GM and the gut immune system on host development and the dynamic progression of disease. However, many challenges remain in this research field, including the mechanism complexity, therapeutic effect differences due to individual heterogeneity, long-term safety, and clinical transformation bottlenecks) that need to be urgently broken through. Therefore, the in-depth analysis of these issues is of great theoretical and practical significance for clarifying the intrinsic connection between the GM and gut immunity, particularly in elucidating the pathogenesis of related clinical diseases such as inflammatory bowel disease (IBD), tumors, and autoimmune diseases (AD). We systematically outline the interaction mechanisms between the microbiota and the immune system, including compositional structure (microbiota diversity and immune system composition), development and maturation processes (early microbiota colonization and immune system establishment), and functional regulation (immune cell differentiation and maintenance of mucosal barrier integrity), as well as their associations with clinical diseases. Finally, we discuss some key considerations for the developing of innovative treatment strategies, such as microbial-targeted interventions, fecal microbiota transplantation (FMT), and synergistic use of immunomodulatory drugs, with the aim of providing a new paradigm for the precise intervention of related diseases.<br><br>GRAPHICAL ABSTRACT: [Image: see text]}, }
@article {pmid41982910, year = {2025}, author = {Santos, S and Salinas, I and Almeida, N and Caicedo, A}, title = {The role of microbiota dysbiosis in Parkinson's disease: Pathophysiology and therapeutic opportunities.}, journal = {Engineering microbiology}, volume = {5}, number = {3}, pages = {100222}, pmid = {41982910}, issn = {2667-3703}, abstract = {Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder characterized by debilitating motor and non-motor symptoms. Its etiology is multifactorial, with no single definitive cause identified, although aging is a significant risk factor. Additional risks include genetic predisposition, family history, and environmental factors such as pesticide exposure and Helicobacter pylori infection. Dysbiosis of the gut microbiota, and in particular bacterial imbalances, has been implicated in the disruption of the gut-brain axis, contributing to both systemic and neuroinflammation. Environmental factors such as antibiotic exposure and toxins can precipitate microbial dysregulation, potentially accelerating PD progression. Understanding the mechanisms of the gut-brain axis and identifying strategies to preserve a healthy microbiome are essential for developing novel therapeutic approaches. This review synthesizes current therapeutic strategies and ongoing research focused on restoring gut-brain balance to combat PD. These approaches include fecal microbiota transplantation, dietary interventions, and probiotic therapies, all of which show promise in mitigating both motor and non-motor symptoms. Furthermore, we emphasize the urgent need for continued research into probiotics and innovative therapeutic approaches for gut-brain axis modulation, presenting novel opportunities for effective PD management.}, }
@article {pmid41983065, year = {2026}, author = {Zhao, X and Lv, Z and Liu, H and Zhang, J}, title = {Fecal microbiota transplantation for intractable diarrhea due to severe dysbiosis and cytomegalovirus enteritis: a case report.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1728176}, pmid = {41983065}, issn = {2296-861X}, abstract = {BACKGROUND: Cytomegalovirus (CMV) enteritis can lead to intractable diarrhea, especially when complicated by severe gut dysbiosis, posing a significant therapeutic challenge.<br><br>METHODS: We present a case of a 40-year-old woman with a history of traumatic brain injury and prolonged broad-spectrum antibiotic use, who developed persistent bloody, mucus-containing diarrhea (up to 40 episodes daily). Colonoscopy with biopsy confirmed CMV enteritis, and 16S rRNA sequencing revealed severe intestinal dysbiosis. Treatment consisted of intravenous ganciclovir combined with multiple sessions of fecal microbiota transplantation (FMT) delivered via jejunal tube, alongside tailored nutritional support.<br><br>RESULTS: Despite initial persistence of symptoms, the combined antiviral and FMT regimen led to resolution of diarrhea, normalization of inflammatory markers, and restoration of enteral tolerance. Follow-up colonoscopy showed mucosal healing and negative CMV staining. Microbiota analysis demonstrated restoration of diversity and a shift toward donor-like taxonomic profiles.<br><br>CONCLUSION: This case highlights CMV as an emerging cause of severe enteritis in non-immunosuppressed surgical patients and supports the efficacy of combined antiviral therapy and FMT for refractory diarrhea associated with dysbiosis and CMV infection.}, }
@article {pmid41983510, year = {2026}, author = {Xie, W and Yuan, J and Feng, C and Shi, H and Zhang, C and Xi, T and Huang, J and Fang, W and Ni, Z and Gu, L and Jiang, N}, title = {Alteration of gut microbiota contributes to peritoneal fibrosis through increased production of trimethylamine N-oxide.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2657048}, pmid = {41983510}, issn = {1949-0984}, mesh = {Animals ; *Methylamines/metabolism ; *Peritoneal Fibrosis/microbiology/metabolism/pathology/etiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; Peritoneal Dialysis/adverse effects ; Peritoneum/pathology/metabolism ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Male ; Mice, Knockout ; Transforming Growth Factor beta1/metabolism ; Disease Models, Animal ; }, abstract = {Peritoneal fibrosis is a common complication in peritoneal dialysis (PD) patients, which results in ultrafiltration failure (UFF) and PD withdrawal. PD patients demonstrate altered structural and functional profiles of the gut microbiota. Herein, we investigated the role of the gut microbiota and trimethylamine N-oxide (TMAO), a bacterial metabolite, in the pathogenesis of PD-associated peritoneal fibrosis. PD mice displayed mesenchymal transition features and fibrosis in the peritoneum, which were accompanied by an altered gut microbiota profile and elevated serum TMAO levels, and these peritoneal histologic abnormalities were ameliorated by gut microbiota depletion. Fecal microbiota transplantation (FMT) from PD patients induced mesenchymal and fibrotic alterations within the peritoneum of wild-type mice, and the effect was more pronounced in mice receiving FMT from PD patients with UFF. Intraperitoneal supplementation with TMAO enhanced PD-induced peritoneal fibrosis in wild-type mice. On the contrary, PD- or FMT-induced mesenchymal features and fibrosis within the peritoneal membrane were lessened in flavin-containing monooxygenase 3 gene knockout mice, which were incapable of synthesizing TMAO. TMAO treatment enhanced high glucose-mediated phenotypic transition and fibrogenesis in cultured peritoneal mesothelial cells and fibroblasts, partly by increasing TGF-β1 synthesis and secretion and subsequent phosphorylation of Smad2/3 and activation of the Wnt/β-catenin pathway. Collectively, we found that altered gut microbiota plays an important role in the development of PD-associated peritoneal fibrosis through dysregulated production of the bacterial metabolite TMAO.}, }
@article {pmid41983911, year = {2026}, author = {Schindler, V and Zeitz, J and Bianca, A and Murray, F and Schuler, J and Pohl, D}, title = {Patients' view on fecal microbiota transplantation in disorders of gut-brain interaction: a survey-based study.}, journal = {Minerva gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-5985.26.03999-9}, pmid = {41983911}, issn = {2724-5365}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has gained popularity over the last years. So far, conflicting data regarding the effect on disorders of gut-brain interaction (DGBI) exist. In this study we aimed to access current knowledge and attitude towards potential FMT of DGBI patients.<br><br>METHODS: A survey on attitudes toward FMT was conducted in DGBI patients. Patients answered questions anonymously before and after having read a brief information sheet on FMT. Data were collected prospectively in 2017-2018 and in 2022-2023.<br><br>RESULTS: In total, 387 patients completed the survey. Forty percent of patients had heard about FMT prior to underlying survey. Prior to a brief information regarding FMT, 38% of patients would have agreed to FMT, while 50% were undecided and 12% would have declined. After a brief information sheet on FMT, decisions significantly changed to 63%, 26% and 11% respectively (P<0.001). The decision of patients to undergo FMT remained unchanged between 2017 and 2022. Type of DGBI and disease severity are significantly associated with treatment decisions (P=0.005).<br><br>CONCLUSIONS: This survey demonstrates great interest of DGBI patients in potential FMT, especially after being informed on details of the procedure. Bearing in mind that in the future FMT may be a clearer option in the treatment of certain DGBIs, patient education will be an important factor.}, }
@article {pmid41985671, year = {2026}, author = {Wang, Y and Liu, X and Li, Z and Kang, A and Bai, Y and Wang, Y and Liu, Y and Zhang, C and Yang, J and Cai, Q and Feng, Y and Yi, H and Zhang, M and Zhang, F and Liu, H and Xu, C}, title = {Oligofructose alleviates hyperandrogenism in polycystic ovary syndrome through gut microbiota-derived bile acids.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.04.036}, pmid = {41985671}, issn = {2090-1224}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, characterized by hyperandrogenism and metabolic dysfunction. Dietary interventions are recommended as one of the first-line therapies. Oligofructose (OFS), a prebiotic fiber, has demonstrated clinical benefits in PCOS; however, its underlying mechanism remains unclear.<br><br>OBJECTIVES: To determine whether OFS alleviates PCOS-like phenotypes through bile acid-dependent mechanisms and to identify downstream ovarian steroidogenic responses.<br><br>METHODS: Letrozole-induced PCOS-like mice received OFS supplementation. Microbiota dependence was assessed using antibiotic depletion and fecal microbiota transplantation. Bile acid involvement was evaluated using cholestyramine. Gut microbial composition and function were profiled by 16S rRNA and metagenomic sequencing, and bile acids were quantified by UHPLC-MS/MS. Ovarian transcriptomics, ex vivo ovarian explants, and primary granulosa cells were used to examine steroidogenic changes, with pharmacological inhibition applied to assess TGR5-related signaling.<br><br>RESULTS: OFS improved reproductive and metabolic abnormalities in PCOS-like mice. These benefits were abolished by microbiota depletion and bile acid sequestration, indicating microbiota- and bile acid-dependent effects. OFS was associated with increased circulating hyodeoxycholic acid (HDCA), which negatively correlated with serum testosterone. HDCA supplementation partially reproduced endocrine improvements under microbiota-depleted conditions. Ovarian transcriptomic and functional analyses demonstrated enhanced aromatization following OFS treatment. In ex vivo ovarian explants and primary granulosa cells, HDCA increased estradiol production, reduced testosterone, and upregulated CYP19A1 (encoding aromatase). Under androgen stimulation, pharmacological inhibition of TGR5 attenuated HDCA-associated increases in estradiol and aromatase activity, supporting involvement of TGR5-related signaling.<br><br>CONCLUSION: OFS alleviates PCOS-like phenotypes in a microbiota- and bile acid-dependent manner and enhances ovarian aromatization. These findings move beyond descriptive bile acid alterations in PCOS by providing functional evidence that dietary fiber-induced bile acid remodeling is associated with modulation of ovarian steroidogenic regulation.}, }
@article {pmid41988171, year = {2026}, author = {Zou, Q and Zhang, Y and Zou, S and Li, Y and Li, H and Yang, M and Lai, H and Niu, R and Yang, X and Zhou, L}, title = {Ciprofloxacin-induced microbiota dysbiosis triggers seizure susceptibility through the microbiota-gut-brain axis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1670694}, pmid = {41988171}, issn = {1664-3224}, mesh = {Animals ; *Dysbiosis/chemically induced ; Male ; *Seizures/chemically induced/etiology/microbiology/metabolism ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Ciprofloxacin/adverse effects ; Blood-Brain Barrier/metabolism ; Rats, Sprague-Dawley ; *Brain-Gut Axis/drug effects ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Epilepsy is linked to inflammation and gut microbiota dysbiosis. Ciprofloxacin-induced microbiota disruption may increase seizure susceptibility. This study investigates underlying mechanisms and the therapeutic potential of fecal microbiota transplantation (FMT).<br><br>METHODS: A total of 64 male Sprague-Dawley rats were categorized into four experimental groups: Control (CTRL), Ciprofloxacin-treated (CPF), CPF with fecal microbiota transplantation (CPF-FMT), and CPF with phosphate-buffered saline (CPF-PBS). Gut microbiota dysbiosis was induced with ciprofloxacin for 14 days, followed by either FMT or PBS for 14 days. Seizure susceptibility was assessed using pentylenetetrazole (PTZ), alongside molecular analyses of gut and blood-brain barrier integrity, neuroinflammatory markers, and cortical transcriptomics.<br><br>RESULTS: Microbiota dysbiosis was associated with increased seizure susceptibility, accompanied by disruption of intestinal and blood-brain barrier (BBB) integrity, thereby exacerbating systemic and neuroinflammation. Dysbiotic rats exhibited significant reductions in microbial diversity and depletion of protective taxa, including f_Muribaculaceae, f_Prevotellaceae, and Lachnospiraceae_NK4A136_group, which correlated with intestinal barrier dysfunction. This dysfunction was associated with reduced tight junction proteins (ZO-1, Occludin, Claudin-5) and inflammatory cell infiltration. Systemic inflammation and disrupted blood-brain barrier integrity resulted in microglial activation and astrocytic proliferation in the brain. Notably, FMT was related to restoration of microbial diversity, improvement of barrier-related markers, attenuation of neuroinflammatory responses, and a reduction in seizure susceptibility.<br><br>CONCLUSION: This study provides evidence linking gut microbiota dysbiosis to seizure susceptibility through neuroinflammatory processes, contributing to the understanding of gut-brain axis involvement in fluoroquinolone-induced seizures.}, }
@article {pmid41989595, year = {2026}, author = {Walker, MR and Schwarzfischer, M and Scharl, M}, title = {The cancer-microbiome axis: Mechanisms and emerging therapeutic strategies.}, journal = {Seminars in immunopathology}, volume = {48}, number = {1}, pages = {}, pmid = {41989595}, issn = {1863-2300}, }
@article {pmid41990750, year = {2026}, author = {Gonzalez Pastor, B and Shkoporov, AN and Hill, C}, title = {Not just passengers: Phages as agents of genetic exchange in fecal microbiota transplantation.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {5}, pages = {780-789}, doi = {10.1016/j.chom.2026.03.017}, pmid = {41990750}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation/methods ; *Bacteriophages/genetics/physiology ; Humans ; *Gene Transfer, Horizontal ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics/virology ; Clostridium Infections/therapy ; Animals ; Clostridioides difficile ; Feces/microbiology ; Virome ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection and is increasingly being explored for other microbiota-associated diseases. However, general research has largely focused on bacterial engraftment, overlooking the contribution of the gut virome. In this perspective, we highlight phage-mediated horizontal gene transfer (HGT) as a potentially influential process occurring following FMT. Donor-derived phages may potentially influence community structure, engraft in resident bacteria, and modulate microbial functions or host physiology. In addition, temperate phages are well-equipped to mobilize bacterial genes, such as metabolic functions, stress-response traits, and antibiotic resistance determinants, raising the possibility that gene flow could well contribute to FMT outcomes. We propose a conceptual model in which phages act as bidirectional mediators of adaptation, not only accompanying bacterial communities but also influencing gut ecosystems in subtle, yet potentially consequential, ways.}, }
@article {pmid41991237, year = {2026}, author = {Wang, MT and Wang, D and Qi, YP and Chen, Q and Qin, XM and Wang, T and Lu, WH and Cao, YY}, title = {Fecal microbiota transplantation alleviates sepsis-induced acute lung injury by improving mitochondrial function.}, journal = {The Korean journal of physiology &amp; pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.4196/kjpp.25.304}, pmid = {41991237}, issn = {1226-4512}, abstract = {Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with limited therapeutic options. This study investigated the protective effects and underlying mechanisms of fecal microbiota transplantation (FMT) in a murine model of sepsis-induced ALI. 16S rRNA sequencing confirmed that FMT rescued sepsis-induced gut microbiota dysbiosis, restoring microbial diversity and composition. The results demonstrated that FMT significantly improved survival, attenuated pulmonary pathological damage and edema, and reduced systemic and pulmonary levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Furthermore, FMT preserved alveolar-capillary barrier integrity, as evidenced by reduced vascular permeability and upregulated expression levels of tight junction proteins (ZO-1 and occludin). Mechanistically, FMT ameliorated mitochondrial dysfunction in lung tissue, as evidenced by the restoration of oxidative phosphorylation capacity, increased ATP production, reduced mitochondrial reactive oxygen species accumulation, and decreased mitochondrial DNA release. These improvements were associated with a rebalancing of mitochondrial dynamics, characterized by increased expression levels of fusion proteins (OPA1, Mfn1, and Mfn2) and decreased expression of a fission protein (Drp1). Our findings highlight the gut-lung axis as a therapeutic target in sepsis and demonstrate that FMT alleviates sepsis-induced ALI by restoring gut microbiota homeostasis and subsequently preserving mitochondrial function. Further clinical studies are warranted to validate these preclinical findings and explore optimal FMT protocols for critical care applications.}, }
@article {pmid41992528, year = {2026}, author = {Yanyan, X and Yanyu, Q and Qiao, G and Jiabo, G and Desong, K and Heiying, J}, title = {Atractylenolide III Alleviates the Lipid Metabolic Disorders in Ovariectomy-Induced Estrogen-Deficient Mice Through Repairing Intestinal Inflammation and Microenvironment.}, journal = {The journal of obstetrics and gynaecology research}, volume = {52}, number = {4}, pages = {e70272}, pmid = {41992528}, issn = {1447-0756}, support = {//National Natural Science Foundation of China/ ; SJCX23_0770//Jiangsu Provincial Department of Education/ ; SJCX23_0874//Jiangsu Provincial Department of Education/ ; MS2023047//Jiangsu Provincial Health Commission/ ; }, mesh = {Animals ; Female ; Ovariectomy/adverse effects ; Mice ; Mice, Inbred C57BL ; *Estrogens/deficiency ; *Sesquiterpenes/pharmacology/administration &amp; dosage ; *Lactones/pharmacology/administration &amp; dosage ; *Lipid Metabolism Disorders/drug therapy/etiology ; *Inflammation/drug therapy ; Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Intestines/drug effects ; }, abstract = {OBJECTIVE: To investigate the mechanism by which Atractylenolide III (ATIII) alleviates ovariectomy-induced, estrogen-deficient lipid metabolism disorders through the repair of intestinal inflammation and the barrier microenvironment.<br><br>METHODS: Female C57BL/six mice (8&#x2009;weeks old) were randomly assigned to three groups: a blank control group (Con, n&#x2009;=&#x2009;10), a sham surgery group (Sham, n&#x2009;=&#x2009;10), and an ovariectomized (OVX) group (n&#x2009;=&#x2009;70). The OVX group was further subdivided into a model group (OVX&#x2009;+&#x2009;HFD), low- and high-dose ATIII groups (ATIII-L, ATIII-H), an estradiol (E2) group, and groups receiving fecal microbiota transplantation (FMT) from the blank control, model, or high-dose ATIII donors. After 60&#x2009;days on a high-calorie diet, treatments were administered for 28 consecutive days. Serum, liver, and intestinal tissues, and cecal contents were collected from six randomly selected mice per group. Body weight was monitored; hepatic and colonic morphology was assessed by H&amp;E staining; serum lipid profiles were determined using an automated biochemical analyzer; ELISA quantified estradiol and inflammatory cytokine levels; expression of colonic barrier-related proteins was evaluated by Western blot; and gut microbiota composition was analyzed via 16S rRNA sequencing.<br><br>RESULTS: Under conditions of estrogen deficiency, a high-calorie diet mimicking modern human intake predisposed mice to significant weight gain (p&#x2009;<&#x2009;0.05) and dyslipidemia, accompanied by a spectrum of pathological alterations including intestinal barrier dysfunction (evidenced by downregulated tight junction proteins), systemic inflammation (reflected by elevated pro-inflammatory cytokines), hepatic steatosis, colonic inflammatory damage, and gut microbiota dysbiosis. ATIII intervention effectively mitigated these abnormalities, as demonstrated by reduced body weight, improved lipid profiles, repaired hepatic and colonic injuries, upregulated intestinal barrier proteins, downregulated inflammatory cytokines, a tendency toward elevated estrogen levels, and enhanced gut microbial diversity.<br><br>CONCLUSIONS: ATIII ameliorates ovariectomy-induced estrogen-deficient dyslipidemia by repairing intestinal barrier function and modulating intestinal inflammation. Concurrently, it exerts beneficial effects on estrogen levels and gut microbiota composition, in which the gut microbiota plays a mediating role. The experiment demonstrated that the active ingredients of traditional Chinese medicine hold significant value in treating lipid metabolism disorders in perimenopausal women, and there is potential for further in-depth research into the mechanism by which they enhance efficacy through modulating gut microbiota.}, }
@article {pmid41993214, year = {2026}, author = {Zhang, H and Ye, P and Yang, W and Dou, Y and Tian, Z and Zhang, N and Cui, N and Sun, L and Liu, Z and Chen, Y and Liu, X and Yang, H}, title = {Berberine protects against hypoxia-induced intestinal injury through modulation of gut microbiota and bile acid metabolism.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1784245}, pmid = {41993214}, issn = {1664-3224}, mesh = {Animals ; *Berberine/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Hypoxia/complications/metabolism ; *Bile Acids and Salts/metabolism ; Intestinal Barrier Function ; Male ; Intestinal Mucosa/metabolism/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; *Intestines/drug effects ; *Intestinal Diseases/etiology/metabolism/prevention &amp; control ; }, abstract = {BACKGROUND: High-altitude hypoxia disrupts intestinal homeostasis by impairing the epithelial barrier, triggering inflammation, and promoting microbial translocation. Berberine (BER), a natural isoquinoline alkaloid with antimicrobial and anti-inflammatory properties, has shown potential in protecting intestinal integrity; however, its efficacy under hypoxic conditions and its interaction with the gut microbiota remain unclear.<br><br>METHODS: A chronic hypoxia mouse model was used to investigate the protective effects of BER against intestinal injury. Microbiota dependency was assessed through antibiotic-mediated depletion and fecal microbiota transplantation (FMT), combined with 16S rRNA gene sequencing, metabolomics, and immune profiling. The functional role of a BER-responsive bacterium was validated by oral administration in antibiotic-treated mice.<br><br>RESULTS: BER supplementation restored epithelial barrier integrity, including tight junctions, antimicrobial peptide expression, and goblet cell function, while reducing inflammation and epithelial apoptosis under hypoxic conditions. BER also reshaped gut microbial composition and network structure, accompanied by coordinated alterations in cecal metabolites, particularly purine metabolites and bile acids. Microbiota depletion abolished the protective effects of BER, whereas FMT from BER-treated donors recapitulated these effects, confirming a microbiota-dependent mechanism. Among BER-responsive taxa, Bacteroides thetaiotaomicron (B. thetaiotaomicron) emerged as a key effector, correlating with metabolite profiles and barrier integrity. Oral administration of B. thetaiotaomicron alone protected against hypoxia-induced intestinal injury, restoring mucin production and antimicrobial peptide expression, and attenuating inflammation and apoptosis. Mechanistically, both BER and B. thetaiotaomicron reactivated bile acid-FXR signaling and normalized intestinal immune homeostasis, including T-cell subset distribution.<br><br>CONCLUSION: These findings demonstrate that BER protects against hypoxia-induced intestinal injury through microbiota-dependent metabolic and immune regulation. B. thetaiotaomicron acts as a central mediator of this protective effect, highlighting microbiota-targeted strategies as potential interventions for maintaining intestinal homeostasis under hypoxic stress.}, }
@article {pmid41993317, year = {2026}, author = {Chaki, T and Maruyama, D and Doan, TN and Xiaoli, T and Prakash, A}, title = {Dietary tryptophan mitigates lung ischemia-reperfusion injury via microbiota-derived indole-3-propionate and aryl hydrocarbon receptor signaling.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.02.714281}, pmid = {41993317}, issn = {2692-8205}, abstract = {BACKGROUND: Lung ischemia-reperfusion (IR) injury drives early morbidity after lung transplantation and cardiothoracic surgery, yet targeted preventive therapies are lacking. The gut-lung axis and microbiota-derived tryptophan metabolites, including indole-3-propionate (IPA), may regulate pulmonary immunity and inflammation. We investigated whether a tryptophan-rich (Trp-Rich) diet attenuates sterile lung IR injury by increasing microbiota-derived indole metabolites and reprogramming alveolar macrophage (AM) inflammatory responses.<br><br>METHODS: C57BL/6 mice received isocaloric tryptophan-standard (Trp-Std; 0.18%) or Trp-Rich (0.60%) diets for 14 days, then underwent unilateral left lung IR (60 min ischemia followed by 60 min reperfusion). Oxygen saturation, lung cytokines, and aryl hydrocarbon receptor (AhR) signaling readouts (Cyp1a1 / Cyp1b1) were evaluated. Gut microbiota was profiled by 16S rRNA sequencing, and targeted metabolomics quantified tryptophan metabolites in feces, portal vein (PV) plasma, and lung tissue. To further assess inflammatory priming in vivo , mice were additionally challenged with intratracheal lipopolysaccharide (LPS). Mechanistic studies compared IPA with related indole metabolites in MH-S cells and primary human AMs, including ex vivo nutritional IR, LPS stimulation, and AhR stimulation and blockade using synthetic agonists and antagonists.<br><br>RESULTS: Trp-Rich feeding improved post-IR oxygenation, reduced lung IL-1&#x3b2;, and increased pulmonary Cyp1a1 / Cyp1b1 gene expression. Trp-Rich diet remodeled the gut microbiota, including enrichment of Bifidobacterium and Lactobacillus , and increased IPA levels across feces, PV plasma, and lung tissue, with lower kynurenine/IPA ratios across matrices. In the LPS intratracheal challenge, Trp-Rich feeding reduced IL-6 levels in lung tissue and systemic plasma. Primary murine AMs isolated from Trp-Rich mice also showed reduced IL-1&#x3b2; and IL-6 release in an ex vivo nutritional IR model. Among tested indole metabolites, IPA showed the strongest dose-dependent suppression of LPS-induced cytokines and chemokines in MH-S cells and primary human AMs, remained active in the ex vivo nutritional IR model, and its anti-inflammatory effect was abrogated by AhR blockade and enhanced by co-treatment with other indole metabolites.<br><br>CONCLUSIONS: A Trp-Rich diet attenuated sterile lung IR injury, coinciding with gut microbiota remodeling, increased systemic and pulmonary IPA, reduced inflammatory priming, and reprogrammed AM responses. These data support diet- or microbiome-directed strategies targeting IPA-AhR signaling to mitigate perioperative lung IR injury.}, }
@article {pmid41993582, year = {2026}, author = {Simões, JLB and Braga, GC and Assmann, CE and Bagatini, MD}, title = {Targeting the gut-immune-brain axis: pharmacological insights from depression in inflammatory bowel disease.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1793292}, pmid = {41993582}, issn = {1663-9812}, abstract = {Inflammatory Bowel Disease (IBD), comprising Crohn's Disease and Ulcerative Colitis, is a chronic inflammatory condition of the gastrointestinal tract with a remarkably high prevalence of psychiatric comorbidities, particularly Major Depressive Disorder (MDD). The traditional monoaminergic hypothesis of depression is insufficient to explain the complex etiology of MDD, paving the way for new paradigms, such as the inflammatory hypothesis of depression. This narrative review critically explores IBD as a human clinical model to investigate the connection between chronic inflammation and depression. It is argued that gut dysbiosis, a central feature of IBD, is a fundamental trigger that, through a compromised gut barrier, drives systemic inflammation and, subsequently, neuroinflammation. We detail the molecular and cellular mechanisms that link intestinal inflammation to central nervous system (CNS) dysfunction, including microglial activation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and kynurenine pathway activation, which diverts tryptophan metabolism from serotonin synthesis to the production of neurotoxic metabolites. Robust epidemiological evidence demonstrating a bidirectional association between IBD and depression is discussed, suggesting a shared pathophysiology rather than a simple cause-and-effect relationship. Furthermore, we review the implications and emerging therapeutics, highlighting the antidepressant effects of immunobiologicals, such as anti-TNF therapies, and the potential of emerging interventions that target the microbiome, such as probiotics, psychobiotics, fecal microbiota transplantation, and anti-inflammatory diets. Furthermore, we address the limitations of the current literature, such as the lack of a quantitative definition for dysbiosis and the scarcity of clinical trials with integrated neuropsychiatric outcomes, and propose directions for future translational research. We conclude that IBD should be considered a systemic disease with significant psychiatric repercussions, advocating for an integrated therapeutic approach that combines immunomodulatory, neuromodulatory, and microbiological interventions to treat both gut and brain pathology effectively.}, }
@article {pmid41993584, year = {2026}, author = {Liang, X and He, J and Wu, Q and Fu, L and Liu, Y}, title = {Gut microbiome in alcohol-associated liver disease: interactions and therapeutic strategies.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1770833}, pmid = {41993584}, issn = {1663-9812}, abstract = {Alcohol-associated liver disease (ALD), a significant cause of chronic liver disease worldwide, is strongly linked to gut microbiome dysregulation. Heavy alcohol use disrupts the gut bacterial equilibrium and damages the intestinal barrier, making it more permeable to microbial toxins (e.g., endotoxins) that trigger liver inflammation. Many studies have investigated ALD, but no single microbial marker has yet been identified as diagnostic. Results from microbiome studies on this condition have been inconsistent; consequently, scientists are developing new microbiome-based indices and multi-omics approaches to improve their ability to predict diseases. The review evaluates current findings on how disturbances in the gut microbiome and deterioration of the intestinal barrier contribute to the development of ALD. The assessment includes microbiome-based treatments such as probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy. Research indicates that probiotics and FMT treatments may enhance liver function and reduce inflammation in patients with ALD. The studies present conflicting results because researchers used different methods and worked with limited numbers of participants. Bacteriophage therapy exists as an experimental treatment method. The development of personalized microbiome treatments, along with biomarker standardization and solutions to technical and ethical challenges, will enable these strategies to enter medical practice. The review integrates existing knowledge of the gut-liver axis in ALD to demonstrate the clinical potential of microbiome-based treatments while highlighting the need for additional research to enhance treatment outcomes.}, }
@article {pmid41993996, year = {2026}, author = {Au Yong, SJ and Lestari Lee, AS and Subramaniyan, V and Long, CM and Husain, S and Reginald, K and Ser, HL}, title = {Gut microbiome modulation in allergic rhinitis: from current evidence to emerging therapies.}, journal = {Frontiers in allergy}, volume = {7}, number = {}, pages = {1761840}, pmid = {41993996}, issn = {2673-6101}, abstract = {Allergic rhinitis (AR) is a common inflammatory disorder of the upper airway that is primarily managed with pharmacotherapy, biologics and allergen immunotherapy. However, a substantial proportion of patients experience incomplete or insufficient symptom control, treatment-related adverse effects, or poor adherence. Increasing evidence has linked AR with alterations in microbial composition across multiple mucosal sites, including the gut, highlighting potential roles for host-microbiome interactions in the regulation of allergic inflammation, although causal relationships remain incompletely defined. This narrative mini-review synthesizes current evidence on gut microbiome-based interventions for allergic rhinitis (AR), including probiotics, prebiotics, synbiotics, postbiotics, and emerging approaches such as fecal microbiota transplantation, engineered microbes, and bacteriophage-based therapies. It examines proposed immunological mechanisms involving type 2 inflammation, regulatory immune pathways, and gut-airway axis signalling, while distinguishing clinically evaluated strategies from experimental or preclinical and assessing their translational readiness. Collectively, available evidence suggests that microbiome-targeted therapies represent a promising conceptual avenue for understanding and potentially modulating AR. However, their clinical application remains constrained by heterogeneous study designs, reliance on extrapolated data from preclinical studies, limited standardized outcome measures, insufficient long-term safety data, and evolving regulatory frameworks. Addressing these challenges through well-designed clinical trials and improved mechanistic characterization will be essential to clarify the role of microbiome-based interventions as adjunctive strategies in AR management.}, }
@article {pmid41994273, year = {2026}, author = {Yu, Z and Qian, W and Chu, Y}, title = {Targeting the gut-lung axis in COPD: from microbial metabolites to fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1798150}, pmid = {41994273}, issn = {1664-302X}, abstract = {Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional syndrome manifested by persistent airway inflammation, oxidative stress, and progressive airflow limitation, with pathology extending far beyond the lung. The gut-lung axis has emerged as a pivotal paradigm for understanding this systemic nature, underscoring the regulatory potency of gut microbiota-derived metabolites in inter-organ immune and metabolic crosstalk. Accumulating evidence suggests that COPD is intricately linked to gut microbiota dysbiosis and widespread disturbances in bioactive metabolites, particularly short-chain fatty acids (SCFAs), tryptophan-related amino acids (AAs), and bile acids (BAs). These metabolic aberrations exacerbate pulmonary inflammation by dysregulating immune homeostasis, compromising intestinal barrier integrity, and skewing redox balance. Fecal microbiota transplantation (FMT), as a strategy capable of comprehensively reconstituting gut microbial and metabolic homeostasis, has demonstrated potential in preclinical and translational settings to attenuate pulmonary injury via the gut-lung axis. This review centers on gut microbiota-associated metabolites, systematically summarizing their roles in COPD pathogenesis and critically evaluating the emerging evidence and mechanistic basis by which FMT recalibrates COPD progression through metabolic pathways, thereby providing a robust theoretical framework for developing precision gut microbiota-targeted systemic therapeutic strategies.}, }
@article {pmid41994742, year = {2026}, author = {Vadukoot Lazar, M and C S Menon, A and Thomas, J}, title = {Type 3c Diabetes Mellitus: Epidemiology, Diagnosis, Management, and Research Imperatives With Insights From the United Arab Emirates and Global Contexts.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e105089}, pmid = {41994742}, issn = {2168-8184}, abstract = {Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic diabetes, is a form of secondary diabetes resulting from pancreatic disease and is frequently misclassified as type 2 DM (type 2 DM). A narrative review of peer-reviewed literature from international databases was conducted, with emphasis on the epidemiology, clinical differences, diagnostic complexities, and management of T3cDM, with a specific focus on the United Arab Emirates (UAE) and global contexts. T3cDM accounts for a notable proportion of global diabetes cases, yet it is underreported due to a lack of dedicated registries and frequent misclassification as type 2 diabetes. The UAE has one of the highest diabetes prevalence rates worldwide, yet T3cDM remains undercaptured. Unlike type 1 DM (T1DM) and T2DM, T3cDM is characterized by both endocrine and exocrine pancreatic insufficiency (EPI). The diagnosis requires evidence of pancreatic pathology, absent autoimmunity, and exocrine dysfunction. Management includes insulin therapy, pancreatic enzyme replacement therapy (PERT), and nutritional supplementation; recent advances include the role of incretin therapies, improved enzyme preparations, and regenerative medicines. Emerging approaches also include metabolomics for prediction and fecal microbiota transplantation. Increasing awareness, dedicating regional registries, and implementing multidisciplinary management strategies are urgently needed in the UAE and globally.}, }
@article {pmid41995553, year = {2026}, author = {Tseng, WC and Chen, KC and Chung, CS and Tseng, PC and Lin, CK and Liao, CH}, title = {Comparative effectiveness of vancomycin and fidaxomicin in the treatment of Clostridioides difficile-associated diarrhea: A single-center experience in Taiwan.}, journal = {Medicine}, volume = {105}, number = {16}, pages = {e48307}, pmid = {41995553}, issn = {1536-5964}, mesh = {Humans ; *Vancomycin/therapeutic use/administration &amp; dosage ; *Fidaxomicin/therapeutic use/administration &amp; dosage ; Male ; Female ; Taiwan ; Retrospective Studies ; Aged ; *Anti-Bacterial Agents/therapeutic use/administration &amp; dosage ; *Clostridium Infections/drug therapy ; *Diarrhea/drug therapy/microbiology ; Middle Aged ; *Clostridioides difficile ; Aged, 80 and over ; Fecal Microbiota Transplantation ; Treatment Outcome ; Adult ; }, abstract = {Clostridioides difficile-associated diarrhea (CDAD) has become an increasingly common healthcare-associated infection worldwide. Although both vancomycin and fidaxomicin are approved for treatment, real-world comparative data from Taiwan remain limited. This study aimed to evaluate the effectiveness of vancomycin and fidaxomicin in treating CDAD and to identify patients at risk of treatment failure who may benefit from fecal microbiota transplantation. This single-center retrospective observational study was conducted at Far Eastern Memorial Hospital from January 2018 to August 2020. Adult patients (≥20 years) diagnosed with CDAD and treated with oral vancomycin (125 mg 4 times daily) and/or fidaxomicin (200 mg twice daily) for 10 days were included. Treatment success and failure rates were compared between groups, and associations with age, sex, and Charlson Comorbidity Index (CCI) were analyzed using a Student t test and chi-square test, with significance defined as P ≤ .05. A total of 166 patients were analyzed (mean age = 72.36 ± 14.72 years; mean CCI = 6.80 ± 2.61). Of these, 161 received vancomycin and 48 received fidaxomicin. The treatment success rate was 53.4% for vancomycin and 79.2% for fidaxomicin. Among vancomycin-treated patients, treatment failure was significantly associated with older age (P = .009) and higher CCI (P = .004). No statistically significant associations were observed for fidaxomicin outcomes with age, sex, and CCI. Fidaxomicin demonstrated superior clinical effectiveness to vancomycin, particularly among older adults and patients with multiple comorbidities. These findings support prioritizing fidaxomicin for high-risk patients and considering fecal microbiota transplantation in refractory cases.}, }
@article {pmid41997122, year = {2026}, author = {Davar, D and Zarour, HM and Trinchieri, G}, title = {Improving immunotherapy in solid tumors using FMT.}, journal = {Cell}, volume = {189}, number = {8}, pages = {2214-2217}, doi = {10.1016/j.cell.2026.03.021}, pmid = {41997122}, issn = {1097-4172}, mesh = {Humans ; *Immunotherapy/methods ; *Fecal Microbiota Transplantation/methods ; *Neoplasms/therapy/immunology/microbiology ; Immune Checkpoint Inhibitors/therapeutic use ; Melanoma/therapy ; Animals ; Carcinoma, Non-Small-Cell Lung/therapy ; Clinical Trials as Topic ; }, abstract = {Recent clinical trials demonstrate that fecal microbiota transplantation (FMT) enhances first-line immune checkpoint inhibitor efficacy in renal cell carcinoma, cutaneous melanoma, and non-small cell lung cancer with acceptable safety. Benefit appears mediated by functional microbiome remodeling, depletion of deleterious taxa, and systemic immunometabolic modulation, supporting microbiome-directed therapeutic strategies for cancer immunotherapy.}, }
@article {pmid41997887, year = {2026}, author = {Allerton, F and Whittle, MJ and Durkin, L and Prior, C and Trehy, M and Swales, H and Duplan, F and Borgonovi, S and Pinchbeck, G and Gajanayake, I and Dunning, M and Sparks, T and Watson, P and Amos, GCA and McCallum, K and Bazelle, J and Kent, A}, title = {Clinical benefit of faecal microbiota transplantation administered via a single retention enema as an adjunctive treatment in dogs with chronic enteropathy: a randomised controlled trial.}, journal = {The Journal of small animal practice}, volume = {}, number = {}, pages = {}, doi = {10.1111/jsap.70137}, pmid = {41997887}, issn = {1748-5827}, support = {//Small Animal Society/ ; //Linnaeus Veterinary Limited, which is part of Mars Veterinary Health, supported the cots of the Open Access Publication Charges/ ; }, abstract = {OBJECTIVES: To evaluate the clinical benefit of faecal microbiota transplantation administered via a single retention enema, as an adjunctive treatment in the management of dogs with chronic enteropathy.<br><br>MATERIALS AND METHODS: Blinded, randomised controlled trial. Dogs with chronic enteropathy (>3&#x2009;weeks of small or mixed intestinal diarrhoea) were randomly allocated to either the faecal microbiota transplantation or standard treatment group (ratio 1:1) via blinded selection. Dogs in the standard treatment group had a diet change only, while dogs in the faecal microbiota transplantation group had a diet change and faecal microbiota transplantation. faecal microbiota transplantation was performed using fresh faecal material from donor dogs, screened for selected enteropathogens and administered via retention rectal enema. Outcomes measured included the Canine Inflammatory Bowel Disease Activity Index, faecal score and the owner's reported improvement. Group comparisons were made using Fisher's exact tests (owner-reported outcomes) and Kruskal-Wallis tests adjusted for ties (Canine Inflammatory Bowel Disease Activity Index and faecal score).<br><br>RESULTS: Forty-two dogs with chronic enteropathy (median Canine Inflammatory Bowel Disease Activity Index score 6 [range 4 to 11]) were included in the study. Twenty-five dogs were randomly assigned to receive faecal microbiota transplantation, while 17 dogs were allocated to standard treatment. A progressive improvement in stool consistency (reduced faecal score) was recorded over time for most dogs in both groups. By Day 90, the rates of owner-defined clinical improvement were 76% (CI 54% to 90%) in the faecal microbiota transplantation group and 73% (CI 40% to 92%) in the standard treatment group. No significant differences were evident between the two groups based on the proportion of owners that reported clinical improvement, Canine Inflammatory Bowel Disease Activity Index score or faecal score.<br><br>CLINICAL SIGNIFICANCE: This study did not demonstrate a clear clinical benefit for adjunctive faecal microbiota transplantation via single retention enema in dogs with chronic enteropathy compared to diet change alone, although the small sample size means that a type II error cannot be excluded. The similar outcome for both groups supports high rates of food responsiveness among this cohort of chronic enteropathy dogs.}, }
@article {pmid41997890, year = {2026}, author = {Rode, AA and Duboc, H and Lamazière, A and Rainteau, D and Humbert, L and Gauliard, E and Chehri, M and Petersen, AM and Helms, M and Schønning, K and Nielsen, HV and Bytzer, P and Engberg, J}, title = {Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2658915}, pmid = {41997890}, issn = {1949-0984}, mesh = {Humans ; *Bile Acids and Salts/metabolism/chemistry/analysis ; *Fecal Microbiota Transplantation/methods ; *Vancomycin/administration &amp; dosage/therapeutic use ; Feces/microbiology/chemistry ; *Clostridium Infections/therapy/microbiology ; Clostridioides difficile/drug effects/physiology/genetics ; *Anti-Bacterial Agents/administration &amp; dosage ; Female ; Recurrence ; Male ; Middle Aged ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Aged ; Adult ; Administration, Oral ; }, abstract = {Patients with Clostridioides difficile infection have high colonic levels of primary bile acids, which are potent germinators of Clostridioides difficile. Several studies have suggested that re-establishing a normal bile acid composition is a key factor in fecal microbiota transplantation (FMT) for recurrent C. difficile infection, yet former studies supporting this lacked controls. In a subgroup from a randomized controlled trial, we compared the bile acid composition in patients with recurrent C. difficile infection treated with either FMT, a bacterial mixture, or vancomycin. The fecal bile acid content was analyzed several times before and after treatments. Furthermore, we used 16S rDNA gene sequencing to analyze the presence of some bacterial species involved in bile acid metabolism. Stool donors served as healthy controls. We observed a higher proportion of primary bile acids in patients with recurrent C. difficile infection than in donors, yet a donor-like dominance of secondary bile acids was observed after successful treatment in all groups. The shift seemed to occur earliest in the FMT group, followed by the vancomycin group, and the latest in the bacterial mixture group. In approximately half of the participants, the rise in secondary bile acids was timely associated with the detection of bile acid-transforming bacteria that were absent before treatment. Our findings indicate that FMT re-establishes the bile acid composition faster than vancomycin, reducing the time of susceptibility to recurrences of C. difficile infection. Hence, bacterial mixtures developed as an alternative to donor stool for treating recurrent C. difficile infection might benefit from including bile acid-metabolizing bacteria.}, }
@article {pmid42001079, year = {2026}, author = {Yang, Y and Kang, C and Pang, R and Huang, S and He, X and Gou, X and Yang, Y and Yan, Y and Ma, X}, title = {Dihydromyricetin exerts neuroprotective effects in acute spinal cord injury by inhibiting NLRP3/Caspase-1 inflammasome through gut microbiome modeling.}, journal = {Journal of inflammation (London, England)}, volume = {23}, number = {1}, pages = {}, pmid = {42001079}, issn = {1476-9255}, support = {2024060//Chengdu Municipal Health Commission Medical Research Project/ ; 25MSZX488//Sichuan Provincial Administration of Traditional Chinese Medicine Research Project/ ; }, abstract = {BACKGROUND: The gut microbiota is closely associated with spinal cord injury (SCI). Dihydromyricetin (DHM), a potent anti-inflammatory compound with neuroprotective properties, has been shown to improve outcomes in various diseases. However, the role of gut microbiota mediating the mechanism neuroprotective effects of DHM in SCI is unknown.<br><br>METHODS: Male Sprague-Dawley rats were randomly divided into three groups: SHAM, SCI, and DHM group. Motor function was assessed using the cylinder rearing test, and alterations in gut microbiota composition and metabolites were analyzed via 16S rRNA sequencing. Subsequently, Western blotting and immunofluorescence staining were employed to evaluate intestinal barrier integrity, as well as changes in proteins associated with the TLR4/NF-&#x3ba;B pathway and NLRP3/Caspase-1. Finally, fecal microbiota transplantation experiments were conducted to elucidate the necessity of gut microbiota in mediating the anti-inflammatory effects of DHM.<br><br>RESULTS: DHM exhibits a therapeutic effect by attenuating the severity of pathological SCI and promoting motor function recovery. Notably, DHM restored a balanced microbiota pattern by increasing the relative abundance of Actinobacteria and Bacteroidetes, while concurrently decreasing that of Proteobacteria. Furthermore, DHM promoted intestinal barrier recovery, reduced blood lipopolysaccharide (LPS) levels, and suppressed the activation of the TLR4/NF-&#x3ba;B pathway and reduced the activity of the NLRP3/Caspase-1 inflammasome, thereby effectively decreasing the subsequent release of inflammatory factors in spinal cord tissue. Furthermore, the results from the two FMT groups demonstrated that the gut microbiota serves as a critical target for DHM to exert its anti-inflammatory effects.<br><br>CONCLUSION: The results of this study demonstrate that restoring microbial balance, repairing intestinal barrier integrity, reducing serum LPS levels, and suppressing the TLR4/NF-&#x3ba;B pathway as well as NLRP3/Caspase-1 inflammasome activity constitute the key regulatory mechanisms underlying the neuroprotective effects of DHM following SCI, thereby opening up possibilities for a novel microbiome-directed therapeutic approach to SCI.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12950-026-00499-5.}, }
@article {pmid42002228, year = {2026}, author = {Liu, S and Huang, Z and Guo, Z}, title = {Fecal Microbiota Transplantation for Gastrointestinal Complications After Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Narrative Synthesis.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2026.04.016}, pmid = {42002228}, issn = {2666-6367}, abstract = {Following allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients frequently develop gastrointestinal complications, including microbiota dysbiosis, infectious syndromes, and graft-versus-host disease (GVHD), which remain major contributors to post-transplant morbidity and mortality. In recent years, several studies have explored microbiome-based interventions, particularly fecal microbiota transplantation (FMT), as a therapeutic strategy for these complications in this highly immunocompromised population. However, substantial variability exists across studies with respect to clinical indications, FMT protocols, and reported outcomes. To systematically evaluate the reported clinical use of FMT for gastrointestinal complications following allo-HSCT, including microbiota dysbiosis, infectious complications, and GVHD. The aim was to characterize study populations, treatment protocols, and reported clinical outcomes, and to synthesize evidence regarding efficacy and safety, with a focus on indication-specific patterns and potential translational relevance for patient management in this highly immunocompromised population. We conducted a PRISMA-compliant systematic review of studies evaluating FMT as a treatment in patients after allo-HSCT. PubMed, Embase, Web of Science, and the Cochrane Library were searched through October 2025. Eligible studies included randomized controlled trials, cohort studies, and prospective or retrospective single-arm studies reporting clinical outcomes following FMT. Given the marked heterogeneity in clinical indications, FMT administration strategies, and outcome definitions, study findings were synthesized using a structured narrative approach, with quantitative data summarized descriptively where appropriate. Twenty studies including patients after allo-HSCT were analyzed. FMT demonstrated high and consistent response rates in non-GVHD indications, whereas GVHD cohorts exhibited more variable responses, with median CR and ORR ranging 50% to 55% in steroid-refractory cases. One-year overall survival was generally favorable in dysbiosis and infection groups (>70%), but more heterogeneous in GVHD. FMT was well tolerated, with predominantly mild gastrointestinal adverse events; serious events were infrequent and mostly disease-related. Current evidence indicates that FMT has been explored as a context-dependent therapy for selected gastrointestinal complications following allo-HSCT, particularly in patients with acute GVHD. Nevertheless, substantial heterogeneity in study design, clinical indications, and outcome assessment limits definitive conclusions regarding efficacy. Well-designed prospective studies with standardized treatment indications, outcome measures, and careful consideration of concurrent immunosuppressive therapies are required to better define the optimal role, timing, and patient selection for FMT in the post-transplant treatment setting.}, }
@article {pmid42002330, year = {2026}, author = {Zhao, Y and Qiao, M and Ma, C and Hou, Q and Hu, J and Yang, J}, title = {A fructan-type polysaccharide from Lycium ruthenicum attenuates liver fibrosis via microbiota-dependent ferroptosis inhibition.}, journal = {Carbohydrate polymers}, volume = {382}, number = {}, pages = {125243}, doi = {10.1016/j.carbpol.2026.125243}, pmid = {42002330}, issn = {1879-1344}, mesh = {Animals ; *Lycium/chemistry ; *Liver Cirrhosis/drug therapy/metabolism/chemically induced/pathology ; *Ferroptosis/drug effects ; *Gastrointestinal Microbiome/drug effects ; Male ; *Fructans/pharmacology/chemistry/therapeutic use/isolation &amp; purification ; *Polysaccharides/pharmacology/chemistry ; Mice ; Mice, Inbred C57BL ; Liver/drug effects/metabolism/pathology ; Oxidative Stress/drug effects ; }, abstract = {Plant-derived polysaccharides represent promising candidates for hepatic fibrosis (HF) therapy through the gut-liver axis. This study investigated the structural characteristics, anti-fibrotic efficacy, and mechanisms of LRMP1, a novel polysaccharide from Lycium ruthenicum Murr. LRMP1 was identified as a homogeneous inulin-type fructan (3.055 kDa) with a → 1)-β-D-Fruf-(2 → backbone terminated by α-D-Glcp-(1 → 2)-β-D-Fruf linkages (DP 4-20). Integrated multi-omics analysis combining hepatic transcriptomics, serum metabolomics, and gut microbiome profiling revealed that LRMP1 ameliorates HF via a gut microbiota-postbiotics-ferroptosis regulatory axis. In both CCl4-induced and MCD diet-induced chronic fibrosis models, LRMP1 significantly attenuated liver injury, fibrosis, inflammation, and oxidative stress, while restoring intestinal barrier integrity. These protective effects correlated with enrichment of beneficial bacteria (Akkermansia muciniphila, Lactobacillus spp.) and pathogen depletion. Mechanistically, LRMP1 suppressed TGF-β signaling and inhibited hepatocyte ferroptosis by restoring the GPX4/SLC7A11 antioxidant system and reducing lipid peroxidation. Serum metabolomics further revealed elevated anti-ferroptotic metabolites and suppressed pro-inflammatory lipids. Crucially, antibiotic depletion abolished LRMP1's efficacy, whereas fecal microbiota transplantation and fermentation supernatant experiments confirmed that microbiota-derived postbiotics selectively protect hepatocytes from ferroptosis. These findings establish LRMP1 as a promising microbiota-targeted polysaccharide for HF intervention through the gut-liver axis.}, }
@article {pmid42002659, year = {2026}, author = {Pang, J and Ma, X and Hong, N and Shen, Z and Li, S and Li, X and Wang, S and Cong, H and Zhang, K and Yang, J and Wu, C}, title = {Gut microbiota mediates the antidepressant-like effects of xiaochaihutang: mechanisms involving inhibition of inflammation and enhancement of barrier function.}, journal = {Journal of natural medicines}, volume = {80}, number = {3}, pages = {881-898}, pmid = {42002659}, issn = {1861-0293}, support = {82374066//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82074041//Innovative Research Group Project of the National Natural Science Foundation of China/ ; }, abstract = {Depression is a common mental disorder that seriously impairs the psychological and physical health of patients. Extensive research has indicated that patients with depression exhibit disturbances in their gut microbiota. Xiaochaihutang (XCHT) is a traditional herbal recipe widely used in China, and previous studies have found it to possess antidepressant properties. However, whether XCHT can modulate depression-associated gut microbiota dysbiosis remains unclear. In this research, we investigated the impact of XCHT on the microbiota-gut-brain axis in depressed rats and elucidated the potential mechanisms. A rat model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Behavioral tests demonstrated that XCHT significantly alleviated depression-like behaviors. 16S rRNA sequencing revealed that XCHT enhanced the diversity and compositional structure of the gut microbiota and specifically increased the abundance of the beneficial bacterium Blautia. Fecal microbiota transplantation (FMT) experiments further confirmed that the antidepressant-like effects of XCHT were mediated through modulation of the gut microbiota. Furthermore, XCHT exhibited anti-inflammatory properties in both the central and peripheral systems and improved the integrity of the intestinal barrier and the blood-brain barrier. These mechanisms were also validated using the FMT approach. Collectively, these findings suggest that the antidepressant-like mechanism of XCHT may be directly linked to the regulation of the microbiota-gut-brain axis. This study demonstrates that XCHT exerts antidepressant-like effects by modulating the microbiota-gut-brain axis, providing novel insights into the potential therapeutic mechanisms and clinical applications for depression.}, }
@article {pmid42002835, year = {2026}, author = {Morineau, N and Tessoulin, B and Guimard, T and Papin, M and Roquilly, A and Le Gouill, S and Montassier, E}, title = {Longitudinal gut microbiome dynamics are associated with clinical outcome and toxicity during ibrutinib therapy.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2659397}, pmid = {42002835}, issn = {1949-0984}, mesh = {Humans ; *Adenine/analogs &amp; derivatives/adverse effects/therapeutic use ; *Piperidines/adverse effects/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Feces/microbiology ; Male ; Female ; Longitudinal Studies ; *Bacteria/classification/genetics/isolation &amp; purification/drug effects/metabolism ; Treatment Outcome ; *Pyrimidines/adverse effects/therapeutic use ; *Antineoplastic Agents/adverse effects/therapeutic use ; Middle Aged ; Diarrhea/chemically induced ; Aged ; *Pyrazoles/adverse effects/therapeutic use ; Metagenomics ; }, abstract = {Accumulating evidence indicates that the gut microbiome influences therapeutic efficacy and toxicity across cancer treatments; however, its longitudinal dynamics during targeted therapies remain poorly characterized. Here, we performed whole-genome shotgun metagenomic sequencing of 291 longitudinal stool samples collected over one year from 30 patients with hematologic malignancies treated with ibrutinib. Overall gut microbial diversity remained stable at the population level but exhibited markedly divergent temporal trajectories according to clinical outcome, with progressive recovery in responders and blunted or delayed restoration in non-responders. Longitudinal modeling revealed distinct species- and pathway-level microbial dynamics between patients with treatment response or nonresponse, including enrichment of saccharolytic, short-chain fatty acid-associated taxa and metabolic pathways in responders, and expansion of bile acid-modifying, proteolytic, and inflammation-associated microbial features in non-responders. Functional profiling further demonstrated opposing temporal trends in pathways related to carbohydrate fermentation, amino-acid metabolism, and secondary bile acid synthesis. In addition, both baseline microbiome composition and longitudinal remodeling were associated with the development of ibrutinib-associated diarrhea. Together, these findings reveal coordinated, outcome-specific remodeling of the gut microbiome during ibrutinib therapy and highlight longitudinal microbiome trajectories, rather than static baseline features, as potential biomarkers of treatment response and toxicity, as well as targets for microbiome-directed interventions. In conclusion, our findings highlight a potential role of gut microbiome dynamics in modulating response to BTK inhibition and support the need for larger, prospective studies to validate these observations.}, }
@article {pmid42004962, year = {2026}, author = {Li, J and Chen, X and Xie, X}, title = {Mechanistic insights into gut microbiota-driven autoimmunity in rheumatoid arthritis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1812972}, pmid = {42004962}, issn = {1664-3224}, mesh = {Humans ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Autoimmunity ; Animals ; Dysbiosis/immunology ; }, abstract = {Rheumatoid arthritis (RA) is a systemic autoimmune disease whose pathogenic drivers and initiating immune events remain incompletely understood. Increasing evidence implicates the gut-joint axis in RA, yet the mechanisms by which intestinal microbiota contribute to disease development still require integrative clarification. This review summarizes current experimental and clinical evidence on the role of gut dysbiosis in promoting autoimmunity in RA. We discuss alterations in microbial composition and their links to barrier dysfunction, immune-cell polarization, microbial metabolites, and antigen-specific immune responses. Human cohort studies and arthritis models suggest that reduced microbial diversity, loss of short-chain fatty acid (SCFA)-producing commensals, and expansion of taxa such as Prevotella copri and Collinsella are associated with impaired epithelial integrity, enhanced Th17/Tfh differentiation, reduced regulatory T- and B-cell activity, and increased autoantibody production. Mechanistic studies further support roles for molecular mimicry, microbially derived citrullinated antigens, and metabolite-mediated signaling in the breakdown of immune tolerance and persistence of synovial inflammation. We also discuss emerging microecology-based interventions, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, together with their translational potential and current limitations. Overall, available evidence places gut microbiota-mediated immune remodeling at the center of RA pathogenesis and supports precision microbiome modulation as a promising adjunctive strategy for disease prevention and treatment.}, }
@article {pmid42006120, year = {2026}, author = {Tang, J and Liu, Y and Wu, N and Lu, J and Zhang, Y and Tong, N and Lü, Q}, title = {Gut microbiota: a potential therapeutic target for hyperuricemia and gout.}, journal = {Bioscience of microbiota, food and health}, volume = {45}, number = {2}, pages = {85-99}, pmid = {42006120}, issn = {2186-6953}, abstract = {The prevalence of hyperuricemia (HUA) and gout has increased in recent decades. Current therapeutic approaches for HUA/gout are often limited by potential risks, necessitating the exploration of safer and more effective treatment options. Emerging evidence highlights the gut microbiota as a pivotal regulator of uric acid (UA) homeostasis. This review synthesizes current advances in microbiota-targeted interventions for HUA/gout, focusing on mechanistic insights and translational potential. We aim to provide a roadmap for optimizing microbiota-based therapies in HUA/gout management by bridging mechanistic discoveries with clinical translation. Gut microbiota can mitigate HUA/gout through several mechanisms, including regulating UA and purine metabolism, alleviating inflammation and modulating immune response, and enhancing the integrity of the intestinal barrier. Therapeutic strategies targeting gut microbiota include probiotics, prebiotics, traditional Chinese medicine, and fecal microbiota transplantation, which offer multi-target and multi-pathway benefits. While these microbiota-targeted therapies offer advantages over conventional drugs, several challenges remain. Future research should prioritize mechanistic elucidation, personalized microbiota modulation, and large-scale trials to optimize therapeutic paradigms for HUA/gout.}, }
@article {pmid42006318, year = {2026}, author = {Kang, L and Feng, C and Tang, Z and Gu, W and Wang, Y and Pei, A and Piao, M}, title = {Pueraria flavones attenuate DSS-induced colitis by regulating the microbiota-bile acid-FXR/TGR5 axis and suppressing mtDNA-cGAS-STING signaling.}, journal = {iScience}, volume = {29}, number = {4}, pages = {115275}, pmid = {42006318}, issn = {2589-0042}, abstract = {Ulcerative colitis (UC) is characterized by inflammation and impaired barrier function. Pueraria flavones (PFs) possess anti-inflammatory properties, though their underlying mechanisms remain poorly understood. This study assessed PFs in a dextran sulfate sodium (DSS)-induced colitis mouse model. PFs alleviated colitis symptoms, including weight loss and colon shortening, in a dose-dependent manner, while restoring barrier integrity and reducing pro-inflammatory cytokines. Mechanistically, PFs inhibited cGAS-STING activation by decreasing mitochondrial DNA (mtDNA) release, thereby limiting cytokine production. Furthermore, fecal microbiota transplantation (FMT) confirmed that PFs exert protective effects through the modulation of the gut microbiota. Metabolomic analysis revealed that PFs increased bile acids, such as tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA), which activated the farnesoid X receptor (FXR)/TGR5 signaling pathway to enhance barrier function. Collectively, these findings suggest that PFs mitigate colitis by remodeling the microbiota-bile acid-FXR axis and suppressing mtDNA-cGAS-STING signaling, presenting a promising therapeutic approach for UC.}, }
@article {pmid42007101, year = {2026}, author = {Tang, H and Wu, M and Tan, S and Liu, C and Cui, Y}, title = {Uterine microbiota dynamics and new therapeutic opportunities in gynecological diseases.}, journal = {American journal of translational research}, volume = {18}, number = {3}, pages = {1768-1791}, pmid = {42007101}, issn = {1943-8141}, abstract = {Traditional view holds that the uterus is a sterile environment. However, with the increased development of molecular biology technologies, this classical theory has been re-examined. Increasing evidence shows that a low-biomass, uniquely structured microecosystem exists in the healthy uterus. Its composition and dynamic changes are crucial in maintaining endometrial homeostasis, regulating immune responses, and influencing embryo implantation. Uterine microecological imbalance is associated with different gynecological diseases, such as chronic endometritis, endometriosis, and uterine-related tumors. This paper systematically reviews the compositional features of the uterine microecology and the dynamic changes in bacterial communities, as well as summarizes the evidence linking these changes to major gynecological diseases. This work examines current treatment and intervention strategies including antibiotics, probiotics, uterine cavity colonization, and fecal microbiota transplantation, and discusses their potential clinical value and methodological challenges. A deeper investigation of the relationship between uterine microecology and gynecological diseases is expected to provide new biomarkers and therapeutic targets for the precise diagnosis and treatment of gynecological disorders.}, }
@article {pmid42007373, year = {2026}, author = {Poznyak, AV and Vatlin, AA and Pavshintsev, VV and Mitkin, NA and Maltseva, ON and Utkina, AS and Orekhov, AN}, title = {An overview of the role of the gut microbiota in rheumatoid arthritis.}, journal = {Microbiome research reports}, volume = {5}, number = {1}, pages = {3}, pmid = {42007373}, issn = {2771-5965}, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease preceded by a prolonged preclinical phase marked by the emergence of autoantibodies and mucosal immune dysregulation. Evidence from human studies and animal models consistently demonstrates that gut microbiota dysbiosis contributes to this transition, particularly through impaired intestinal barrier function, activation of pro-inflammatory pathways, and molecular mimicry. Specific taxa - including Prevotella copri, Collinsella aerofaciens, and reductions in butyrate-producing bacteria - have been linked to heightened systemic inflammation, increased T helper 17 responses, and the generation of RA-associated autoantibodies. Current research also indicates that anti-rheumatic medications such as methotrexate, sulfasalazine, and minocycline produce measurable shifts in gut microbial composition, suggesting that microbiota-drug interactions may influence treatment response. Therapeutic approaches aimed at modifying gut ecology - including dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation - show early potential in restoring microbial balance, improving intestinal barrier integrity, and reducing inflammatory markers, although evidence in the preclinical RA stage remains limited. Additionally, emerging data highlight the importance of intestinal autophagy and microRNA networks in regulating epithelial integrity and systemic immune activation. Taken together, the literature supports a mechanistic link between gut dysbiosis and the onset of RA. It points to microbiota-targeted strategies as promising avenues for delaying or preventing disease progression. Future studies should prioritize longitudinal analyses and interventional trials focusing specifically on individuals at risk for RA.}, }
@article {pmid42008253, year = {2026}, author = {Narang, H and Talukdar, D and Kumar, B and Mathur, P and Ningombam, A and Singh, M and Bajaj, A and Markandey, M and Kalaivani, M and Verma, M and Kaur, M and Bakshi, S and Jana, P and Jamdhade, M and Bhardwaj, N and Puraswani, M and Ashita,  and Ahmed, N and Goyal, MK and Mubbunu, M and Thomas, DM and Mundhra, S and Prasad, S and Garg, R and Gupta, A and Shalimar,  and Gunjan, D and Mahapatra, SJ and Agarwal, S and Saraya, A and Garg, P and Makharia, G and Kedia, S and Das, B and Ahuja, V}, title = {Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized Clinical Trial.}, journal = {JAMA internal medicine}, volume = {186}, number = {6}, pages = {657-666}, pmid = {42008253}, issn = {2168-6114}, mesh = {Humans ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Double-Blind Method ; *Gastrointestinal Diseases/therapy/microbiology ; *Drug Resistance, Multiple, Bacterial ; Middle Aged ; Adult ; *Gastrointestinal Microbiome ; Feces/microbiology ; India ; }, abstract = {IMPORTANCE: Gut colonization by multidrug-resistant organisms (MDROs) is a risk factor for infection with these pathogens. There are no approved therapeutic interventions to combat it.<br><br>OBJECTIVE: To assess the efficacy of fecal microbiota transplant (FMT) in causing MDRO decolonization and decreasing antimicrobial resistance (AMR) genes and its impact on gut microbiome, virome, and mycobiome composition in patients with gastrointestinal (GI) diseases.<br><br>This randomized, double-blind, sham-controlled clinical trial was conducted in a gastroenterology ward and intensive care unit at a tertiary care center in India. Participants were patients with GI diseases with persistent MDRO colonization. Patient recruitment occurred from July 2022 to June 2024, with follow-up completed in July 2024. Data were analyzed from October 1, 2024, to April 25, 2025.<br><br>INTERVENTION: FMT via colonoscopy or sham intervention (sigmoidoscopy with saline injection).<br><br>MAIN OUTCOMES AND MEASURES: Co-primary outcomes were MDRO decolonization rate and decrease in antimicrobial resistance genes (AMR) at 4 weeks after the intervention. Secondary outcomes included changes in stool microbiome (16S ribosomal RNA amplicon sequencing), virome (viruslike particles shotgun sequencing), and mycobiome (ITS2 sequencing); incidence of MDRO infections; and adverse events within 4 weeks.<br><br>RESULTS: Of 114 randomized patients (mean [SD] age, 40.6 [12.5] years; 80 [70.2%] male; 52 patients [45.6%] with pancreatitis; 43 patients [37.7%] with cirrhosis; 19 patients [16.7%] with other GI disorders), 58 received FMT and 56 received the sham intervention. Most patients were colonized with carbapenem-resistant Enterobacteriaceae or extended-spectrum &#x3b2;-lactamase-producing Enterobacteriaceae at baseline (55 patients [94.8%] in the FMT group and 56 patients [100%] in the sham group). Five patients (2 in the FMT group, 3 in the sham group) were lost to follow-up. Intention-to-treat analysis showed no significant differences in MDRO decolonization (18 patients [31.0%] in the FMT group vs 17 patients [30.4%] in the sham group; absolute difference, 0.6% [95% CI, -16.2% to 17.6%]; P&#x2009;=&#x2009;.94) or AMR genes (median [IQR], 2.5 [1.2 to 3.0] genes in the FMT group vs 2.0 [1.0 to 3.0] genes in the sham group; P&#x2009;=&#x2009;.68), with comparable adverse events. Among 71 patients who underwent 16S ribosomal RNA gene sequencing at 4 to 6 weeks after the intervention, enrichment of bacteria capable of producing short-chain fatty acids was observed in the FMT group. These microbial alterations were not observed in the sham group. However, viral diversity remained unchanged after FMT. Mycobiome analysis revealed that FMT induced only modest, transient alterations in the gut mycobiome.<br><br>CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that while a single session of FMT did not significantly enhance MDRO decolonization or decrease AMR genes in patients with GI diseases, it modulated gut microbiome diversity and composition.<br><br>TRIAL REGISTRATION: Clinical Trials Registry-India Registration No. 2022/07/043847.}, }
@article {pmid42008254, year = {2026}, author = {Kelly, BJ and Woodworth, MH and Kwon, JH}, title = {Fecal Microbiota Transplant for Multidrug Resistance-No Benefit Without Disruption?.}, journal = {JAMA internal medicine}, volume = {186}, number = {6}, pages = {666-667}, doi = {10.1001/jamainternmed.2026.0668}, pmid = {42008254}, issn = {2168-6114}, }
@article {pmid42009386, year = {2026}, author = {Couturier, J and Kenner, E and Nicula, M and Chowdhury, F and Surette, M and Pai, N}, title = {Protocol for a pilot feasibility randomised controlled trial of fecal microbiota transplantation for adolescent anorexia nervosa.}, journal = {BMJ open}, volume = {16}, number = {4}, pages = {e109115}, pmid = {42009386}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adolescent ; *Anorexia Nervosa/therapy/psychology ; Pilot Projects ; Feasibility Studies ; Child ; Female ; Male ; Randomized Controlled Trials as Topic ; Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Despite its serious impact, anorexia nervosa (AN) remains one of the least understood mental illnesses, with significant gaps in effective treatment options. No medications have been deemed effective and only 50% of individuals respond to conventional psychotherapies. Gastrointestinal (GI) bacteria have been found to be altered in individuals with AN. While, Fecal microbiota transplantation (FMT) has shown potential for alleviating anxiety and depression, its effects remain understudied for individuals with AN. This study aims to determine whether oral capsular FMT is acceptable to adolescents with AN and results in clinical improvement in weight and/or psychological symptoms.<br><br>METHODS: This study will randomise 20 adolescents with AN, ages 12-17 years, to receive either FMT or placebo capsules. These 20 youth, as well as an additional 10 youth who decline trial enrolment, will participate in qualitative interviews. We will track recruitment rates and collect psychological and biological measures (blood, stool, urine and saliva) at multiple timepoints to assess how gut microbiota and their metabolites may influence the symptoms of AN. Interviews with participants and caregivers will explore their experiences and views on FMT as a treatment approach.<br><br>ETHICS AND DISSEMINATION: This study has received ethics approval by the Hamilton Integrated Research Ethics Board (#17493) and investigational drug approval by Health Canada (Dossier ID: c292423). Informed consent will be obtained by research staff from all participants. Findings will be disseminated through academic conferences, clinical forums and partnerships with advocacy organisations to reach clinicians, researchers and individuals with lived experience.<br><br>TRIAL REGISTRATION NUMBER: NCT06593366.}, }
@article {pmid42009997, year = {2026}, author = {Swain, MP and Mehta, CH and Padya, BS and Sharma, S and Velagacherla, V and Mitra, A and Mohanty, S and Mukherjee, T}, title = {Microbiome modulating remedies for chronic diseases: a review of current interventions and future directions.}, journal = {Inflammopharmacology}, volume = {34}, number = {5}, pages = {2973-3028}, pmid = {42009997}, issn = {1568-5608}, }
@article {pmid42010713, year = {2026}, author = {Tang, J and Wang, L and Yang, Z and Song, Y and Wu, S and Liang, Q and Li, Z and Zhou, S and Xiong, H and Chen, D and Li, J and Li, F}, title = {Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine in Ggt1-deficient mice.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {42010713}, issn = {2049-2618}, support = {32272874//National Natural Science Foundation of China/ ; 2021YFF1000601//National Key R&amp;D Program of China/ ; 2662025DKPY008//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Male ; Mice ; STAT5 Transcription Factor/metabolism ; *Gastrointestinal Microbiome/physiology ; Mice, Knockout ; *Spermatogenesis ; *gamma-Glutamyltransferase/genetics/deficiency/metabolism ; *Infertility, Male/microbiology/metabolism ; *Dysbiosis/microbiology ; STAT3 Transcription Factor/metabolism ; Fecal Microbiota Transplantation ; Testis/metabolism ; Signal Transduction ; *Glycine/analogs &amp; derivatives/metabolism ; Phenylacetates/metabolism ; Suppressor of Cytokine Signaling 3 Protein ; }, abstract = {BACKGROUND: Male infertility represents a global health concern, with emerging evidence linking gut microbiota dysbiosis to dysspermatogenesis and subfertility. However, the molecular mediators and regulatory mechanisms by which gut microbiota influences testicular functions remain poorly defined.<br><br>RESULTS: This study demonstrates that male gamma-glutamyl transferase 1-deletion (Ggt1[-/-]) mice exhibits infertility phenotypes, including reduced germ and testicular Leydig cell numbers, increased rates of abnormal sperm, and altered reproductive hormone levels. Metabolomic analysis reveals elevated levels of the gut microbial-derived metabolite phenylacetylglycine (PAGly) in serum and testes of Ggt1[-/-] mice, with in vivo injection experiments indicating its role in impairing spermatogenesis. Moreover, blocking PAGly effectively restores the impaired spermatogenesis in Ggt1[-/-] mice. Fecal metagenomic and metabolomic analyses show that gut microbiota in Ggt1[-/-] mice induces elevation of phenylacetic acid, a precursor metabolite of PAGly. Strikingly, fecal microbiota transplantation from Ggt1[-/-] mice (Ggt1[-/-]-FMT) recapitulates the infertility phenotypes including reduced germ cells and increased rates of abnormal sperm. Mechanistically, integrated CUT&amp;Tag and ATAC-Seq analyses reveal that transcription factor STAT5B occupies regulatory elements near Klk1b transcription start sites&#xa0;(TSS), confirming that transcription factor STAT5B directly regulates Klk1b gene transcription. Concretely, PAGly activates &#x3b2;2-adrenergic receptor (&#x3b2;2AR) on Leydig cells, triggering STAT3 phosphorylation, subsequent SOCS3 upregulation, and STAT5B phosphorylation suppression; p-STAT5B with transcriptional activation function is reduced, then Klk1b gene transcription is compromised, and therefore spermatogenesis is disrupted.<br><br>CONCLUSION: Ggt1 deletion-induced gut microbiota dysbiosis disrupts spermatogenesis via &#x3b2;2AR-STAT3-SOCS3-STAT5B-Klk1bs signaling pathway. Specifically, PAGly-induced &#x3b2;2AR activation promotes STAT3 phosphorylation, which induces SOCS3 to suppress p-STAT5B&#xa0;dependent Klk1bs transcription. This mechanism underscores the critical role of gut-derived metabolites in regulating testicular function and identifies potential targets for microbiota-modulated male infertility. Video Abstract.}, }
@article {pmid42011573, year = {2026}, author = {Zheng, X and Ye, DD and Weng, XY and Huang, ZW and Li, YH and Zhang, LS and Chen, MY and Liu, FY and Zhu, JY and Dong, MG and Zheng, XB and Huang, XQ}, title = {[Therapeutic effects of Baitouweng Decoction on ulcerative colitis mice with dampness-heat syndrome via inhibiting CaSR-Gq/11-MAPK signaling pathway based on fecal microbiota transplantation].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {51}, number = {5}, pages = {1259-1272}, doi = {10.19540/j.cnki.cjcmm.20251210.706}, pmid = {42011573}, issn = {1001-5302}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Drugs, Chinese Herbal/administration &amp; dosage ; *Colitis, Ulcerative/drug therapy/metabolism/genetics/therapy/microbiology ; Male ; *Receptors, Calcium-Sensing/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Humans ; *MAP Kinase Signaling System/drug effects ; Female ; Disease Models, Animal ; }, abstract = {This study aimed to investigate whether Baitouweng Decoction(BTD) exerts pharmacodynamic effects on ulcerative colitis(UC) mice with dampness-heat syndrome in the large intestine by modulating the gut microbiota and its metabolites to inhibit the calcium sensing receptor(CaSR)-G-protein alpha subunit Q/G-protein alpha subunit 11(Gq/11)-mitogen activated protein kinase(MAPK) signaling pathway. In the experiment, mice were divided into the following groups: a normal group, a model group, a Baitouweng Decoction fecal microbiota transplantation(BTD-FMT) group, a normal-FMT group, and a normal-FMT + Akkermansia muciniphila group. Except for the normal group, a UC with dampness-heat syndrome model was established in all mice. The corresponding fecal supernatant or Akkermansia muciniphila was administered on days 9, 11, 13, 15, 17, 19, and 21. Items below were recorded: body weight, diet, dampness-heat syndrome modeling conditions, and disease activity index(DAI) scores. The distribution and fluorescence intensity of fluorescein isothiocyanate(FITC)-Dextran in the gut were detected using a small animal 3D live imaging system. Pathological changes in the colon and tongue tissues were observed using hematoxylin-eosin(HE) staining. The mRNA expression of inflammatory factors and Muc2 in colon tissue was measured by quantitative real-time PCR(qRT-PCR). The expression levels of forkhead box protein p3(Foxp3) and retinoic acid related orphan receptor γt(RORγt) in colon tissue were analyzed by immunohistochemistry. Goblet cell and mucin expression were analyzed by alcian blue-periodic acid-Schiff(AB-PAS) staining. Western blot was employed to detect the expression of Zonula occludens-1(ZO-1), Occludin, Claudin-1, CaSR, G-protein alpha subunit αQ(Gnaq), G-protein alpha subunit 11(Gna11), extracellular signal-regulated kinase 1/2(ERK1/2), c-Jun N-terminal kinase(JNK), mitogen-activated protein kinase p38(p38 MAPK, p38), phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2), phosphorylated c-Jun N-terminal kinase(p-JNK), and phosphorylated mitogen-activated protein kinase p38(p-p38 MAPK, p-p38) in colon tissue. The results indicated that compared with the normal group, model mice with dampness-heat syndrome showed significant increases in rectal temperature, water intake, DAI scores, total movement trajectories/distance traveled in the open field test, and dampness-heat syndrome scores. Compared with the model group, BTD-FMT exerted therapeutic effects on UC mice with dampness-heat syndrome, which were evidenced by significantly ameliorated dampness-heat symptoms and tongue tissue pathology, reduced DAI scores, restored colon length, decreased colon histopathological scores, and modulated immune responses. Furthermore, BTD-FMT downregulated the mRNA expression of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) while upregulating interleukin-10(IL-10) and interleukin-4(IL-4) expression. Barrier protein levels were appropriately upregulated, alleviating increased intestinal barrier permeability. Additionally, the expression balance between Foxp3 and RORγt was restored, the goblet cell repair and mucin expression were promoted, and the expression of key proteins in the CaSR-Gq/11-MAPK signaling pathway was suppressed in colon tissue. In terms of therapeutic effect, BTD-FMT was superior to normal-FMT. Supplementation with Akkermansia muciniphila partially mimicked the therapeutic effects of BTD-FMT and achieved a synergistic effect when combined with normal-FMT. In conclusion, BTD exerts anti-inflammatory and intestinal mucosal barrier repair effects in UC mice with dampness-heat syndrome via gut microbiota and metabolite modulation, and the CaSR-Gq/11-MAPK signaling pathway inhibition. Akkermansia muciniphila enhances the effect of normal-FMT.}, }
@article {pmid42012708, year = {2026}, author = {Kværner, AS and Birkeland, E and Avershina, E and Botteri, E and Bucher-Johannessen, C and Knudsen, MD and Hjartåker, A and Page, CM and Hov, JR and Song, M and Randel, KR and Hoff, G and Rounge, TB and Berstad, P}, title = {Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator.}, journal = {European journal of nutrition}, volume = {65}, number = {4}, pages = {}, pmid = {42012708}, issn = {1436-6215}, abstract = {BACKGROUND: Alcohol consumption is one of the major risk factors of colorectal cancer (CRC), yet the mechanisms underlying this relationship, particularly the role of gut microbes, are not fully understood.<br><br>OBJECTIVE: To study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions.<br><br>METHODS: Screening participants with a positive faecal immunochemical test at ages 55&#x2013;77 were eligible for the CRCbiome study. Alcohol intake was assessed using a validated, semi-quantitative food frequency questionnaire and linked with shotgun metagenome based gut microbial profiles to study associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis.<br><br>RESULTS: Of 1468 participants with dietary data, 414 were diagnosed with advanced lesions. Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend&#x2009;=&#x2009;0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10&#xa0;g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in &#x3b1;- and &#x3b2;-diversity, and differentially abundant bacteria. A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria.<br><br>CONCLUSION: Alcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions. Trial registration: The BCSN is registered at clinicaltrials.gov (National clinical trial (NCT) no. 01538550).<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-026-03960-6.}, }
@article {pmid42012958, year = {2026}, author = {Green, ER and Negretti, NM and Brunner, TH and Shealy, NG and Moser, FA and Drury, SL and Traina, KA and Reyes Ruiz, VM and Yang, TS and Lehmann, CJ and Byndloss, MX and van de Plas, R and Zackular, JP and Light, SH and Sucre, JMS and Skaar, EP}, title = {The intestinal microbiota impacts nutritional immunity and resistance to Acinetobacter baumannii pneumonia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {17}, pages = {e2534432123}, doi = {10.1073/pnas.2534432123}, pmid = {42012958}, issn = {1091-6490}, support = {U54 DK134302/DK/NIDDK NIH HHS/United States ; R01 AG078803/AG/NIA NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; 2022-A-19568//Pew Charitable Trusts (Pew)/ ; K08 HL143051/HL/NHLBI NIH HHS/United States ; R01 AI138581/AI/NIAID NIH HHS/United States ; T32 GM008554/GM/NIGMS NIH HHS/United States ; 1AY2AX000077//HHS | NIH | Advanced Research Projects Agency for Health (ARPA-H)/ ; R35 GM138369/GM/NIGMS NIH HHS/United States ; T32 GM150375/GM/NIGMS NIH HHS/United States ; GT15104//HHMI (HHMI)/ ; 022792//Burroughs Wellcome Fund (BWF)/ ; T32 HL094296/HL/NHLBI NIH HHS/United States ; R35 GM146969/GM/NIGMS NIH HHS/United States ; R01 HL168556/HL/NHLBI NIH HHS/United States ; T32 ES007028/ES/NIEHS NIH HHS/United States ; R01 AI101171/AI/NIAID NIH HHS/United States ; K22 AI166265/AI/NIAID NIH HHS/United States ; R01 AI168302/AI/NIAID NIH HHS/United States ; }, mesh = {*Acinetobacter baumannii/immunology/pathogenicity ; Animals ; *Gastrointestinal Microbiome/drug effects/immunology ; Mice ; *Acinetobacter Infections/immunology/microbiology ; Humans ; Anti-Bacterial Agents/pharmacology/adverse effects ; Dysbiosis/microbiology/immunology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Female ; Male ; *Pneumonia, Bacterial/microbiology/immunology ; Neutrophils/immunology ; Disease Models, Animal ; }, abstract = {Broad-spectrum antibiotics are frequently administered to intensive care unit patients as part of empiric care. This treatment has been associated with subsequent infections by the emerging nosocomial pathogen Acinetobacter baumannii; however, the mechanisms underlying this linkage remain unclear. Here, we observe an association between antibiotic treatment and microbiota disruption that precedes A. baumannii infection in a hospitalized patient cohort and demonstrate in a murine model that broad-spectrum antibiotic administration drives susceptibility to intranasal infection with this pathogen. Reconstitution of the intestinal microbiota by fecal microbiota transplant restores control of A. baumannii bloodstream dissemination, implicating microbiota dysbiosis as a key driver of pulmonary disease. Using single-cell RNA sequencing, we determine that antibiotic pretreatment reduces the abundance of transcripts related to phagocyte effector functions in the lung, including nutritional immunity pathways that restrict pathogen access to essential nutrient metals. Depletion studies identify neutrophils and inflammatory monocytes as central mediators of microbiota-dependent protection, and loss of the nutritional immunity components lipocalin-2 or calprotectin abrogates the effects of antibiotics on infected mice, demonstrating a causal relationship between microbiota dysbiosis and impaired phagocyte-mediated nutritional immunity. Together, these findings provide a mechanism for the increased severity of A. baumannii pneumonia following antibiotic exposure and highlight the intestinal microbiota as a potential therapeutic target to prevent nosocomial infections with this and other healthcare-associated pathogens.}, }
@article {pmid42013837, year = {2026}, author = {Zheng, M and Yan, H and Hao, W and An, H and Chen, X and Wu, Q and Ge, X and Ye, H and Zhou, M and Zhou, G and Yang, X and Hu, M and Zhang, P and Pan, W and Tang, R and Zheng, K and Huang, XF and Yu, Y}, title = {Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {5}, pages = {959-974.e7}, doi = {10.1016/j.chom.2026.03.020}, pmid = {42013837}, issn = {1934-6069}, mesh = {Animals ; *Ergothioneine/metabolism/pharmacology ; *Gastrointestinal Microbiome/drug effects/physiology ; *Cognitive Dysfunction/chemically induced ; Mice ; *Antipsychotic Agents/adverse effects ; Hippocampus/metabolism/drug effects ; Male ; Olanzapine/adverse effects ; Dysbiosis/chemically induced ; Humans ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Clozapine/adverse effects ; }, abstract = {Chronic antipsychotic use is associated with neuronal damage and cognitive impairment, with the gut microbiome increasingly implicated. However, the specific microbial metabolites and mechanisms involved remain unknown. Here, we demonstrate that chronic olanzapine treatment induces gut microbial dysbiosis, compromises intestinal barrier integrity, and causes cognitive deficits in mice. Multi-omics analyses reveal profound depletion of the microbiota-associated metabolite ergothioneine in blood and brain, a finding validated in the blood of olanzapine-treated patients and risperidone- and clozapine-treated mice. This deficiency correlates with a loss of ergothioneine-producing bacteria (Cyanobacteria and subordinate taxa). Fecal microbiota transplantation from olanzapine-treated mice confers cognitive impairment, while ergothioneine supplementation mitigates it. Mechanistically, ergothioneine attenuates hippocampal oxidative stress and inhibits the redox-sensitive phosphatase protein tyrosine phosphatase 1B (PTP1B). Furthermore, hippocampal neuronal-specific PTP1B deletion abolishes olanzapine-induced synaptic and cognitive deficits. Our findings identify depletion of microbiota-derived ergothioneine as a mechanism underlying antipsychotic-induced cognitive impairment, highlighting therapeutic strategies to mitigate this side effect.}, }
@article {pmid42015224, year = {2026}, author = {Atzeni, A and Mingaila, J and Alzbutas, G and Lukoševičius, R and Drūteika, J and Łuczyńska, K and Ramonaitė, R and Pietras, T and Sipowicz, K and Kiudelytė, D and Keršytė, K and Keževičiūtė, E and Najūtė, G and Kupčinskas, J and Mayneris-Perxachs, J and Baltriukienė, D and Burokas, A}, title = {Comorbid Alzheimer's Disease and Type 2 Diabetes Microbiota Shape Age-Associated Gut-Brain Axis Profiles.}, journal = {Aging cell}, volume = {25}, number = {5}, pages = {e70488}, pmid = {42015224}, issn = {1474-9726}, support = {S-PD-24-95//Research Council of Lithuania/ ; }, mesh = {*Alzheimer Disease/microbiology/epidemiology ; Humans ; *Diabetes Mellitus, Type 2/microbiology/epidemiology ; *Gastrointestinal Microbiome ; Female ; Aged ; Animals ; Male ; Mice ; Middle Aged ; Aged, 80 and over ; *Aging ; *Brain/metabolism ; Comorbidity ; Fecal Microbiota Transplantation ; }, abstract = {Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share metabolic and inflammatory mechanisms, potentially mediated by the gut microbiota, yet the neurobiological impact of comorbid AD+T2DM microbiota from elderly donors remains unexplored. Fecal microbiota from healthy, AD, T2DM, and AD+T2DM postmenopausal female donors (aged 56-89 years) was transplanted into antibiotic-treated male mice. Behavioral testing, blood profiling, hippocampal neurotrophic gene expression, and 16S rRNA sequencing with taxonomic, functional, and metabolic analyses were performed. Human AD+T2DM microbiota displayed the greatest dysbiosis, characterized by enrichment of pro-inflammatory taxa, depletion of butyrate-producing genera, and loss of neuroprotective metabolic pathways. FMT induced robust engraftment, with AD+T2DM recipients diverging most from controls (PERMANOVA R[2] = 0.209, p = 0.001) and healthy recipients (PERMANOVA R[2] = 0.111, p = 0.002). Donor age contributed significantly to recipient microbiota variation (R[2] = 0.028, p = 0.006), suggesting transmission of aging-associated microbial signatures. Hippocampal neurotrophic gene expression was most suppressed in AD+T2DM recipients (adjusted p value < 0.05) and negatively correlated with disease- and aging-associated taxa and microbial functions (|r| > 0.4, FDR p < 0.05). AD recipients showed reduced olfactory discrimination and increased daytime locomotor activity. Metabolic network analysis revealed depletion of flavonoid, isoflavonoid, and lignan biosynthesis pathways in disease recipients. These findings suggest that microbiota from elderly donors with comorbid AD+T2DM may induce gut-brain axis alterations, linking aging, metabolic dysfunction, and neurodegeneration through convergent taxonomic, functional, and neurotrophic changes. We underscore the potential role of age-associated gut microbial signatures in modulating neurobiological outcomes.}, }
@article {pmid42015288, year = {2026}, author = {Chen, P and Geng, Q and Zhu, W and Jiang, H}, title = {Gut microbiota-driven pre-metastatic niche formation in colorectal cancer liver metastasis: mechanisms and translational significance.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {}, pmid = {42015288}, issn = {1757-4749}, support = {CMCM202402//Key Project of Changzhou Medical Center of Nanjing Medical University/ ; }, abstract = {BACKGROUND: Liver metastasis of colorectal cancer (CRC) remains a major clinical challenge, closely linked to poor prognosis and limited therapeutic efficacy. Emerging evidence implicates the gut microbiota in orchestrating the formation and maturation of the hepatic pre-metastatic niche (PMN) through the gut-liver axis.<br><br>MAIN BODY: Dysbiosis-induced disruption of intestinal barrier integrity facilitates microbial translocation, which triggers hepatic inflammation, immune suppression, metabolic reprogramming, and vascular remodelling, together creating a permissive soil for metastatic seeding. Among pathogenic taxa, Fusobacterium nucleatum has emerged as a key driver because it persistently colonises both primary tumours and hepatic metastases while modulating immunotolerance and chemoresistance. Therapeutically, narrow-spectrum antimicrobial approaches that target pro-metastatic taxa show promise for safely and selectively correcting microbiota-mediated PMN formation. In addition, faecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors and anti-angiogenic therapy has yielded encouraging responses in refractory metastatic CRC by boosting anti-tumour immunity and restoring hepatic microvascular architecture.<br><br>CONCLUSION: Future research should integrate multidimensional biomarker assessment with personalised, microbiota-based therapeutic frameworks to achieve effective and durable prevention of CRC liver metastasis.}, }
@article {pmid42015346, year = {2026}, author = {Li, Z and Samui, S and Liu, J and Yang, Y and Liu, X and Chen, Q and Li, J and Gopinath, D and Luo, P and Shan, D}, title = {Gut microbiome and metabolic health: mechanisms and precision interventions.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2644677}, pmid = {42015346}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics ; Precision Medicine ; *Metabolic Diseases/microbiology/metabolism/therapy ; Prebiotics/administration &amp; dosage ; Obesity/microbiology/metabolism ; Diabetes Mellitus, Type 2/microbiology/metabolism ; Metabolic Syndrome/microbiology/metabolism ; }, abstract = {The gut microbiome is increasingly recognized as a fundamental regulator of metabolic health, shaping energy balance, insulin sensitivity, inflammatory tone, and inter-organ communication through a broad spectrum of microbial metabolites that engage host signaling pathways. In this review, we synthesize current mechanistic insights into how gut microbial communities shape metabolic function, with particular emphasis on short-chain fatty acids, secondary bile acid signaling, gut barrier integrity, immune modulation, and the microbiota-gut-brain-pancreas axis. We further summarize disease-associated alterations in microbial composition and function across obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and metabolic syndrome, highlighting key microbial and metabolic features that contribute to metabolic dysfunction. Evidence from germ-free models, fecal microbiota transplantation studies, and strain-level interventions suggests that shifts in microbial ecology may causally shape metabolic outcomes. We also critically evaluate emerging microbiome-centered therapeutic strategies, including targeted probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, while addressing factors that underlie inter-individual variability in treatment responses. In addition, we discuss the growing influence of multi-omics technologies, microbial metabolic modeling, and machine learning approaches in advancing precision microbiome medicine. To integrate these advances within a coherent framework, we outline a precision microbiome intervention pipeline linking multidimensional profiling to functional stratification and targeted therapeutic design. We also introduce a conceptual Precision Microbiome Intervention Triangle to mechanistically explain heterogeneity in responses to microbiome-targeted therapies. Collectively, these insights establish and position the gut microbiome as both a mechanistic driver and a modifiable therapeutic target in metabolic disease, and highlight key challenges and future directions for the development of personalized microbiome-based metabolic interventions.}, }
@article {pmid42016722, year = {2026}, author = {Hansen, SH and Bhattacharjee, N and Hu, C and Maseng, MG and Grannö, O and Bang, C and Olbjørn, C and Perminow, G and Valeur, J and Bengtson, MB and Frigstad, SO and Andersen, S and Aabrekk, TB and Detlie, TE and Franke, A and Kristensen, VA and Halfvarson, J and Høivik, ML and Iyer, RK and Hov, J}, title = {Bacterial clusters are associated with the risk of severe disease progression in inflammatory bowel disease irrespective of conventional disease categories.}, journal = {Microbiome research reports}, volume = {5}, number = {1}, pages = {4}, pmid = {42016722}, issn = {2771-5965}, abstract = {Background: Inflammatory bowel diseases (IBDs) are complex conditions marked by chronic inflammation in the gastrointestinal tract. Traditional classification separates IBD into Crohn's disease and ulcerative colitis, but this division may not fully capture disease heterogeneity. Here, we examine whether microbiome-driven subtyping can describe novel clinical IBD phenotypes. To achieve this, we applied unsupervised clustering to fecal microbiota profiles from the population-based Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) cohort. Methods: A Gaussian Mixture Model (GMM) was used to cluster participants with IBD based on microbiome composition and examine associations between clusters and clinical outcomes, including inflammatory markers and disease severity during the first year after inclusion. Results: Three microbiome-based clusters were identified: CLO (dominated by Clostridia UCG-014), ALF (Agathobacter, Lachnoclostridium, and Faecalibacterium), and RUM (Ruminococcus gnavus). Participants in the RUM cluster had a higher risk of future severe disease than those in the CLO cluster, even among participants with remission-to-mild disease at inclusion (21% vs. 6%, P < 0.00001). This association could not be explained by antibiotic use or baseline disease severity. Cluster membership alone performed comparably to fecal calprotectin in distinguishing severe disease, and a combined model significantly improved accuracy (P < 0.0001). Conclusion: Our findings demonstrate a connection between microbiome composition and the risk of severe disease development, which is partly independent of inflammation levels at the time of sampling. Microbiome-informed subgrouping could lead to more personalized treatment strategies. Further validation is needed to determine the clinical utility of these clusters.}, }
@article {pmid42018414, year = {2026}, author = {Boumasmoud, M and León-Sampedro, R and Beusch, V and Benz, F and Arnoldini, M and Hall, AR}, title = {Interspecies interaction controls Escherichia coli growth in human gut microbiome samples.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {17}, pages = {e2527793123}, pmid = {42018414}, issn = {1091-6490}, support = {310030_192428//Swiss NSF/ ; }, mesh = {Humans ; *Escherichia coli/growth &amp; development ; *Gastrointestinal Microbiome/physiology ; Feces/microbiology ; }, abstract = {Gut microbial community composition varies from one person to another. Potentially, this means the ecological interactions experienced by individual strains or species also vary among microbiomes of different people. However, testing this directly in human microbiomes and identifying ecological drivers involved are challenging. Here, we use replicated anaerobic microcosms to quantify variability of population growth for a key commensal species among microbiome samples from different individuals and to identify underlying intra- and interspecific interactions. In a reciprocal transplant experiment, both absolute and relative growth performance of different Escherichia coli strains varied among gut microbiome samples from healthy individuals. This was partly explained by intraspecific competition: growth performance of individual E. coli strains was associated with displacement of resident conspecifics. However, the determinants of E. coli growth varied among samples. In one microbiome sample with a distinctive taxonomic composition, culture acidification by resident microbes impaired growth of all E. coli strains. We identified a strain of Clostridium butyricum contributing to this effect and showed that transferring it into other microbiomes predictably altered pH, fermentation product profiles (butyrate accumulation and acetate/lactate depletion), and population growth of other species including E. coli, thereby reshaping overall taxonomic composition. Our results suggest natural interindividual gut microbiome variation translates to variable ecological interactions with incoming bacteria, but these dynamics can be manipulated by a generalizable interspecies interaction.}, }
@article {pmid42019770, year = {2026}, author = {Xie, M and Kong, L and Hou, L and Chen, Y and Hou, J}, title = {Atopic dermatitis: Multi-omics insights into microbiota-driven modulation of the gut-skin axis.}, journal = {Microbial pathogenesis}, volume = {216}, number = {}, pages = {108504}, doi = {10.1016/j.micpath.2026.108504}, pmid = {42019770}, issn = {1096-1208}, mesh = {Humans ; *Dermatitis, Atopic/microbiology/therapy/genetics/immunology ; *Gastrointestinal Microbiome/physiology ; *Skin/microbiology/immunology ; Metabolomics ; Metagenomics ; Receptors, Aryl Hydrocarbon/metabolism ; Fatty Acids, Volatile/metabolism ; Biomarkers ; Multiomics ; }, abstract = {Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease resulting from complex interactions among host genetics, immune dysregulation, and microbial imbalance. Recent advances in multi-omics technologies have revealed distinct AD endotypes characterized by specific genetic variants, microbial enterotypes, and metabolite profiles. Emerging evidence highlights the gut-skin axis as an important regulatory pathway, in which alterations in gut microbiota influence the production of key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan-derived aryl hydrocarbon receptor (AHR) ligands, thereby modulating Th2-dominant inflammatory responses. Integrated analyses combining metagenomics, metabolomics, and single-cell transcriptomics have further identified endotype-specific signatures, such as Bacteroides-enriched profiles associated with lipopolysaccharide-driven inflammation and Prevotella-dominant clusters linked to enhanced AHR activation and epithelial barrier repair. These findings provide a basis for precision stratification and the development of targeted therapeutic strategies, including genotype-guided biologics, microbiota modulation, engineered probiotics, phage therapy, and fecal microbiota transplantation. This review summarizes current evidence integrating host genetics, microbiota networks, and multi-omics biomarkers to provide a comprehensive framework for understanding AD endotypes and to highlight potential avenues for precision diagnosis and targeted interventions.}, }
@article {pmid42020750, year = {2026}, author = {Grieshop, MP and Behr, AA and Bowden, S and Lin, JD and Molari, M and Reynolds, GZ and Brooks, EF and Doyle, B and Moore, AA and Rodriguez-Nava, G and Salinas, JL and Banaei, N and Bhatt, AS}, title = {Transposable elements are driving rapid adaptation of Enterococcus faecium.}, journal = {Nature}, volume = {653}, number = {8116}, pages = {1139-1147}, pmid = {42020750}, issn = {1476-4687}, mesh = {*Enterococcus faecium/genetics/pathogenicity/isolation &amp; purification ; *DNA Transposable Elements/genetics ; Humans ; Genome, Bacterial/genetics ; *Adaptation, Physiological/genetics ; Metagenome/genetics ; Promoter Regions, Genetic/genetics ; Feces/microbiology ; }, abstract = {Bacterial pathogens adapt rapidly to clinical and within-host selective pressures[1]. Insertion sequences (IS) are transposable elements that can contribute to pathogenic adaptation[2], but their activity and consequences in contemporary clinical populations are not well characterized. Here, combining large-scale genomic surveys with long-read sequencing of clinical isolates and longitudinal gut metagenomes, we quantify pathogen IS dynamics from global patterns to within-host evolution. Across 19,485 publicly available high-contiguity ESKAPEE pathogen genomes, Enterococcus faecium genomes are the most IS dense, dominated by replicative ISL3 family elements, which have proliferated in clinical lineages over the past 30 years. We find extensive chromosomal structural variation, largely involving ISL3, within a new single-hospital collection of bloodstream isolates. Long-read metagenomic sequencing of 28 longitudinal stool samples from 12 haematopoietic cell transplantation (HCT) recipients demonstrates within-host IS dynamics and their regulatory consequences. In one patient, an ISL3 insertion upstream of a folate transporter formed a strong promoter, increasing transcription and improving relative fitness under folate limitation. Enhanced folate scavenging may enable E. faecium to thrive in the setting of microbiome collapse, which is common in HCT and other critically ill patients[3]. Together, these results show that a recent ISL3 expansion is driving rapid evolution in healthcare-associated E. faecium, with consequences for its metabolic fitness that may help explain its increasing clinical burden. Several other pathogens also show elevated IS loads in our survey, which suggests that IS expansion-mediated evolution might be more broadly relevant.}, }
@article {pmid42022531, year = {2026}, author = {Wang, Y and Fu, J and Zhan, J and Liang, Y and Chen, R and Su, L and Zhou, Q and Zhang, Y and Cong, W and Xu, F}, title = {Panax ginseng-Polygonum cuspidatum is beneficial for alleviating atherosclerosis in ApoE[-/-] mice by modulating the composition of gut microbiota and related metabolites.}, journal = {Frontiers in cardiovascular medicine}, volume = {13}, number = {}, pages = {1773819}, pmid = {42022531}, issn = {2297-055X}, abstract = {BACKGROUND: Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Panax ginseng and Polygonum cuspidatum (GP) herb pair has traditionally been used for cardiovascular diseases. Some active compounds in GP have shown anti-atherosclerotic effects and the effects of GP still needs more evidence-based supports. Therefore, this study aims to investigate the potential effects of GP on atherosclerosis and explore the underlying mechanisms.<br><br>METHODS: Fifty C57BL/6J ApoE[-/-] mice were randomly assigned to five groups: model, statin, low-dose GP, medium-dose GP and high-dose GP. They were fed a high-fat diet (HFD) to induce atherosclerosis. Ten wild-type C57BL/6J mice were given chow diet and served as controls. After 12-week intervention, their aortic tissues were collected for Oil Red O staining, colon tissues for Alcian staining and immunofluorescence, and serum samples for measurement of lipid levels and inflammatory cytokines. Then, their fecal DNA was extracted for metagenomic sequencing, while cecum and ileocecal valves were for untargeted metabolomics. Finally, fecal microbiota transplantation was performed to assess the contribution of gut microbiota to observed effects. Twenty additional ApoE[-/-] mice were randomized to two groups: FMT-Mod and FMT-GPH, given feces from the model or high-dose GP group.<br><br>RESULTS: Atherosclerotic plaques accumulated in the aorta and aortic sinus after HFD, while statin and high-dose GP alleviated this burden. TC, TG, LDL-C, MCP-1, MCP-3 and IL-2 showed significant increase after HFD, while statin and GP decreased LDL-C, MCP-1 and MCP-3. The goblet cells, ZO-1 and Occludin decreased after HFD, while statin and GP increased them, indicating that the intestinal barrier integrity was improved. Additionally, the composition of gut microbiota was modulated by GP. Some candidate taxa were identified, such as Bifidobacteriales, Bacteroidetes and Escherichia coli. Twenty-two metabolites were differentially abundant among the control, model and GP groups. Nineteen of them were modulated by HFD and reversed by GP, including 1-methylnicotinamide, dopamine and lysoPA (0:0/18:0). Mice given fecal transplants from the high-dose GP group showed less aortic plaques, lower levels of some lipid and inflammatory cytokines, more goblet cells, more expression of ZO-1 and Occludin, and more 1-methylnicotinamide than those given fecal transplants from the model group.<br><br>CONCLUSION: This study suggests that GP is beneficial for alleviating atherosclerosis in HFD-induced ApoE[-/-] mice, potentially by modulating the composition of gut microbiota and related metabolites.}, }
@article {pmid42023455, year = {2026}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {The Gut Microbiome in Sleep Disorders: A Review of Recent Evidence.}, journal = {Actas espanolas de psiquiatria}, volume = {54}, number = {2}, pages = {586-601}, pmid = {42023455}, issn = {1578-2735}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sleep Wake Disorders/microbiology/therapy/physiopathology ; Dysbiosis/complications/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Alterations in the gut microbiome have been shown to influence sleep through gut-brain interactions. However, the interplay between the gut microbiome and sleep disorders remains insufficiently understood. This narrative review provides an overview of recent evidence on the role of the gut microbiome in sleep disorders, examining host-microbial regulation of the sleep cycle, the relationship between gut microbiome dysbiosis and sleep disorders, the influence of the gut microbiome on sleep-related breathing disorders, sleep deprivation, and sleep fragmentation, as well as microbial therapeutic approaches to sleep disorders. Through its effects on bacterial metabolites, immune responses, and neuronal signaling, the gut microbiome might be potentially involved in the regulation of sleep-wake cycles. Disturbances in sleep have been associated with shifts in gut microbiome composition, but this relationship remains incompletely understood and it suggests a bidirectional nature. Evidence indicates that interventions targeting the gut microbiome, such as the use of psychobiotics and fecal microbiota transplantation, may have potential for improving sleep outcomes, but further research is needed to determine their actual effectiveness. Understanding the full range of factors influencing the gut microbiome and their interactions with other variables will be essential for elucidating the mechanisms behind gut-sleep interactions. Thus, future studies should focus on clarifying causality, identifying key biomarkers, and developing microbial-based interventions to establish effective therapeutic strategies.}, }
@article {pmid42023457, year = {2026}, author = {Li, J and Liu, J and Chen, M and Wang, Y and Zhou, C}, title = {Observation of the Therapeutic Effect of Washed Microbiota Transplantation on Childhood Autism Spectrum Disorder.}, journal = {Actas espanolas de psiquiatria}, volume = {54}, number = {2}, pages = {263-275}, pmid = {42023457}, issn = {1578-2735}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology ; Male ; Female ; Child ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; Child, Preschool ; Gastrointestinal Microbiome ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: This retrospective study evaluated the efficacy and safety of washed microbiota transplantation (WMT) via trans colonic endoscopic administration tube for children with autism spectrum disorder (ASD).<br><br>METHODS: The clinical data of 19 children with ASD treated between November 2021 and December 2023 were analysed. The data included scores on the Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and PedsQL&#x2122; 3.0 Gastrointestinal Symptoms Scales (PedsQL-GI) before treatment and one and six months post-WMT, as well as faecal 16S rRNA sequencing results (vs. healthy controls).<br><br>RESULTS: ABC, CARS and PedsQL-GI scores improved significantly over time (all p < 0.001, large effect sizes). CARS and PedsQL-GI scores decreased notably at one and six months after treatment. ABC scores reduced significantly only at six months posttreatment. PedsQLGI scores at six months posttreatment further declined relative to those atone month posttreatment, whereas ABC and CARS scores remained stable. Subgroup analysis showed greater score reductions in the high-score ASD and constipation subgroups than in other patients. Faecal microbiota analysis revealed structural differences between ASD and healthy children. WMT altered gut flora structure and increased beneficial bacteria (e.g., Faecalibacterium).<br><br>CONCLUSIONS: Preliminary findings suggest that WMT may improve gastrointestinal and core symptoms in children with ASD, especially those in high-score subgroups. Caution is needed given this study's small sample size, and large prospective studies are required for validation.}, }
@article {pmid42023591, year = {2026}, author = {Lei, P and Qi, Z and Ma, Q and Zhao, B and Wen, B and Jiang, W and Xi, W and Liu, Y and Xun, Y and Zhang, S and Wang, Y and Guo, Y and Wang, W and Ma, X and Jia, M and Fan, Y}, title = {Gut microbiota reshapes host energy metabolism to modulate depressive behaviors.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2662556}, pmid = {42023591}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Energy Metabolism ; Male ; Animals ; *Major Depressive Disorder/microbiology/metabolism/therapy ; Mice ; Female ; Fecal Microbiota Transplantation ; *Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Middle Aged ; Adult ; Mice, Inbred C57BL ; Disease Models, Animal ; Metabolomics ; Mitochondria/metabolism ; }, abstract = {Disturbances in energy metabolism are a key pathophysiological feature of major depressive disorder (MDD). The gut microbiota, as a critical regulator of host metabolism, may influence systemic energy homeostasis and contribute to depression. To investigate this, we performed a multi-omics analysis integrating targeted metabolomics and shotgun metagenomics on samples from 100 MDD patients and 68 healthy controls. MDD patients exhibited significant disruptions in central energy pathways (glycolysis, TCA cycle, and ornithine cycle), which correlated with symptom severity and cognitive impairment. We identified 36 bacterial species whose abundances were linked to mitochondrial fatty acid synthesis, ketogenesis, and amino acid metabolism, and were associated with altered levels of core metabolites like lactate and L-glutamic acid. Mediation analysis established a "gut microbiota-energy metabolites-depressive phenotype" axis, where metabolites mediated the effects of specific bacteria (e.g., Dorea_formicigenerans) on symptoms. To validate causality, we used a chronic social defeat stress mouse model with simultaneous autologous fecal microbiota transplantation (FMT). FMT effectively reshaped the gut microbiota, ameliorated depression-like behaviors, and reversed the stress-induced shift toward anaerobic glycolysis in serum and the central nervous system. Critically, FMT restored mitochondrial morphology and structural integrity in the prefrontal cortex and hippocampus, renormalizing the relationship between metabolism and behavior. Our findings elucidate the gut microbiota's role in MDD pathogenesis via host energy metabolism regulation and posit early autologous FMT as a novel strategy to correct central energy imbalances.}, }
@article {pmid42025006, year = {2026}, author = {Song, H and Wang, J and Hao, Y and Li, X and Yan, S and Han, S and Zhao, J and Han, Y and Sun, S and Chen, X and Purba, MA and Chen, H and Li, C}, title = {Gut microbiota dysbiosis induced by tibial dyschondroplasia in turn accelerates disease pathogenesis through the gut-bone axis in broilers.}, journal = {Poultry science}, volume = {105}, number = {7}, pages = {106927}, pmid = {42025006}, issn = {1525-3171}, mesh = {Animals ; *Chickens ; *Dysbiosis/veterinary/microbiology ; *Osteochondrodysplasias/veterinary/microbiology ; *Poultry Diseases/microbiology/pathology ; Fecal Microbiota Transplantation/veterinary ; *Gastrointestinal Microbiome ; Tibia/pathology ; Male ; }, abstract = {Tibial dyschondroplasia (TD) is a common and economically significant skeletal disorder in broilers, characterized by unmineralized, avascular cartilage plugs protruding into the metaphyseal region. Despite some evidence connecting the gut microbiota to skeletal disorders, the specific microbial drivers of TD pathogenesis remain unclear. In this study, we performed fecal microbiota transplantation in both healthy and TD model broilers to assess the influence and contribution of gut microbiota dysbiosis to TD pathogenesis. The broilers were allocated into 4 groups: CON (normal control group broilers), TD (TD model broilers), TDRN (TD model broilers that received FMT from normal broilers) and NRTD (normal broilers that received FMT from TD model broilers). Results demonstrated that FMT successfully transferred the TD phenotype from diseased to healthy broilers (NRTD group), whereas transplantation from healthy donors did not reverse the TD phenotype in TD broilers (TDRN group). This to some extent indicates that gut microbiota as a critical pathogenic driver. Microbiome analysis revealed significant depletion of Lactobacillus and enrichment of Streptococcus and Escherichia-Shigella in all TD-affected groups (TD, TDRN, NRTD) compared to controls (P < 0.05). Metabolomic profiling identified seven stably dysregulated metabolites. Among them, chenodeoxycholic acid showed a strong positive correlation with Lactobacillus abundance and tibial mineral content, while 2-methoxyestradiol (an estrogen metabolite) exhibited inverse associations. Collectively, these findings provide evidence that gut microbiota dysbiosis causally contributes to TD and define the Lactobacillus-chenodeoxycholic acid axis and estrogen metabolism as promising targets for preventive and management strategies against TD in broilers.}, }
@article {pmid42025145, year = {2026}, author = {Liem, J and Chen, X and Lim, JJ and Mao, Q and Cui, JY and Lin, YS}, title = {Impact of the gut microbiome on hepatic cytochrome P450 3A4 (CYP3A4) in humanized pregnane X receptor-constitutive androstane receptor-CYP3A4/3A7 mice.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {54}, number = {5}, pages = {100284}, doi = {10.1016/j.dmd.2026.100284}, pmid = {42025145}, issn = {1521-009X}, mesh = {Animals ; *Cytochrome P-450 CYP3A/metabolism/genetics ; Female ; Male ; *Pregnane X Receptor/metabolism/genetics ; Mice ; Humans ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism/enzymology ; Constitutive Androstane Receptor ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Transgenic ; Feces/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The interaction between the gut microbiome and drug metabolism is bidirectional and can influence the pharmacokinetics of certain drugs. In mice, the gut microbiome has been shown to influence Cyp3a11. However, evidence for microbial regulation of human cytochrome P450 3A4 (CYP3A4) is lacking. We aimed to bridge this gap by manipulating the microbiome of a humanized mouse model expressing CYP3A4, CYP3A7, pregnane X receptor and constitutive androstane receptor. Three groups of male and female humanized mice were studied: conventional (CV), germ-free (GF), and germ-free mice conventionalized (GFCV) using sex-matched pooled human fecal samples. The presence of microbiome upregulated CYP3A4 expression by 7.6-fold in male CV mice (P < .001) but downregulated CYP3A4 expression by 1.69-fold in female CV mice (P = .012) compared with GF mice. The human fecal microbiome transplant to sex-matched GF mice resulted in decreased microbial diversity (P < .05 in males and P < .01 in females) and was not effective in restoring CYP3A4 expression, suggesting complex underlying microbe-CYP3A4 interactions. We show that the hepatic CYP3A4 mRNA and protein expression were strongly correlated (R = 0.91; P = 2.6 × 10[-6]). A total of 57 bacterial species from the mouse gut microbiome were identified to be significantly correlated with CYP3A4 protein expression (P < .05). Five bile acids and no short-chain fatty acids were correlated with CYP3A4 protein expression. In summary, alterations in the gut microbiome influenced hepatic CYP3A4 in humanized mice in a sex-dependent manner, with distinct microbes strongly correlating with this regulatory pattern. SIGNIFICANCE STATEMENT: To the best of our knowledge, this study is the first to evaluate the expression of cytochrome P450 3A4 under different microbial conditions in a humanized mouse model, including conventionalization of germ-free mice using pooled sex-matched human feces. Alterations in the gut microbiome influenced hepatic cytochrome P450 3A4 in a sex-dependent manner and were strongly correlated with microbial species.}, }
@article {pmid42025824, year = {2026}, author = {Lin, J and Zhu, Q and Wang, T and Sun, J and Yin, R and Zhang, Y and Dai, H and Qiao, S and Gao, S and Hu, S and Liu, H}, title = {Reconstitution of gut microbiota by medicinal plant isoflavones ameliorates heart failure with preserved ejection fraction.}, journal = {Pharmacological research}, volume = {228}, number = {}, pages = {108199}, doi = {10.1016/j.phrs.2026.108199}, pmid = {42025824}, issn = {1096-1186}, mesh = {Animals ; *Isoflavones/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Heart Failure/drug therapy/physiopathology/microbiology/metabolism ; Male ; Mice, Inbred C57BL ; *Stroke Volume/drug effects ; *Pueraria/chemistry ; *Plant Extracts/pharmacology/therapeutic use ; Plants, Medicinal ; Mice ; Ventricular Function, Left/drug effects ; }, abstract = {Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with limited therapeutic options. Gut microbiota and microbiota-derived metabolites impact the progression and severity of HFpEF-related cardiometabolic dysfunctions. Here, we demonstrated that the isoflavone extract of Pueraria lobata (Iso-Pl), puerarin, or its microbial metabolite S-equol, improved left ventricular diastolic dysfunctions, reduced hypertension, and ameliorated metabolic disorders in an HFD and L-NAME-induced HFpEF mouse model. Antibiotic depletion and fecal microbiota transplantation experiments revealed an important contribution of gut microbiota to Iso-Pl efficacy. It reshaped gut microbiota composition and function, and reprogrammed microbial-mediated lysine and phenylalanine metabolism. Metabolomics analysis confirmed that Iso-Pl enhanced the production of beneficial metabolites, butyrate and S-equol, while reducing the lysine and phenylalanine-related trimethyllysine (TML) and phenylacetylglycine (PAGly) that have been reported to accumulate and aggravate HFpEF. Moreover, treatment with Iso-Pl, puerarin, and S-equol upregulated estrogen receptor β (ESR2) and activated the downstream eNOS-cGMP-PKG signaling axis in mice, while concurrently inhibiting the pro-inflammatory mitogen-activated protein kinase (MAPK) pathway. These activities collectively contributed to the alleviation of HFpEF by Iso-Pl. Collectively, our findings demonstrate that the cardioprotective effects of Iso-Pl are closely linked with the gut microbiota-dependent metabolic reprogramming and highlight P. lobata isoflavones as promising therapeutic agents for HFpEF.}, }
@article {pmid42025932, year = {2026}, author = {Liu, Z and Zhang, T and Wang, S and Yin, H and Shao, X and Gao, L and Lu, X}, title = {Gut microbiota: A critical regulator of oxaliplatin-induced peripheral neurotoxicity development.}, journal = {Neurotoxicology}, volume = {114}, number = {}, pages = {103460}, doi = {10.1016/j.neuro.2026.103460}, pmid = {42025932}, issn = {1872-9711}, mesh = {Animals ; *Oxaliplatin/toxicity ; Rats, Sprague-Dawley ; *Gastrointestinal Microbiome/drug effects/physiology ; Male ; Rats ; *Peripheral Nervous System Diseases/chemically induced/microbiology ; *Antineoplastic Agents/toxicity ; Fecal Microbiota Transplantation ; Ganglia, Spinal/drug effects/metabolism ; Cytokines ; }, abstract = {BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common dose-limiting toxicity that significantly affects patients' quality of life. Although neuroinflammation has been implicated, the precise contribution of the gut-nerve axis remains incompletely understood. This study aimed to investigate the role of gut microbiota and associated inflammatory signaling in OIPN.<br><br>METHODS: An OIPN model was established in Sprague Dawley rats. Gut microbiota depletion was achieved via antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT) from healthy donors was performed to restore microbial communities. Mechanical allodynia and cold hypersensitivity were assessed using the von Frey filament test and the acetone test, respectively. Systemic inflammation was evaluated by measuring serum cytokine levels via enzyme-linked immunosorbent assay (ELISA). The composition of the gut microbiota was analyzed by 16S rRNA gene sequencing. Intestinal barrier integrity and local inflammation were assessed through histopathology, immunofluorescence, and quantification of tight junction proteins (ZO-1, occludin) and inflammatory markers (NF-&#x3ba;B, TNF-&#x3b1;) via quantitative polymerase chain reaction (qPCR) and Western blotting. Network pharmacology was employed to screen for potential common targets of oxaliplatin and neurotoxicity. Molecular alterations in the dorsal root ganglia (DRG) were examined using histology, qPCR, Western blotting, and immunofluorescence, with a focus on the TLR4/MyD88/NF-&#x3ba;B signaling pathway and pro-inflammatory cytokines.<br><br>RESULTS: Antibiotic-mediated depletion of gut microbiota significantly attenuated OXA-induced neuropathic pain and systemic inflammation, as evidenced by reduced levels of tumor necrosis factor-alpha (TNF-&#x3b1;), interleukin-6 (IL-6), and interleukin-1beta (IL-1&#x3b2;), whereas FMT reversed these protective effects. Analysis of 16S rRNA gene sequencing revealed that OXA altered gut microbiota composition, including reduced alpha diversity, altered beta diversity, a decreased Firmicutes/Bacteroidetes ratio, and taxonomic changes. These alterations were partially restored following FMT under the present experimental conditions. Functional prediction analysis indicated enrichment of the lipopolysaccharide (LPS) biosynthesis pathway. Consistently, OXA treatment was associated with elevated LPS levels in plasma and feces, which were reduced by ABX treatment and increased following FMT. OXA was also associated with impaired intestinal barrier integrity, as evidenced by decreased expression of ZO-1 and Occludin and increased inflammatory markers (NF-&#x3ba;B, TNF-&#x3b1;) in the colon, changes that were modulated by microbiota status. Network pharmacology analysis identified inflammation-related pathways and potential targets. In the DRG, OXA treatment was associated with neuronal injury, increased expression of pro-inflammatory cytokines (TNF-&#x3b1;, IL-1&#x3b2;, IL-6, and IL-8), and activation of the TLR4/MyD88/NF-&#x3ba;B signaling pathway, which were attenuated by antibiotic treatment and reappeared following FMT.<br><br>CONCLUSIONS: These findings support a microbiota-associated contribution to OIPN and suggest that gut microbiota may influence intestinal and peripheral inflammatory responses. Increased endotoxin burden and activation of TLR4-related signaling pathways may represent potential mechanisms linking the gut and nervous system in OIPN. Targeting the gut-nerve axis may offer a promising direction for future therapeutic strategies, although further studies are required to establish causality and identify specific microbial mediators.}, }
@article {pmid42026738, year = {2026}, author = {Cao, B and Zhou, X and Cao, X and Shi, J and Liu, C and Yuan, B}, title = {Application of Gut Microbiota in the Treatment and Efficacy Evaluation of Tic Disorders: A Systematic Review.}, journal = {Journal of child and adolescent psychopharmacology}, volume = {36}, number = {5}, pages = {257-265}, doi = {10.1177/10445463261445906}, pmid = {42026738}, issn = {1557-8992}, mesh = {Humans ; *Tic Disorders/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; *Probiotics/administration &amp; dosage/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy ; Treatment Outcome ; Child ; }, abstract = {OBJECTIVE: To systematically review existing evidence on the role of gut microbiota in the pathogenesis of tic disorders (TD) and to assess the therapeutic potential of microbiome-targeted interventions such as probiotics and fecal microbiota transplantation in the management of TD.<br><br>METHODS: A comprehensive search was conducted in PubMed, Web of Science, EMBASE, and The Cochrane Library (up to May 26, 2025). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered in PROSPERO (CRD420251067880).<br><br>RESULTS: Eleven studies were included, with four focusing on gut microbiome-based therapies and seven studies with gut microbiota and its metabolites as outcome indicators. At the genus level, children with TD exhibited specific alterations in gut microbiota: increased abundance of Bacteroides, Faecalibacterium, and Ruminococcus, alongside decreased levels of Bifidobacterium and Prevotella. This functional dysbiosis may trigger neuroinflammation via disrupted short-chain fatty acid metabolism and impaired intestinal barrier function, ultimately disturbing the glutamate and &#x3b3;-aminobutyric acid neurotransmitter balance and leading to dysfunction in the cortico-striato-thalamo-cortical circuit. Meanwhile, probiotics as an intervention have been consistently reported to alleviate tic symptoms, although clinical evidence remains limited.<br><br>CONCLUSION: Gut microbiota may contribute to TD pathogenesis via immune modulation and neurotransmitter metabolism. While microbiota-based strategies show promise, heterogeneity and methodological limitations in current studies necessitate further high-quality research to validate mechanisms and support clinical application.}, }
@article {pmid42026772, year = {2026}, author = {Gao, T and Zheng, M and Geng, F and Fu, Y and Yang, Y and Li, X and Wang, Y and Zhu, D and Wang, Z and Lu, L}, title = {Autonomic modulation following fecal microbiota transplantation in chronic insomnia.}, journal = {Postgraduate medicine}, volume = {138}, number = {4}, pages = {417-429}, doi = {10.1080/00325481.2026.2664261}, pmid = {42026772}, issn = {1941-9260}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; *Sleep Initiation and Maintenance Disorders/therapy/physiopathology ; Adult ; Double-Blind Method ; Polysomnography ; Middle Aged ; *Autonomic Nervous System/physiopathology ; Heart Rate/physiology ; Treatment Outcome ; Gastrointestinal Microbiome ; }, abstract = {OBJECTIVE: To determine whether fecal microbiota transplantation (FMT) modulates autonomic function in chronic insomnia disorder and whether autonomic rebalancing mediates sleep improvement.<br><br>METHODS: This prespecified exploratory analysis was embedded within a multicenter, double-blind, randomized, placebo-controlled trial of FMT for chronic insomnia. The original trial was designed to evaluate the efficacy and safety of the FMT-based treatment protocol, with polysomnography-measured sleep efficiency at 1&#x2009;month as the primary endpoint. Eighty adults were randomly assigned to receive either FMT (n&#x2009;=&#x2009;40) or placebo capsules (n&#x2009;=&#x2009;40). Overnight polysomnography was conducted at baseline and 1&#x2009;month, and heart rate variability indices were derived to quantify autonomic regulation. Sleep outcomes included PSG-derived metrics and validated subjective questionnaires. Associations between changes in autonomic parameters and sleep outcomes were examined using correlation analyses. Mediation analysis was performed to evaluate whether autonomic changes statistically mediated FMT-associated improvements in sleep. Gut microbiota composition was profiled using 16S rRNA gene sequencing.<br><br>RESULTS: In the original trial, the FMT-based treatment met its prespecified primary endpoint, with significantly improved polysomnography-measured sleep efficiency at 1&#x2009;month. In this exploratory analysis, FMT significantly reduced the LF/HF ratio (-0.10; 95% CI, -0.18 to -0.02; p&#x2009;=&#x2009;0.010). A reduction in LF/HF was associated with longer TST (&#x3b2;&#x2009;=&#x2009;-0.41; p&#x2009;=&#x2009;0.004). Mediation analysis showed that LF/HF accounted for 49.7% of the FMT effect on TST (ACME&#x2009;=&#x2009;19.44&#x2009;min; p&#x2009;=&#x2009;0.018). FMT induced microbial compositional remodeling associated with the nocturnal LF/HF ratio, including enrichment of Lachnospira eligens, Christensenellaceae R-7 group, Ruminococcaceae, and Coprococcus, and depletion of Prevotella copri, Streptococcus, and Faecalibacterium.<br><br>CONCLUSIONS: These findings provide clinical exploratory evidence for autonomic system as a potential pathway through which microbiota-targeted interventions may alleviate insomnia. Further studies are needed to determine the durability and clinical significance of these findings.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05917379 (June 23, 2023).}, }
@article {pmid42027687, year = {2026}, author = {Wu, H and Yu, M and Huang, S and Peng, Y and Wei, G and Huang, C}, title = {The Gut-Brain Axis as a Mediator of Environmental Endocrine Disruptors in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Mechanistic Synthesis.}, journal = {Biological psychiatry global open science}, volume = {6}, number = {3}, pages = {100717}, pmid = {42027687}, issn = {2667-1743}, abstract = {The rising global prevalence of attention-deficit/hyperactivity disorder (ADHD) underscores the importance of environmental factors, particularly environmental endocrine-disrupting chemicals (EEDs), whose mechanistic links to ADHD remain unclear. The gut-brain axis, a key modulator of neurodevelopment, is susceptible to EEDs and is altered in ADHD, suggesting a potential mediating pathway. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and PROSPERO registration (CRD420251152480), we systematically searched PubMed, Web of Science, and Embase (January 2014-July 2025) for studies on EEDs, gut microbiota, and ADHD. Data from 127 included studies (observational, experimental, interventional) were narratively synthesized to evaluate the gut-brain axis as a mediator. We found 1) consistent epidemiological associations between prenatal/childhood EED exposure (e.g., phthalates, bisphenol A, pesticides) and increased ADHD risk; 2) a distinct gut microbial signature in ADHD featuring reduced alpha diversity, elevated Firmicutes/Bacteroidetes ratio, depletion of beneficial taxa (Lactobacillus, Bifidobacterium), and impaired short-chain fatty acid (SCFA) production; 3) evidence that EED exposure induces convergent gut dysbiosis; and 4) interventional studies indicating that modulating the microbiota (via probiotics, synbiotics, fecal microbiota transplantation) can ameliorate ADHD-related behaviors. These findings support a novel mechanistic model wherein EEDs disrupt gut microbiota homeostasis, thereby contributing to ADHD pathogenesis via immune-inflammatory, microbial metabolite (e.g., SCFA), and neuroendocrine pathways along the gut-brain axis. This review synthesizes evidence positioning the gut-brain axis as a critical mediator linking EED exposure to ADHD. It proposes a unifying etiological framework and highlights the microbiome as a promising target for preventive and therapeutic strategies. Future longitudinal and intervention studies are needed to establish causality.}, }
@article {pmid42029022, year = {2026}, author = {Bornbusch, SL and Muletz-Wolz, CR}, title = {Applying microbial ecology frameworks to microbial therapies for wildlife.}, journal = {mSystems}, volume = {11}, number = {5}, pages = {e0059825}, pmid = {42029022}, issn = {2379-5077}, support = {PRFB-2209096//National Science Foundation/ ; IOS-2131060//National Science Foundation/ ; }, mesh = {Animals ; *Animals, Wild/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Humans ; Prebiotics/administration &amp; dosage ; Gastrointestinal Microbiome ; Ecology ; }, abstract = {Microbial ecology is increasingly incorporated into human and animal medicine via the study and purposeful manipulation of host-associated microbiomes. Microbial therapies-treatments with the aim of beneficially modulating microbiomes-are a burgeoning area of research and industry. These microbial therapies include prebiotic dietary items, live probiotics, and whole microbiota transplants (e.g., fecal microbiota transplants). Although microbial therapies for humans and domestic animals are now widely produced for commercial use and application, evidence supporting the efficacy of commercial microbial therapies is mixed. We suggest that microbial therapies are most effective when paired with concepts from ecology and rigorous empirical research. This is particularly relevant for the development and use of microbial therapies in wildlife animal species, in which we see large-scale variation in microbial communities across hosts of varying ecologies. Identifying and developing microbial therapies that can simultaneously be accessible and effective in a variety of hosts poses a novel challenge for microbial ecologists, animal scientists, and human and animal medical professionals. In addition to pre- and probiotics, we suggest that whole microbiota transplants provide a method of microbial supplementation that may better align with species-specific microbial ecology. Moving forward, emerging methods used in human medicine such as machine learning, network analysis, and microbiome engineering using high-throughput culturomics will likely be key to identifying and applying functionally relevant (e.g., disease suppressive) microbial taxa for wildlife therapies.}, }
@article {pmid42029644, year = {2026}, author = {Prince, AM and Zeltiņa, I and Reinis, A and Valciņa, O and Krūmiņa, A}, title = {HBV and the Microbiome-PubMed Database Literature Review.}, journal = {Infectious disease reports}, volume = {18}, number = {3}, pages = {}, pmid = {42029644}, issn = {2036-7430}, abstract = {OBJECTIVE: Hepatitis B virus (HBV) is a globally distributed infectious disease affecting the liver. This literature review aims to summarize all available relevant information on the PubMed database about HBV's connection to the microbiome and to consider possible treatment adjuncts.<br><br>MATERIALS AND METHODS: Database used: PubMed. Keywords used: "HBV", "Hepatitis B", "microbiome". In the PubMed database, 179 research publications were identified using these keywords; 69 studies were excluded as they were irrelevant or retracted. Of the remaining, 110 were analyzed in this literature review, and four additional literature sources were used to supply background information and context. Information was summarized. The analysed studies in total included 14,814 participants (excluding animal studies), of whom 8564 were HBV-infected individuals.<br><br>RESULTS: Results characterizing abundance or decrease in specific bacterial, viral, and fungal species are heterogeneous; multiple studies support that the HBV patient oral and fecal microbiome is different from that in healthy controls (HCs) and varies throughout disease progression. The HBV seems to transform the microbiome negatively, leading to dysbiosis and decreased microbial diversity in most studies. Evidence links HBV microbiome changes with influence on HbeAg seroconversion, HBV-DNA load, metabolic pathways, liver cirrhosis, and hepatocellular carcinoma. The research proposes that members of microbiota could potentially promote or protect against liver injury in HBV. Four studies proposed that the plasma virome in HBV patients was primarily composed of members of the Anelloviridae. One study researched a parasite (Entamoeba gingivalis) in HBV patients. Two studies analyzed HBV patients' fungal profiles.<br><br>CONCLUSIONS: Microbiota research, although promising, at the present moment is heterogeneous. HBV patients' microbiota is distinguishable from HCs, and multiple studies have tried to identify the HBV characteristic microbiome; however, more precise information is needed to draw conclusions. Fecal microbiota transplantation and probiotics have the potential to be therapy adjuncts for HBV patients, but more research is needed.}, }
@article {pmid42032216, year = {2026}, author = {Choi, Y and Ryu, S and Kang, A and Lee, W and Park, J and Kang, MG and Jang, KB and Kwon, Y and Kwak, MJ and Jeong, KC and Song, M and Kim, Y}, title = {Fecal virome transplantation alleviates weaning stress-induced behavioral alterations and intestinal health by reshaping the gut microbiome.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {42032216}, issn = {2045-2322}, support = {RS-2025-16068814//National Research Foundation of Korea/ ; }, abstract = {UNLABELLED: Weaning is a critical developmental period that can be accompanied by gut microbial dysbiosis, intestinal inflammation, and stress-related behavioral alterations. In this mouse study, we evaluated whether fecal microbiota transplantation (FMT) or fecal virome transplantation (FVT) derived from pre- and post-weaning piglets could differentially influence stress-related phenotypes after antibiotic pretreatment. Compared with FMT from post-weaning piglets (Post-FMT), FMT from pre-weaning piglets (Pre-FMT) was associated with higher open-arm time in the elevated plus maze and greater inner-zone exploration in the open field test. In post-FMT mice, subsequent FVT from pre-weaning piglets (Pre-FVT) was associated with higher open-arm time and inner-zone exploration than FVT from post-weaning piglets (Post-FVT). Pre-FVT was also associated with enrichment of several taxa linked to short-chain fatty acid production, including Muribaculaceae, Akkermansia, Bifidobacterium, and Butyricimonas. It was further associated with lower colonic expression of pro-inflammatory cytokine genes, higher expression of barrier-related genes, longer colon length, altered fecal metabolite profiles, and lower serum corticosterone concentrations. In brain tissues, Pre-FVT was associated with higher GABAR and BDNF transcript levels and lower CRHR1 transcript levels than Post-FVT. Collectively, these findings provide preliminary evidence that piglet-derived FVT may contribute to changes in microbiome- and gut-brain-axis-related readouts in mice under the conditions tested.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-49647-0.}, }
@article {pmid42032281, year = {2026}, author = {Tonkin-Hill, G and Shao, Y and Zarebski, AE and Mallawaarachchi, S and Xie, O and Mäklin, T and Thorpe, HA and Davies, MR and Bentley, SD and Lawley, TD and Corander, J}, title = {Strain-level transmission inference across multi-kingdom metagenomic data using TRACS.}, journal = {Nature microbiology}, volume = {11}, number = {6}, pages = {1626-1638}, pmid = {42032281}, issn = {2058-5276}, support = {2025515//Department of Health | National Health and Medical Research Council (NHMRC)/ ; DE240100316//Department of Education and Training | Australian Research Council (ARC)/ ; 220540/Z/20/A//Wellcome Trust (Wellcome)/ ; }, mesh = {Humans ; *Metagenomics/methods ; Algorithms ; Polymorphism, Single Nucleotide ; Streptococcus pneumoniae/genetics ; Plasmodium falciparum/genetics ; Feces/microbiology ; COVID-19/transmission ; Malaria, Falciparum/transmission ; Gastrointestinal Microbiome/genetics ; Metagenome ; Infant ; High-Throughput Nucleotide Sequencing ; }, abstract = {Coexisting strains of the same species within metagenomic data pose a substantial challenge to inferring transmission of pathogenic and commensal microbes. Here we present TRAnsmission Clustering of Strains (TRACS), a highly accurate algorithm for estimating genetic distances between strains at the level of individual single nucleotide polymorphisms, which is robust to intra-species diversity within the host. Analysis of faecal microbiota transplantation datasets and extensive simulations demonstrates that TRACS outperforms existing methods. We use TRACS to infer transmission networks in patients colonized with multiple strains, including severe acute respiratory syndrome coronavirus 2 amplicon sequencing data, deep population sequencing data of Streptococcus pneumoniae and single-cell genome sequencing data from patients infected with Plasmodium falciparum. Applying TRACS to gut metagenomic samples from a mother-infant cohort revealed species-specific transmission rates and identified increased the persistence of Bifidobacterium breve in infants, a finding previously missed owing to the presence of multiple strains. Our study shows that TRACS can be used across microbial kingdoms to uncover strain dynamics.}, }
@article {pmid42032982, year = {2025}, author = {Huang, S and Yang, Q and Zhou, W}, title = {[Gut microbiota involved in cancer invasion and metastasis].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {50}, number = {12}, pages = {2186-2200}, pmid = {42032982}, issn = {1672-7347}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neoplasm Metastasis ; *Neoplasm Invasiveness ; *Neoplasms/microbiology/pathology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Epithelial-Mesenchymal Transition ; }, abstract = {The gut microbiota, as the "second genome" of the human body, plays a crucial role in maintaining the host's homeostasis and regulating the disease process. The latest research indicates that intestinal microecological imbalance is an important cause that triggers and accelerates tumor metastasis. The gut microbiota mainly promotes tumor invasion and metastasis through the following 2 mechanisms: 1) Contact-dependent mechanism, specific pathogenic bacteria directly adhere and invade tumor cells through surface proteins, inducing epithelial-mesenchymal transition and cytoskeleton remodeling; 2) non-contact-dependent mechanism, metabolites derived from the microbiota act on distant organs through the bloodstream, activating signaling pathways to construct pre-metastatic ecological niches and inducing systemic immunosuppression. Precise intervention strategies for the gut microbiota include supplementing specific probiotics with anti-cancer potential, selective antibiotics or phage therapy against specific pathogenic bacteria, fecal microbiota transplantation and microbial vaccines. Although preliminary studies have shown promising results, the high heterogeneity of the microbiota, the bidirectional action of metabolites, and the safety of long-term colonization remain bottlenecks for clinical translation. In the future, it is necessary to further clarify the key transfer-promoting microbiota and their characteristic metabolic and signaling mechanisms, promote the development of individualized and precise microbiota intervention strategies, and strengthen clinical translation research, in order to ultimately achieve the goal of effectively preventing and treating tumor metastasis by regulating the gut microbiota.}, }
@article {pmid42034536, year = {2026}, author = {Yao, Y and Liu, Y and Li, Y and Lu, B and Cui, X and Pan, X}, title = {Re: Fecal Microbiota Transplantation plus Pembrolizumab and Axitinib in Metastatic Renal Cell Carcinoma: The Randomized Phase 2 TACITO Trial.}, journal = {European urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eururo.2026.04.003}, pmid = {42034536}, issn = {1873-7560}, }
@article {pmid42035251, year = {2026}, author = {Li, C and Wan, W and Li, C and Zhu, D and Li, J and Yang, S and Chen, W and Chen, H and Yu, C}, title = {The microbiota-gut-brain axis as a driver of secondary brain injury after aneurysmal subarachnoid hemorrhage: from bidirectional vicious cycle to therapeutic opportunities.}, journal = {Reviews in the neurosciences}, volume = {}, number = {}, pages = {}, pmid = {42035251}, issn = {2191-0200}, abstract = {Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating stroke subtype with high morbidity and mortality, significantly contributed to by secondary brain injuries such as early brain injury and delayed cerebral ischemia. Despite advances in acute management, effective neuroprotective strategies remain an unmet need. The microbiota-gut-brain axis (MGBA), a pivotal bidirectional communication network, has recently emerged as a critical modulator of pathophysiology in acute brain injuries. However, its precise role and therapeutic potential in aSAH are not systematically defined. This review synthesizes clinical and preclinical evidence to move beyond correlation and delineate the spatiotemporal dynamics and the mechanisms that may underlie of MGBA dysregulation post-aSAH. We conceptualize a self-amplifying "brain-gut-brain" vicious cycle: the initial brain injury may disrupt intestinal barrier integrity and microbiota ecology via neuroendocrine and inflammatory pathways; in turn, gut-derived signals (e.g., altered microbial metabolites, endotoxin translocation) may propagate systemic inflammation and exacerbate neuroinflammation, blood-brain barrier disruption, and cerebral ischemia. We dissect this cycle by detailing the key molecular bridges (tryptophan metabolites, short-chain fatty acids, bile acids), signaling pathways (e.g., TLR4/NF-κB, NLRP3 inflammasome), and central effectors involved. Furthermore, we provide a critical, stratified evaluation of MGBA-targeting therapeutic strategies - including probiotics, prebiotics, fecal microbiota transplantation, and metabolite supplementation - assessing their mechanistic rationale, level of evidence, and translational challenges. Finally, we outline future directions emphasizing the need for defining therapeutic windows, establishing causal proof, and integrating MGBA modulation into multimodal neurocritical care. Harnessing the MGBA presents a novel and promising paradigm for developing adjunctive neuroprotective therapies to improve outcomes after aSAH.}, }
@article {pmid42036378, year = {2026}, author = {Chen, D and Zhang, B and Wang, O and Zhang, X and Huang, J}, title = {[Effects of high-fat diet on gut microbiota in rats transplanted with gut microbiota from normal/high triglyceridemic individuals].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {55}, number = {2}, pages = {261-268}, doi = {10.19813/j.cnki.weishengyanjiu.2026.02.014}, pmid = {42036378}, issn = {1000-8020}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Male ; Rats ; Rats, Sprague-Dawley ; *Triglycerides/blood ; Humans ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Hypertriglyceridemia/microbiology ; }, abstract = {OBJECTIVE: Using sterile SD rats as a model, the fat accumulation and changes in the intestinal flora of rats transplanted with normal/high triglyceride(TG) population under high-fat diet were studied.<br><br>METHODS: 10-week-old male sterile rats were randomly divided into 3 groups according to body weight, with 6 rats in each group. The non-colonizing group was gavaged with normal saline, the normal lipid group was gavaged with normal TG(<1.7 mmol/L) human intestinal flora, and the high TG group was gavaged with high TG(&#x2265;1.7 mmol/L) human intestinal flora. Rats were given fecal bacterial solution by gavage at a dose of 1 mL per 100 g of body weight, every other day, for a total of 3 times, followed by 2 weeks of adaptive growth of the microbiota. After the transplanting was completed, a 9-week feeding experiment with high-fat diet(fat energy supply ratio 40.5%) was conducted. The body weight of the rats was measured weekly, and feces were collected every three weeks. After the experiment, liver, perirenal, subcutaneous and brown fat were weighed. The fat weight was used to represent the fat accumulation of the rats, and lipid indicators were determined. Liver HE staining was used to observe steatosis, and high-throughput sequencing was used to analyze the intestinal flora of the rats.<br><br>RESULTS: After the experiment, compared with the colonized normal TG population microbiota group, there were no significant differences in body weight, perirenal, subcutaneous and brown fat mass, and blood lipid levels in the colonized high TG microbiota group. Liver HE staining sections showed that both the colonized high TG and non-colonized dyslipidemia microbiota groups could observe more severe steatosis and obvious fat vacuums. The intestinal microbiota profiles of the two groups of rats colonized with different population microbiota showed different variation patterns at the phylum and genus levels. At 0 weeks of high-fat diet, the F/B ratios of the microbiota phylum in rats colonized with the feces of the high-TG population and those colonized with the feces of the normal TG population were 1.24 and 0.48, respectively. After 9 weeks of high-fat diet, The F/B ratios of the Firmicutes and Bacteroidetes phyla of the bacteria phyla in rats colonized with the feces of the high TG population and those colonized with the feces of the normal TG population were 3.37 and 0.81, respectively. In the fecal colonization group of rats in the high TG population under a high-fat diet, more obvious intestinal flora disorders occurred, the relative abundance of beneficial bacteria was inhibited, and the relative abundance of pathogenic bacteria increased.<br><br>CONCLUSION: Under high-fat diet, the colonization of intestinal flora in volunteers with different blood lipid levels has a certain relationship with the weight changes and fat accumulation of rats. The species composition and abundance of flora in different populations have undergone significant changes.}, }
@article {pmid42039746, year = {2026}, author = {Tian, W and Peng, S and Xu, F and Kong, X and Li, Y and Zhang, W and Liu, Z and Zhang, H and Wang, J and Wang, L}, title = {Disruption of intestinal barrier and immune homeostasis links gut microbiota dysbiosis to aggravated experimental autoimmune myasthenia gravis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1726788}, pmid = {42039746}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology/microbiology ; Th17 Cells/immunology ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Regulatory/immunology ; Disease Models, Animal ; Cytokines/blood ; RNA, Ribosomal, 16S/genetics ; *Myasthenia Gravis, Autoimmune, Experimental/immunology/microbiology/pathology ; *Homeostasis ; Fecal Microbiota Transplantation ; *Intestinal Mucosa/immunology/microbiology ; Female ; }, abstract = {INTRODUCTION: Myasthenia Gravis (MG) is an acquired autoimmune disease. The imbalance between Th17 and Treg cells plays a crucial role in the pathogenesis of MG. A stable intestinal microbiota is essential for maintaining immune balance, a function primarily mediated by the Th17/Treg axis. This study aims to explore the role of gut microbiota in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG) to identify potential new treatment strategies.<br><br>METHODS: An EAMG model was established in Lewis rats by immunization with the AChR&#x3b1;97-116 peptide segment. The composition and structure of the gut microbiota were analyzed by 16S rRNA sequencing. The serum levels of inflammatory cytokines (IFN-&#x3b3;, TNF-&#x3b1;, IL-17, IL-10), AChR-Ab, and LPS were measured using the ELISA method. Colon tissues were subjected to Hematoxylin and eosin (H&amp;E) staining, and Claudin-1 and Muc2 expression was analyzed via immunofluorescence. A microbiota disorder animal model was established by administering an antibiotic mixture via gavage, followed by fecal microbiota transplantation. Splenic CD3+CD4+IL-17A+ Th17 cells and CD3+CD4+CD25+Foxp3+ Treg cells were quantified by flow cytometry.<br><br>RESULTS: 1. Compositional and structural changes of the gut microbiota in EAMG. Compared with HC, the serum levels of IFN-&#x3b3;, TNF-&#x3b1;, IL-17, and AChR-Ab in EAMG were significantly increased (P < 0.0001), while the serum level of IL-10 was significantly decreased (P < 0.0001), and the serum level of LPS was increased (P < 0.01). The protein levels of Claudin-1 (P < 0.001) and Muc2 (P < 0.05) in the colon were significantly reduced in EAMG. 2. Relative to rats receiving HC microbiota transplantation (HMb), those receiving EAMG microbiota transplantation (MMb) exhibited significantly elevated serum levels of AChR-Ab (P < 0.01), TNF-&#x3b1; (P < 0.05), IL-17 (P < 0.05), and LPS (P < 0.01), alongside significantly reduced colonic levels of Claudin-1 (P < 0.05) and Muc2 (P < 0.0001). 3. Compared with the EAMG group, the ABX + EAMG group (EAMG with microbiota dysbiosis) exhibited significantly lower colonic levels of Claudin-1 and Muc2 (P < 0.05), a significantly greater splenic Th17/Treg cell imbalance (P < 0.01), and significantly higher serum AChR-Ab levels (P < 0.01).<br><br>DISCUSSION: The gut microbiota is intricately linked to the progression of EAMG. Microbiota dysbiosis can exacerbate intestinal barrier damage in EAMG and may further influence the pathological changes of myasthenia by disrupting the Th17/Treg immune balance. These findings suggest a novel therapeutic strategy for the treatment of myasthenia gravis by re-establishing microbial homeostasis.}, }
@article {pmid42039828, year = {2026}, author = {Li, Z and Xie, C and Pan, C}, title = {The oral-gut-brain axis: how periodontitis influence depression.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1778744}, pmid = {42039828}, issn = {1664-302X}, abstract = {Depression has a high global prevalence and is a common mental-emotional disorder that severely jeopardizes human health. However, current treatment options remain limited, necessitating the exploration of novel pathological mechanisms and intervention targets. Recent studies indicate that periodontitis, as a prevalent chronic oral infectious disease, not only causes local microbial dysbiosis and inflammatory responses but may also influence central nervous system function through the "oral-gut-brain axis," thereby contributing to the pathogenesis and progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, as well as neuropsychiatric disorders like depression. This review systematically examines the impact of periodontitis on oral microbiota and its subsequent translocation and colonization in the gut microbiota through pathways including swallowing and bloodstream circulation, ultimately leading to structural and functional dysregulation of the gut microbiota. The interaction between oral and gut microbiota can influence the brain through the "gut-brain axis," including disturbances in neurotransmitter metabolism, activation of systemic immune responses, and direct or indirect effects of bacterial metabolites (such as short-chain fatty acids, lipopolysaccharides, etc.) on the blood-brain barrier and neural function. This suggests that periodontal health management may serve as a novel strategy for the prevention and treatment of depression. This article further summarizes the potential of oral interventions for periodontitis (such as mechanical debridement and local/systemic antimicrobial therapy), microbiota modulation methods (such as probiotics, prebiotics, and fecal microbiota transplantation), and multidisciplinary collaborative comprehensive treatment strategies in improving microbial homeostasis and alleviating depressive symptoms. Finally, this paper points out the current research limitations in mechanistic details, causal relationships, and clinical translation, while envisioning the feasibility and prospects of developing personalized treatment strategies by targeting the "oral-gut-brain axis" in the future.}, }
@article {pmid42040311, year = {2026}, author = {Dong, B and Zhong, B and Zuo, J and Liao, L and Zeng, W and Xiong, M and Wei, Y and Zhang, D and Fan, X}, title = {Identification and Validation of Ferroptosis-Related Biomarkers and Therapeutic Targets in ARDS: A Bioinformatics and Experimental Study.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {566825}, pmid = {42040311}, issn = {1178-7031}, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disease with high mortality and limited effective therapies. Recent studies link ferroptosis-an iron-dependent regulated cell death-to ARDS pathogenesis. This study aimed to identify/validate ferroptosis-related diagnostic biomarkers, therapeutic targets, and fecal microbiota transplantation (FMT)'s protective role in ARDS.<br><br>METHODS: Bioinformatic analyses of GEO datasets (GSE76293/GSE151263) included differential expression profiling, WGCNA, PPI network, and machine learning (LASSO/RF) to screen hub genes, with ROC analysis for diagnostic efficacy. An LPS-induced ARDS rat model with FMT intervention was validated via qRT-PCR, IHC, Western blot, and histological staining.<br><br>RESULTS: Thirty-seven ferroptosis-linked differentially expressed genes (FDEGs) were identified, enriched in ferroptosis, mitophagy, and immune pathways. Three hub genes (MAPK8, CREB1, GPX4) showed robust diagnostic utility (LASSO AUC=0.931; RF AUC=0.993 in GSE76293) and correlated with monocytes/neutrophils/activated NK cells. LPS suppressed their mRNA/protein levels in rats, reversed by FMT.<br><br>CONCLUSION: MAPK8, CREB1, and GPX4 are potential diagnostic biomarkers and therapeutic targets for ARDS. FMT protects against ARDS by reversing these genes' downregulation and suppressing ferroptosis, providing new insights into ARDS pathogenesis and ferroptosis-targeted interventions.}, }
@article {pmid42041380, year = {2026}, author = {Alvaro, ME and Caserta, S and Martino, EA and Skafi, M and Bruzzese, A and Amodio, N and Lucia, E and Olivito, V and Labanca, C and Mendicino, F and Vigna, E and Morabito, F and Gentile, M}, title = {Gut Microbiota and Acute Myeloid Leukemia: State of the Art, Clinical Signals, and Translational Opportunities.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {42041380}, issn = {2079-6382}, abstract = {Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity-particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome-drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes.}, }
@article {pmid42042323, year = {2026}, author = {Granata, G and Petrosillo, N}, title = {Newer Therapeutics to Selectively Kill Clostridioides difficile and Restore the Microbiome.}, journal = {Infectious disease reports}, volume = {18}, number = {2}, pages = {}, pmid = {42042323}, issn = {2036-7430}, abstract = {BACKGROUND: The antibiotic ibezapolstat and the live biotherapeutic product live-JSLM are promising future approaches for treating Clostridioides difficile infection. Ibezapostat is a highly specific antibiotic for Clostridioides difficile, with minimal impact on the intestinal flora. Live-JSLM is designed to restore healthy intestinal microbiota, thus preventing recurrence of Clostridioides difficile infection. In this narrative review, we reviewed available data on ibezapostat and live-JSLM, considering that they are prototypes of two distinct, unique mechanisms of action against Clostridioides difficile.<br><br>METHODS: Data sources: PubMed and SCOPUS databases were searched from 1 January 2012 to 15 November 2025. Original articles reporting data on ibezapolstat and live-JSLM were included.<br><br>RESULTS: 31 studies were included. When compared to conventional anti-Clostridioides difficile antibiotics, ibezapolstat had a similar level of effectiveness and minimal impact on the gut microbiota. The available data confirm live-JSLM safety and efficacy in restoring the gut microbiota following the conclusion of the standard anti-Clostridioides difficile antibiotic regimen.<br><br>CONCLUSIONS: The results on ibezapolstat efficacy are promising, but require confirmation in larger patient populations through double-blind, randomised phase III trials. In the near future, an integrated approach may enhance the management of Clostridioides difficile infection: starting with highly specific antibiotics, i.e., ibezapolstat, followed by microbiome-based therapies such as live-JSLM.}, }
@article {pmid42043039, year = {2026}, author = {Lauriola, M and Valkenburg, S and Dejongh, S and Zadora, W and Krukowski, H and Evenepoel, P and Raes, J and Farré, R and Glorieux, G and Meijers, B}, title = {Kidney Function Modulates Gut Microbial Metabolism.}, journal = {Toxins}, volume = {18}, number = {4}, pages = {}, pmid = {42043039}, issn = {2072-6651}, support = {860329//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/metabolism/microbiology/physiopathology ; *Colon/microbiology/metabolism ; Male ; Tryptophan/metabolism ; Feces/microbiology/chemistry ; *Kidney/physiopathology ; Fatty Acids, Volatile/metabolism ; Indoles/metabolism ; Kynurenine/metabolism ; Rats ; Amino Acids/metabolism ; Fermentation ; Rats, Wistar ; Cresols/metabolism ; *Bacteria/metabolism ; }, abstract = {Growing evidence suggests that chronic kidney disease (CKD) profoundly disrupts gut microbiome and its activity. This study explores how CKD affects colon microbial metabolism, focusing on (1) the representativeness of fecal metabolomics, (2) saccharolytic and proteolytic fermentation metabolites, and (3) the gut microbiome's role in the partitioning of tryptophan in its metabolic pathways. Tryptophan's main metabolic pathways include the indolic and the kynurenine pathways, which lead, respectively, to the formation of indoxyl sulfate and kynurenine, both contributing to uremic toxicity. Using a rat model of CKD, we evaluated whether fecal concentrations of microbial compounds, on which most studies are based, reflect the colonic concentrations in contact with the gut mucosa. Thus, we quantified the concentration and content of amino acids, indole, p-cresol, and also short-chain fatty acids, in different colon sections. We demonstrated that CKD promotes increased proteolytic fermentation and an augmented tryptophan partitioning into both the indolic and kynurenine pathways. Depletion of the indolic pathway obtained upon antibiotic treatment leads to a further enhancement of the kynurenine pathway.}, }
@article {pmid42045958, year = {2026}, author = {Huang, J and Chen, Z and Wang, M and Yang, C and Wang, A and Chen, Y}, title = {Efficacy and safety of fecal microbiota transplantation in reducing recurrence of colorectal adenomas after endoscopic resection: study protocol for a multicenter, open-label, randomized, no-treatment-controlled trial.}, journal = {Trials}, volume = {27}, number = {1}, pages = {}, pmid = {42045958}, issn = {1745-6215}, support = {C2401027//Shenzhen Medical Research Fund/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Colorectal Neoplasms/surgery/microbiology/pathology ; *Neoplasm Recurrence, Local/prevention &amp; control ; *Adenoma/surgery/pathology/microbiology ; *Colonoscopy/adverse effects ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Gastrointestinal Microbiome ; Time Factors ; }, abstract = {BACKGROUND: Endoscopic resection is the standard treatment for colorectal adenoma (CRA), a key precursor to colorectal cancer (CRC). However, a high rate of recurrence post-procedure poses a significant challenge for long-term CRC prevention. Growing evidence suggests gut microbial dysbiosis contributes to adenoma development and recurrence. This trial will test the hypothesis that restoring a healthy gut microbiome with fecal microbiota transplantation (FMT) can reduce the recurrence of CRA after endoscopic resection.<br><br>METHODS: This protocol describes a multicenter, open-label, randomized, no-treatment-controlled trial that will enroll 466 participants with CRA following endoscopic resection. Participants will be randomly assigned in a 1:1 ratio to receive either FMT or no treatment (control). The FMT intervention consists of an initial colonoscopic infusion and oral capsules, followed by oral maintenance capsules at months 3, 6, and 9. The primary outcome is the rate of CRA recurrence at the 12-month follow-up colonoscopy. Key secondary outcomes include the incidence of all polypoid lesions, changes in the gut and mucosal microbiota composition, the incidence of CRC, and a comprehensive assessment of adverse events to evaluate safety.<br><br>DISCUSSION: This trial is designed to provide high-quality evidence on the efficacy and safety of FMT for preventing CRA recurrence. The findings may support a novel, microbiome-based strategy for the secondary prevention of CRC and provide mechanistic insights into the role of the gut microbiota in colorectal carcinogenesis.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT06205862. Registered on 16 January, 2024. https://clinicaltrials.gov/study/NCT06205862 .}, }
@article {pmid42046871, year = {2026}, author = {Yang, Y and Tan, X and Zhang, Z and Liang, L and Wu, Z and He, J and Wang, Y and Dong, M and Zheng, J and Zhang, H and Feng, S and Cheng, W and Cui, B and Wei, H and Li, Q}, title = {Metagenomic sequencing reveals high reproducibility of human donor microbiota transplanted into germ-free mice via lower gut route.}, journal = {Journal of Zhejiang University. Science. B}, volume = {27}, number = {4}, pages = {375-389}, pmid = {42046871}, issn = {1862-1783}, support = {2021YFA0805904//the National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Humans ; Mice ; Germ-Free Life ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Metagenomics ; Reproducibility of Results ; High-Throughput Nucleotide Sequencing ; Male ; *Metagenome ; Mice, Inbred C57BL ; Female ; }, abstract = {Human flora-associated (HFA) mice are often used to simulate the structure of human intestinal microbiota and to study the causal relationships between diseases and gut microbiota. However, several factors affect the colonization efficiency of human microbiota in germ-free (GF) mice, and the differential effects of gavage and lower gut transplantation on colonization are still unclear. In this study, we explored the reproducibility of the recipient-to-donor gut microbiota community structure and function under different transplantation routes and the differences in microbial colonization between recipients via gavage transplantation (GT_mice group) and lower gut transplantation (LGT_mice group). High-throughput sequencing of the metagenome was performed on the feces of each subject, and the composition of microbiome of each group was analyzed. As expected, the introduction of human fecal microbiota into GF mice via lower gut transplantation had a high transfer efficiency, which was evident from the similar species community structure to that of the donor (Adonis R[2]=0.713 960 for LGT_mice group‒donor group; Adonis R[2]=0.774 095 for GT_mice group‒donor group) and a higher bacterial colonization rate. The findings provide unique insights into improving the accuracy of constructing humanized microbiota transplantation models, aiding our understanding of the relationships between the human gut microbiota and disease.}, }
@article {pmid42046887, year = {2026}, author = {Li, M and Yue, A and Gu, L and Li, F and Ye, N and Xu, S and Gong, Z and Li, D and Xu, P}, title = {Microbiota-metabolite axis in endometriosis: Pathogenic mechanisms and clinical implications.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-17}, doi = {10.7555/JBR.39.20250566}, pmid = {42046887}, issn = {1674-8301}, abstract = {Growing evidence highlights the role of microbiota, including those of the gut, reproductive tract, and endometrial tissue, as critical functional drivers in the pathogenesis of endometriosis (EM). Studies have revealed a characteristic microbial imbalance in patients with EM, marked by a reduced abundance of beneficial bacteria and enrichment of opportunistic pathogens. These microbial communities exert their influence primarily through metabolic activity, as demonstrated by metabolomic studies showing their capacity to modulate host immune and endocrine responses. This imbalance leads to multiple key metabolic disturbances, including decreased levels of short-chain fatty acids, particularly butyrate; a shift in tryptophan metabolism toward the kynurenine pathway; elevated β-glucuronidase activity; increased lipopolysaccharide production; and altered secondary bile acid profiles. Functionally, these metabolic alterations converge to promote EM by disrupting immune homeostasis, enhancing estrogen signaling, and driving systemic inflammation, collectively creating a permissive microenvironment for ectopic lesion growth and invasion. Targeted interventions, such as probiotics, high-fiber dietary strategies, fecal microbiota transplantation, and selective modulation of microbial or host metabolic enzymes, are emerging as promising non-hormonal therapeutic approaches. Nonetheless, further studies incorporating longitudinal cohort designs and integrative multi-omics approaches are essential to establish causality and facilitate the development of precise diagnostic and personalized treatment strategies.}, }
@article {pmid42047661, year = {2026}, author = {Parker, G}, title = {Faecal Transplantation for Bipolar Disorder.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437261445768}, pmid = {42047661}, issn = {1497-0015}, }
@article {pmid42048405, year = {2026}, author = {Wang, H and Wu, Z and Zhang, Y and Tang, L and Shi, G and Ma, L and Huang, Z and Zhou, J}, title = {Fecal microbiota transplantation mitigates respiratory infection in rats exposed to hypobaric hypoxia by modulating the NLRP3 inflammasome and mucosal immunity.}, journal = {PloS one}, volume = {21}, number = {4}, pages = {e0347857}, pmid = {42048405}, issn = {1932-6203}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/immunology ; *Fecal Microbiota Transplantation ; *Inflammasomes/metabolism/immunology ; Rats ; *Hypoxia/complications/immunology/microbiology ; Male ; Gastrointestinal Microbiome ; *Immunity, Mucosal ; Rats, Sprague-Dawley ; *Respiratory Tract Infections/therapy/microbiology/immunology ; Dysbiosis/therapy ; Fatty Acids, Volatile/blood ; Streptococcus pneumoniae ; RNA, Ribosomal, 16S/genetics ; Cytokines/metabolism ; }, abstract = {OBJECTIVE: To investigate the role of the gut-lung axis in respiratory infection under hypobaric hypoxia and the therapeutic potential of fecal microbiota transplantation (FMT).<br><br>METHODS: Rats were exposed to hypobaric hypoxia (simulated 5000 m) for 14 days. Gut microbiota and serum short-chain fatty acids (SCFAs) were analyzed via 16S rRNA sequencing and GC-MS. Rats were then infected with Streptococcus pneumoniae and treated with FMT. Lung inflammation, NLRP3 inflammasome activity, cytokines, bacterial load, and secretory IgA (sIgA) were assessed.<br><br>RESULTS: Hypobaric hypoxia triggered gut dysbiosis, marked by reduced abundance of Firmicutes D and Lactobacillus, elevated Bacteroidota, and decreased SCFA levels..FMT restored microbiota composition, increased acetic and butyric acid levels, and attenuated lung inflammation. FMT also enhanced NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1), elevated IL-1&#x3b2;, IL-6, and TNF-&#x3b1; in BALF, reduced bacterial colonies, and increased airway sIgA in infected rats.<br><br>CONCLUSIONS: FMT alleviates hypobaric hypoxia-aggravated respiratory infection by restoring gut microbiota, modulating SCFAs, and enhancing NLRP3-mediated mucosal immunity, highlighting the gut-lung axis as a therapeutic target.}, }
@article {pmid42049093, year = {2026}, author = {Hu, JJ and Feng, SY and Wu, L and He, SY and Chen, XF and Li, GH and Min, Y and Xu, HL and Sun, QS and Xie, S and Jian-Liu,  and Chen, F and Liu, KX and Deng, F}, title = {Chac1 deficiency confers sepsis resistance by enriching gut microbiota-derived indole-3-carboxylic acid to drive macrophage metabolic shifts.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.04.065}, pmid = {42049093}, issn = {2090-1224}, abstract = {INTRODUCTION: Sepsis is a life-threatening dysregulated host response to infection, lacks effective therapies. ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) is elevated in sepsis and correlates with severity, but its functional role in the pathogenesis of sepsis-induced organ damage is unclear.<br><br>OBJECTIVES: We aimed to define the contribution of CHAC1 to sepsis-induced organ injury and elucidate the underlying mechanisms involving gut microbiota-derived metabolites and host immunity.<br><br>METHODS: Chac1[-/-] mice were subjected to LPS-induced endotoxemia to evaluate organ injury. The gut microbiota's role was defined by 16S rRNA gene sequencing, microbiota depletion and fecal microbiota transplantation (FMT). The effect of microbiota-derived metabolite indole-3-carboxylic acid (ICA) was assessed in vivo. Underlying mechanisms were investigated via macrophage depletion, AHR pharmacological/genetic inhibition, and in vitro studies with RAW264.7 cells and bone marrow-derived macrophages.<br><br>RESULTS: Serum CHAC1 was elevated in septic patients and mice, correlating with disease severity. Chac1 deficiency protected against sepsis-induced multi-organ injury, an effect that was gut microbiota-dependent. Chac1[-]/[-] mice exhibited a remodeled gut microbiota, with enrichment of Akkermansia muciniphila and increased levels of the tryptophan metabolite ICA. Exogenous ICA or A. muciniphila supplementation recapitulated the protective phenotype. ICA treatment improved survival, attenuated inflammation, and reduced organ injury by activating the aryl hydrocarbon receptor (AHR) in macrophages. This was evidenced by AHR nuclear translocation, and siRNA-mediated AHR knockdown abolished ICA's effects. ICA reprogrammed macrophage metabolism, inhibiting glycolysis (reduced lactate) and enhancing oxidative phosphorylation (increased ATP, oxygen consumption rate), leading to suppressed pro-inflammatory responses.<br><br>CONCLUSION: Chac1 deficiency confers sepsis resistance by enriching protective gut microbiota and elevating ICA, which acts as a major downstream effector. ICA activates the AHR in macrophages, driving a metabolic shift from glycolysis to oxidative phosphorylation that dampens inflammation and organ injury. This CHAC1-microbiota-ICA-AHR-macrophage axis identifies ICA as a promising therapeutic candidate and CHAC1 as a potential prognostic biomarker for sepsis.}, }
@article {pmid42051335, year = {2026}, author = {Li, B and Ren, Z and Li, H and Li, M and Zhong, H and Nie, Q and Chen, J and Wu, R and Zheng, JS and Deng, K and Cai, Y}, title = {Microbiota-metabolites interaction associated with glycemic improvement following a dietary herbal intervention in type 2 diabetes.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1793130}, pmid = {42051335}, issn = {2296-861X}, abstract = {BACKGROUND: Type 2 diabetes (T2D) is a global metabolic disorder characterized by chronic hyperglycemia and disruption of the gut microbiome. Nutritional and microbiota-targeted interventions have emerged as promising strategies for glycemic management, yet longitudinal clinical evidence integrating microbial and metabolic mechanisms remains limited. This study investigated microbiota-metabolites alterations during a standardized dietary herbal intervention (QingYun7, QY7) and explored their relationship with glycemic regulation across both animal study and clinical settings.<br><br>METHODS: The metabolic and microbial effects of QY7 were first evaluated in diabetic rats through measurements of blood glucose, and gut microbiota composition. Subsequently, a prospective cohort of 385 patients with T2D received QY7, with longitudinal monitoring of fasting, random, and 2-h postprandial glucose, gut microbiota, and serum metabolites across multiple time points. Fecal microbiota transplantation (FMT) from patients before and after intervention into antibiotic-treated mice was performed to evaluate the causal contribution of the gut microbiome to glycemic improvement. Mediation analyses were conducted to delineate potential pathways linking gut microbes, serum metabolites, and glucose outcomes.<br><br>RESULTS: In diabetic rats, QY7 administration significantly reduced blood glucose, and restored gut microbial composition. In the clinical cohort, the intervention was associated with rapid and sustained reductions in fasting, random, and postprandial glucose levels, accompanied by consistent remodeling of the gut microbiome and serum metabolite profile. FMT experiments demonstrated that microbiota derived from post-intervention patients conferred improved glycemic responses in recipient mice, supporting a causal role of gut microbiota in metabolic regulation. Serum metabolomic profiling revealed significant alterations, including enrichment of branched-chain amino acid related pathways. Mediation analyses identified key metabolites, phenyllactic acid, 3-methyl-2-oxobutanoic acid, and anandamide, as mediators linking specific bacterial taxa (Alistipes shahii and Limosilactobacillus mucosae) to fasting and postprandial glucose levels.<br><br>CONCLUSION: This study provides translational evidence that a dietary herbal intervention associated with glycemic improvement in T2D through microbiota-mediated metabolic reprogramming. Gut microbiome alterations induced by the intervention exerted causal effects on blood glucose regulation, with serum metabolites acting as potential key intermediaries. These findings highlight the mechanistic insight in nutrition-based microbiome modulation strategy in T2D.}, }
@article {pmid42051455, year = {2026}, author = {Du, X and Su, H and Huang, Y and Liu, J and Li, Q and Yang, X and Tao, X and Li, R}, title = {Gut microbiome dysbiosis in PCOS: from pathogenesis to microbiome-targeted therapies.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1747766}, pmid = {42051455}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy/etiology/pathology ; *Dysbiosis/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; Female ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {(PCOS), one of the most common endocrine and metabolic disorders in women of reproductive age, has a complex pathogenesis that continues to be unraveled by ongoing research. The condition is defined by three key features: hyperandrogenemia, ovulatory dysfunction, and insulin resistance. Recent studies have highlighted the gut microbiome and its metabolites as crucial regulators in PCOS development. Evidence suggests that gut dysbiosis and intestinal barrier dysfunction play a pivotal role in the onset and progression of PCOS. This review comprehensively examines the central role of gut microbiota in PCOS pathogenesis, including shifts in microbial communities such as bacteria, fungi, and viruses, and their impact on critical metabolites like short-chain fatty acids, bile acids, and tryptophan metabolites, which modulate host metabolism and reproductive function. Furthermore, based on mechanistic insights, the review explores targeted gut microbiota interventions, systematically evaluating clinical evidence for dietary modifications, probiotic/prebiotic supplementation and fecal microbiota transplantation. These approaches provide novel perspectives for precision medicine in PCOS treatment. The findings not only deepen our understanding of PCOS pathogenesis but also establish a strong theoretical foundation for innovative microbiome-based therapeutics.}, }
@article {pmid42051692, year = {2026}, author = {Wang, LM and Chen, C and Danzheng, JC and Zhao, J}, title = {Gut microbiome in sepsis: from dysbiotic biomarker to precision and palliative decision-making.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1811304}, pmid = {42051692}, issn = {2296-858X}, abstract = {Sepsis is a major cause of mortality in critically ill patients, necessitating improved early detection, risk stratification, and individualized clinical decision-making. The gut microbiome actively regulates host immunity, metabolism, and barrier function, engaging in bidirectional interactions with sepsis progression. Evidence suggests that gut dysbiosis not only accompanies sepsis but may also accelerate it. Characteristic shifts, including reduced microbial diversity, expansion of opportunistic pathogens, and decreased short-chain fatty acid production, could offer early prognostic signals prior to clinical decline. Advances in multi-omics and computational analytics are enabling the translation of microbial signatures into actionable clinical insights, supporting phenotype-specific stratification in sepsis. Emerging microbiome-targeted interventions such as next-generation probiotics, synbiotics, metabolite supplementation, and fecal microbiota transplantation show potential for modulating host responses in a stage-specific manner. Within a precision medicine framework, microbiome-derived biomarkers may refine both critical care management and palliative decision-making. In advanced or refractory sepsis, these insights could help tailor treatment intensity, prioritize symptom control, and avoid non-beneficial therapeutic escalation. Realizing this potential will require prospective validation and standardized approaches to integrate microbiome data into personalized, goal-concordant sepsis care.}, }
@article {pmid42053098, year = {2026}, author = {Saad, M and Redman, A and Ata, NA and Anton, C and Fei, L and Vitale, DS and Zhang, Y and Abu-El-Haija, M and Trout, AT}, title = {Predictive Power of Imaging: Assessing Parenchymal Fibrosis in Pediatric Chronic Pancreatitis.}, journal = {Pancreas}, volume = {55}, number = {6}, pages = {e603-e610}, doi = {10.1097/MPA.0000000000002658}, pmid = {42053098}, issn = {1536-4828}, mesh = {Humans ; Female ; *Pancreatitis, Chronic/diagnostic imaging/pathology/surgery ; Fibrosis ; Adolescent ; Male ; *Pancreas/pathology/diagnostic imaging ; Child ; Cross-Sectional Studies ; Predictive Value of Tests ; Exocrine Pancreatic Insufficiency ; Child, Preschool ; Magnetic Resonance Imaging/methods ; Young Adult ; Infant ; Pancreatectomy ; Islets of Langerhans Transplantation ; }, abstract = {OBJECTIVES: The primary aim is to identify pancreatic parenchymal imaging markers of fibrosis in children with chronic pancreatitis (CP). Secondary aims include describing the pattern of histopathologic fibrosis in different pancreatic regions and examining the impact of fibrosis on exocrine pancreatic insufficiency (EPI) and baseline glycemic status.<br><br>METHODS: Single-center cross-sectional study that included children aged 0-21 years who underwent total pancreatectomy islet auto-transplantation (TPIAT) before December 2022. Those with prior pancreatic surgeries, missing imaging, or missing histology were excluded.<br><br>RESULTS: Ninety-five patients (56% female, median age 13.3&#xa0;y) were included. Multiple parenchymal imaging variables were significantly associated with histologic pancreatic fibrosis. A 5&#xa0;mL decrease in segmented pancreas volume [odds ratio (OR)=1.2, 95% CI: 1.1-1.4, P <0.05] and a 0.1 unit decrease in T1 signal intensity ratio (SIR) pancreas/spleen (P /s) (OR=1.7, 95% CI: 1.2-2.2, P <0.05) had increased fibrosis odds. A multivariable model with pancreas volume and T1 SIRp/s predicted severe fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.8 (95% CI:0.7-0.9). Histologic fibrosis scores showed substantial agreement between pancreatic sampling locations (kappa=0.7, 95% CI: 0.6-0.9). EPI by fecal elastase (FE-1) was associated with increased odds of severe fibrosis (OR=11.7, 95% CI: 2.5-54.1, P <0.05) and higher Ammann scores were seen in participants with prediabetes and diabetes [9.0, interquartile range (IQR): 8.0-12.0, P =0.08].<br><br>CONCLUSIONS: The pancreatic parenchyma provides insights into pediatric CP through fibrosis assessment, which correlates with pancreatic function. A predictive model using pancreas volume and T1 SIR shows promise for forecasting pancreatic parenchymal fibrosis in children with CP.}, }
@article {pmid42053886, year = {2026}, author = {Wu, XM and Hou, LY and Liu, C and Hu, Y and He, Q}, title = {Targeting the Gut Microbiota-Bile Acid-FXR Axis: The Therapeutic Mechanism of Yudantong Decoction in Cholestatic Liver Disease.}, journal = {Current medical science}, volume = {}, number = {}, pages = {}, pmid = {42053886}, issn = {2523-899X}, support = {Grant No. L222131//Beijing Municipal Natural Science Foundation/ ; 82104926//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {OBJECTIVE: To elucidate the therapeutic mechanism of Yudantong decoction (YDTD) in cholestatic liver disease (CLD), focusing on the gut microbiota-bile acid-intestinal farnesoid X receptor (FXR) axis.<br><br>METHODS: A CLD mouse model induced by &#x3b1;-naphthylisothiocyanate was treated with YDTD. Hepatic injury, gut microbiota composition (16S rRNA sequencing), bile acid profiles (high-performance liquid chromatography-tandem mass spectrometry,&#xa0;HPLC-MS/MS), intestinal FXR/NLRP3 signaling, and barrier function were assessed. Fecal microbiota transplantation, bile salt hydrolase (BSH) inhibition, and FXR antagonism were employed for mechanistic validation.<br><br>RESULTS: CLD mice exhibited hepatocellular steatosis, lobular necrosis, and elevated serum markers. These pathological changes were associated with gut dysbiosis, impaired bile acid metabolism via bile salt hydrolase (BSH) suppression, FXR signaling inhibition, and NLRP3 inflammasome activation. YDTD restored BSH activity and bile acid homeostasis, upregulated FXR expression, suppressed NLRP3 inflammasome activation, and improved intestinal barrier integrity. Fecal microbiota transplantation experiments confirmed that YDTD-modified microbiota mediated these therapeutic benefits, whereas pharmacological inhibition of BSH or FXR attenuated YDTD's therapeutic effects.<br><br>CONCLUSION: YDTD alleviates CLD, at least in part, by targeting the gut microbiota-bile acid-FXR signaling pathway, highlighting the gut microbiota as a promising therapeutic target for CLD.}, }
@article {pmid42054188, year = {2026}, author = {Yuan, C and Wang, M and Yuan, Y and Jin, X and Wang, K}, title = {High-Salt Diet Promotes Kidney Stone Formation Through Gut Microbiota-Dependent Inflammatory Pathways.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {9}, pages = {e71854}, doi = {10.1096/fj.202503466R}, pmid = {42054188}, issn = {1530-6860}, support = {82270799//MOST | National Natural Science Foundation of China (NSFC)/ ; 82570894//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024ZYD0053//Science and Technology Department of Sichuan Province (SPDST)/ ; 2024NSFSC1499//SPDST | Natural Science Foundation of Sichuan Province ()/ ; 2025HXBH053//Postdoctoral Research and Development Fund of West China Hospital, Sichuan University/ ; 2023SCUH0054//Fund of Sichuan University/ ; 2023HXFH014//Clinical Research Incubation Project of West China Hospital of Sichuan University/ ; CZ2026001//National Outstanding Physician Fund/ ; }, mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; Animals ; *Kidney Calculi/metabolism/etiology/microbiology/pathology/chemically induced ; Humans ; Mice ; Mice, Inbred C57BL ; Male ; *Inflammation/metabolism/pathology ; *Sodium Chloride, Dietary/adverse effects ; Female ; Methylamines/metabolism ; NF-kappa B/metabolism ; Middle Aged ; Calcium Oxalate/metabolism ; Signal Transduction ; }, abstract = {High salt intake is a recognized risk factor for calcium oxalate (CaOx) kidney stones, but the underlying biological mechanisms beyond urinary calcium excretion remain unclear. We investigated whether a high-salt diet promotes CaOx stone formation through gut microbiota-dependent inflammatory pathways involving trimethylamine (TMA), trimethylamine N-oxide (TMAO), and NF-κB signaling. In a clinical cohort of 153 subjects, high salt intake was independently associated with CaOx stones after multivariable adjustment (adjusted OR 2.52, 95% CI 1.10-5.94, p = 0.031). The gut microbiota of high-salt diet stone formers was enriched for inflammation-associated bacteria and NF-κB, tight junction, and sodium-calcium reabsorption pathways. In C57BL/6J mice, a one-month high-salt diet disrupted intestinal barrier integrity, induced renal inflammation with elevated TNF-α, IL-6, and IL-1β, and increased CaOx crystal deposition. 16S rRNA sequencing showed depletion of beneficial genera (Akkermansia, Bifidobacterium) and enrichment of TMA-producing bacteria. Cecal TMA and plasma TMAO were elevated in high-salt mice, while urinary TMA and TMAO were reduced, indicating impaired renal metabolite clearance. Fecal microbiota transplantation from high-salt diet donors reproduced the elevated TMAO, renal inflammation, and crystal deposition in recipient mice, confirming a causal role for the gut microbiota. In vitro, TMA disrupted tight junction proteins in Caco-2 intestinal epithelial cells, and TMAO activated NF-κB and increased CaOx crystal adhesion in HK-2 renal tubular cells; both effects were reversed by the NF-κB inhibitor QNZ. These findings identify the gut microbiota-TMA/TMAO-NF-κB axis as a mechanism linking high salt intake to CaOx kidney stone formation.}, }
@article {pmid42056116, year = {2026}, author = {Ao, RF and Huang, YS and Hu, YT and Yong, HR and Wang, SC and Li, HZ and Gao, JW and Tu, C and Zhuang, JS and Zhong, ZM}, title = {Intermittent fasting alleviates hyperalgesia in ovariectomized mice via gut microbiota remodeling.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00990-0}, pmid = {42056116}, issn = {2055-5008}, support = {82404244//the National Natural Science Foundation of China/ ; 82304154//the National Natural Science Foundation of China/ ; 2024A1515010611//the Basic and Applied Basic Research Foundation of Guangdong Province/ ; }, abstract = {Pain is a common symptom of menopause, yet effective therapeutic options are limited. Intermittent fasting (IF) has emerged as a promising dietary intervention; however, its effects on menopausal pain are still unclear. In this study, we established a hyperalgesia model in mice through ovariectomy (OVX) and subjected them to an alternate-day fasting regimen. IF significantly elevated the pain thresholds for mechanical, hot and cold stimuli in OVX mice and reduced the expression of pain-related molecules, including transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG). Moreover, IF remodeled the gut microbiota and metabolite profile, marked by a substantial increase in the abundance of Akkermansia muciniphila and its key metabolite, indole-3-propionic acid (IPA). Depletion of the gut microbiota via antibiotic treatment abolished the analgesic effects of IF on OVX-induced hyperalgesia. Conversely, fecal microbiota transplantation from IF-treated donors restored microbial composition and alleviated hyperalgesia in OVX recipients. Administration of A. muciniphila increased IPA levels and alleviated hyperalgesia in OVX mice. Importantly, exogenous IPA supplementation not only alleviated hyperalgesia but also reduced the excitability of DRG neurons. Together, these findings demonstrate that IF mitigates estrogen deficiency-related hyperalgesia through remodeling gut microbiota and metabolite profile, and identify IPA as a potential therapeutic target, offering new perspectives for the clinical management of menopausal pain.}, }
@article {pmid42057349, year = {2026}, author = {Cheng, C and Wang, J and Xie, J and Yin, H and Xu, Z and Xie, Y and He, T and Jiang, Z and Wang, Y and Wu, W and Lou, W and Wang, J and Liu, L and Pu, N}, title = {Gut microbiota and pancreatic cancer: tumorigenesis, progression, and clinical applications.}, journal = {Cancer biology &amp; medicine}, volume = {23}, number = {5}, pages = {678-702}, pmid = {42057349}, issn = {2095-3941}, support = {82572967//National Natural Science Foundation of China/ ; 82503105//National Natural Science Foundation of China/ ; 82473459//National Natural Science Foundation of China/ ; 82273382//National Natural Science Foundation of China/ ; 20254Y0181//Shanghai Municipal Health Commission Scientific Research Project/ ; 20244Y0023//Shanghai Municipal Health Commission Scientific Research Project/ ; 201940019//Shanghai Municipal Health Commission Scientific Research Project/ ; 23XD1400600//Program of Shanghai Academic/Technology Research Leader/ ; 24SF1900300//Shanghai Science and Technology Commission Innovative Pharmaceutical Products Application Demonstration Project/ ; SACA-CY24B09//Shanghai Anticancer Association EYAS PROJECT/ ; Y-2022METAZQN-0003//Beijing Xisike Clinical Oncology Research Foundation/ ; Y-Gilead2024-PT-0002//Beijing Xisike Clinical Oncology Research Foundation/ ; Y-HR2022MS-0251//Beijing Xisike Clinical Oncology Research Foundation/ ; ZSLCYJ202329//Shanghai "Rising Stars of Medical Talents" Youth Development Program, the Clinical Research of Zhongshan Hospital/ ; 202305AF150148//Liu Liang Expert Workstation of Yunnan Province/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome ; Disease Progression ; Animals ; *Carcinoma, Pancreatic Ductal/microbiology/pathology/therapy ; Tumor Microenvironment/immunology ; Dysbiosis/microbiology ; *Carcinogenesis ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies of the digestive system, with a 5-year survival rate of only 13%, which is largely due to late-stage diagnosis and limited therapeutic options. Emerging evidence indicates that the gut microbiota has a critical role in PDAC tumorigenesis, progression, and therapeutic response. This review comprehensively summarizes current insights into gut microbiota-PDAC interactions, highlighting microbial alterations across taxonomic, functional, and clinical dimensions. Gut dysbiosis, which is marked by depletion of beneficial species and enrichment of pathogenic taxa, contributes to carcinogenesis through chronic inflammation, immune dysregulation, and metabolic reprogramming. In particular, the loss of butyrate-producing bacteria reduces anti-inflammatory activity and weakens CD8[+] T cell function, thereby promoting tumor development. In addition to initiation, the gut microbiota also shapes PDAC progression through direct translocation to pancreatic tissue and systemic regulation of the tumor microenvironment (TME), influencing immune cell dynamics and fostering therapeutic resistance. Clinically, distinct microbial signatures are emerging as potential diagnostic and prognostic biomarkers. Moreover, microbiota-targeted interventions, including probiotics, synbiotics, fecal microbiota transplantation (FMT), metabolite supplementation, and dietary modulation, show promise as adjunctive therapeutic strategies. However, significant challenges remain in defining causal mechanisms and translating these findings into practice. Future research should integrate multi-omics profiling with well-designed clinical trials to delineate the gut microbiota-PDAC interaction network, guide precision microbiota-based interventions, and ultimately enable earlier detection and personalized treatment of this lethal disease.}, }
@article {pmid42058119, year = {2026}, author = {Qu, HL and Li, JN and Gao, Y and Zhang, XB and Yang, SD}, title = {From association to intervention: Semantic trajectories and knowledge frontiers in epilepsy-gut microbiota research revealed by bibliometrics and NLP.}, journal = {IBRO neuroscience reports}, volume = {20}, number = {}, pages = {609-624}, pmid = {42058119}, issn = {2667-2421}, abstract = {BACKGROUND: Research on the epilepsy-gut microbiota axis is accelerating, yet its conceptual evolution and translational signals remain difficult to track across disciplines. Here, we propose a semantic-bibliometric fusion framework that combines network-based science mapping with phrase- and topic-level natural language processing (NLP) to resolve both structural and linguistic dynamics in the field.<br><br>METHODS: Publications indexed in the Web of Science Core Collection from January 1997 to November 17, 2025 were retrieved and analyzed using CiteSpace, VOSviewer, Pajek, and Scimago Graphica, complemented by an NLP pipeline for topic modeling and temporal phrase tracking. In total, 516 records were included.<br><br>RESULTS: Annual output rose sharply after 2021 and peaked in 2024, with China and the United States leading contributions. Beyond conventional hotspots, semantic analyzes revealed a field-wide shift from early infection/safety-oriented discourse to mechanism- and intervention-driven themes dominated by the microbiota-gut-brain axis.<br><br>CONCLUSION: The most prominent and expanding intervention clusters involved the ketogenic diet, short-chain fatty acids, probiotics, and fecal microbiota transplantation, while "Mendelian randomization" emerged as a nascent frontier signaling movement from correlation to causal inference. By integrating knowledge-network topology with discourse dynamics, this study delivers an up-to-date, multi-resolution map of epilepsy-microbiome research and highlights actionable directions for future work, including causal validation, multi-omics stratification, and trial-ready microbiome-informed interventions.}, }
@article {pmid42058800, year = {2026}, author = {Hegde, AV and Gupta, S and Mohan, LN and Rozario, A}, title = {Unforeseen consequence of colovesical fistula in diverticulitis presenting as septic cellulitis: A case report.}, journal = {World journal of methodology}, volume = {16}, number = {2}, pages = {111784}, pmid = {42058800}, issn = {2222-0682}, abstract = {BACKGROUND: Colovesical fistula (CVF) is an uncommon but serious complication most often linked to diverticular disease of the colon. Its diagnosis can be at times challenging as the symptoms are nonspecific, and timely intervention is crucial to avoid morbidity.<br><br>CASE SUMMARY: A 65-year-old Indian male was admitted with right lower limb cellulitis and was in septic shock. Despite initial management, he remained oliguric with persistent loose stools. On post-fasciotomy day 4, fecaluria was noted, prompting suspicion of a bowel-urinary tract fistula. Microscopic urine examination confirmed fecal matter. A computed tomography urogram with cystogram revealed a CVF at the sigmoid colon, likely secondary to diverticulitis. Baseline carcinoembryonic antigen levels were normal. An exploratory laparotomy was performed, which revealed dense adhesions between the sigmoid colon and bladder were noted, and the findings were consistent with diverticulitis though no discrete diverticulum was separately visualized. The fistulous tract was excised (frozen section was negative for malignancy), a two-layer bladder repair was performed, and the affected sigmoid colon segment was resected using a Hartmann's procedure. Multiple bladder washes were also done. Postoperatively, the patient recovered well, with resolution of oliguria and diarrhea. He was discharged on postoperative day 8. Histopathology confirmed diverticulitis without malignancy. A successful stoma reversal occurred 2 months later, and he remained symptom-free at the 6-month follow-up.<br><br>CONCLUSION: CVF should be considered in cases of persistent urinary symptoms or fecaluria, particularly in patients with risk factors such as older age and diverticular disease, even in regions with low incidence of colonic diverticula. Early diagnosis using imaging modalities and prompt surgical management are key to favorable outcomes.}, }
@article {pmid42060056, year = {2026}, author = {Böhm, D and Guchelaar, HJ and Smidt, ML and Deenen, MJ}, title = {Microbiome-Modulating Strategies in Anticancer Therapy: A Review of Current Evidence and Recommendations for Further Treatment Improvement.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {42060056}, issn = {1867-1314}, abstract = {In the last decades, the relationship between the gut microbiome and response to anticancer therapy has been extensively studied. Increasing evidence shows that gut microbes can influence both the therapeutic efficacy and toxicity of anticancer therapy through multiple mechanisms, including immune regulation, drug metabolism, and modulation of the tumor microenvironment. Unlike host genetics, the gut microbiome can be relatively easily modified by non-invasive interventions. While most microbiome-modulating strategies are still in the experimental phase and not yet widely applied, they offer the potential to optimize the efficacy and safety of anticancer therapies. Several microbiome-modulating strategies, including probiotics, postbiotics, antibiotics, dietary components, fecal microbiota transplantations (FMT) and bacterial specific inhibitors, have been explored in preclinical and clinical studies that provided initial evidence that gut microbiome modulation may enhance treatment efficacy and reduce toxicity. In this review, we summarize the current evidence on microbiome-based interventions aimed at improving anticancer therapy outcomes. We discuss the key results from preclinical and clinical interventions, and evaluate their safety and feasibility. We also address major limitations in current research and outline future directions to translate microbiome-modulating strategies into clinical practice. By providing an overview of these strategies, this review aims to support the development of personalized strategies to optimize anticancer therapy through targeted modulation of the gut microbiome.}, }
@article {pmid42061262, year = {2026}, author = {Zhao, H and Akram, MZ and Comer, L and Corion, M and Fako, E and Everaert, N}, title = {Early gut microbiota transplantation in broiler chicks exerts effects on intestinal health depending on the donor's microbial composition.}, journal = {Poultry science}, volume = {105}, number = {7}, pages = {106999}, pmid = {42061262}, issn = {1525-3171}, mesh = {Animals ; *Chickens/microbiology/physiology ; *Gastrointestinal Microbiome ; Male ; *Fecal Microbiota Transplantation/veterinary ; Random Allocation ; *Intestines/physiology/microbiology ; Immunity, Innate ; Female ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy for modulating the gut microbiota to enhance broilers' health. This study investigated the effects of FMT of broilers (FMT1), laying hens (FMT2), and broiler breeders (FMT3) as donor on the intestinal health of chicks as recipients. A total of 144 newly hatched Ross 308 male broilers were randomly assigned to four groups and reared until D 14. For the first three days after hatching, the control group received 1 mL of saline daily via oral gavage, while the FMT groups received their respective inocula. Body weight, intestinal length, and ileal histomorphology were assessed on D 5, D 7, and D 14. In addition, on D 7 and D 14, ileal tissues and serum were collected. The expression of critical genes related to barrier function, nutrient transport, mitochondrial function, antioxidant defense, signal transduction, innate immunity, cytokine response, and programmed cell death were measured using high-throughput qPCR. Furthermore, serum metabolites related to tryptophan metabolism were also determined. Group differences were analyzed using one-way ANOVA with Tukey's post-hoc test. Partial Least Squares Regression (PLSR) model was used to evaluate the interaction between observed changes and dominant microbiota. No significant effects on body weight or intestinal length were observed. On D 7, FMT1 induced innate immune stress, characterized by upregulated Toll-like receptor signaling, apoptosis, and mitochondrial biogenesis. In contrast, FMT2 and FMT3 improved intestinal histomorphology. Notably, FMT2 enhanced antioxidant defenses and changed tryptophan metabolism, while reducing reliance on glucose transporters. Meanwhile, FMT3 suppressed pyroptosis and enhanced barrier integrity. PLSR analysis identified 9 features that contribute over 30% of observed variations, with Olsenella, Blautia, and unclassified Lachnospiraceae being the most pronounced. By D 14, most effects had diminished, although antioxidant effects in FMT1 and immune markers in FMT2 and FMT3 persisted. Overall, FMT exerted donor-dependent patterns of influence on intestinal health, and our study proved programming of gut physiology through fecal microbiota transplantation.}, }
@article {pmid42061404, year = {2026}, author = {Su, Q and Chen, S and Lau, LH and Lui, RN and Wang, Y and Xu, Z and Cheung, CP and Ching, JYL and Shen, X and Peng, Y and Tun, HM and Ianiro, G and Rubin, D and Chang, EB and Chan, FKL and Ng, SC}, title = {Artificial intelligence-driven donor-recipient gut microbiome matching for optimized fecal microbiota transplantation.}, journal = {Cell reports}, volume = {45}, number = {5}, pages = {117301}, doi = {10.1016/j.celrep.2026.117301}, pmid = {42061404}, issn = {2211-1247}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Artificial Intelligence ; *Gastrointestinal Microbiome/genetics ; *Tissue Donors ; Female ; Metagenome ; Male ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapy for gastrointestinal diseases, yet its clinical efficacy remains individually variable. Here, we analyze multi-kingdom and functional profiles in pre- and post-FMT metagenomes from 515 FMTs across 30 cohorts and 12 diseases, in which 94 metagenomes from 44 FMTs are newly collected. We reveal a robust association between clinical efficacy and post-FMT microbiome convergence of recipients toward donors, across diseases. To predict post-FMT microbial convergence, we develop MOZAIC (Microbiome Matching Optimization via Artificial Intelligence), a framework that integrates multi-dimensional donor-recipient microbiota features. MOZAIC achieves an average area under the curve (AUC) of 0.88 and accuracy/recall >0.80 in forecasting microbiome convergence, with 78.7% accuracy in predicting clinical outcomes, and retrospectively simulates a 1.44-fold improvement (from 49.4% to 71.0%) in clinical response rates over baseline. This study establishes microbiome convergence as a key mediator of FMT and provides a scalable tool for precision matching in microbiota-based therapies.}, }
@article {pmid42061692, year = {2026}, author = {Duan, L and Liang, J and Zhang, W and Liu, Z and Kang, H and Huang, D and Wang, Z and Jiang, G and Gao, A}, title = {EtCBN-associated olfactory dysfunction involves Irf7 signaling and a microbiota-metabolite axis.}, journal = {Chemico-biological interactions}, volume = {434}, number = {}, pages = {112109}, doi = {10.1016/j.cbi.2026.112109}, pmid = {42061692}, issn = {1872-7786}, mesh = {Animals ; Mice ; *Signal Transduction/drug effects ; Male ; Molecular Docking Simulation ; *Interferon Regulatory Factor-7/metabolism/chemistry ; Mice, Inbred C57BL ; Olfactory Bulb/pathology/drug effects/metabolism ; *Olfaction Disorders/chemically induced/metabolism ; *Microbiota/drug effects ; }, abstract = {Liquid crystal monomers (LCMs) are emerging environmental contaminants with neurotoxic potential; however, their impact on olfactory function, a key early indicator of neurodegenerative diseases, is unknown. Here, we observed that exposure to LCM mixtures at an environmentally relevant dose (180 μg/kg) was associated with olfactory deficits in mice. Further investigation focused on a prevalent LCM monomer (EtCBN) found in indoor dust, a compound known to disrupt endothelial cell proliferation, as a key component of this effect. Mice exposed to environmentally relevant (20 μg/kg) or elevated (200 μg/kg) EtCBN for 12 weeks exhibited significant olfactory impairment, supported by behavioral deficits, magnetic resonance imaging (MRI)-based olfactory bulb atrophy, histopathological changes, and neuroinflammation. Molecular docking predicted that EtCBN may interact with Irf7 with a binding energy of -4.86 kcal/mol, suggesting a potential interaction that could serve as a candidate molecular initiating event (MIE). This interaction was associated with elevated IL-1β and TNF-α levels and may be linked to the onset of neuroinflammation. In addition, a reduced abundance of Dubosiella was found to correlate with phenylalanine accumulation, potentially further contributing to Irf7 activation through a microbiota-metabolite-inflammation axis. Fecal microbiota transplantation (FMT) and probiotic supplementation provided evidence suggesting a role for the intestinal microbiota. Exogenous nicotinamide adenine dinucleotide (NAD[+]) was observed to be associated with mitigation of these effects. Together, these findings are consistent with a proposed adverse outcome pathway (AOP) framework that suggests a link between the EtCBN-Irf7 interaction and LCM-associated neurotoxicity, offering potential mechanistic insights and therapeutic targets for olfactory dysfunction.}, }
@article {pmid42062245, year = {2026}, author = {Korten, NM and Blischke, L and Thelen, AC and Schulze Eckel, A and van Egmond, M and Verspohl, V and Neumann, M and Kneisel, L and Tran, M and Beyer, C and Herpertz-Dahlmann, B and Keller, L and Bang, C and Andreani, NA and Seitz, J and Trinh, S and Voelz, C}, title = {From gut to brain: effects of fecal microbiota transplants from humans to rats on hippocampal gene regulation - a study on anorexia nervosa.}, journal = {Translational psychiatry}, volume = {16}, number = {1}, pages = {}, pmid = {42062245}, issn = {2158-3188}, mesh = {*Fecal Microbiota Transplantation ; *Hippocampus/metabolism ; *Anorexia Nervosa/therapy/microbiology/genetics/metabolism ; Animals ; Female ; Humans ; *Gastrointestinal Microbiome ; Rats, Wistar ; Rats ; Brain-Derived Neurotrophic Factor/metabolism ; Adult ; Adolescent ; Anti-Bacterial Agents/pharmacology ; Young Adult ; Disease Models, Animal ; Gene Expression Regulation ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a novel approach for understanding anorexia nervosa (AN), a complex eating disorder characterized by severe underweight, fear of weight gain and distorted body image. Patients with AN show alterations in the gut microbiome, brain structure, and inflammatory processes, indicating the importance of the microbiome‒gut‒brain axis in AN pathology. This study aimed to investigate whether FMT from patients with AN into antibiotic-treated rats could transfer a phenotype associated with the disease inducing AN-like symptoms and hippocampal alterations. Female Wistar rats received antibiotics followed by FMT from healthy controls, patients with AN, or water. Gut microbiota effects were assessed through 16S rRNA gene sequencing, alongside post-mortem analyses of glial cells, neurogenesis markers, and inflammatory markers. The results revealed dysregulated microbial diversity after antibiotic treatment, which was partially restored after FMT. Successful transfer of human bacterial species was observed, but AN-like symptoms and changes in glial/neuronal counts were not detected. Notably, a decrease in hippocampal Bdnf expression was detected in the antibiotic control group, which was reversed by healthy control stool transplantation but not in the AN-transplanted group. Similar patterns were observed for neuroinflammation and Mki67, a marker of cell neogenesis. These findings suggest potential links between microbial changes, neuroinflammation and neuroplasticity in the hippocampus with the potential to correct deficits with FMT. Future studies should extend these findings by exploring the combination of FMT and starvation phases to better understand the roles of specific microbial populations in neuroinflammatory processes and, ultimately, clinical outcomes in AN.}, }
@article {pmid42062271, year = {2026}, author = {Jang, S and Kim, YJ and Park, J and Kim, D and Kim, TH and Lee, S and Kim, DJ and Ryu, CM and Seo, HW}, title = {A Muribaculaceae-enriched microbiota exacerbates TLR4-dependent Acinetobacter baumannii-induced hyperinflammatory sepsis.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-72435-3}, pmid = {42062271}, issn = {2041-1723}, abstract = {Host survival during sepsis depends not only on pathogen burden but also on inflammatory thresholds calibrated by the gut microbiota. Here, we show that different survival outcomes were observed in genetically equivalent female C57BL/6 mouse populations depending on their specific gut microbiota configuration. A Muribaculaceae-enriched gut microbiota, characterized by the dominance of Sangeribacter muris KT1-3, predisposed mice to fatal sepsis caused by Acinetobacter baumannii via TLR4-dependent hyperinflammation. This lethal phenotype, reproduced by colonization with S. muris strain KT1-3, was transferable by fecal microbiota transplantation and co-housing. Notably, fixed-dose LPS challenge and ex vivo stimulation assays demonstrated that this configuration induces a heightened TLR4-dependent inflammatory responsiveness independent of bacterial replication. Single-cell transcriptomics revealed that these microbiota-derived factors establish a transcriptionally pre-activated macrophage state, resulting in production of excessive pro-inflammatory cytokines upon challenge. Mechanistically, S. muris strain KT1-3 releases heat-stable and low-molecular-weight (<3 kDa) metabolites that are sufficient to potentiate systemic cytokine surges under a fixed-dose endotoxin challenge in vivo, effectively lowering the host's activation threshold for TLR4-driven signaling. Tlr4-deficient mice harboring the KT1-3-enriched susceptible microbiota survived despite persistent bacterial dissemination, demonstrating that the microbiota-TLR4 axis dictates hyperinflammatory A. baumannii-induced sepsis outcomes by modulating inflammatory magnitude rather than pathogen clearance. Our results provide a conceptual framework for how specific gut microbiota configurations modulate host susceptibility and drive infection resilience.}, }
@article {pmid42063504, year = {2026}, author = {Yu, B and Zhao, WW and Tao, L and Li, K}, title = {The microbiota-gut-brain axis perspective: mechanisms and intervention strategies for the comorbidity of chronic constipation and depression.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1800520}, pmid = {42063504}, issn = {1664-302X}, abstract = {BACKGROUND: Chronic constipation and depression are highly prevalent worldwide. These two conditions frequently co-occur in clinical practice. Accumulating evidence indicates that gut microbiota dysbiosis mediates this comorbidity through the microbiota-gut-brain axis (MGBA).<br><br>METHODS: This narrative review systematically summarizes current research on MGBA bidirectional communication mechanisms, gut microbiota alterations in comorbid patients, and microbiota-targeted intervention strategies.<br><br>RESULTS: The MGBA facilitates bidirectional communication through four major pathways: neural pathways via the vagus nerve, immune pathways via cytokines, endocrine pathways via the HPA axis, and metabolic pathways via short-chain fatty acids and neurotransmitter precursors. Gut dysbiosis is associated with comorbidity and may contribute to its pathogenesis through multiple mechanisms. First, neurotransmitter metabolism becomes dysregulated, particularly in the serotonin and GABA systems. Second, chronic low-grade inflammation develops with elevated pro-inflammatory cytokines. Third, intestinal barrier dysfunction occurs, leading to increased permeability and bacterial translocation. Fourth, HPA axis hyperactivity emerges. Fifth, production of microbial metabolites is altered, including short-chain fatty acids and tryptophan metabolites. Comorbid patients exhibit characteristic microbiota signatures. These include reduced abundance of butyrate-producing bacteria such as Faecalibacterium, Roseburia, and Coprococcus. Microbial diversity decreases significantly. Pro-inflammatory taxa become enriched. Several evidence-based interventions show promise. These include psychobiotics, fecal microbiota transplantation, and dietary modifications such as Mediterranean diet and high-fiber intake. Exercise and integrative approaches including traditional Chinese medicine also demonstrate beneficial effects.<br><br>CONCLUSION: The gut microbiota represents a critical hub connecting gastrointestinal and mental health. Microbiota-targeted therapies offer promising strategies for managing chronic constipation-depression comorbidity. Future research should establish causal relationships and develop reliable microbial biomarkers. Precision medicine approaches based on individual microbiome profiles are needed to optimize therapeutic outcomes.}, }
@article {pmid42067917, year = {2026}, author = {Fang, Q and Huang, S and Zhang, C and Li, M and Ye, Z and Guo, H and Xiao, M and Wang, S and Yu, L and Zhang, H and Zhao, J and Tian, F and Chen, W and Zhai, Q}, title = {Capsaicin ameliorates glycemic levels via gut microbiota-derived 5-aminolevulinic acid in mice.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {42067917}, issn = {2049-2618}, support = {BX20250339//Postdoctoral Fellowship Program and China Postdoctoral Science Foundation/ ; U23A20259//National Natural Science Foundation of China/ ; JUSRP622013//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Capsaicin/pharmacology ; Fecal Microbiota Transplantation ; *Aminolevulinic Acid/metabolism ; Male ; TRPV Cation Channels/genetics/metabolism ; Bacteria/classification/metabolism/genetics ; *Blood Glucose/drug effects ; Mice, Inbred C57BL ; Metagenomics ; Metabolomics ; Specific Pathogen-Free Organisms ; }, abstract = {BACKGROUND: Capsaicin, a natural alkaloid in chili peppers, regulates glycemic levels; however, its mechanisms and therapeutic potential remain unclear. This study aimed to elucidate the role of gut microbiota and their metabolites in mediating capsaicin's glycemic regulatory effects. We conducted experiments in specific pathogen-free (SPF) and germ-free (GF) mice, transient receptor potential vanilloid 1 (TRPV1) receptor ablation studies, and fecal microbiota transplantation (FMT) to demonstrate the involvement of gut microbiota in capsaicin-mediated glycemic control. Metagenomics and metabolomics analyses were employed to identify key microbial strains and metabolic pathways. Keystone strains and metabolites were supplemented in GF mice without capsaicin intervention to validate their effects on glycemic regulation. In vitro co-culture experiments were performed to investigate the mutualistic relationships among keystone strains under capsaicin treatment.<br><br>RESULTS: Gut microbiota constitute an important component of capsaicin-mediated glycemic regulation, acting in concert with but not solely dependent on TRPV1 signaling. Gut microbiota altered by capsaicin promote the production of 5-aminolevulinic acid (5-ALA), which contributes to heme synthesis and enhances glycemic control. Supplementation with Akkermansia muciniphila, Ligilactobacillus murinus, or 5-ALA in GF mice recapitulates the glycemic benefits of capsaicin. Furthermore, capsaicin enriches Akkermansia muciniphila, which in turn supports the growth of Ligilactobacillus murinus.<br><br>CONCLUSION: Capsaicin-induced changes in the gut microbiota promote 5-ALA synthesis, leading to improved glycemic control. These findings suggest that dietary or probiotic interventions targeting gut microbiota, particularly Akkermansia muciniphila and 5-ALA, may offer promising strategies for managing glycemic disorders, including type 2 diabetes (T2D). Video Abstract.}, }
@article {pmid42068031, year = {2026}, author = {Chen, S and Feng, H and Wang, Y and Huang, J and Xu, S and Gong, Y and Liu, X and Ouyang, Y and Ye, Q and Zheng, D and Sun, K and Wang, A and Chen, Y}, title = {Intestinal epithelial Syndecan-1 maintains mucosal homeostasis in inflammatory bowel disease by enhancing Faecalibacterium prausnitzii biofilm formation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2665870}, pmid = {42068031}, issn = {1949-0984}, mesh = {Animals ; *Syndecan-1/genetics/metabolism ; *Inflammatory Bowel Diseases/microbiology/metabolism/genetics ; Mice ; *Intestinal Mucosa/microbiology/metabolism ; Gastrointestinal Microbiome ; *Biofilms/growth &amp; development ; Mice, Knockout ; Humans ; *Faecalibacterium prausnitzii/physiology/genetics/growth &amp; development ; Mice, Inbred C57BL ; Homeostasis ; Disease Models, Animal ; Dextran Sulfate ; Colitis/microbiology/chemically induced ; Male ; Fecal Microbiota Transplantation ; }, abstract = {Despite the rising global incidence of inflammatory bowel disease (IBD), curative therapies remain unavailable. While our previous work implicated the intestinal proteoglycan Syndecan-1 (SDC1) in IBD-associated barrier dysfunction and inflammation, the underlying mechanism was unclear. This study aimed to elucidate how SDC1 maintains intestinal barrier integrity through interactions with the gut microbiome. In DSS-induced colitis, global knockout of Sdc1 (Sdc1[-/-]) exhibited exacerbated inflammatory infiltration and greater impairment of barrier structure and function than wild-type (WT). Formation of intestinal organoids was independent of genotype, indicating that Sdc1[-/-] does not impair barrier function via disrupting epithelial development. The heightened colitis susceptibility in Sdc1[-/-] mice was abolished in the antibiotic-treated pseudo-germ-free models, and transmissible to WT mice via fecal microbiota transplantation. Similar results were reproduced in a germ-free mouse model. Metagenomic sequencing identified Faecalibacterium prausnitzii as the most significantly depleted species upon Sdc1 knockout. In vitro, SDC1-attached glycosaminoglycans (heparan sulfate (HS) and chondroitin sulfate (CS)) but not the SDC1 core protein promoted F. prausnitzii growth. Prokaryotic transcriptome profiling indicated that HS/CS induces cobalamin biosynthesis in F. prausnitzii. The critical role of cobalamin as a mediator was confirmed, as its synthetic inhibition significantly diminished the growth-promoting effect of HS/CS. Mechanism studies showed that HS/CS enhanced biofilm formation in F. prausnitzii, thereby facilitating cobalamin biosynthesis. Oral administration of HS ameliorated DSS-induced colitis and promoted mucosal colonization of F. prausnitzii, independent of the host genotype. Finally, human IBD biopsies revealed a positive correlation between epithelial SDC1 and mucosal F. prausnitzii, as well as an inverse correlation with bacterial translocation and the number of LPS‑positive cells. Our study elucidates a novel mechanism in which the glycosaminoglycan chains of SDC1 promote F. prausnitzii colonization and growth through enhanced biofilm formation and cobalamin synthesis, thereby highlighting the therapeutic potential of HS for IBD and offering a new basis for host-directed microbiota regulation.}, }
@article {pmid42068814, year = {2026}, author = {Kanannejad, Z and Taylor, WR and Ghatee, MA and Mohkam, M}, title = {Microbial regulation of immune tolerance during embryonic implantation and pregnancy.}, journal = {Journal of reproductive immunology}, volume = {175}, number = {}, pages = {104898}, doi = {10.1016/j.jri.2026.104898}, pmid = {42068814}, issn = {1872-7603}, mesh = {Female ; Humans ; Pregnancy ; *Immune Tolerance ; *Embryo Implantation/immunology ; Animals ; Fecal Microbiota Transplantation ; *Dysbiosis/immunology ; *Microbiota/immunology ; T-Lymphocytes, Regulatory/immunology ; Probiotics/administration &amp; dosage ; Placenta/immunology/microbiology ; *Pregnancy Complications/immunology/microbiology ; }, abstract = {Maternal immune tolerance is essential for successful embryo implantation and maintenance of pregnancy. The maternal microbiome, particularly in the gut, vagina, and possibly the placenta, has emerged as an important regulator of immune adaptation during gestation. Through continuous interaction with the maternal immune system, the microbiota influence key immune cell populations such as regulatory T cells, uterine natural killer cells, and dendritic cells. These cells promote a tolerogenic environment necessary for embryo acceptance and proper placental development. Microbial-derived metabolites, including short-chain fatty acids and tryptophan derivatives, play important roles in modulating cytokine production and immune cell differentiation. Disruption of microbial balance, or dysbiosis, has been associated with a range of pregnancy complications, including implantation failure, preeclampsia, gestational diabetes, and preterm birth. Additionally, the maternal microbiome may influence fetal immune development, with implications for the offspring's long-term health. Emerging translational research suggests that interventions targeting the maternal microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, may beneficially modulate immune responses during pregnancy. While these approaches are promising, variability in individual microbiome composition and immune responses underscores the need for personalized strategies. In summary, the maternal microbiome is a dynamic and influential factor in shaping immune tolerance during pregnancy. A deeper understanding of microbiota-immune interactions may pave the way for novel, microbiome-based therapies to enhance reproductive outcomes and promote maternal-fetal health.}, }
@article {pmid42068877, year = {2026}, author = {Liao, W and Gao, J and Zhang, J and Wu, Y and Jiang, Y and Liu, H and Chen, S and Xiu, L and Zhong, G}, title = {Haizao Yuhu Decoction alleviates goiter via the gut-thyroid axis: Microbiota-derived SCFAs promote hormone synthesis and restore apoptosis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {156}, number = {}, pages = {158256}, doi = {10.1016/j.phymed.2026.158256}, pmid = {42068877}, issn = {1618-095X}, mesh = {Animals ; *Apoptosis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; *Thyroid Gland/drug effects/metabolism ; Male ; Rats ; *Goiter/drug therapy/chemically induced/metabolism ; *Fatty Acids, Volatile/metabolism ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Propylthiouracil ; Thyroid Hormones/biosynthesis ; Disease Models, Animal ; }, abstract = {BACKGROUND AND PURPOSE: Haizao Yuhu Decoction (HYD) is a classic Traditional Chinese Medicine for goiter, but its mechanism related to the "gut-thyroid axis" remains unknown. This study investigates whether HYD treats goiter via this axis and elucidates the underlying mechanisms.<br><br>METHODS: A rat goiter model was induced with propylthiouracil (PTU), followed by two weeks of HYD treatment. Gut microbiota was analyzed by metagenomic sequencing; fecal and serum short-chain fatty acids (SCFAs) were quantified by targeted LC-MS/MS analysis. Thyroid function was assessed via iodine content and hormone levels. Key proteins in hormone synthesis and apoptosis were evaluated by Western blot and immunohistochemistry. Fecal microbiota transplantation (FMT) supported microbiota causality.<br><br>RESULTS: HYD alleviated goiter and hypothyroidism. It restored gut microbiota diversity and enriched SCFA-producing bacteria (e.g., Bifidobacterium pseudolongum), coincident with increased SCFAs including butyrate. These SCFA changes correlated with reduced HDAC1/2/3/8 in thyroid tissue, consistent with enhanced histone acetylation, and were accompanied by upregulation of NIS, TG, TPO, and DUOX2. Concurrently, elevated SCFAs were associated with AKT/Mdm2 pathway inhibition, p53 stabilization, downstream activation of P21 and Caspase-3, and suppression of Bcl-2, supporting a model of promoted thyroid cell apoptosis. FMT supported that HYD-modulated microbiota alone reproduced these effects.<br><br>CONCLUSION: HYD alleviates PTU-induced goiter in rats in a manner associated with gut microbiota remodeling and increased SCFA production, which correlate with enhanced thyroid hormone synthesis and restored apoptosis-a relationship supported by FMT experiments. However, direct interactions between HYD and PTU cannot be fully excluded. These findings are consistent with a model in which HYD acts through the gut-thyroid axis, providing mechanistic insights into its therapeutic effects.}, }
@article {pmid42069299, year = {2026}, author = {Meng, F and Xue, M and Li, H and Tao, G and Chen, W and Li, Y and Pei, H and Liu, Z and Yin, D and Qin, S and Xue, J and Liu, B}, title = {Consumption of hydrogen-rich water ameliorates atherosclerosis by modulating gut microbiota and enhancing short-chain fatty acid levels.}, journal = {Life sciences}, volume = {397}, number = {}, pages = {124418}, doi = {10.1016/j.lfs.2026.124418}, pmid = {42069299}, issn = {1879-0631}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Atherosclerosis/metabolism/microbiology/prevention &amp; control/pathology ; Mice ; *Hydrogen/pharmacology ; Mice, Inbred C57BL ; Male ; *Water/chemistry/pharmacology ; Propionates/metabolism ; Macrophages/metabolism/drug effects ; Fecal Microbiota Transplantation ; Plaque, Atherosclerotic ; Inflammation ; Mice, Knockout, ApoE ; }, abstract = {AIMS: Molecular hydrogen (H2) is a safe gaseous signaling molecule with anti-inflammatory properties. This study aimed to explore the anti-atherosclerotic effects of hydrogen-rich water (H2W) and clarify the underlying mechanism involving the gut microbiota and its metabolites.<br><br>MATERIALS AND METHODS: ApoE[-/-] mice were administered H2W to evaluate atherosclerotic plaque development and stability. Gut microbiota composition and short-chain fatty acid levels were analyzed. Antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) were used to verify the mediating role of the gut microbiota. In vitro assays were performed to examine the effects of propionate on macrophage inflammation and polarization.<br><br>KEY FINDINGS: H2W consumption significantly attenuated plaque formation and enhanced plaque stability in ApoE[-/-] mice, accompanied by altered gut microbiota structure and short-chain fatty acid profiles. Antibiotic treatment abolished the protective effects of H2W, while FMT from H2W-treated mice transferred the anti-atherosclerotic phenotype. H2W notably increased propionate levels in cecal contents and serum. Propionate directly suppressed inflammatory responses and M1 macrophage polarization in vitro.<br><br>SIGNIFICANCE: This study demonstrates that H2W alleviates atherosclerosis by modulating the gut microbiota-propionate-macrophage axis. Our findings highlight H2W as a promising and safe intervention for atherosclerosis and provide new mechanistic insights into the crosstalk between gut microbial metabolites and vascular inflammation.}, }
@article {pmid42069657, year = {2026}, author = {de Oliveira Andrade, F and Staley, C and Jin, L and Ozgul-Onal, M and McDermott, M and Kenanoglu, S and de Oliveira, KA and Verma, V and Hilakivi-Clarke, L}, title = {Gut microbiome modulates breast cancer risk in socially isolated mice.}, journal = {Breast cancer research : BCR}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13058-026-02292-x}, pmid = {42069657}, issn = {1465-542X}, abstract = {BACKGROUND: Breast cancer risk and mortality are associated with disrupted gut microbiome functions which in turn can affect tumor immune responses. One source of disruption could be stress. Social isolation (SI) stress consistently increases breast cancer risk and mortality in preclinical models and women, but whether SI promotes mammary tumor growth by affecting gut microbiome has not been studied.<br><br>METHODS: We investigated if increased E0771 mammary tumorigenesis in SI female C57BL/6 mice was associated with changes in their gut microbiome by treating mice with an antibiotic mix that suppresses bacterial abundance and by performing fecal microbiota transplantation (FMT) from SI or group-housed (GH) donors to GH host. The effect of SI on anti-tumor CD8&#x2009;+&#x2009;T and immunosuppressive Foxp3&#x2009;+&#x2009;Treg cells was also studied.<br><br>RESULTS: Fecal bacteria that were present at different abundances between GH and SI mice were short chain fatty acid (SCFA) producers, and the most consistent change across three replicate studies was decreased fecal abundance of Akkermansia genus in SI mice. In addition, fecal propionic acid levels were reduced in SI mice, compared with GH mice, in agreement with Akkermansia being propionic acid producer. SI reduced the activation of CD8&#x2009;+&#x2009;T cells systemically and in the tumor microenvironment, while the levels and activation of immunosuppressive Foxp3 Tregs were increased. Antibiotic treatment reversed increased mammary tumorigenesis and immunosuppression in SI mice but did not affect GH mice. Further, FMT from SI donors increased tumor growth in GH host, compared with FMT from GH donor.<br><br>CONCLUSION: Gut dysbiosis caused by SI may be driving their increased mammary tumorigenesis, potentially through gut dysbiosis induced immunosuppression.}, }
@article {pmid42072400, year = {2026}, author = {Lin, Y and Lu, P and Ding, Q and Liu, M}, title = {Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, pmid = {42072400}, issn = {2227-9059}, abstract = {The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis-reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts-collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift-from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation-thereby advancing the goal of precision medicine in IBD.}, }
@article {pmid42072403, year = {2026}, author = {Shajahan, SR and Hamid, N and Okunsai, B and Shari, N and Ramli, MDC}, title = {Microbiota-Gut-Brain Axis in Alzheimer's Disease: Linking Oxidative Stress, Mitochondrial Dysfunction and Amyloid Pathology-A Systematic Review.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, pmid = {42072403}, issn = {2227-9059}, abstract = {Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer's disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer's disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit.}, }
@article {pmid42073392, year = {2026}, author = {Yang, M and Chen, Q and Meng, Z and Gu, X and Bai, C}, title = {The Microbiota-Gut-Brain Axis in Insomnia: Mechanisms and Intervention Strategies.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {42073392}, issn = {2075-1729}, support = {82574999//National Natural Science Foundation of China/ ; zyyzdxk-2023264//National Administration of Traditional Chinese Medicine/ ; 2024-JYB-JBZD-038//The Fundamental Research Funds for the Central Universities/ ; }, abstract = {Insomnia is one of the most common sleep disorders. Traditionally, its pathophysiology has been interpreted mainly from the perspective of the central nervous system (CNS). However, accumulating evidence suggests that the microbiota-gut-brain axis (MGBA), a bidirectional communication network linking the gut and the CNS, may play an important role in the development, maintenance, and treatment of insomnia. This review summarizes the major signaling pathways of the MGBA and discusses its potential mechanisms in insomnia. Current evidence indicates that gut microbiota and their metabolites may influence sleep-wake homeostasis through neural, immune, endocrine, and circadian pathways. At the same time, insomnia-related stress responses, immune imbalance, and lifestyle disturbances may in turn affect the gut microbiota, thereby forming a bidirectional regulatory network. Animal and clinical studies further support a close association between gut microbial dysbiosis and insomnia. In addition, this review systematically summarizes factors that may affect the MGBA, including diet, lifestyle, psychosocial stress, medications, and medical exposures. On this basis, MGBA-targeted interventions, such as dietary modification, prebiotics and probiotics, lifestyle interventions, fecal microbiota transplantation, and natural medicines, may provide promising new strategies for the prevention and treatment of insomnia. Nevertheless, the current evidence still relies largely on animal studies and cross-sectional research, and further longitudinal studies and high-quality interventional trials are needed to clarify causality, long-term efficacy, and standardized therapeutic approaches.}, }
@article {pmid42073476, year = {2026}, author = {Ichim, C and Boicean, A and Mihaila, R and Todor, SB and Anderco, P and Birlutiu, V}, title = {Effect of Fecal Microbiota Transplantation on Arterial Stiffness in Alcohol-Related Liver Cirrhosis: A Prospective Pilot Study.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {42073476}, issn = {2075-1729}, abstract = {BACKGROUND: Alcohol-related liver disease is frequently associated with systemic vascular dysfunction and increased arterial stiffness. This may contribute to adverse clinical outcomes. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy in liver cirrhosis, but its influence on vascular stiffness in humans remains insufficiently characterized.<br><br>METHODS: This prospective study evaluated arterial stiffness in patients with alcohol-related liver cirrhosis undergoing FMT. A control group received standard care. Vascular stiffness was assessed non-invasively using an oscillometric arteriograph based on pulse wave analysis. Measurements were performed at baseline and at one and three months after FMT under standardized conditions. The main indices assessed included aortic pulse wave velocity, augmentation index, ejection duration and return time. Direct microbiome sequencing and metabolomic profiling were not performed.<br><br>RESULTS: At baseline, the study and control groups had comparable vascular stiffness profiles. Only minor differences in selected hemodynamic parameters were observed. At one month after intervention, no statistically significant differences in arterial stiffness indices were observed between groups. Longitudinal analysis within the FMT group also showed no significant changes in direct markers of arterial stiffness across the three-month follow-up period. A non-significant tendency toward reduced ejection duration was noted.<br><br>CONCLUSIONS: In patients with advanced alcohol-related liver cirrhosis, FMT did not produce measurable short-term improvements in arterial stiffness. These findings suggest that short-term vascular effects of microbiota modulation may be difficult to detect in patients with advanced alcohol-related liver cirrhosis. Larger studies including earlier-stage patients, longer follow-up and direct microbiome and metabolomic assessment are needed to clarify potential vascular effects of FMT.}, }
@article {pmid42073922, year = {2026}, author = {Zheng, M and Wei, X and Chen, R and Wang, C and Xin, L}, title = {The Gut Microbiota and Autism Spectrum Disorder: Current Research and Therapeutic Insights.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {42073922}, issn = {2076-328X}, abstract = {Autism Spectrum Disorder (ASD) is a collective term for neurodevelopmental disorders with core features of social communication impairment, restricted and repetitive behaviors, and narrow interests. These include classic autism, Asperger's syndrome, and pervasive developmental disorder not otherwise specified. ASD is currently managed with behavioral interventions, rehabilitation training, and family support, but there is no curative medication. Recent studies suggest that some patients with ASD may experience gastrointestinal symptoms. Perhaps this is associated with the disturbances of gut microbiota. Increasing evidence has demonstrated that the composition of gut microbiota in ASD individuals is different from that in normal population and may be associated with neurodevelopmental processes via the gut-brain axis. This article reviews the evidence for the association between gut microbiota and ASD, describes the characteristics of microbial changes, and analyzes the mechanism by which changes in the composition of the microbiota affect the occurrence and development of ASD. Finally, we review recent advances in microbiota-targeted therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation, which provide new approaches to alleviate and improve autism-related symptoms and point out the future research direction.}, }
@article {pmid42074015, year = {2026}, author = {Papacocea, RI and Iliuță, FP and Papacocea, IR}, title = {Gut Microbiome Dysregulation Across Schizophrenia Spectrum Disorders: Bacteria-, Fungi- and Virome-Level Alterations with Molecular and Immunological Implications.}, journal = {International journal of molecular sciences}, volume = {27}, number = {8}, pages = {}, pmid = {42074015}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Schizophrenia/microbiology/immunology ; *Virome ; *Bacteria ; Dysbiosis/microbiology ; *Fungi ; Animals ; }, abstract = {Schizophrenia spectrum disorders (SSD) are severe psychiatric conditions characterized by disturbances in cognition, emotion, and behavior, with increasing evidence suggesting an involvement of the gut microbiome in their pathophysiology. This PRISMA-informed structured review synthesizes 114 studies using a taxa-centered framework that maps microbial changes across SSD stages and phenotypes and serves as a structural basis for identifying cross-study patterns. Across heterogeneous cohorts, convergent alterations include depletion of short-chain fatty acid (SCFA)-producing taxa (including Faecalibacterium, Roseburia, and Coprococcus) and enrichment of potentially pro-inflammatory and fermentative taxa (such as Proteobacteria, Enterobacteriaceae, Streptococcus, Collinsella, and Desulfovibrio). These taxonomic patterns suggest potential functional alterations, including reduced SCFA availability. Reduced abundance of butyrate-producing taxa has been associated with impaired intestinal barrier function and increased microbial translocation (e.g., lipopolysaccharide), which may contribute to the activation of immune pathways, including Toll-like receptor 4 signaling and elevated inflammatory markers such as IL-6 and TNF-α. Additional alterations reported across studies include changes in lactate metabolism, bile acid profiles, aromatic amino acid metabolism, and the tryptophan-kynurenine pathway. These pathways may interact with neurobiological processes relevant to SSD, including glutamate-GABA balance, NMDA receptor function, microglial activation, and synaptic regulation, although much of the current evidence remains associative. Multi-kingdom studies and fecal microbiota transplantation models provide further support for the functional relevance of these observations, though causal relationships remain to be fully established. Overall, SSD-associated dysbiosis appears to reflect ecosystem-level metabolic alterations rather than isolated taxonomic abnormalities, supporting a Microbiota-Gut-Immune-Glia conceptual framework and highlighting the gut ecosystem as a potential therapeutic target.}, }
@article {pmid42074174, year = {2026}, author = {Ratajczyk, K and Kaczorowska, E and Wyka, K and Tarasiuk-Zawadzka, A and Fichna, J and Gajos, A}, title = {Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {8}, pages = {}, pmid = {42074174}, issn = {1422-0067}, support = {Medical University of Lodz (#503/6-127-01/503-61-001 to AG and #503/1-156-04/503-11-001 to JF).//Medical University of Lodz/ ; }, mesh = {Humans ; *Parkinson Disease/metabolism/microbiology/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism ; Animals ; Signal Transduction ; *Brain-Gut Axis ; Neurotransmitter Agents/metabolism ; }, abstract = {The formulation of the gut-brain-microbiota axis (GBA) theory has led to new research directions that have expanded our understanding of the pathogenesis, phenotypic variability, and clinical course of Parkinson's disease (PD). Models of PD pathogenesis, based on the Braak hypothesis, suggest a subtype of the disease in which pathological changes begin in the gut many years before the onset of brain pathology and the manifestation of motor symptoms. Gut microbiota may influence nervous system function along the GBA by influencing intestinal permeability, chronic inflammation, and α-synuclein aggregation. Accumulating evidence suggests that the gut microbiota may also regulate the synthesis and metabolism of neurotransmitters, including dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and γ-aminobutyric acid (GABA), both in the gut and brain, and indirectly stimulate central nervous system activity via the vagus nerve, which receives signals from the enteric nervous system. Research on the effects of microbiota on GBA has paved the way for the identification of novel treatment strategies, including probiotics, prebiotics, synbiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT), aimed at not only symptomatic but also disease-modifying treatment of PD. In this article, we propose a novel approach to GBA as a link between gut microbiota and gut and brain neurotransmitter metabolism in PD. We review the latest research on the gut epithelial barrier. We analyze and summarize the potential of therapeutic interventions targeting gut microbiota and their impact on neurotransmitter regulation in PD.}, }
@article {pmid42075006, year = {2026}, author = {Zhang, X and Chen, F and Luo, Y and Li, D and Ji, J and Ma, L and Ma, C and Hu, X}, title = {Young Human-Derived Microbiota Ameliorates Cognitive Decline and Reproductive Senescence in Aged Mice.}, journal = {Nutrients}, volume = {18}, number = {8}, pages = {}, pmid = {42075006}, issn = {2072-6643}, support = {2023YFF1104005//National key research and development program/ ; }, mesh = {Animals ; Mice ; Humans ; Male ; Bifidobacterium/growth &amp; development ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/microbiology/therapy ; *Cellular Senescence/physiology ; Mice, Inbred C57BL ; Reproduction/physiology ; Dysbiosis/microbiology/therapy ; *Aging/physiology/psychology ; }, abstract = {Background/Objectives: Age-related gut microbiota dysbiosis leads to systemic oxidative stress, chronic inflammation, and multi-organ functional decline. However, there is limited evidence supporting microbiota-based therapies for aging. This study aimed to examine the effect of gut microbiota from young donors, particularly those with increasing Bifidobacteria levels through dietary intervention, on age-related declines in fertility, cognition, and reproduction. Methods: We conducted experiments using gut microbiota from young human donors, with or without pre-conditioning with barley leaves (BL), to transplant into aged male mice. Hippocampal metabolome and behavioral assessments were used to identify differences in recognitive regulation during aging. Moreover, testis tissue, semen quality, and offspring studies were determined to investigate the beneficial effects on fertility and underlying mechanism. Conclusions: This preliminary dietary treatment promotes the growth of Bifidobacterium in aged recipient mice. Aged male mice received young fecal microbiota transplants (yFMTs), BL-conditioned yFMTs (BLyFMTs), and a combined treatment of BLyFMT plus recipient BL supplementation. The combined approach significantly increased intestinal Bifidobacterium levels and effectively restored hippocampal metabolomic profiles and cognitive behavior. Additionally, yFMT-based treatments mitigated structural damage to the seminiferous tubules and prevented the germ cell depletion. Consistently, those interventions improved sperm quality and mechanistically enhanced hypothalamic-pituitary-gonadal (HPG) axis activity in aged recipients. These findings highlight Bifidobacterium as a key factor in microbiome-driven rejuvenation, enhancing the effectiveness of yFMTs in addressing aging-related declines.}, }
@article {pmid42075029, year = {2026}, author = {Asayesh, M and Nazarzadeh, A and Jamshidi, S and Keramat, S and Ryszkiel, I and Stanek, A}, title = {Modulation of Gut Microbiota Through Dietary Fibers to Enhance Regulatory T Cell-Based Immunotherapy in GVHD Following Hematopoietic Stem Cell Transplantation.}, journal = {Nutrients}, volume = {18}, number = {8}, pages = {}, pmid = {42075029}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Graft vs Host Disease/therapy/immunology/microbiology/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Dietary Fiber/administration &amp; dosage ; *T-Lymphocytes, Regulatory/immunology ; *Immunotherapy/methods ; Prebiotics ; Dysbiosis ; Fecal Microbiota Transplantation ; Probiotics ; }, abstract = {Graft-versus-host disease (GVHD) is one of the principal complications seen in the recipients of allogenic hematopoietic stem cell transplantation (allo-HSCT), and persists as a leading cause of post-transplant morbidity and mortality. Increasing evidence highlights the crucial influence of the gut microbiome (GM) on transplant outcomes. Microbial dysbiosis, characterized by reduced bacterial diversity and pathogenic overgrowth, is strongly associated with higher rates of complications and mortality. Patients with lower microbial diversity exhibit poorer overall survival (OS) and an increased incidence of acute GVHD (aGVHD). Conversely, restoration of beneficial commensal communities has been shown to enhance immune homeostasis, mitigate GVHD severity, and decrease infection risk. Emerging therapeutic strategies now focus on modulating the intestinal microbiome through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT). It has been demonstrated that bacterial metabolites, such as short-chain fatty acids (SCFAs) from the diet, especially a diet rich in fibers, reduce the occurrence/severity of GVHD by inducing regulatory T cells (Tregs), which release anti-inflammatory cytokines and regulate the host immune system. Hence, the implementation of dietary fibers (DFs) could increase beneficial commensals, Treg induction, and improve outcomes such as GVHD and OS in recipients of allo-HCT. Hereupon, this review addresses how a fiber-rich diet modulates GM composition, reinforces epithelial barrier integrity, and improves the efficacy of Treg-based immunotherapy by stabilizing their regulatory phenotype and increasing their functional persistence, ultimately leading to a reduction in GI complications associated with GVHD. Unlike prior reviews that primarily cover the microbiome-GVHD axis or Treg therapies in isolation, this review emphasizes fermentable dietary fibers as a mechanistically grounded, clinically actionable strategy to support Treg stability and persistence via microbiota-derived metabolites. We integrate mechanistic evidence with emerging clinical feasibility data and ongoing trials of prebiotic supplementation in allogeneic HSCT.}, }
@article {pmid42075307, year = {2026}, author = {Burdette, RA and Whitt, CC and Cios Phillips, KJ and Worthington, MT and Behm, BW and Warren, CA}, title = {Treating Initial and Recurrent C. difficile: A Retrospective Analysis of 100 Referred Patients.}, journal = {Microorganisms}, volume = {14}, number = {4}, pages = {}, pmid = {42075307}, issn = {2076-2607}, abstract = {Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI.}, }
@article {pmid42075777, year = {2026}, author = {Lagos, I and Pérez de Arce, E and Faggiani, I and D'Amico, F and Zilli, A and Furfaro, F and Massironi, S and Cicerone, C and Solitano, V and Parigi, TL and Peyrin-Biroulet, L and Danese, S and Allocca, M}, title = {The Role of Microbiota and Fecal Transplantation in Inflammatory Bowel Disease.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {42075777}, issn = {2076-0817}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; Crohn Disease/therapy/microbiology ; Colitis, Ulcerative/therapy/microbiology ; Feces/microbiology ; Treatment Outcome ; }, abstract = {Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii-a key butyrate producer with anti-inflammatory properties-was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD.}, }
@article {pmid42077461, year = {2026}, author = {Wu, J and Qiu, Y and Deng, J and Li, Y and Jia, B and Cao, Z and Tao, J and Guo, J}, title = {Faecal microbiota transplantation and glucolipid metabolic disorders: the interventional role of gut microbiota.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1806638}, pmid = {42077461}, issn = {1664-2392}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Animals ; *Metabolic Diseases/therapy/microbiology/metabolism ; }, abstract = {Glucolipid metabolic disorders (GLMD) have emerged as a significant global public health issue, posing a significant threat to human health. With changes in modern social structures and an ageing population, the incidence of GLMD is on the rise and is increasingly affecting younger populations. Faecal microbiota transplantation (FMT) directly modifies the gut microbiota to reestablish its equilibrium and metabolites, consequently reinstating gut barrier integrity, mitigating chronic low-grade inflammation, and affecting the onset and progression of GLMD through the regulation of the gut-liver axis. This paper reviews the application of FMT in the treatment of GLMD, emphasizing research outcomes and efficacy assessments in clinical trials and animal studies. As a simple and secure intervention, FMT is anticipated to provide new therapeutic alternatives for GLMD patients in the future with the deepening of relevant research, the screening of specific probiotics and the revelation of functional mechanisms. This paper aims to clarify the potential mechanism of FMT in addressing GLMD, summarise recent research developments in this field, and anticipate the opportunities and challenges of FMT in clinical application.}, }
@article {pmid42079588, year = {2026}, author = {Qie, RJ and Qin, JB and Wu, HY and Ji, ZH}, title = {Key messengers in the gut-nose axis: mechanisms of gut microbial metabolites in the immunomodulation of allergic rhinitis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1796775}, pmid = {42079588}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Rhinitis, Allergic/immunology/metabolism/microbiology/therapy ; *Immunomodulation ; Animals ; *Nasal Mucosa/immunology/metabolism/microbiology ; }, abstract = {Allergic rhinitis (AR) is a common clinical chronic inflammatory respiratory disease, in which immune imbalance serves as a core component of its complex pathogenesis. In recent years, the gut-nose axis has emerged as a novel pathway mediating immune crosstalk between the intestinal tract and the nasal cavity, garnering significant academic attention. Gut microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines) are profoundly involved in the pathophysiology of AR by reshaping the nasal mucosal immune microenvironment via systemic circulation and neural pathways and regulating the Th2/Treg balance, innate lymphoid cells (ILC2s), and mast cell functions. This article systematically reviews the immunomodulatory mechanisms of core gut microbial metabolites, explores their impact on nasal mucosal epithelial barrier function and immune cell activity, and summarizes metabolite-based clinical intervention strategies, including postbiotic therapy (bioactive compounds derived from microbial cells or metabolites), precision nutritional interventions, and fecal microbiota transplantation. Additionally, the paper analyzes current challenges such as heterogeneity and dose-response effects, aiming to provide a theoretical foundation for understanding the immunomodulatory mechanisms of the gut-nose axis and a reference for developing novel precision strategies for the prevention and treatment of AR.}, }
@article {pmid42079748, year = {2026}, author = {Zheng, L and Jia, T and Li, Y and Zhang, Z and Su, H and Zhang, R}, title = {The interplay between gastrointestinal dysfunction and gut microbiota dynamics in sepsis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1761536}, pmid = {42079748}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sepsis/microbiology/physiopathology/complications/immunology ; *Dysbiosis/microbiology ; Animals ; *Gastrointestinal Diseases/microbiology ; *Gastrointestinal Tract/microbiology/physiopathology ; Intestinal Mucosa/microbiology ; Multiple Organ Failure ; }, abstract = {Sepsis frequently involves early gastrointestinal dysfunction, in which intestinal barrier breakdown and microbiota dysbiosis amplify systemic inflammation and contribute to multi-organ failure. Emerging evidence indicates that the gut is not merely a bystander in sepsis but an active driver of pathogenic cascades through epithelial injury, mucosal immune dysregulation, ischemia-reperfusion stress, and impaired motility, collectively promoting microbial translocation and immune deviation. In parallel, sepsis is associated with profound remodeling of the gut microbiome, characterized by reduced commensal diversity, expansion of pathobionts, and functional shifts in key microbial metabolites, including short-chain fatty acids, bile acids, and tryptophan-derived products, which further compromise mucosal integrity and host immune tone. This narrative review synthesizes experimental, translational, and clinical findings to elucidate the bidirectional interaction gut barrier-microbiota interplay in sepsis and to summarize mechanistic links across epithelial, immune, and metabolic signaling pathways, including gut-liver and gut-brain axes relevant to sepsis-associated organ dysfunction. dysfunctional microbial community leads to systemic immune deviation, multi-organ dysfunction and sepsis-associated encephalopathy, a common and severe neurological complication of sepsis. We also discuss emerging therapeutic strategies targeting the gut-microbiota axis-such as early enteral nutrition, prebiotics/postbiotics, defined microbial consortia, fecal microbiota transplantation, and metabolite-based supplementation-and evaluate their potential and limitations in septic populations. Finally, we highlight key challenges, including unresolved causality, inter-individual variability, context-dependent responses, and safety concerns, underscoring the need for longitudinal multi-omic profiling, host-microbiome phenotyping, and mechanism-informed interventional trials to enable precision microbiome-based approaches for sepsis.}, }
@article {pmid42081036, year = {2026}, author = {Yang, F and Liu, S and Liu, G and Luo, L and Lu, X and Lin, W and Chen, J and Lin, R}, title = {Fecal microbiota transplantation from different pig breeds alters fat deposition and gut microbiota in mice.}, journal = {Applied microbiology and biotechnology}, volume = {110}, number = {1}, pages = {}, pmid = {42081036}, issn = {1432-0614}, support = {2023J01446//Natural Science Foundation of Fujian Province/ ; 2019-144//Fujian Modern Agricultural Pig Industry Technology System Project/ ; }, abstract = {Gut microbiota plays a vital role in nutrient digestion, energy metabolism, and immune regulation in pigs. However, the core bacterial species influencing fat deposition remain poorly defined due to the complexity and diversity of the intestinal microbial ecosystem. In this study, healthy Putian Black (PT) pigs and Duroc × Landrace × Yorkshire (DLY) pigs of similar ages were used as fecal microbiota transplantation (FMT) donors, with male ICR mice as recipients. A control group (CM) received saline, while the experimental groups were gavaged fecal suspensions from PT pigs (PM) or DLY pigs (DM). Results showed that intramuscular fat content, triglyceride levels, and adipogenic gene expression (PPARG, FABP4, LPL, ATGL) were extremely significant higher in the PM group than in the DM group (P<0.01). 16 S rRNA sequencing revealed that both PM and DM groups had lower Firmicutes abundance but higher Bacteroidetes abundance compared to the CM group (P<0.05). Notably, the PM group exhibited higher Firmicutes and lower Bacteroidetes abundance than the DM group (P<0.05). Correlation analysis identified S_uncultured_bacterium_g_Prevotella as negatively correlated with FASN and DGAT2 expression (P<0.01), while Lactobacillus species showed positive correlations with PPARG, FASN, and ATGL expression (P<0.05). These findings demonstrate that FMT alters gut microbiota composition and host gene expression, thereby influencing fat deposition, with Prevotella and Lactobacillus emerging as potential key genera. KEY POINTS: ∙ FMT resulted in extremely significant higher intramuscular fat content in the PM group compared to the DM group. ∙ Lactobacillus may be a key genus regulating fat deposition in PT pigs. ∙ Prevotella may be a key genus regulating fat deposition in DLY pigs.}, }
@article {pmid42083059, year = {2026}, author = {Diop, K and Benlaïfaoui, M and Hunter, S and Méndez-Salazar, EO and Hakozaki, T and Richard, C and Prifti, DK and Kourtian, S and Proulx-Rocray, F and Naimi, S and Ponce, M and Messaoudene, M and Cauchois, F and Belkaid, W and Bataille, V and Lee, K and Mihalcioiu, C and Watson, IR and Elkrief, A and Routy, B}, title = {Metagenomics and culturomics reveal the dual role of the gut microbiome in the development of immune-related toxicities and the efficacy of immune checkpoint inhibitors in cancer.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-026-02419-4}, pmid = {42083059}, issn = {2049-2618}, support = {284894//Fonds de recherche du Qu&#xe9;bec/ ; }, abstract = {BACKGROUND: Despite their major impact on cancer treatment, immune checkpoint inhibitors (ICI) are frequently associated with immune-related adverse events (irAE). Growing evidence suggests that the occurrence of irAE may be correlated with enhanced ICI efficacy, although the underlying mechanisms remain unknown. Most studies investigating the role of the gut microbiome in oncology have relied on sequencing approaches, particularly shotgun metagenomics. Although microbiome profiling revealed strong associations between specific bacterial taxa and clinical outcomes, it has limitations, including an inability to detect low-abundance bacteria and to recover live cultivable bacteria. To overcome these limitations, we combined shotgun metagenomics and culturomics on fecal samples collected from patients with melanoma and non-small cell lung cancer (NSCLC), at baseline and at the onset of immune related (ir)-colitis.<br><br>RESULTS: We first validated across three independent cohorts of 589 patients with melanoma or NSCLC treated with ICI that grade&#x2009;&#x2265;&#x2009;2 irAE were associated with significantly longer overall survival (OS) and progression-free survival (PFS). Complementary analysis using shotgun metagenomics and culturomics revealed that patients who developed grade&#x2009;&#x2265;&#x2009;2 irAE had a lower alpha diversity compared to those who did not develop grade&#x2009;&#x2265;&#x2009;2 irAE. Metagenomics results showed enrichment of Ruminococcus gnavus and Streptococcus vestibularis at baseline in grade&#x2009;&#x2265;&#x2009;2 irAE patients, while Clostridium paraputrificum and Streptococcus spp. were isolated by culturomics from baseline stool samples from ir-colitis patients. Longitudinal analysis of paired stool samples revealed a shift in microbiome composition with enrichment of Paraclostridium bifermentans and Clostridium paraputrificum, lower lipopolysaccharide and higher flagellin concentrations at baseline compared with the time of ir-colitis. Fecal microbiome transplantation from a patient with ir-colitis into mice induced surrogate markers of colonic inflammation and enhanced the anti-tumor activity of combined anti-PD-1/CTLA-4. P. bifermentans isolated from this patient sample demonstrated direct epithelial barrier disruption in Caco-2 monolayers, characterized by decreased ZO-1 and Occludin&#xa0;immunofluorescence signal and increased TNF-&#x3b1; and IL-1&#x3b2; expression. Moreover, in the dextran sodium sulfate (DSS) colitis model, P. bifermentans worsened weight loss. In a separate tumor model, it amplified the anti-tumor effect of dual ICI. This beneficial effect was also&#xa0;maintained after treatment with P. bifermentans&#x2009;<&#x2009;3&#xa0;kDa filtered supernatant.<br><br>CONCLUSION: Altogether, our results suggest that P. bifermentans promotes subclinical colitis while increasing the efficacy of dual ICI. This provides a potential microbiome-derived link between irAE and improved anti-tumor responses. Video Abstract.}, }
@article {pmid42083117, year = {2026}, author = {Helliwell, JA and Sciberras, P and Dosis, A and Burke, J and Chilton, CH and Wood, HM and Jayne, DG}, title = {Modulation of the gut microbiota as a novel strategy to prevent anastomotic leak after colorectal surgery: Systematic scoping review.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {28}, number = {5}, pages = {e70472}, pmid = {42083117}, issn = {1463-1318}, mesh = {Humans ; *Anastomotic Leak/prevention &amp; control/microbiology ; *Gastrointestinal Microbiome/physiology/drug effects ; Probiotics/therapeutic use ; *Colorectal Surgery/adverse effects ; Fecal Microbiota Transplantation ; Animals ; Female ; Male ; }, abstract = {BACKGROUND: Anastomotic leak (AL) remains a major source of morbidity following colorectal surgery. Increasing evidence implicates the gut microbiome in the pathogenesis of AL, with certain microbial species disrupting tissue repair through collagen degradation. Perioperative modulation of the microbiome may offer a novel strategy to improve anastomotic healing. This scoping review aimed to map available evidence on microbiome-targeted interventions, synthesise mechanistic insights, and identify translation gaps in relation to anastomotic outcomes.<br><br>METHODS: A systematic scoping review was performed. MEDLINE, Embase and Cochrane Central Registry of Controlled Trials databases were searched from database inception to 5th August 2025. Studies were eligible if they investigated perioperative interventions that modulated the gut microbiome and evaluated anastomotic healing or leak rates. Both clinical and preclinical studies were included. A narrative synthesis was performed by charting key findings.<br><br>RESULTS: Of 4209 records screened, 27 studies met the inclusion criteria: 9 clinical and 18 preclinical. Interventions included bowel preparation, probiotics, synbiotics, arginine/omega-3 supplementation, dietary modification, faecal microbiota transplantation (FMT), phosphate, tranexamic acid, morphine and infliximab. Among clinical studies, only oral antibiotics combined with mechanical bowel preparation were associated with a significant reduction in leak rates. Preclinical studies showed interventions such as high-fibre diets, FMT, rectal tranexamic acid and phosphate supplementation improved anastomotic healing via enhanced microbial diversity, suppression of pathogenic organisms, or inhibition of collagenolytic activity.<br><br>CONCLUSION: This review highlights a range of microbiome-targeted interventions with potential to reduce AL. While clinical evidence remains limited, several preclinical strategies demonstrate promise and warrant evaluation in early-phase human trials.}, }
@article {pmid42083350, year = {2026}, author = {Bashir, S and Shah, IM and Javeed, S and Rafiquee, A and Mir, B and Hassan Mir, R and Geer, MI and Ganie, MA}, title = {Beyond Conventional Therapy: A Comprehensive Review of Herbal, Traditional, and Emerging Interventions for Polycystic Ovary Syndrome.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240406897251206074722}, pmid = {42083350}, issn = {1875-5666}, abstract = {Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disorder that leads to significant changes in the reproductive, metabolic, and psychological domains of women's health in their reproductive years. In addition, the conventional therapies (lifestyle modification, metformin, oral contraceptives, and ovulation-inducing agents) that are the mainstay of management of the syndrome may still not be able to fully address the diverse pathophysiology of PCOS as well as the long-term risks associated with it. This narrative review highlights clinical and mechanistic data from studies on various complementary and alternative medicine (CAM) modalities as first-line treatments for PCOS, in addition to conventional therapy. Correspondingly, herbal and botanical agents (berberine, cinnamon, licorice, Vitex agnus-castus, curcumin, and epigallocatechin gallate) modulate insulin signalling, androgen synthesis, inflammatory pathways, and oxidative stress, with initial clinical trials reporting improvements in metabolism and hormones to a similar extent as standard therapies in selected populations. Traditional Chinese Medicine (TCM), both multi-herb prescriptions and acupuncture, provides tailored formulas that might not only regulate ovulation and endocrine parameters but also lower metabolic indices, despite the high variability across studies. Stress reduction, physical fitness, and the quality of life are among the achievements of mind-body interventions (yoga, tai chi, qigong, and mindfulness-based stress reduction). Improvements in hyperinsulinemia, hypolipidemia, ovulation, and hyperandrogenemia, along with the related insulinresistant and vitamin D-deficient phenotypes, have been steadily reported with the use of the nutraceutical combinations of inositols, vitamin D, omega-3 fatty acids, Nacetylcysteine, coenzyme Q10, and resveratrol. New non-conventional methods, such as fecal and vaginal microbiota transplantation, platelet-rich plasma, and kisspeptin analogues, have been identified as potential therapeutic routes but are still in their infancy in terms of development. Although CAM therapies have multiple advantages in controlling many PCOS domains, the official integration into clinical practice would require standardization, rigorous randomized controlled trials, and continuous safety monitoring. If correctly and cautiously applied, CAM may be useful as an adjunct alongside established therapy, rendering PCOS management more holistic and personalized.}, }
@article {pmid42083540, year = {2026}, author = {YuXuan, G and Iqbal, MK and Khan, B and Khan, H and Ud Din Shah, SS and Al-Hussain, F and Kiyani, MM and Bashir, S}, title = {The Gut-Brain Connection: Exploring the Connection Between the Gastrointestinal System and Parkinson's Disease.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273419693251206130059}, pmid = {42083540}, issn = {1996-3181}, abstract = {Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by motor and non-motor symptoms. Recent studies indicate that the gut-brain axis contributes to both the initiation and progression of PD, a disorder that primarily affects the central nervous system. This article reviews current research on the interaction between the central nervous system and the gastrointestinal tract in PD. The vagus nerve, areas of the enteric nervous system (ENS), systemic inflammation, and the microbiome are all involved in this interaction. For example, recent studies have shown PD-related effects such as abnormal distribution of gut bacteria, increased gut barrier permeability, and α-synuclein transport from the gut to the brain. A comprehensive evaluation of motor and non-motor symptoms was conducted. Additionally, we explored drugs that specifically target the gastrointestinal system, the possible gastrointestinal symptoms of PD, and how these symptoms may serve as early indicators of the disease. Our article also discusses dietary modifications, probiotics, and fecal microbiota transplantation as potential treatments for PD. By reviewing clinical and basic scientific research as well as translational applications, this article highlights the relationship between the central nervous system and the digestive system in PD. A better understanding of this complex connection may lead to improved detection and treatment of this debilitating disease and offer new opportunities for prevention and therapy. Finally, this paper suggests directions for further research in this area.}, }
@article {pmid42083785, year = {2026}, author = {Wu, Y and Liu, J and Ren, Y and Zou, C}, title = {Unravelling the Gut-Skin Axis in Chronic Urticaria: Dysbiosis, Metabolites and Immunological Mechanisms.}, journal = {Experimental dermatology}, volume = {35}, number = {5}, pages = {e70261}, doi = {10.1111/exd.70261}, pmid = {42083785}, issn = {1600-0625}, support = {2025C02080//the Key Research and Development Plan of Zhejiang Province/ ; WKJ-ZJ-2409//the National Health Commission Scientific Research Fund/ ; }, mesh = {Humans ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome ; Animals ; *Chronic Urticaria/immunology/microbiology/metabolism ; *Skin/immunology/metabolism ; Mice ; Fatty Acids, Volatile/metabolism ; Mast Cells/immunology ; }, abstract = {Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence suggests that gut microbiota dysbiosis represents a potentially modifiable upstream factor, which has been predominantly investigated in patients with chronic spontaneous urticaria (CSU). Multi-omics and Mendelian randomization studies have provided convergent evidence linking gut dysbiosis to systemic inflammation and mast cell instability. This is characterized primarily by the depletion of short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium, Roseburia and Bifidobacterium) and the relative enrichment of pro-inflammatory Proteobacteria (particularly Enterobacteriaceae). Mechanistically, these alterations may lower the mast cell activation threshold and promote systemic immune dysregulation through specific metabolic shifts, such as the depletion of SCFAs and unsaturated fatty acids, and the translocation of endotoxins (e.g., lipopolysaccharide) due to compromised intestinal barrier function. In this review, we discuss how the use of Mendelian randomization (MR) and germ-free mouse models can advance the gut-urticaria axis (with a primary focus on CSU) from mere correlation to causation, while highlighting the crucial need to account for clinical confounders. Finally, we evaluate the clinical translational potential and associated challenges of microbiome-targeted interventions (e.g., probiotics, faecal microbiota transplantation) as novel adjuvant therapies.}, }
@article {pmid42086265, year = {2026}, author = {Bénard, MV and Van Der Spek, MJ and Davids, M and Visser, CE and Zoetendal, EG and Rethans, B and Zwezerijnen-Jiwa, FH and Visschedijk, MC and Oldenburg, B and Weersma, RK and Ponsioen, CY}, title = {Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised controlled trial (TURN2 study).}, journal = {BMJ open}, volume = {16}, number = {5}, pages = {e107097}, pmid = {42086265}, issn = {2044-6055}, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Gastrointestinal Microbiome ; *Feces/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Adult ; Male ; Female ; Enema ; }, abstract = {INTRODUCTION: The interaction between the gut microbiota and the host immune system is implicated in the pathogenesis of inflammatory bowel disease, including ulcerative colitis (UC). Targeting the gut microbiota with faecal microbiota transplantation (FMT) from a healthy donor has shown promise in inducing remission in patients with active UC. However, mixed results and protocol heterogeneity have limited its practical application. Our previous Transfer of Faeces in Ulcerative Colitis; Restoring Homeostasis (TURN) trial found a correlation of clinical response with specific strains and butyrate production. Since most gut microbes, including many butyrate producers, are anaerobes, anoxic processing of donor stool may be essential to increase efficacy of FMT in UC. This trial aims to enhance FMT efficacy by applying strict anoxic processing, selecting donors based on microbial composition and using repetitive dual-route administration.<br><br>METHODS AND ANALYSIS: This randomised, double-blind, placebo-controlled, multicentre study evaluates the efficacy of strictly anoxic prepared donor FMT compared with anoxic prepared autologous FMT in patients with mild to moderate active UC. An open-label extension option is available for non-responders in the autologous arm. Included patients will receive 4&#x2009;weekly FMTs, comprising two double-route administrations (nasoduodenal administration combined with enema) and two single enemas. Donors are selected based on their microbiota profile, informed by our previous TURN trial and literature. A total of 76 patients evaluable for the primary endpoint will be included. The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score. An interim analysis will be conducted midway through the study by a Data Safety Monitoring Board to monitor efficacy and safety. Other outcomes of this study include the evaluation of clinical, endoscopic and histological response. In addition to clinical results, this study aims to provide valuable insights into specific microbial strains, metabolites and mechanisms correlated with response, aiding in the development of future microbial therapies.<br><br>ETHICS AND DISSEMINATION: Ethics approval was obtained from the medical ethics committee of the Amsterdam University Medical Centre in the Netherlands (reference number 2018_057). All participants will provide written informed consent. The results of the trial will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.<br><br>TRIAL REGISTRATION NUMBER: Prospectively registered in May 2018 in the Dutch Trial Register (NTR/LTR) as NL7770. Assigned NL-OMON52507 following the transition of the Dutch Trial Register to the Overview of Medical Research in the Netherlands. Also registered at ClinicalTrials.gov (NCT05998213).}, }
@article {pmid42088008, year = {2026}, author = {Sgarbossa, C and Forth, E and Squires, S and Groth, A and Farid, M and Gallant, K and Desai, D and Redfearn, W and Milev, R}, title = {Neurobiological effects of microbial treatments within psychiatry: a systematic review.}, journal = {Frontiers in psychiatry}, volume = {17}, number = {}, pages = {1745964}, pmid = {42088008}, issn = {1664-0640}, abstract = {OBJECTIVE: Though microbial interventions such as probiotics and fecal microbiota transplantation have had a growing body of evidence suggesting their efficacy in alleviating the symptoms of psychiatric illnesses, their exact mechanisms of action and impacts on the brain are still not fully characterized. The aim of this review is to compile and summarize the current literature regarding neurobiological changes associated with microbial interventions targeting psychiatric symptoms in healthy and psychiatric populations.<br><br>METHODS: A systematic search of four databases was conducted using key terms related to neuroimaging, microbial interventions, and psychiatric illnesses and/or symptoms. All results were then evaluated based on specific eligibility criteria.<br><br>RESULTS: 10 studies met eligibility criteria and were included in this systematic review. Three of the five healthy control studies and all five of the studies conducted within psychiatric populations, observed significant neurobiological changes associated with probiotic intervention either in areas with psychiatric relevance, in the direction of a healthier profile, or correlated with improved psychiatric and/or affective symptoms. The interventions used in these studies consisted of probiotics with bacterial species primarily from the lactobacillus and bifidobacterium genera, at doses ranging from 1-900 billion CFU, taken for durations ranging from 4 weeks to 6 months.<br><br>CONCLUSIONS: The findings from this review suggest that probiotic intervention may be associated with neurobiological changes, and that these changes could play a role in ameliorating psychiatric symptoms. More research is needed to replicate these findings, explore other psychiatric populations and microbial interventions, and fully elucidate the mechanisms driving these promising neurobiological and clinical changes.}, }
@article {pmid42088511, year = {2026}, author = {Smout, J and Lesker, TR and Hoenicke, L and Ortiz, D and Zou, M and Kruse, F and Pirr, S and Willers, M and Härtel, C and Falk, C and Torow, N and Viemann, D and Strowig, T and Huehn, J}, title = {Probiotic-conditioned microbiota from preterm infants modulate immune response to pathogen challenge in a microbiota-humanized mouse model.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1761680}, pmid = {42088511}, issn = {1664-3224}, mesh = {Animals ; *Probiotics/administration &amp; dosage/pharmacology ; *Gastrointestinal Microbiome/immunology ; Mice ; *Infant, Premature/immunology ; Humans ; Female ; Infant, Newborn ; Disease Models, Animal ; Immunity, Innate ; Animals, Newborn ; *Escherichia coli Infections/immunology/microbiology ; Enteropathogenic Escherichia coli/immunology ; Feces/microbiology ; }, abstract = {Early-life host-microbe interactions critically shape immune development, lifelong homeostasis, and disease susceptibility. The PRIMAL trial (Priming Immunity at the Beginning of Life) demonstrated that multistrain probiotics shifted the gut microbiota of very preterm infants toward eubiosis without affecting sepsis incidence, yet the immunological consequences remained unresolved. To explore this, we colonized germ-free female mice with fecal samples from probiotic- or placebo-treated preterm infants from the PRIMAL trial. Microbiota composition was vertically transmitted and stable across generations. At steady-state, 3-week-old pups colonized with probiotic-conditioned microbiota exhibited markedly reduced populations of innate immune cells, particularly in the colon, with subtler effects in the small intestine and spleen, while adaptive immune subsets were less affected. Upon enteropathogenic Escherichia coli challenge at day 5, pups harboring probiotic-conditioned microbiota displayed reduced growth and impaired bacterial clearance, correlating with diminished numbers of key innate immune cell populations. These findings demonstrate that probiotic-driven shifts in human-derived microbial communities can attenuate immune cell development in mice and alter early-life infection outcomes. Our study underscores the complex, context-dependent effects of probiotics on the neonatal microbiota-immune axis and provides mechanistic insight into how interventions in preterm infants may influence susceptibility to infection.}, }
@article {pmid42088615, year = {2026}, author = {Zhang, Z and Li, C and Tang, Y and Liu, B and Wang, J and Kong, L and Bao, W and Lai, H and Chen, T and Li, J}, title = {Indole-3-Carbaldehyde from Limosilactobacillus reuteri Boosts Chemotherapy Response in Diffuse Large B Cell Lymphoma by Blocking the Mechanistic Target of Rapamycin Pathway.}, journal = {Research (Washington, D.C.)}, volume = {9}, number = {}, pages = {1267}, pmid = {42088615}, issn = {2639-5274}, abstract = {Diffuse large B cell lymphoma (DLBCL) presents a critical clinical challenge due to declining chemosensitivity and difficult-to-manage dose-limiting toxicities. Although gut microbiota modulation shows potential for "toxicity reduction and efficacy enhancement", its mechanism in DLBCL remains unclear. Comparative analysis revealed a marked reduction of beneficial bacteria in patients with DLBCL versus healthy volunteers, with a marked decrease in the abundance of core probiotics, particularly Limosilactobacillus reuteri. Fecal microbiota transplantation from healthy donors into DLBCL mouse models reduced tumor burden, improved chemosensitivity, and alleviated intestinal toxicity. A core probiotic strain, L. reuteri HG001, was isolated and shown to replicate these effects alone, with the tryptophan metabolite indole-3-carbaldehyde (ICAld) identified as the key component responsible for its adjunctive antitumor activity. Mechanistic studies demonstrated that ICAld exerts significant adjunctive antitumor effects both in vitro and in vivo in a dose-dependent manner in mouse models; it acts by activating the aryl hydrocarbon receptor (AHR)/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/reactive oxygen species (ROS) axis, inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway, promoting apoptosis, and synergizing with cyclophosphamide. An aryl hydrocarbon receptor antagonist reversed both the chemosensitizing and intestinal protective effects of L. reuteri HG001 and ICAld. This study elucidates a microbiota-mediated mechanism in DLBCL and supports L. reuteri HG001 as a probiotic adjuvant to enhance therapy while reducing toxicity.}, }
@article {pmid42090907, year = {2026}, author = {Su, X and Li, A and Liu, J and Guo, Y and Yu, H and Yu, J and Wang, R and Garza, DR and Qu, J and Wen, B and Liu, B}, title = {From microbes to molecules: Gut microbiota as a prerequisite threshold determinant for cancer immunotherapy efficacy.}, journal = {Microbiological research}, volume = {309}, number = {}, pages = {128539}, doi = {10.1016/j.micres.2026.128539}, pmid = {42090907}, issn = {1618-0623}, mesh = {*Gastrointestinal Microbiome/immunology/physiology ; Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; Animals ; Fatty Acids, Volatile/metabolism ; Treatment Outcome ; }, abstract = {Cancer immunotherapy, represented by immune checkpoint inhibitors, adoptive cell therapy, and cancer vaccines, has revolutionized the clinical management of multiple malignant tumors, yet profound interindividual heterogeneity in treatment response and widespread primary/acquired resistance remain the most critical bottlenecks restricting its long-term clinical benefits. Accumulating preclinical and clinical evidence has unequivocally established the gut microbiota as a pivotal regulator of host anti-tumor immune responses. However, the vast majority of existing studies and reviews frame the gut microbiota as a mere adjuvant enhancer of immunotherapy efficacy, focusing solely on its role in boosting the upper limit of treatment effects, while neglecting its more fundamental role as a prerequisite for establishing a responsive immune baseline. In this review, we propose a unifying, evidence-based original core hypothesis: the gut microbiota is not merely an enhancer of cancer immunotherapy efficacy, but an indispensable prerequisite condition that sets the minimal baseline threshold for therapeutic responsiveness-a central thesis that distinguishes this review from previous descriptive work. Guided by this hypothesis, we systematically dissect the taxonomic and functional characteristics of threshold-determining gut microbiota, and clarify that microbial metabolites (e.g., short-chain fatty acids, bile acids, tryptophan derivatives) act as core molecular mediators translating microbial signals into host immune activation, which is critical for establishing the baseline efficacy threshold required for effective immunotherapy. We further perform a critical synthesis of clinical data from prospective cohorts, randomized controlled trials, and microbiota intervention studies, validating that threshold-based microbial signatures serve as non-invasive predictive biomarkers for immunotherapy outcomes, and propose mechanism-driven translational strategies targeting the gut microbiota (e.g., fecal microbiota transplantation, probiotic supplementation, dietary modulation) to reset the impaired immunotherapy efficacy threshold. This review provides a novel theoretical framework for understanding the microbiota-immunotherapy axis, which not only deepens the mechanistic insight into microbial metabolite-mediated immune regulation, but also facilitates the development of microbiota-guided personalized cancer immunotherapy and the overcoming of primary treatment resistance.}, }
@article {pmid42092466, year = {2026}, author = {Gavini, CK and Raux, L and Labouèbe, G and Gornick, E and Mc Hugh, S and Elshareif, N and Calcutt, NA and Di Summa, PG and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V}, title = {A gut-adipose-nerve axis mediates inulin protection against Western diet-induced somatosensory dysfunction.}, journal = {Brain, behavior, and immunity}, volume = {137}, number = {}, pages = {106795}, doi = {10.1016/j.bbi.2026.106795}, pmid = {42092466}, issn = {1090-2139}, abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation potentially via modifying short chain fatty acid (SCFA) levels, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates (inulin) producing SCFA could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that inulin improved thermal and mechanical sensory function indirectly by improving metabolic health and remodeling immune cells in adipose tissue depots. Interestingly, in separate genetic experiments we found that deletion of the SCFA receptor FFAR2 (GPR43) in myeloid cells altered thermal sensitivity and adipose inflammatory gene expression, indicating that immune SCFA sensing can modulate pain-related behavior. These findings identify mechanisms by which dietary fiber indirectly preserves PNS function through effects on adiposity and systemic inflammation and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.}, }
@article {pmid42092473, year = {2026}, author = {Liu, T and Zhao, Y and Wang, X and Ding, L and Yu, G and Lin, X and Wu, X}, title = {Comparative pharmacodynamic material basis of oral and colonic administration of Baitouweng decoction in experimental ulcerative colitis.}, journal = {Journal of ethnopharmacology}, volume = {368}, number = {}, pages = {121805}, doi = {10.1016/j.jep.2026.121805}, pmid = {42092473}, issn = {1872-7573}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/pathology/metabolism ; Male ; *Drugs, Chinese Herbal/administration &amp; dosage/pharmacology/pharmacokinetics ; Administration, Oral ; *Colon/drug effects/metabolism/pathology ; Rats, Sprague-Dawley ; Disease Models, Animal ; Dextran Sulfate ; Rats ; Fecal Microbiota Transplantation ; Molecular Docking Simulation ; Feces/chemistry ; Biomarkers/blood ; Cytokines ; *Anti-Inflammatory Agents/administration &amp; dosage/pharmacology ; }, abstract = {Baitouweng Decoction (BTWD) is a traditional Chinese medicine formula widely used in clinical practice for treating ulcerative colitis (UC). However, its precise therapeutic mechanisms remain unclear.<br><br>AIM OF THE STUDY: This study investigates the therapeutic effects of BTWD administered via colon and oral routes in a UC model induced by fecal microbiota transplantation (FMT) and dextran sodium sulfate (DSS). It further explores the distinct pharmacological mechanisms associated with each route of administration.<br><br>MATERIALS AND METHODS: Male rats with UC induced by human-derived FMT and DSS were treated with BTWD via oral or colonic administration. Therapeutic outcomes were evaluated through clinical indicators and histopathology. Drug metabolites in serum and colon contents were analyzed by Ultra Performance Liquid Chromatography-Q Exactive-Orbitrap Mass Spectrometer (UPLC-QE-Orbitrap MS). Serum and fecal metabolomics identified disease-related biomarkers. Potential active substances were screened by correlating serum and fecal biomarkers with BTWD-derived components. Key active substances and targets were identified through network pharmacology and molecular docking, clarifying the pharmacological basis of each administration route. Surface plasmon resonance (SPR) and Western blot were performed to experimentally validate the binding interactions and target protein expression.<br><br>RESULTS: Both administration routes of BTWD significantly alleviated UC symptoms. Compared to the model group, BTWD-treated rats exhibited reduced weight loss, lower disease activity index (DAI) scores, and recovered colon length. Serum levels of pro-inflammatory cytokines IL-6, IL-17, and IL-1&#x3b2; were decreased, while anti-inflammatory IL-10 was increased. Expression of Occludin and MUC2 proteins in colon tissue was significantly upregulated. In total, 82 serum and 70 colon components were identified following oral administration, while colonic administration yielded 73 serum and 78 colon components. Correlation analysis screened 36 active components associated with colonic administration and 25 with oral administration. Network pharmacology and molecular docking suggested that core components from colon administration (Anemoside B4, Betulonic acid) may act via targets such as EGFR, LCK, and MET, while oral components (Berberine, Oxyepiberberine) may target AURKA, MET, and PTGS2. SPR confirmed direct binding of anemoside B4 and berberine to EGFR with KD values of 9.47E-04&#xa0;M and 2.96E-04&#xa0;M, respectively. Western blot revealed route-dependent modulation of EGFR, PTGS2, LCK and AURKA expression, corroborating the predicted targeting.<br><br>CONCLUSION: BTWD is effective in treating UC through both colonic and oral administration. This study provides a comprehensive "efficacy-component-metabolism-target" analysis that reveals distinct pharmacological mechanisms underlying each administration route. These findings support the traditional use of BTWD and offer a theoretical foundation for developing optimized, route-specific therapies for UC.}, }
@article {pmid42093245, year = {2026}, author = {Hamdan, A and Al Nabhani, Z}, title = {Reframing obesity through the gut microbiota: functional dysbiosis and metabolic disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {29}, number = {4}, pages = {377-384}, pmid = {42093245}, issn = {1473-6519}, mesh = {Humans ; *Dysbiosis/microbiology ; *Obesity/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Prebiotics/administration &amp; dosage ; *Metabolic Diseases/microbiology/etiology ; Diet/adverse effects ; Fecal Microbiota Transplantation ; Animals ; Insulin Resistance ; Intestinal Barrier Function ; }, abstract = {PURPOSE OF REVIEW: Obesity and its metabolic complications remain major global health challenges. Beyond excess caloric intake, emerging evidence implicates diet-induced gut microbiota dysfunction as a modulator of metabolic homeostasis. This review examines recent advances in understanding how functional alterations of the gut microbiota contribute to obesity pathogenesis.<br><br>RECENT FINDINGS: Current data indicate that obesity is characterized less by specific microbial taxa and more by disruption of key microbial functions. Diet-induced dysbiosis alters short-chain fatty acid production, bile acid metabolism, tryptophan-derived signaling, and intestinal barrier integrity. These changes promote metabolic endotoxemia, impair enteroendocrine hormone secretion, and disrupt gut-brain and gut-liver communication, contributing to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Experimental and clinical studies further suggest that microbiota-targeted interventions, including dietary fiber enrichment, prebiotics, synbiotics, and fecal microbiota transplantation, can partially restore microbial metabolic function and improve selected metabolic outcomes.<br><br>SUMMARY: Obesity is increasingly conceptualized as a state of diet-driven functional gut microbiota disruption. Targeting microbial metabolic pathways rather than individual taxa may offer a promising adjunctive strategy to complement established therapies for obesity-related metabolic disease.}, }
@article {pmid42093801, year = {2026}, author = {Busmail, H and Weerakoon, S and Mandefro, BT and Sundara, SV and Lu, X and Avula, S and Mohammed, L}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review of Efficacy and Safety.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106453}, pmid = {42093801}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal tract associated with immune dysregulation and alterations in the gut microbiota. Growing evidence suggests that intestinal microbial dysbiosis plays an important role in disease pathogenesis, prompting interest in microbiome-targeted therapies, such as fecal microbiota transplantation (FMT). This systematic review aimed to evaluate the efficacy and safety of FMT in adult patients with IBD. A comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2020 and 2025 using keywords related to "fecal microbiota transplantation" and "inflammatory bowel disease." Eligible studies included randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses involving adult patients with UC or CD. Due to clinical and methodological heterogeneity, a structured narrative synthesis was performed in accordance with Synthesis Without Meta-analysis (SWiM) guidelines. Nine studies comprising 1,847 participants met the inclusion criteria, including five RCTs, two systematic reviews, and two meta-analyses. In patients with UC, clinical remission rates ranged from 32% to 40%, with response rates between 44% and 52%. In CD, remission rates ranged from 24% to 31%, although evidence remained limited and heterogeneous. Multi-donor stool preparations and repeated FMT administrations were associated with improved clinical outcomes compared with single-donor protocols or single-dose protocols. Adverse events occurred in approximately 12-15% of patients and were predominantly mild gastrointestinal symptoms, while serious adverse events were rare (<2%). Current evidence suggests that FMT may induce clinical remission in a subset of patients with UC, while evidence in CD remains less consistent. Larger randomized trials with standardized protocols and long-term follow-up are needed to determine optimal donor selection, dosing strategies, and long-term safety.}, }
@article {pmid42094762, year = {2026}, author = {Pan, Z and Zhang, T and Ren, Z and Zhang, H and Wang, J and Ma, Y and Man, R and Peng, J and Yu, Y}, title = {Microbiota-immune crosstalk in the regulation of intestinal motility in constipation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1828926}, pmid = {42094762}, issn = {1664-302X}, abstract = {Constipation is a common functional gastrointestinal disorder with a complex pathogenesis. Traditional studies have primarily explained its development in terms of reduced intestinal motility or impaired defecatory coordination; however, these mechanisms alone cannot fully account for the multifactorial pathological processes underlying the condition. In recent years, increasing attention has been directed toward the roles of intestinal microbial dysbiosis and alterations in immune homeostasis in the development of constipation. The gut microbiota continuously interacts with the intestinal immune system through its structural components, metabolic products, and secreted molecules. These interactions modulate the mucosal immune microenvironment and participate in the regulation of intestinal motility by influencing the enteric nervous system, interstitial cells of Cajal, and smooth muscle function. Conversely, the immune system can reshape the composition and spatial distribution of the gut microbiota through mechanisms such as the mucosal barrier, immunoglobulin A, and antimicrobial peptides, thereby forming a bidirectional regulatory network. Accumulating evidence suggests that during the onset and progression of constipation, microbial dysbiosis, shifts in immune homeostasis, and abnormalities in intestinal motility may evolve through a progressively amplifying dynamic process, ultimately establishing a self-sustaining chronic cycle. In addition, microbiota-targeted interventions-including probiotics, prebiotics, and fecal microbiota transplantation-have demonstrated potential benefits in improving stool frequency and stool consistency in several clinical studies. However, the immunological mechanisms underlying these effects remain relatively underexplored. This review systematically summarizes the molecular mechanisms by which gut microbiota-immune interactions regulate intestinal motility. By integrating current evidence on disease progression and clinical studies, we propose a conceptual model of the "microbiota-immune-motility regulatory axis," aiming to provide a new perspective for understanding the pathogenesis of constipation and for optimizing microbiota-based therapeutic strategies.}, }
@article {pmid42094772, year = {2026}, author = {Luo, H and Shen, Z and Jian, Y and Wang, M and Luo, S and Wang, J and Nan, L and Tang, L and Rehman, MU and Carbonero, F}, title = {Editorial: Unravelling the wildlife gut microbiome: the crucial role of gut microbiomes in wildlife conservation strategies.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1838495}, pmid = {42094772}, issn = {1664-302X}, }
@article {pmid42095982, year = {2026}, author = {Răzniceanu, V and Țichindeleanu, A and Răducu, EV and Trella, &#x218;E and Nenu, I}, title = {Gut dysbiosis and nitric oxide dysregulation in cirrhosis progression: mechanistic insights and pathophysiological implications.}, journal = {Journal of physiology and biochemistry}, volume = {82}, number = {1}, pages = {}, pmid = {42095982}, issn = {1877-8755}, mesh = {Humans ; *Dysbiosis/metabolism/microbiology/immunology ; *Nitric Oxide/metabolism ; *Gastrointestinal Microbiome ; *Liver Cirrhosis/metabolism/microbiology/pathology/physiopathology ; Animals ; Disease Progression ; Liver/metabolism/pathology ; Hypertension, Portal/metabolism/microbiology ; Signal Transduction ; Nitric Oxide Synthase Type III/metabolism ; }, abstract = {Cirrhosis represents the end stage of chronic liver injury, characterized by progressive fibrosis and architectural distortion that precipitate portal hypertension and systemic complications. Recent evidence positions gut microbiota dysbiosis and nitric oxide (NO) dysregulation as central, interacting pathophysiological mechanisms in cirrhosis progression. Intestinal barrier dysfunction facilitates bacterial translocation and thereby exposes the liver to lipopolysaccharides and pathogen-associated molecular patterns that trigger hepatic inflammation via Toll-like receptor signalling, a phenomenon aggravated by dysbiosis. This immune activation stimulates inducible NO synthase in Kupffer cells and systemic endothelium, generating excess NO that drives splanchnic vasodilation and worsens portal hypertension. Paradoxically, intrahepatic endothelial NO synthase activity becomes impaired, reducing sinusoidal NO availability and increasing intrahepatic vascular resistance. These interconnected disturbances perpetuate inflammation and fibrogenesis, contributing to cirrhosis decompensation and spontaneous bacterial peritonitis. Despite substantial mechanistic insight into these pathways, therapeutic translation remains limited. Statins show promise by restoring intrahepatic eNOS function and reducing portal pressure, while microbiota-targeted interventions (antibiotics, probiotics, fecal transplantation) address gut-derived inflammation. This review synthesizes our current understanding of the gut-liver-NO axis in cirrhosis, highlighting how dysbiosis and aberrant NO signalling reinforce each other through inflammatory feedback loops, and identifies critical gaps between mechanistic knowledge and clinical application that warrant further investigation.}, }
@article {pmid42096120, year = {2026}, author = {Wu, R and Yao, G}, title = {Research advancement on the correlation between gut microbiota and chronic kidney disease.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {6}, pages = {}, pmid = {42096120}, issn = {1572-9699}, support = {010086//the Beijing Major Epidemic Prevention and Control Key Specialty Intensive Care Medicine Construction Project under Grant/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Renal Insufficiency, Chronic/microbiology/therapy ; Dysbiosis/microbiology ; Probiotics ; Animals ; }, abstract = {Chronic kidney disease (CKD) represents a significant global health challenge, with its progression and complications associated with dysbiosis of the gut microbiota. Patients with CKD demonstrate stage-dependent alterations in the composition of gut microbiota and a reduction in diversity, which is characterized by a decline in beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and an increase in pathogenic species. This dysbiosis disrupts the gut-kidney axis, resulting in a depletion of protective metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids, while facilitating the accumulation of toxic metabolites including trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and p-cresyl sulfate (pCS). These toxins contribute to the progression of CKD and cardiovascular complications through mechanisms that involve oxidative stress, inflammation (e.g., NF-ĸB/NLRP3 activation), fibrosis (e.g., TGF-β/Smad signaling), and endothelial dysfunction. Therapeutic strategies aimed at modulating the gut microbiota encompass dietary interventions (such as increasing fiber and plant-based protein), microecological agents (including probiotics and prebiotics), fecal microbiota transplantation (FMT), and adsorbents (e.g., targeting uremic toxins). Although these approaches show promise in delaying CKD progression and alleviating complications, they necessitate further validation through large-scale clinical trials to confirm their efficacy, safety, and the development of personalized protocols. Investigating the gut-kidney axis may provide novel biomarkers and therapeutic opportunities for enhancing CKD outcomes.}, }
@article {pmid42097400, year = {2026}, author = {Wang, H and Li, T and Yang, J and Zhang, W and Chen, S and Song, M and Wang, S and Liu, C}, title = {Drinking water temperatures modulate gut microbiota-L-cysteine axis to enhance adipose thermogenesis and alleviate obesity-related metabolic disorders in mice.}, journal = {Life sciences}, volume = {397}, number = {}, pages = {124438}, doi = {10.1016/j.lfs.2026.124438}, pmid = {42097400}, issn = {1879-0631}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Thermogenesis/physiology ; Mice ; Male ; *Obesity/metabolism ; *Drinking Water ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Adipose Tissue/metabolism ; *Metabolic Diseases/metabolism/etiology ; *Cysteine/metabolism ; Temperature ; Energy Metabolism ; }, abstract = {AIMS: Although people living in different countries prefer to drink water at various temperatures, the influence of drinking water temperature on metabolic homeostasis remains largely unexplored. This study investigated how different drinking-water temperatures affect metabolic regulation and the underlying gut microbiota-metabolite interactions.<br><br>MATERIALS AND METHODS: High-fat diet (HFD)-fed mice were given water at 0&#xa0;&#xb0;C, 25&#xa0;&#xb0;C, or 40&#xa0;&#xb0;C. Metabolic alterations were assessed by histopathology, serum biochemistry, and body-composition analysis, with food intake and core temperature monitored. Gut microbiota causality was examined using antibiotic depletion and reciprocal fecal microbiota transplantation (FMT). 16S rRNA gene sequencing and metabolomics were performed to characterize fecal microbial and metabolite profiles. Adipose stromal vascular fraction (SVF) cells were used in vitro to examine the effects of L-cysteine on lipid metabolism.<br><br>KEY FINDINGS: Both 0&#xa0;&#xb0;C and 40&#xa0;&#xb0;C water ameliorated HFD-induced metabolic dysfunction through increased energy expenditure, reduced liver steatosis, and enhanced adipose-tissue thermogenesis, independent of differences in intake. Cold water selectively enriched Bifidobacterium pseudolongum and Adlercreutzia equolifaciens, whereas warm water increased Bacteroides acidifaciens, Alistipes inops and Alistipes obesi, indicating distinct microbiota configurations. Antibiotic ablation blunted these benefits, while cross-group FMT reproduced the metabolic and thermogenic phenotypes, confirming a microbiota-dependent mechanism. Despite divergent microbiota structures, both temperature regimens consistently elevated L-cysteine, which reduced lipid accumulation and enhanced thermogenic gene expression in SVF cells.<br><br>SIGNIFICANCE: These findings highlight drinking-water temperature as a simple, safe, and sustainable lifestyle factor with translational potential to mitigate obesity-related metabolic dysfunction, potentially via a gut microbiota-L-cysteine axis that enhances adipose thermogenesis and systemic metabolic homeostasis.}, }
@article {pmid42097699, year = {2026}, author = {Xu, T and Lu, R and Oakland, DN and Estaleen, R and Rawlings, A and Montano, H and Diab, S and Michaelis, JS and Pop, M and Bankole, A and Reilly, CM and Luo, XM}, title = {Double humanised lupus mouse model with human immune system and faecal microbiota from patients with SLE.}, journal = {Lupus science &amp; medicine}, volume = {13}, number = {1}, pages = {}, pmid = {42097699}, issn = {2053-8790}, mesh = {Animals ; *Lupus Erythematosus, Systemic/immunology/microbiology/therapy ; Humans ; Disease Models, Animal ; Mice ; *Fecal Microbiota Transplantation ; Female ; Feces/microbiology ; Immunoglobulin G/blood ; Gastrointestinal Microbiome ; Immunoglobulin M/blood ; Hematopoietic Stem Cell Transplantation ; T-Lymphocytes/immunology ; Terpenes ; Spleen/immunology ; Male ; }, abstract = {OBJECTIVE: We aimed to create a double humanised lupus mouse model with a human immune system and faecal microbiota from patients with SLE.<br><br>METHODS: We established the Double humanised SLE (DhuSLE) mouse by engrafting NSG immunodeficient mice with human CD34[+] haematopoietic stem and progenitor cells (NSG-hu mice) and performing faecal microbiota transplantation from patients with SLE (SLE-FMT).<br><br>RESULTS: While FMT in general transiently suppressed the development of human T cells in NSG-hu mice, SLE-FMT but not FMT from non-SLE donors promoted superficial skin lesions. Importantly, the combination of SLE-FMT and pristane in NSG-hu, now called the DhuSLE-P mouse, induced proteinuria although this clinical sign observed in mice did not reflect that of the microbiota donors. DhuSLE-P mice exhibited a higher level of human IgM in the circulation than NSG-hu mice, which was positively correlated with the frequency of plasma cells in the spleen. In the splenic sections of DhuSLE-P mice, nuclear BCL6 was minimally detected but CD138 expression was evident, suggesting that most plasma cells generated were not class switched and produced IgM. Some human IgG was detected in the kidney of DhuSLE-P mice with a trend towards increased total IgG in the serum. Analysis of the faecal microbiota revealed that the gut microbiota compositions were different between DhuSLE-P mice and NSG-hu mice due to SLE-FMT but not the injection of pristane.<br><br>CONCLUSION: Together, these results introduced the first humanised lupus mouse model combining the human immune system and gut microbiota from patients with SLE. However, limitations exist and the model may benefit from methods that promote antibody class switching. On further development, the DhuSLE model can be useful for elucidating mechanisms and/or evaluating SLE treatments.}, }
@article {pmid42097977, year = {2026}, author = {Krifors, A and Larsson, T and Wångdahl, A and Stensvold, CR}, title = {Time to rethink Blastocystis in faecal microbiota transplantation.}, journal = {Trends in parasitology}, volume = {42}, number = {6}, pages = {439-441}, doi = {10.1016/j.pt.2026.04.005}, pmid = {42097977}, issn = {1471-5007}, mesh = {Humans ; *Blastocystis/physiology ; *Blastocystis Infections/parasitology ; *Fecal Microbiota Transplantation/standards ; Feces/parasitology ; *Gastrointestinal Microbiome ; }, abstract = {Blastocystis commonly colonises the human gut, but its presence has traditionally led to the exclusion of faecal microbiota transplantation donors. Emerging evidence links it to greater microbial diversity and favourable metabolic profiles, while no harm is seen in immunocompetent recipients. Routine screening may be unnecessary, except for subtype-specific testing in immunocompromised patients.}, }
@article {pmid42098025, year = {2026}, author = {Fukushima, H and Ishikawa, D and Nagahara, A}, title = {[Gut Microbiota Transplantation for Esophageal and Gastric Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {53}, number = {3}, pages = {175-181}, pmid = {42098025}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Stomach Neoplasms/therapy/microbiology/immunology ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Fecal Microbiota Transplantation ; }, abstract = {Immune checkpoint inhibitors(ICIs)have remarkably improved survival with durable response for patients with multiple cancer type. But, the accurate predictors of response and toxicity to immunotherapy are still unclear. In recent years, the human microbiota, specially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The gut microbiome, which refers to the microorganisms and their genes, affects the host immunity both locally and systemically. Modulation of the gut microbiota alters the immune systems and affects the efficacy of ICI. Many clinical trials targeting the gut microbiota, such as fecal microbiota transplantation(FMT)and biotics intervention, are currently being conducted. In this review, we consider the evidence on the role of the microbiome in cancer patients and research began the impact of FMT on the efficacy of ICIs in cancer. ln the future, research on carcinogenesis mechanisms and advance cancer treatment focusing on the human microbiota will become in creakingly active.}, }
@article {pmid42098851, year = {2026}, author = {Dong, J and Cao, Y and Chen, X and Xie, T and Zhang, X and Zhao, Q and Shi, C and Miao, Q and Xu, Z and Yan, L and Dong, L}, title = {Buyang Huanwu Decoction promotes neurorepair after spinal cord injury through a Lactobacillus johnsonii-indole-3-lactic acid-AhR-PI3K/Akt axis.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {}, pmid = {42098851}, issn = {1749-8546}, support = {YSJ2025009//Postgraduate Research &amp; Practice Innovation Program of Yan'an University/ ; 22XYJ0002//Xi'an Innovation Capability Strong Foundation Plan - Medical Research Project/ ; 2025PT-01//Platform Construction Project of Shaanxi Province's Health and Wellness Scientific Research and Innovation Capacity Enhancement Program/ ; }, abstract = {BACKGROUND: Spinal cord injury (SCI) induces gut microbiota dysbiosis, which significantly affects recovery. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine formula, has shown therapeutic effects on SCI. Although BHD is known to modulate gut microbiota, whether its benefits are mediated through the gut-spinal cord axis remains unclear.<br><br>METHODS: A rat SCI model was established. BHD was administered orally, and fecal microbiota transplantation (FMT) from BHD-treated rats (BHD-FMT) was performed to assess neuroprotective and gut-protective effects. Behavioral testing, histology, and immunofluorescence evaluated motor recovery, inflammation, and neuroregeneration. Gut microbiota profiling was performed using 16S rDNA sequencing and metagenomics, while targeted metabolomics quantified tryptophan metabolites. Transcriptomics validated key pathways, and a microbiota-metabolite-signaling network was constructed.<br><br>RESULTS: BHD significantly improved motor function, reduced spinal inflammation, and promoted neuronal survival and axonal regeneration. It restored gut function, reduced colonic inflammation, and enhanced ZO-1 and Occludin expression, which were further confirmed by FMT. BHD-FMT reshaped the gut microbiota and enriched Lactobacillus johnsonii, which correlated positively with recovery. Metabolomics showed increased tryptophan metabolites, including indole-3-lactic acid (ILA) and indole-3-propionic acid (IPA), with ILA strongly associated with functional improvement. Transcriptomic analysis and Western blot validation demonstrated that BHD-FMT activated the AhR-PI3K/Akt pathway, which was suppressed by an AhR antagonist.<br><br>CONCLUSION: BHD promotes neuroregeneration after SCI by reshaping gut microbiota and enhancing tryptophan metabolism, potentially exerting its effects through the L. johnsonii-ILA-AhR-PI3K/Akt network. These findings reveal a gut-spinal cord axis-mediated mechanism of BHD and highlight microecological targets for SCI therapy.}, }
@article {pmid42099129, year = {2026}, author = {Occhiali, E and Renard, D and Molkhou, C and Kerdelhué, G and Clavier, T and Baulier, C and Achamrah, N}, title = {Systematic Review with Qualitative Synthesis of Gut Microbiota Alterations after Acute Brain Injury.}, journal = {Journal of neurotrauma}, volume = {}, number = {}, pages = {8977151261449708}, doi = {10.1177/08977151261449708}, pmid = {42099129}, issn = {1557-9042}, abstract = {Acute brain injury (ABI), traumatic or nontraumatic, profoundly disrupts the gut microbiota (GM). To provide intensive care physicians with a clearer understanding of this phenomenon, we conducted a systematic review with qualitative synthesis. Due to significant heterogeneity in study designs, populations, and outcomes, a meta-analysis was not feasible. Instead, findings were synthesized thematically, focusing on study types, microbiota metrics, and clinical associations. Across studies, ABI is consistently associated with reduced microbial diversity, a decline in the relative abundance of several species, and increased interindividual variability in GM composition. Notably, phyla, such as Pseudomonadota, Bacteroidota, and Verrucomicrobiota, are frequently enriched, whereas Bacillota tends to be depleted. These patterns of dysbiosis appear largely consistent regardless of ABI etiologies. Furthermore, GM alterations can occur within a few hours postinjury and often return to baseline levels within months. The review highlights the metabolic, immune, and neuronal disruptions induced by ABI, which may contribute to gastrointestinal dysfunction and negatively influence patient prognosis. Moreover, standard intensive care unit (ICU) therapies may exacerbate GM disturbances. Importantly, dysbiosis has been linked to adverse clinical outcomes (delayed recovery, increased mortality). Emerging therapeutic strategies (metabolite supplementation, fecal microbiota transplantation) have shown potential to modulate the GM and support postinjury recovery. However, the underlying mechanisms of ABI-related dysbiosis and its consequences remain incompletely understood. Future research should aim to clarify the pathophysiological drivers of GM disruption, explore the potential prognostic value of GM dynamics, and assess how ICU therapies influence GM evolution. Developing GM-targeted interventions may offer novel opportunities to modulate ABI-related complications and improve patient outcomes.}, }
@article {pmid42099164, year = {2026}, author = {Nayak, RK and Mohapatra, SR and Sahoo, SK and Sahu, SK and Chowdhury, B and Banu, Z and Das, NR}, title = {Gut Microbiota Dysbiosis in Alzheimer's Disease and Possible Therapeutic Options.}, journal = {Current Alzheimer research}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672050448298260303052535}, pmid = {42099164}, issn = {1875-5828}, abstract = {Human microbiota consists of trillions of microbial cells dominated by bacteria, which live in the human body, while the term microbiome refers to the collective genetic material of microorganisms. Among them, the gut microbiota has emerged as pivotal, producing its own metabolites, neurotransmitter precursors, and immune mediators that affect brain development and function. These signals function via the complex, bidirectional Gut-Brain Axis (GBA). This is a communication network that connects the gastrointestinal tract to the central nervous system. This axis plays an important role in the regulation of gastrointestinal homeostasis, neurodevelopment, emotional regulation, and cognitive processes. Increasing evidence suggests that microbial dysbiosis within the gastrointestinal tract is involved in the pathogenesis and progression of several neurological and neurodegenerative disorders, including mood disorders, schizophrenia, autism spectrum disorder, Alzheimer's Disease (AD), Parkinson's Disease (PD), and Huntington's Disease. These insights have opened new therapeutic possibilities, and multiple microbiota-targeted interventions, such as dietary modification, prebiotics, probiotics, postbiotics, psychobiotics, antibiotics, and Fecal Microbiota Transplantation (FMT), are now being explored for their therapeutic value, especially in Alzheimer's disease.}, }
@article {pmid42099577, year = {2026}, author = {Penton, CR and Vadakattu, G}, title = {The root rhizosphere as a functional analog to the gut microbiome: Cases for microbial symbiosis and dysbiosis in parallel contexts.}, journal = {PNAS nexus}, volume = {5}, number = {5}, pages = {pgag132}, pmid = {42099577}, issn = {2752-6542}, abstract = {Microbiomes associated with both the human gut and plant root rhizosphere are essential for the maintenance of host health and function as holobionts where both the host and microbiome operate as an integrated unit. Though substantial differences exist in both host biology and environment, these systems share functional parallels: both are enriched by host-derived nutrients, undergo successional shifts during development, and maintain core microbiomes that are taxonomically variable yet functionally redundant. Central to both systems is the balance that is maintained where beneficial microbes regulate nutrient cycling, modulate host immune response, and suppress pathogens in the presence of biotic and abiotic influences that may serve to disrupt this equilibrium. When dysbiosis occurs, there is a disruption in the composition and/or function of the associated microbiome and a loss of beneficial functional guilds, which results in a reduction in host fitness. These shared dynamics underscore dysbiosis as a cross-kingdom pathology that may be treated with similar interventions. Probiotics and prebiotics mirror microbial inoculants and organic amendments; synbiotics incorporate both biotic and abiotic factors, while fecal and soil microbiome transplants represent parallel strategies to restore a beneficial microbiome. By framing dysbiosis within a "One Health" perspective and illustrating the connectedness between human and plant health, this review advocates for microbial stewardship as a unifying strategy to mitigate disease, enhance resilience, and ensure sustainable health across both systems.}, }
@article {pmid42099620, year = {2026}, author = {Mo, M and Chen, L and Wang, Y and Lin, X and Li, H and Chen, B and Yuan, J and Tao, E}, title = {The gut-lung axis in childhood asthma: from early-life programming to microbiome-informed precision medicine-a narrative review.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1814901}, pmid = {42099620}, issn = {1664-3224}, mesh = {Humans ; *Asthma/microbiology/immunology/etiology/therapy ; *Gastrointestinal Microbiome/immunology ; Precision Medicine ; *Lung/immunology/microbiology ; Child ; Dysbiosis ; }, abstract = {The gut-lung axis links early-life microbial programming to long-term respiratory health, offering a pivotal framework for understanding childhood asthma pathogenesis. This review synthesizes current evidence on how disruptions in microbial-immune crosstalk during critical developmental windows shape asthma susceptibility. Perinatal determinants-including maternal diet, delivery mode, antibiotic exposure, and breastfeeding-establish gut microbial communities that educate the developing immune system. Distinguishing itself from recent reviews, this review offers three novel contributions: (i) an integrated multi-omics framework linking early-life microbial maturation trajectories to specific asthma endotypes; (ii) a systematic synthesis of the molecular mechanisms by which microbial metabolites-including short-chain fatty acids, tryptophan derivatives, and bile acids-orchestrate gut-lung immune crosstalk; and (iii) a clinically actionable precision medicine algorithm that translates multi-omics profiling into personalized risk prediction, endotype-driven therapy selection, and targeted preventive strategies. Dysbiosis, characterized by delayed microbial maturation and depletion of short-chain fatty acid-producing taxa, compromises epithelial barrier integrity and skews immune homeostasis toward pro-allergic type-2 responses. Microbial metabolites, particularly short-chain fatty acids (acetate, propionate, butyrate) and tryptophan derivatives (indole-3-lactic acid, indole-3-propionic acid), serve as key molecular mediators that regulate regulatory T cells differentiation, reinforce mucosal barriers, and modulate distal airway inflammation. Microbial signatures correlate with specific asthma endotypes, offering opportunities for patient stratification. We critically evaluate emerging microbiome-targeted interventions-including strain-specific probiotics, prebiotics, postbiotics, and fecal microbiota transplantation-highlighting both therapeutic promise and the need for rigorous, well-powered clinical trials. Integrating multi-omics microbial profiling with host genetics and clinical phenotyping holds potential for microbiome-informed precision medicine, enabling personalized risk prediction, endotype-driven therapy selection, and novel preventive strategies targeting the gut-lung axis from the earliest stages of life.}, }
@article {pmid42100690, year = {2026}, author = {Gao, Q and Xiong, M and Zhou, S and Lu, J and Ren, B and Peng, Q and Zeng, M and Song, H}, title = {Gut microbiota and uveitis: exploring novel mechanisms of inflammatory ocular diseases via the gut-eye axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1749111}, pmid = {42100690}, issn = {1664-302X}, abstract = {Uveitis is an inflammatory ocular condition that primarily affects young adults and is often associated with systemic and autoimmune disorders. This disease primarily affects intraocular structures such as the iris, ciliary body, and choroid. Clinically, it manifests through a series of symptoms, including eye redness, pain, and blurred vision, which significantly impact the quality of life for patients worldwide. Recently, the role of gut microbiota (GM) in the immune regulation and pathogenesis of inflammatory diseases has garnered significant scientific interest. This study aimed to investigate the potential association between GM and uveitis, with the objective of demonstrating novel mechanisms underlying inflammatory ocular diseases through the emerging concept of the "gut-eye axis." Current research suggests that gut dysbiosis may influence the immune status of distal organs via various pathways, including molecular mimicry, modulation by microbial metabolites, disruption of intestinal immune homeostasis, and compromise of the intestinal mucosal barrier. Building on these mechanisms, we further explored innovative therapeutic strategies targeting GM and its metabolites, including probiotics, prebiotics, antibiotics, immunomodulators, phage therapy, fecal microbiota transplantation, and dietary interventions. This review systematically examined the association between GM dysbiosis and uveitis pathogenesis, offering new insights and directions for future research in this emerging field and establishing a theoretical foundation for developing targeted therapies based on the modulation of the microbiome.}, }
@article {pmid42100955, year = {2026}, author = {Alsheikh, ZSA and Qingsong, T and Qinjie, L and Youkun, C}, title = {Re-arming checkpoint blockade in MSS colorectal cancer: A precision-microbiome playbook from mechanisms to clinic.}, journal = {Turkish journal of surgery}, volume = {42}, number = {2}, pages = {267-278}, pmid = {42100955}, issn = {2564-6850}, abstract = {Immune checkpoint blockade transforms outcomes for the 15% of colorectal cancers (CRCs) with mismatch-repair deficiency; yet most tumours remain refractory. Beneficial gut microbes can change this. Akkermansia muciniphila, Bacteroides fragilis, and short-chain fatty acid producers prime dendritic cells to produce interleukin (IL)-12, polarise Th1 cells, and reinvigorate CD8[+] T-cells. Antibiotics, Western-style diets, and Fusobacterium nucleatum foster myeloid suppression and β-catenin- or IL-17-mediated signalling, which blunt checkpoint activity. Multi-omics analyses link biosynthetic genes for inosine, riboflavin, and folate to durable clinical benefit. Faecal microbiota transplantation from responders has produced objective regressions in otherwise refractory microsatellite-stable disease. This narrative review maps CRC-microbiota-immune crosstalk, evaluates biomarkers and interventions, and proposes a CRC-specific, three-tiered clinical algorithm. We outline standards for trial design and manufacturing processes to facilitate the translation of microbiota-guided therapy into routine practice.}, }
@article {pmid42101655, year = {2026}, author = {Miwa, T and Hsu, CL and Shimizu, M and Bloom, PP and Schnabl, B}, title = {Covert hepatic encephalopathy as a multi-organ syndrome: the gut-liver-muscle-brain axis, diagnosis, treatment, and multidisciplinary care.}, journal = {Journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {42101655}, issn = {1435-5922}, support = {R00 AA031328/AA/NIAAA NIH HHS/United States ; JP24K18908//Japan Society for the Promotion of Science/ ; }, abstract = {Covert hepatic encephalopathy (CHE) is a highly prevalent complication of liver cirrhosis. Despite the absence of overt symptoms, CHE is strongly associated with impaired quality-of-life, overt hepatic encephalopathy, and mortality. Over the past two decades, evidence regarding the pathophysiology, diagnosis, and treatment of CHE has accumulated considerably, and clinical guidelines recommend screening in patients with cirrhosis. Nevertheless, diagnostic and therapeutic algorithms have not been fully implemented in real-world practice, and many patients remain undiagnosed and untreated. Understanding the natural history of CHE is essential to improve cirrhosis care, as it provides a framework for appropriate screening, treatment decision-making, and patient counseling. CHE is a multi-organ syndrome with complex interactions between the liver, gut, skeletal muscle, kidneys, and brain, with impaired ammonia handling and systemic inflammation acting as central drivers of this organ crosstalk. Hyperammonemia induces astrocytic dysfunction, brain edema, and neuroinflammation, while systemic inflammation, oxidative stress, sarcopenia, gut dysbiosis, and altered microbial metabolites, including bile acids and short-chain fatty acids, further modulate disease expression. In this review, we summarize current understanding of CHE pathophysiology, diagnostic testing, including psychometric batteries and point-of-care tools, such as the Stroop test and animal naming test, and therapeutic options, ranging from lactulose and rifaximin to microbiome-targeted approaches, including fecal microbiota transplantation. We also highlight major challenges in CHE management, including limited implementation of testing, inadequate biomarkers, diagnostic difficulties in geriatric cirrhosis, and unmet needs in fall and driving risk management, and emphasize the importance of multidisciplinary team-based approaches to improve patient outcomes.}, }
@article {pmid42101707, year = {2026}, author = {He, LJ and Zhang, SC and Cai, YC}, title = {The role of gut microbiota in thyroid cancer: from pathogenesis to diagnosis and treatment.}, journal = {Journal of endocrinological investigation}, volume = {}, number = {}, pages = {}, pmid = {42101707}, issn = {1720-8386}, support = {2024ZD0525600//National Major Science and Technology Projects of China/ ; }, abstract = {In recent years, the key role of the gut microbiota (GM) in the diagnosis, prognosis, and treatment of thyroid cancer (TC) has become increasingly clear. This review examines the complex interactions between gut dysbiosis and the occurrence and development of TC; focuses on changes in specific microbiotas that are directly related to tumor stage, lymph node metastasis, and drug resistance; and evaluates the potential of these microbiotas as novel biomarkers for treating TC. To elucidate the underlying molecular mechanisms, this review systematically evaluates the pathways through which the GM regulates the host immune response through metabolites (such as short-chain fatty acids and lipopolysaccharides) and reveals the core role of chronic inflammation in the formation of the microenvironment and the immune escape of TC. Furthermore, by exploring the effects of the microbiota on the hypothalamic-pituitary-thyroid axis and the peripheral thyroid hormone conversion, this review elucidates the profound role of the GM in the regulation of thyroid homeostasis. Based on this evidence, this review highlights the clinical applications of intervention strategies targeting the microbiota, including probiotics, dietary adjustments, and fecal microbiota transplantation, as adjuvant approaches for TC management.}, }
@article {pmid42101756, year = {2026}, author = {Cai, S and Sun, C and Wu, Q and Yao, X}, title = {Saikosaponin D Attenuates Postherpetic Neuralgia and Reduces Inflammation by Regulating Gut Microbiota in a Rodent Model.}, journal = {Biochemical genetics}, volume = {}, number = {}, pages = {}, pmid = {42101756}, issn = {1573-4927}, support = {WZ24A20//Explore the improvement effect and immune mechanism of stellate ganglion block combined with Xiaochaihu decoction on post-herpetic neuralgia of the head and face based on the "intestinal flora-intestine-brain axis"/ ; WZ24A20//Explore the improvement effect and immune mechanism of stellate ganglion block combined with Xiaochaihu decoction on post-herpetic neuralgia of the head and face based on the "intestinal flora-intestine-brain axis"/ ; }, abstract = {Saikosaponin D (SSD) is a triterpenoid saponin derived from Bupleuri Radix and has therapeutic potential for the treatment of neuropathic pain. This study investigates the roles and underlying mechanisms of SSD in cellular and mouse models of resiniferatoxin (RTX)-induced postherpetic neuralgia (PHN). C57BL/6 mice were randomly assigned into four groups: control, RTX, RTX + vehicle, and RTX + SSD. Mechanical and thermal sensitivity were assessed to evaluate pain behaviors. Gut microbiota was depleted using antibiotic treatment, and fecal microbiota transplantation was used to restore gut flora in RTX-treated mice that received either vehicle or SSD. In vitro, RTX-stimulated human neuroblastoma SH-SY5Y cells were used as a cellular model of PHN. TRPA1 expression levels in mouse dorsal root ganglion and SH-SY5Y cells were measured by RT-qPCR and immunofluorescence staining. The levels of proinflammatory cytokines were evaluated in serum samples and SH-SY5Y cells via RT-qPCR or ELISA. Western blot was performed to assess protein levels of genes involved in TLR4/NF-κB and JAK/STAT3 pathways. Results showed that SSD attenuated RTX-induced neuralgia in mice. In both in vitro and in vivo models, SSD significantly reduced TRPA1 expression and proinflammatory cytokine levels. The protective effects of SSD against neuralgia were abolished following antibiotic-mediated gut microbiota depletion in mice. Fecal microbiota transplantation from SSD-treated mice alleviated RTX-induced neuralgia and inflammation in PHN model mice. Moreover, SSD reduced TLR4 protein level and reduced phosphorylation ratios of NF-κB p65, STAT3, and JAK in the lumbar spinal cord of RTX-treated mice and in SH-SY5Y cells. In conclusion, SSD alleviates RTX-induced PHN and inflammation in mice by modulating gut microbiota via the TLR4/NF-κB and JAK/STAT3 pathways.}, }
@article {pmid42102609, year = {2026}, author = {Zeng, M and Feng, A and Zhang, B and Li, S and Guo, P and Zhu, D and Zhang, Y and Zhang, Z and Tie, Q and Wu, Y and Feng, W and Zheng, X}, title = {A novel triterpenoid from Alisma orientale alleviates allergic asthma through the gut microbiota-acetate-FFAR2 immunoregulatory axis.}, journal = {International immunopharmacology}, volume = {182}, number = {}, pages = {116809}, doi = {10.1016/j.intimp.2026.116809}, pmid = {42102609}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/immunology ; *Asthma/drug therapy/immunology/chemically induced ; *Triterpenes/pharmacology/therapeutic use ; Mice ; *Alisma/immunology ; Humans ; Acetates/metabolism ; *Anti-Asthmatic Agents/pharmacology/therapeutic use ; Ovalbumin/immunology ; Mice, Inbred BALB C ; Lung/drug effects/immunology/pathology ; *Receptors, G-Protein-Coupled/genetics/metabolism ; Dendritic Cells/immunology/drug effects ; Disease Models, Animal ; Male ; Female ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Allergic asthma is characterized by immune dysregulation and airway inflammation, and increasing evidence implicates gut microbiota-derived metabolites in its pathogenesis. However, the microbial and metabolic mediators underlying the anti-asthmatic effects of natural products remain insufficiently defined. This study investigated the protective effects of a novel triterpenoid (Tri) isolated from Alisma orientale against ovalbumin-induced allergic asthma and explored the underlying mechanisms.<br><br>METHODS: The therapeutic effects of Tri were evaluated in ovalbumin-induced allergic asthma mice by assessing airway hyperresponsiveness, histopathological changes, and inflammatory mediators. Gut microbiota depletion, fecal microbiota transplantation, 16S rDNA sequencing, targeted short-chain fatty acid analysis, and lung transcriptomic profiling were performed to characterize microbiota-associated changes related to Tri treatment. In addition, Lactobacillus murinus and acetate intervention experiments were conducted in vivo. A co-culture system of 16HBE cells and bone marrow-derived dendritic cells (BMDCs), together with free fatty acid receptor 2 (FFAR2) silencing or overexpression, was used to further assess the involvement of FFAR2 in the immunoregulatory actions associated with Tri.<br><br>RESULTS: Tri markedly attenuated airway hyperresponsiveness, inflammatory cell infiltration, collagen deposition, and the production of asthma-related inflammatory mediators in asthmatic mice. These protective effects were attenuated after gut microbiota depletion and were partially transferred by fecal microbiota transplantation. Tri restored gut microbial homeostasis, increased the abundance of Lactobacillus murinus, and elevated short-chain fatty acids, particularly acetate. Supplementation with Lactobacillus murinus or acetate reproduced the anti-asthmatic effects of Tri and was associated with upregulation of FFAR2 and restoration of the Th17/Treg balance. In the co-culture system, FFAR2 silencing or overexpression further supported the involvement of FFAR2 in the immunoregulatory effects of Tri and acetate.<br><br>CONCLUSION: Tri alleviates OVA-induced allergic asthma and is associated with microbiota-derived acetate, enhanced FFAR2-related signaling, and restoration of Th17/Treg balance. These findings suggest that microbiota-derived acetate and FFAR2-related immune regulation may contribute to the anti-asthmatic effects of Tri, although further loss-of-function studies are required to establish direct causality.}, }
@article {pmid42102900, year = {2026}, author = {Hamerlinck, H and Boelens, J and De Looze, D and Messiaen, AS and Vandendriessche, S and Holvoet, T and Verhasselt, B}, title = {Seven years of stool banking: Clinical and microbiological insights from the Ghent Stool Bank.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {169}, number = {}, pages = {108744}, doi = {10.1016/j.ijid.2026.108744}, pmid = {42102900}, issn = {1878-3511}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Retrospective Studies ; Female ; *Clostridium Infections/therapy/microbiology ; Male ; Middle Aged ; Treatment Outcome ; Clostridioides difficile ; *Biological Specimen Banks ; Aged ; Adult ; Tissue Donors ; }, abstract = {OBJECTIVES: The Ghent Stool Bank (GSB) was founded in 2018 at Ghent University Hospital to provide safe, ready-to-use fecal suspensions for fecal microbiota transplantation (FMT), primarily targeting recurrent Clostridioides difficile infection (rCDI) and supporting clinical trials.<br><br>METHODS: This retrospective cohort study explores the relationship between donor characteristics and rCDI treatment outcomes following FMT.<br><br>RESULTS: Between 2018 and 2024, 12.0% of screened candidates qualified as donors after rigorous evaluation, resulting in 159 approved donations. Forty-four FMT procedures were carried out in forty rCDI patients, achieving a primary cure rate of 77.1%, which increased to 85.7% following a second treatment. Donor microbiome diversity did not show association with treatment outcomes, and no statistically significant differences in taxa abundance were observed. Notably, fecal suspensions stored for up to five years were as effective as those stored for shorter periods. Additionally higher donor age did not appear to negatively impact treatment success in rCDI patients.<br><br>CONCLUSION: These findings support the role of stool banks like the GSB in ensuring safe FMT procedures. Allowing higher donor age and longer storage periods may help sustain sufficient high&#x2011;quality donor availability. Future efforts should focus on improving safety, enhancing donor-recipient compatibility through microbiome profiling and increasing public awareness.}, }
@article {pmid42103164, year = {2026}, author = {Cheng, C and Zheng, L and Bao, X and Wei, L and Jiang, H and Jiang, T}, title = {An integrated study of gut microbiota and serum metabolites in T2DM-ED rats after fecal microbiota transplantation.}, journal = {Free radical biology &amp; medicine}, volume = {252}, number = {}, pages = {227-248}, doi = {10.1016/j.freeradbiomed.2026.05.012}, pmid = {42103164}, issn = {1873-4596}, mesh = {Animals ; Male ; *Fecal Microbiota Transplantation ; Rats ; *Diabetes Mellitus, Type 2/complications/microbiology/therapy/pathology ; *Gastrointestinal Microbiome ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Erectile Dysfunction/therapy/microbiology/etiology/pathology/metabolism ; *Dysbiosis/microbiology/therapy ; NF-kappa B/metabolism/genetics ; *Arachidonic Acid/metabolism/blood ; Apoptosis ; Signal Transduction ; Myeloid Differentiation Factor 88/metabolism/genetics ; Penis/pathology/metabolism ; Toll-Like Receptor 4/genetics/metabolism ; *Diabetes Mellitus, Experimental/complications ; Rats, Sprague-Dawley ; }, abstract = {Erectile dysfunction (ED) is a highly prevalent and refractory complication of type 2 diabetes mellitus (T2DM), with penile cavernosal dysfunction, inflammation, apoptosis, and fibrosis as core pathological features. Here we identify gut microbiota dysbiosis and its downstream metabolite arachidonic acid (AA) as critical mediators of T2DM-associated erectile dysfunction (T2DM-ED) through a systemic gut-penis axis. Gut dysbiosis is sufficient to induce an ED phenotype, as demonstrated by fecal microbiota transplantation (FMT) from T2DM-ED rats into pseudo-germ-free recipients, which successfully transferred the erectile impairment with significantly decreased ICP/MAP ratios. Recipient rats showed impaired colonic barrier integrity, mucosal damage, goblet cell depletion, and downregulated tight junction proteins (Occludin, Claudin-4). Multi-omics integration of 16S rRNA sequencing and serum metabolomics identified AA as a key elevated metabolite that drives inflammatory signaling via the HIF-1α and NF-κB pathways. In penile corpus cavernosum tissue, ED-FMT rats displayed smooth muscle loss, fibrosis, increased apoptosis, and hyperactivation of the TLR4-MyD88-NF-κB-HIF-1α axis. In primary corpus cavernosum smooth muscle cells (CCSMCs), AA stimulation recapitulated pathological activation, including a pro-apoptotic shift in the Bax/Bcl-2 ratio, elevated Cleaved Caspase-3, reduced α-SMA, increased COX-2, stabilized HIF-1α, and excessive PGE2 production; these effects were abolished by pharmacological inhibition of NF-κB. Mechanistically, gut dysbiosis-induced systemic AA accumulation triggers inflammatory damage, apoptosis, and functional impairment in penile smooth muscle via the TLR4-MyD88-NF-κB/HIF-1α cascade. These findings define a gut-AA-NF-κB-penis axis that drives T2DM-ED pathogenesis, highlighting AA and its downstream signaling as promising therapeutic targets for diabetic erectile dysfunction.}, }
@article {pmid42103932, year = {2026}, author = {Wang, F and Zeng, W and Zhang, Z and Li, N and Cui, Z and Bai, J and Yan, J and Zhang, Y and Miao, Y and Gu, L and Xiong, B}, title = {Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age.}, journal = {EMBO molecular medicine}, volume = {18}, number = {6}, pages = {2404-2435}, pmid = {42103932}, issn = {1757-4684}, support = {2023YFD1300502//MOST | National Key Research and Development Program of China (NKPs)/ ; BYSYSZKF2023029//State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital/ ; KYCX25_1007//Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; }, mesh = {Animals ; *Oocytes/physiology/drug effects/metabolism/cytology ; Female ; *Glutamic Acid/metabolism ; *Gastrointestinal Microbiome ; Mice ; Fecal Microbiota Transplantation ; Aging ; Metabolome ; Fertility ; }, abstract = {The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.}, }
@article {pmid42104017, year = {2026}, author = {Sun, Q and Gao, Y and Zheng, J and Liao, R and Jiang, H and Zhu, Z and Xie, M and Yu, Y and Zhu, Y and Li, W and Shangguan, W and Li, L and Shi, X and Yang, Q and Zeng, J and Wang, Z and Zhao, J and Cheng, B and Wu, P}, title = {Akkermansia muciniphila drives viscero-visceral crosstalk via 5-HT3aR-mediated sensitization of dichotomizing gut-bladder neurons.}, journal = {Experimental &amp; molecular medicine}, volume = {58}, number = {5}, pages = {1608-1625}, pmid = {42104017}, issn = {2092-6413}, support = {82503289//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82570912, 82370782, 82173304//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2025M782052//China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; Humans ; *Receptors, Serotonin, 5-HT3/metabolism ; *Neurons/metabolism ; *Urinary Bladder/innervation/metabolism ; Irritable Bowel Syndrome/metabolism/microbiology/etiology ; Mice ; *Urinary Bladder, Overactive/metabolism/etiology/microbiology ; Female ; Male ; Ganglia, Spinal/metabolism ; Gastrointestinal Microbiome ; Akkermansia ; Disease Models, Animal ; }, abstract = {The comorbidity of overactive bladder (OAB) and irritable bowel syndrome (IBS) presents a major clinical challenge, with the underlying neural and microbial mechanisms of the gut-bladder axis poorly understood. Here we aimed to delineate the complete causal pathway from a specific gut microorganism to bladder dysfunction and validate it as a therapeutic target. We combined analysis of human OAB-IBS cohorts with a postinflammatory mouse model, integrating retrograde neuronal tracing, multiomics (16S rDNA and metabolomics), fecal microbiota transplantation, urodynamics, dorsal root ganglion (DRG) electrophysiology and pharmacological and/or surgical interventions. We first confirmed a direct anatomical link, identifying dichotomized DRG neurons co-innervating the colon and bladder. Patients with OAB-IBS and mice exhibited a shared gut dysbiosis characterized by Akkermansia muciniphila enrichment. This comorbidity occurred in the absence of local bladder inflammation or urinary colonization with A. muciniphila, confirming a functional, noninfectious mechanism. Fecal microbiota transplantation of A. muciniphila or patient microbiota causally exacerbated visceral hypersensitivity, the OAB phenotype and DRG hyperexcitability. Mechanistically, A. muciniphila enrichment shunted host tryptophan metabolism toward the serotonin (5-HT) pathway. The resulting excess 5-HT acted on specifically upregulated colonic 5-HT3a receptors to drive neuronal sensitization. Crucially, pharmacological blockade of the colonic 5-HT3a receptor or surgical severing of the mesenteric nerves reversed the bladder dysfunction and visceral hypersensitivity. Our findings delineate a novel pathway wherein A. muciniphila drives functional gut-bladder comorbidity by promoting a gut-derived serotonergic signal that sensitizes shared afferent neurons, establishing the gut-specific 5-HT3a receptor as a key, druggable therapeutic target.}, }
@article {pmid42105281, year = {2026}, author = {Zhao, Z and Shi, R and Ye, J and Wang, D and Zhao, B and Ren, B and Wang, L and Liu, X and Liu, X}, title = {Gut microbiota-regulated glutathione metabolic rhythms restore obesity-induced colonic inflammatory oscillations.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2670048}, pmid = {42105281}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Glutathione/metabolism ; *Obesity/microbiology/metabolism/complications ; Diet, High-Fat/adverse effects ; Circadian Rhythm ; Colon/microbiology/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Male ; Fecal Microbiota Transplantation ; Inflammation ; *Colitis/microbiology/metabolism ; Oligosaccharides ; }, abstract = {Obesity disrupts circadian inflammatory rhythms, a defining feature of metabolic syndrome. However, the mechanisms connecting microbial and host circadian communication remain unclear. By using the fermentable fiber fructo-oligosaccharide (FOS) to restore microbial rhythmicity, we found that a high-fat diet (HFD) disrupts microbiota-regulated oscillations in glutathione metabolism, thereby dampening colonic inflammatory rhythms independently of the core clock machinery. Fecal microbiota transplantation (FMT) further supported a causal role for rhythmic fecal microbial signals in restoring inflammatory oscillations. Integrated multi-omics analysis highlighted circadian glutathione metabolism as a prominent candidate pathway linking microbial rhythmicity to host inflammatory oscillations. Importantly, colon-specific knockdown of Gclc, the rate-limiting enzyme in glutathione synthesis, abolished the restorative effects of microbial rhythms, functionally positioning host glutathione metabolism as a critical downstream mediator. Collectively, our study supports the existence of a microbiota-glutathione axis that contributes to the regulation of colonic inflammatory rhythms, uncovering a new chronobiological layer of microbial control over host inflammation.}, }
@article {pmid42106371, year = {2026}, author = {Shi, X and Hu, Y and Wang, C and Hua, G and Liu, S}, title = {Gut microbiota and their role in male reproductive health.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00845-0}, pmid = {42106371}, issn = {2396-8370}, support = {No. 2023YFD1300604)//the National Key R&amp;D Program of China/ ; }, abstract = {The gut microbiota, as the "second genome" of the human body, plays a central regulatory role in maintaining host physiological homeostasis; conversely, its dysbiosis can impair male reproductive function via the "gut-testis axis", leading to a series of pathological manifestations such as abnormal semen quality, sexual dysfunction, and reproductive organ damage. Gut microbiota exerts multidirectional effects on host metabolism, immunity, endocrinology, and the neural system, collectively forming a complex regulatory network for male reproduction. Among these, microbiota-derived metabolites such as short-chain fatty acids (SCFAs), serotonin (5-HT), and secondary bile acids, function as systemic signaling molecules that exert direct and indirect effects on the testis through blood circulation and modulation of gut barrier integrity, regulation of systemic inflammation, epigenetic reprogramming, respectively. The potential and limitations of microbiota-targeted intervention strategies, including probiotics, prebiotics, synbiotics, traditional natural herbal extracts, and fecal microbiota transplantation (FMT), are also discussed. Finally, we propose that future interventions should be tailored to individual gut microbiota profiles to achieve precise regulation of male reproductive function. This review aims to provide a new systems biology perspective for understanding the complex etiology of male infertility and to lay a theoretical foundation for the development of innovative microbiome-based diagnostic tools and therapeutic strategies.}, }
@article {pmid42107896, year = {2026}, author = {Zheng, W and Xu, Q and Ren, M and Wang, Z and Wang, M and Gao, Y and Zhang, J and Zhang, M and Chen, Y}, title = {Polysaccharide from Armillariella tabescens mycelia alleviates lipopolysaccharide-induced neuroinflammation via regulating the microbiota-gut-brain axis.}, journal = {International immunopharmacology}, volume = {182}, number = {}, pages = {116814}, doi = {10.1016/j.intimp.2026.116814}, pmid = {42107896}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Lipopolysaccharides ; Male ; *Brain/drug effects/pathology ; Mice ; *Fungal Polysaccharides/pharmacology/therapeutic use ; Mycelium/chemistry ; *Neuroinflammatory Diseases/chemically induced/drug therapy ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Brain-Gut Axis/drug effects ; *Polyporaceae ; }, abstract = {Neuroinflammation is a prevalent pathological characteristic of numerous neurodegenerative disorders. Inhibition of neuroinflammation can slow the progression of these diseases. Armillariella tabescens is a valuable medicinal fungus that is often used in traditional Chinese medicine to treat acute and chronic hepatitis, appendicitis, otitis media and cholecystitis. Its mycelium polysaccharide (ATMP) has excellent biological activities, including anti-inflammatory, antioxidation and anti-aging. However, the mechanism of ATMP against neuroinflammation has not been elucidated. This study aimed to investigate the intervention effects of ATMP on lipopolysaccharide (LPS)-induced neuroinflammation and to elucidate the underlying mechanisms. The neuroprotective effects of ATMP were evaluated by behavioral tests, histological analysis of brain and colon tissues, and quantification of relevant inflammatory biomarkers. Gut microbiota composition and metabolic changes were assessed by 16S rRNA gene sequencing and serum non-targeted metabolomics. Fecal microbiota transplantation (FMT) was used to confirm gut microbiota-dependent effects of ATMP. Additionally, real-time quantitative PCR was performed to determine the expression of genes in related metabolic pathways. The results demonstrated that ATMP significantly alleviated LPS-induced cognitive impairment, inhibited brain inflammation and neuronal damage, attenuated intestinal inflammation and repaired the intestinal barrier function. Its neuroprotective effect was mediated via the microbiota-gut-brain axis (MGBA) by regulating gut microbiota composition and modulating amino acid and fatty acid metabolites, particularly balancing linoleic acid (LA) and arachidonic acid (AA) metabolic pathways. This work provides new mechanistic insights into the protective effect of ATMP against neuroinflammation and highlights its potential as an MGBA-mediated intervention strategy.}, }
@article {pmid42109273, year = {2026}, author = {Lorentsen, RD and Borup, C and Poulsen, A and Jørgensen, EM and Rohde, U and Hansen, SH and Rainteau, D and Lamazière, A and Munck, LK}, title = {Prevalence of Bile Acid Diarrhea and Effect of Budesonide on the Bile Acid Homeostasis in Flare of Microscopic Colitis.}, journal = {Gastro hep advances}, volume = {5}, number = {6}, pages = {100954}, pmid = {42109273}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Microscopic colitis (MC) and bile acid diarrhea (BAD) are common causes of chronic watery diarrhea. Retrospective studies suggest that BAD coexists in a subset of patients with MC, but the interplay and therapeutic implications remain unclear. We aimed to determine the prevalence of BAD in patients with an MC flare using biochemical markers, to assess the effects of budesonide on BAD biomarkers, and to correlate with clinical outcomes.<br><br>METHODS: In this prospective multicenter study conducted at 3 Danish secondary care outpatient clinics, 49 patients with an MC flare were treated with budesonide for 6 weeks. 7&#x3b1;-hydroxy-4-cholesten-3-one (C4) levels &#x2265;46 ng/mL defined BAD. C4 allows timely testing but has 47% sensitivity. Fecal bile acids (BAs) and fibroblast growth factor 19, stool habits, and quality of life were evaluated.<br><br>RESULTS: BAD was diagnosed in 6 (12%; 95% confidence interval, 5%-25%) of 49 patients (C4 range 47-92 ng/mL). Three patients had a gray zone C4 between 33 and 46 ng/mL. Patients with BAD had lower fibroblast growth factor 19 and high levels of primary and total BA in spot stool samples. Budesonide significantly reduced diarrhea and improved health-related quality of life in all patients. In patients with BAD, budesonide normalized stool BA, but C4 levels remained elevated.<br><br>CONCLUSION: These data demonstrate that some patients with MC flare have BAD. In patients with MC and BAD, budesonide reduced diarrhea symptoms and normalized stool BA levels but did not improve an underlying dysregulation of BA homeostasis. Clinicians may consider testing for BAD in patients with recurrent MC. Trials on therapies targeting BAD in MC patients are warranted.}, }
@article {pmid42110505, year = {2026}, author = {Li, J and Zhang, H and Zhang, P and Hu, J}, title = {Potential Benefits of Gut Microbiota Modulation in Chronic Obstructive Pulmonary Disease.}, journal = {International journal of chronic obstructive pulmonary disease}, volume = {21}, number = {}, pages = {594405}, pmid = {42110505}, issn = {1178-2005}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Pulmonary Disease, Chronic Obstructive/microbiology/therapy/physiopathology/metabolism ; Animals ; Humans ; *Dysbiosis/therapy ; Disease Models, Animal ; *Lung/physiopathology/microbiology/metabolism/pathology ; *Fecal Microbiota Transplantation ; Male ; Mice, Inbred C57BL ; Metabolomics/methods ; Anti-Bacterial Agents ; Female ; *Bacteria/genetics/metabolism/drug effects/growth &amp; development/classification ; Middle Aged ; Ribotyping ; Aged ; Case-Control Studies ; Mice ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory/immunology/metabolism ; }, abstract = {BACKGROUND: The gut-lung axis is increasingly recognized. This study aimed to find out whether and how the gut microbiome involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).<br><br>METHODS: Gut microbiota was characterized via 16S rRNA gene sequencing in COPD patients and a smoking-induced mouse model. Gut dysbiosis was induced by antibiotic cocktail (ABX) and restored by fecal microbiota transplantation (FMT). Plasma metabolomics was conducted using liquid chromatography-mass spectrometry (LC-MS), and pathway analysis was performed with MetaboAnalyst 5.0. Differentially expressed genes were identified by RNA sequencing and functionally interpreted through gene set enrichment analysis (GSEA).<br><br>RESULTS: Both COPD patients and mice showed altered gut microbiota, characterized by a unique microbial composition and reduced diversity. ABX induced gut dysbiosis exacerbated pathological lung changes, impaired lung function, and promoted Treg cell exhaustion in COPD mice. Restoration of gut homeostasis via FMT attenuated these alterations. Higher plasma levels of acetylcholine (ACh) were observed in COPD mice, while the highest ACh levels were found in ABX treated COPD mice compared to controls. Notably, ACh levels correlated positively with genus Parasutterella, which was more abundant in COPD mice, and inversely with genera Candidatus Saccharimonas and Lactobacillus, which were predominant in control mice. Metabolomic pathways analysis revealed enrichment in unsaturated fatty acids biosynthesis and purine metabolism in COPD mice relative to controls.<br><br>CONCLUSION: These findings highlight the involvement of the gut microbiome in COPD development and suggest that maintaining gut homeostasis may represent a novel therapeutic strategy for COPD.}, }
@article {pmid42111070, year = {2026}, author = {Zurdo-López, M and Sagredo Del Rio, M and Cháfer Rudilla, M and Ibarra, A and Doncel-Pérez, E}, title = {Microbiota and Guillain-Barré syndrome: role of microbial metabolites, biomarkers, and emerging therapeutic strategies.}, journal = {Frontiers in neurology}, volume = {17}, number = {}, pages = {1815899}, pmid = {42111070}, issn = {1664-2295}, abstract = {Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy that follows infection and is characterized by immune-mediated demyelination or axonal injury of the peripheral nervous system. While established triggers such as Campylobacter jejuni are well recognized, increasing evidence implicates the gut microbiota as a key modulator of immune responses relevant to GBS pathogenesis. The intestinal microbiota produces a diverse array of bioactive metabolites, including short-chain fatty acids (SCFAs), tryptophan-derived indoles, and neurotransmitter-like molecules, which influence immune tolerance, gut barrier integrity, and neuroinflammatory signaling. SCFAs, particularly butyrate, exert anti-inflammatory effects and support epithelial and blood-nerve barrier function. Microbial tryptophan metabolites regulate astrocyte and microglial activity via aryl hydrocarbon receptor (AHR) signaling, thereby restraining central and peripheral neuroinflammation. In contrast, dysbiosis-associated metabolites such as lipopolysaccharide (LPS) may enhance systemic inflammation, disrupt immune tolerance, and promote autoantibody production through mechanisms including molecular mimicry. Studies suggest that specific microbial taxa and metabolite signatures may serve as diagnostic or prognostic biomarkers in GBS, offering insights into disease susceptibility and progression. Microbiota-targeted therapeutic strategies are emerging as promising adjuncts to immunotherapy. Probiotics and prebiotics may restore beneficial microbial communities and rebalance immunoregulatory metabolite production, while host-directed metabolic interventions such as creatine supplementation may further support mitochondrial function, immunometabolic homeostasis, and neuroprotection. Fecal microbiota transplantation (FMT), though still experimental in GBS, has shown benefit in related neuroinflammatory disorders by reestablishing eubiosis and dampening immune activation. Future studies integrating metagenomic, metabolomic, and immunologic profiling in well-characterized GBS cohorts are essential to validate these findings and advance personalized microbiota-based interventions.}, }
@article {pmid42111748, year = {2026}, author = {Chowdhary, R and Goyal, MK and Arora, K and Sehgal, T and Dawer, P and Anirudh, FNU and Berinstein, J and Bishu, S and Matt-Amaral, L}, title = {Gut Microbiota and Extraintestinal Cancers: Mechanistic Insights and Microbiome-Targeted Interventions.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {10}, number = {}, pages = {e70409}, pmid = {42111748}, issn = {2397-9070}, abstract = {The gut microbiota is a dynamic community of bacteria, viruses, fungi, and archaea that plays a pivotal role in regulating host immunity, metabolism, and systemic homeostasis. Dysbiosis, characterized by an imbalance in the microbial composition, is being increasingly recognized as a contributor not only to gastrointestinal cancers but also to extraintestinal malignancies. Mechanistic studies highlight the gut-microbiota-cancer axis, where microbial metabolites such as bile acids, short-chain fatty acids (SCFAs), and tryptophan derivatives influence genetic, epigenetic, and immune pathways, influencing carcinogenesis. Germ-free models demonstrate that commensal signals are essential for CD4[+] and CD8[+] T-cell differentiation, IgA production, and anti-tumor immunity. Dysbiosis-induced immune dysregulation is believed to impair immune checkpoint inhibitor (ICI) efficacy, while specific taxa such as Bifidobacterium and Akkermansia have been shown to enhance therapeutic responses. Emerging evidence links gut microbiota to breast cancer via estrogen metabolism "estrobolome" to lung cancer through the gut-lung axis and modulation of ICI responses, to melanoma by shaping systemic T-cell function and immunotherapy outcomes, and to prostate cancer through androgen receptor signaling and microbial metabolite interactions. These findings underscore the systemic oncogenic and tumor-suppressive potential of microbial communities. Microbiome-targeted interventions, including fecal microbiota transplantation (FMT), defined live biotherapeutics, probiotics, prebiotics, dietary modulation, and postbiotic delivery, are being actively investigated to optimize cancer treatment. While early trials have demonstrated feasibility, variability between individuals and methodological challenges remain significant hurdles. Hence, understanding how gut microbes influence extraintestinal cancers could revolutionize diagnostics, risk prediction, and treatment strategies.}, }
@article {pmid42112133, year = {2026}, author = {Liu, H and Zhang, R and Mao, Z and Zhang, H and Lu, J}, title = {The cardioprotective mechanism of total saponins from mountain cultivated ginseng against doxorubicin-induced heart failure: Insights from gut-heart axis modulation based on gut microbiota and fecal metabolomics.}, journal = {Journal of ginseng research}, volume = {50}, number = {3}, pages = {100983}, pmid = {42112133}, issn = {1226-8453}, abstract = {BACKGROUND: Mountain cultivated ginseng (MCG) has been reported to exert superior therapeutic efficacy in heart failure (HF) models, but the mechanism of total saponins from MCG (TSMCG) remains unclear.<br><br>METHODS: This study aimed to elucidate the mechanism of TSMCG protects against doxorubicin-induced HF through the gut-heart axis. The phytochemical profile of TSMCG was identified using UPLC/Q-TOF-MS. TSMCG (50 or 200&#xa0;mg/kg) was administered to mice daily for one week before and after doxorubicin exposure. Cardiac function was evaluated via echocardiography, followed by blood biochemical and cardiac histological analyses. Metabolic profiles and gut microbiota composition were analyzed. Fecal microbiota transplantation experiments were employed for mechanistic validation.<br><br>RESULTS: TSMCG treatment significantly improved cardiac function in HF mice, as evidenced by increased ejection fraction. TSMCG markedly attenuated doxorubicin-induced myocardial injury (CK-MB, NT-proBNP, AST, LDH), oxidative stress (SOD, MDA, CAT, GSH), and cardiac fibrosis. TSMCG effectively regulated key metabolic pathways, particularly tryptophan and bile acid metabolism, and alleviated gut microbiota dysbiosis, particularly Parasutterella and Akkermansia, in HF mice. Close associations between differential microbiota and metabolites were observed. The cardioprotective effects of TSMCG were associated with fecal microbiota transplantation.<br><br>CONCLUSION: These findings elucidated the gut-heart axis-based mechanism by which TSMCG alleviated doxorubicin-induced HF and highlighted its potential as a candidate for HF intervention.}, }
@article {pmid42112348, year = {2026}, author = {Hua, M and Luo, J and Li, P and Zhang, Y and Zhang, X and Wu, Y and Dong, H}, title = {The microbiota-systemic lupus erythematosus axis: mechanisms, diagnostics, and therapeutic frontiers.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1782828}, pmid = {42112348}, issn = {1664-3224}, mesh = {*Dysbiosis/immunology/therapy ; *Microbiota ; *Lupus Erythematosus, Systemic/diagnosis/immunology/microbiology/therapy ; Humans ; Animals ; Molecular Mimicry ; Autoimmunity ; }, abstract = {Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which host-microbiota crosstalk plays a pivotal role in immune dysregulation. Recent metagenomic studies have revealed that disease-specific dysbiosis--characterized by the expansion of pathobionts and depletion of immunoregulatory commensals--occurs across the gut, oral cavity, skin, and genital tract. Integrative multi-omics analyses have identified three mechanistic pathways linking microbial imbalance to autoimmunity: (1) microbial peptides trigger molecular mimicry and epitope spreading, activating autoreactive lymphocytes: (2) microbial metabolites disrupt redox homeostasis, impair epithelial barriers, and skew the AhR-mediated Th17/Treg balance; and (3) dysbiosis alters epigenetic regulation by inhibiting DNA methyltransferases, leading to hypomethylation of SLE-risk genes. Translational studies have shown that microbiome-targeted interventions, including probiotics, prebiotics, fecal microbiota transplantation, and even B cell-depleting chimeric antigen receptor T-cell (CAR-T) therapy, can restore microbial balance, reduce autoantibody levels, and modulate the gut-immune axis. Furthermore, microbial signatures are emerging as potential biomarkers for disease activity and treatment response. Despite this promise, challenges remain, such as the impact of immunosuppressants on the microbiota, spatial heterogeneity in host-microbe interactions, and limitations in causal inference. Looking forward, integrating single-cell metagenomics, microbiota-directed diets, and engineered microbial consortia may pave the way for personalized microbiome-based therapies. Reframing SLE as a "meta-organismal imbalance" positions microbial ecology at the forefront of precision medicine.}, }
@article {pmid42112377, year = {2026}, author = {Tschang, MA and Deo-Campo Vuong, R and Eilers, B and Chac, D and Waalkes, A and Penewit, K and Easton, A and Schuessler, B and Daniels, R and Weil, AA and Salipante, SJ and Gibbons, SM and Schindler, AG}, title = {If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1816919}, pmid = {42112377}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; Corticosterone/blood ; *Stress, Psychological/therapy/microbiology ; Male ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Anxiety ; Behavior, Animal ; Stress, Physiological ; }, abstract = {BACKGROUND: The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures.<br><br>METHODS: We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into aliquots ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the frozen aliquots, and blood was collected to compare corticosterone relative to that after delivery via traditional gavage.<br><br>RESULTS: Plasma corticosterone levels were found to be significantly lower in mice receiving frozen aliquots compared to oral gavage. Furthermore, relative to controls, microbial signatures of mice receiving FMT via frozen aliquots were more similar to those of the donors at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta diversity distances.<br><br>CONCLUSION: Together, these results establish antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.}, }
@article {pmid42112384, year = {2026}, author = {Oyedokun, PA and Oyeleke, BT and Akanji, OO and Oyelaran, AO and O, KP and Akanbi, GB and Oyedokun, PO and Oyedokun, MD and Naomi, CC and Imoleayo, OO and Akhigbe, RE}, title = {The role of the microbiome in gynecological cancers: implications for diagnosis and treatment.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1718883}, pmid = {42112384}, issn = {1664-3224}, mesh = {Humans ; Female ; *Genital Neoplasms, Female/therapy/diagnosis/microbiology/etiology ; *Microbiota ; Dysbiosis ; Animals ; Tumor Microenvironment ; Fecal Microbiota Transplantation ; }, abstract = {Gynecological malignancies such as cancer of the cervix, ovary, endometrium, vulva, and vagina pose a severe global health burden. Although conventionally attributed to genetic mutation, hormonal imbalance, and chronic viral infection, including high-risk human papillomavirus, recent evidence suggests that the human microbiome plays a central role in their pathogenesis and development. This review summarizes existing evidence that microbial dysbiosis, specifically the depletion of beneficial Lactobacillus species and overrepresentation of anaerobic organisms such as Fusobacterium, Atopobium, and Sneathia, is implicated in carcinogenesis pathways. These include chronic inflammation, immune modulation, loss of epithelial barrier integrity, microbial metabolite toxicity, and estrogen metabolism by the estrobolome. Dysbiosis in the gut and reproductive tract has been associated with HPV persistence, tumor microenvironment remodeling, and immune surveillance/therapy resistance. Consequently, microbial signatures are being investigated as a potentially successful non-invasive biomarker for early diagnosis, prognosis, and monitoring of therapy in gynecological oncology. In addition, emergent microbiome-based therapies are being considered as potential adjunct therapies, including probiotics, prebiotics, dietary manipulation, vaginal microbiota transplantation, and fecal microbiota transplantation. This review connects the basic research microbiome research to translational and clinical practice, identifies associated limitations, and highlights how it may transform gynecological cancer prevention, detection, and treatment.}, }
@article {pmid42113681, year = {2026}, author = {Wang, S and Yuan, X and Wang, T and Yang, M and Dong, P and Han, H}, title = {Mechanisms and Therapeutic Targeting of the Gut Microbiota-Immune-Brain Axis in Alzheimer's Disease.}, journal = {Immunological investigations}, volume = {}, number = {}, pages = {1-31}, doi = {10.1080/08820139.2026.2669375}, pmid = {42113681}, issn = {1532-4311}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease globally. The main pathological features of AD are amyloid-β (Aβ) deposition and tau hyperphosphorylation. Recent studies suggest that the gut microbiota-immunity-brain axis plays an important role in the onset and progression of AD. Gut microbiota dysbiosis may impair intestinal barrier integrity and promote the entry of pro-inflammatory mediators into the circulation. Pro-inflammatory signals in the bloodstream may further activate the central immune system, drive microglial polarization, and increase the release of inflammatory factors in the brain. The resulting neuroinflammatory cascade may aggravate Aβ accumulation, tau phosphorylation, and cognitive impairment, although this mechanism has not been conclusively established in humans.<br><br>METHODS AND RESULTS: Based on relevant literature on AD, gut microbiota, immunity, neuroinflammation, and the gut-brain axis, this article systematically reviews the mechanism of action of the microbiota-immunity-brain axis in AD. Current intervention strategies targeting this axis, including probiotics, fecal microbiota transplantation, dietary interventions, and traditional Chinese medicine, were also discussed. Such intervention measures have the potential to regulate the balance of the gut microbiota, reduce neuroinflammation, and slow the progression of AD pathology.<br><br>CONCLUSION: It is essential to integrate multi-omics approaches in future research to deepen the understanding of AD pathogenesis and support the development of more precise and personalized treatment strategies.}, }
@article {pmid42114686, year = {2026}, author = {Liu, J and Bai, Y and Feng, Y and Shao, X and Ma, H and Yan, X and Ye, Y and Wei, S and Lai, J and Yan, P}, title = {Gut microbiota and SCFA dysregulation drive MDPV-induced behavioral and neuroimmune adaptations in male mice.}, journal = {Brain, behavior, and immunity}, volume = {137}, number = {}, pages = {106800}, doi = {10.1016/j.bbi.2026.106800}, pmid = {42114686}, issn = {1090-2139}, abstract = {BACKGROUND: 3,4-methylenedioxypyrovalerone (MDPV), a synthetic cathinone-derived novel psychoactive substance, exhibits potent stimulant effects and high abuse potential. However, the neurobiological mechanisms underlying MDPV dependence, particularly those involving the gut microbiota, remain unclear.<br><br>METHODS: Male C57BL/6 mice were used to establish an MDPV-induced behavioral sensitization model. Gut microbiota composition and short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and metabolomics. Antibiotics and fecal microbiota transplantation (FMT) were employed to manipulate microbiota, while valeric acid supplementation was used to assess functional effects. Microglial activation and inflammatory cytokines in the VTA were evaluated.<br><br>RESULTS: Repeated MDPV administration (1&#xa0;mg/kg) induced robust behavioral sensitization, accompanied by alterations in gut microbiota and SCFA profiles. Antibiotic-induced microbiota depletion abolished sensitization. FMT from control donors attenuated sensitization, whereas FMT from MDPV-treated donors restored it in antibiotic-treated mice. Valeric acid was significantly associated with behavioral outcomes, and its supplementation mitigated sensitization, reduced microglial activation in the VTA, and decreased pro-inflammatory cytokines (IL-1&#x3b2;, IL-6, TNF-&#x3b1;).<br><br>CONCLUSIONS: Gut microbiota and their metabolites, particularly valeric acid, regulate MDPV-induced behavioral sensitization by modulating neuroinflammation and microglial activation. Targeting microbiota-SCFA signaling may offer a potential therapeutic strategy for MDPV -induced neurobehavioral effects.}, }
@article {pmid42115187, year = {2026}, author = {Zhang, J and Chen, F and Xu, X and Zhang, L and Zhang, L and Qin, B and Li, K and Liu, Q and Hou, H and Li, Y and Liu, C and Li, Y and Shi, J and Teng, T and Wang, C and Zhou, X}, title = {Gut microbiota dysbiosis drives depression-like behavior in adolescent rats via lysine-regulated mTOR autophagy pathway.}, journal = {Translational psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41398-026-04095-2}, pmid = {42115187}, issn = {2158-3188}, abstract = {The prevalence of major depressive disorder (MDD) is increasing globally, particularly among adolescents. Although gut-brain axis dysfunction has been implicated in adolescent depression, the mechanisms by which gut microbiota dysbiosis drives depressive behaviors and potential antidepressant targets remain unclear. In this study, fecal microbiota transplantation (FMT) was performed from either healthy controls (HCs) or adolescents with MDD into antibiotic-treated adolescent rats. FMT from MDD adolescents induced depressive-like behaviors in recipient rats. Metagenomic sequencing revealed that FMT from MDD adolescents led to alterations in gut microbiota in recipient rats. While qPCR, Western blotting, immunofluorescence, and transmission electron microscopy (TEM) confirmed that these rats exhibited prefrontal cortex (PFC) autophagy hyperactivation, evidenced by a reduction in SQSTM1/p62 levels, an elevation in the LC3-II/LC3-I ratio, upregulated Beclin1, and increased numbers of autolysosomes. Similar autophagy-related transcriptional changes were observed in peripheral blood from MDD adolescents. Furthermore, ELISA showed reduced plasma lysine levels in MDD adolescents and decreased lysine concentrations in the PFC of FMT-MDD rats. The antidepressant effect of lysine and its interaction with autophagy were explored in a chronic unpredictable mild stress (CUMS) rat model with or without rapamycin (the autophagy activator, RAPA). Lysine supplementation alleviated depressive-like behaviors and suppressed PFC autophagy hyperactivation, while these effects were abolished by RAPA co-treatment. These findings reveal lysine deficiency as a metabolic bridge between gut microbiota imbalance and neuronal autophagy dysregulation, suggesting a gut microbiota-lysine-autophagy axis as an innovative mechanism and therapeutic focus for adolescent depression.}, }
@article {pmid42116139, year = {2026}, author = {Liaqat, A}, title = {A spotlight on the inflammatory role of uremic toxins in the dysbiosis-CKD axis: a review.}, journal = {Journal of inflammation (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12950-026-00505-w}, pmid = {42116139}, issn = {1476-9255}, abstract = {There is growing evidence that gut-derived metabolites activate specific signaling pathways that lead to renal inflammation and injury, suggesting that the gut-kidney axis plays a significant role in the inflammatory processes that underlie chronic kidney disease (CKD). Alterations in the gut microbiota in CKD patients known as dysbiosis increases the production of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and Trimethylamine N-oxide. These toxins trigger pro-inflammatory signaling pathways in renal tubular cells by initiating a series of inflammatory events, such as immune dysregulation, oxidative stress, and endotoxemia. As a result, cytokines like TNF-α, IL-6, and IL-1β are expressed more frequently, creating a chronic inflammatory environment that increase kidney damage and the progression of CKD. Emerging therapeutic strategies that alter gut microbiota composition, such as prebiotics, probiotics, dietary fiber, and fecal microbiota transplantation, have demonstrated promise in decreasing the burden of inflammation-inducing toxins. As research reveals new linkages between microbial metabolites and inflammatory signaling in CKD, addressing uremic toxin-mediated inflammation could revolutionize disease management. Understanding these interrelated signaling systems provides a more detailed understanding of how gut microbes influence renal inflammation at the molecular level. The aim of this review is to investigate the underlying signaling pathways by which gut-renal dysbiosis induces inflammation in CKD. The review attempts to guide the development of targeted treatment approaches that can reduce the inflammatory load and slow the progression of CKD by examining the mechanisms in which gut-derived uremic toxins alter oxidative stress, immunological responses, and inflammatory cascades.}, }
@article {pmid42117718, year = {2026}, author = {Hao, W and Stocker, N and Gaugler, B and Mohty, M and Malard, F}, title = {The Role of the Gut Microbiota in Allogeneic Hematopoietic Cell Transplantation.}, journal = {American journal of hematology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajh.70360}, pmid = {42117718}, issn = {1096-8652}, abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment for patients with high-risk hematologic malignancies. Over the last decade, gut microbiota composition during allo-HCT has been associated with patients' outcomes. Treatment-related factors, in particular the use of broad-spectrum antibiotics and the conditioning regimen, frequently induce gut dysbiosis, which is associated with immune dysregulation, toxicity, and adverse outcomes, particularly after allo-HCT. Microbial metabolites further modulate immune responses and therapeutic efficacy. Emerging microbiota-targeted strategies-including antibiotic stewardship, nutritional interventions, probiotics, fecal microbiota transplantation, and postbiotics-show promise in reducing graft-versus-host disease, controlling inflammation, and improving treatment responses.}, }
@article {pmid42118793, year = {2026}, author = {Kawashima, M and Aoki, T and Hamada, H and Watanabe, C and Oyanagi, E and Kono, T and Yamagata, T and West, NP and Yano, H}, title = {Continuous high-fat high-sugar diet overrides the therapeutic potential of fecal microbiota transplantation from exercised and/or inulin-conditioned donors in obese mice.}, journal = {PloS one}, volume = {21}, number = {5}, pages = {e0349286}, pmid = {42118793}, issn = {1932-6203}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Inulin/pharmacology/administration &amp; dosage ; Male ; *Diet, High-Fat/adverse effects ; *Obesity/therapy/etiology/microbiology/metabolism ; Mice ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Physical Conditioning, Animal ; Fatty Acids, Volatile/metabolism ; Mice, Obese ; Feces/microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic strategy for obesity and related metabolic disorders. Exercise and dietary fiber intake, such as inulin supplementation, have been shown to differentially modulate the gut microbiota and synergistically improve metabolic health. The present study aimed to investigate whether FMT from lean donor mice subjected to voluntary exercise and/or inulin supplementation could ameliorate metabolic dysfunction in high-fat high-sugar diet (HFHSD)-induced obese mice. Four-week-old male C57BL/6J mice were fed HFHSD throughout the experimental period and assigned to one of five groups: sham FMT, FMT from sedentary donors, from exercised donors, from inulin-supplemented donors, or from donors receiving both interventions. Following 12 weeks of obesity induction, mice were treated with antibiotics and then underwent a 4-week FMT protocol. Physical and metabolic parameters, gut microbial composition, and cecal short-chain fatty acid (SCFA) levels were examined in both donors and recipients. The results demonstrated that FMT from exercised and/or inulin-supplemented donors failed to improve obesity-related phenotypes or glucose intolerance in recipients. These outcomes were accompanied by only partial alterations in gut microbiota and SCFA profiles. Collectively, our findings suggest that persistent HFHSD exposure compromises the colonization and function of beneficial microbes, limiting the metabolic benefits of FMT. Successful application of FMT in severe obesity may require prior optimization of the host intestinal environment through dietary interventions or microbiome-targeted strategies.}, }
@article {pmid42121529, year = {2026}, author = {Lei, M and Xu, H and Jin, X and Chen, X and Chen, K and Yang, Z and Xie, Y and Li, D and Ao, M and Zhu, Y and Yu, L}, title = {Theabrownin from Dark Tea Attenuates Age-Related Cognitive Decline in Naturally Aged Mice by Modulating Gut Microbiota and Metabolites.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {9}, pages = {}, pmid = {42121529}, issn = {2304-8158}, support = {202505AF350038//Yunnan Academician (Expert) Workstation/ ; No. 32502186//Young Scientists Fund (Category C) of the National Natural Science Foundation of China/ ; 2023XCZX001//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Dietary factors play an important role in cognitive health during aging. Dark tea has shown potential cognitive benefits, but its key bioactive component and underlying mechanisms remain unclear. In a naturally aged C57BL/6J mouse model, instant dark tea (IDT) samples with different fermentation degrees were evaluated together with behavioral outcomes using composition-effect relationship analysis. This analysis identified theabrownin (TB) as the component most strongly associated with improved cognitive performance. Compared with aged controls, TB increased Y-maze spontaneous alternation from 51.91% to 71.59% and reduced escape latency on day 5 of the Morris water maze from 44.84 s to 26.59 s. In contrast, the corresponding TB-depleted fraction produced no comparable cognitive improvement. TB also alleviated hippocampal injury and neuroinflammation. Antibiotic treatment abolished the cognitive benefits of TB, whereas fecal microbiota transplantation partially restored them. Multi-omics analyses suggested that TB treatment was associated with gut microbiota remodeling and increased serum acetate and 3-hydroxybutyrate; both metabolites partially recapitulated these benefits. Together, these findings show that TB attenuates age-related cognitive decline in naturally aged mice and suggest that modulation of gut microbiota and metabolites may contribute to this effect, supporting its potential as a functional food ingredient for healthy brain aging.}, }
@article {pmid42122957, year = {2026}, author = {Terry, C and Hall, LA and Halle-Smith, J and Edwards, LA and Sivakumar, S and Chapple, I and Beggs, A and Iqbal, T and Roberts, KJ}, title = {Pancreatic Cancer in the Holobiont and Therapeutic Targets: A Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {9}, pages = {}, pmid = {42122957}, issn = {2077-0383}, abstract = {Increasing evidence suggests pancreatic cancer develops within a host-microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome-tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes.}, }
@article {pmid42123931, year = {2026}, author = {Maragno, P and Amoroso, C and Conforti, S and Michelon, M and Honcharyuk, I and Ciafardini, C and Noviello, D and Strati, F and Caprioli, F and Facciotti, F and Vecchi, M}, title = {The Assessment of Multidimensional Clinical, Biological and Patient-Reported Outcomes to Evaluate the Efficacy of Add-On Lactobacillus rhamnosus GG Supplementation in Mild Ulcerative Colitis: A Randomized Pilot Trial.}, journal = {Nutrients}, volume = {18}, number = {9}, pages = {}, pmid = {42123931}, issn = {2072-6643}, mesh = {Humans ; *Colitis, Ulcerative/therapy/drug therapy/microbiology ; Pilot Projects ; Female ; Male ; *Lacticaseibacillus rhamnosus ; Adult ; Double-Blind Method ; Middle Aged ; Mesalamine/therapeutic use/administration &amp; dosage ; *Probiotics/administration &amp; dosage/therapeutic use ; *Dietary Supplements ; Patient Reported Outcome Measures ; Quality of Life ; Gastrointestinal Microbiome/drug effects ; Treatment Outcome ; *Cholecalciferol/administration &amp; dosage/therapeutic use ; Leukocyte L1 Antigen Complex/analysis ; Feces/chemistry/microbiology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; }, abstract = {Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca' Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4[+] T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management.}, }
@article {pmid42123938, year = {2026}, author = {Chiang, CK and Lai, CL and Chiu, MH and Huang, CJ}, title = {The Gut-Lung Axis in Allergic Asthma: A Narrative Review of Microbial Dysbiosis, Immune Regulation, and Nutritional Modulation.}, journal = {Nutrients}, volume = {18}, number = {9}, pages = {}, pmid = {42123938}, issn = {2072-6643}, support = {CGH-MR-B-11316//Cathay General Hospital/ ; }, mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Asthma/immunology/microbiology ; *Lung/immunology/microbiology ; Animals ; Diet ; }, abstract = {Allergic asthma is a prevalent chronic inflammatory disease of the airways whose pathogenesis has traditionally been attributed to localized immune dysfunction within the lung. However, accumulating evidence from microbiome research supports a broader system-level perspective in which cross-organ interactions contribute to disease susceptibility and progression. In particular, the gut-lung axis has emerged as a key regulatory pathway linking intestinal microbial ecology, immune development, and respiratory health. This review synthesizes current epidemiological, mechanistic, and experimental evidence supporting the role of gut microbiota dysbiosis in allergic asthma. We examine how early-life environmental and nutritional exposures and gut microbiota establishment during critical developmental windows shape long-term immune tolerance and asthma susceptibility. We then summarize characteristic features of asthma-associated gut dysbiosis and discuss how microbial-derived metabolites, including short-chain fatty acids, tryptophan metabolites, pro-allergic lipid mediators such as 12,13-dihydroxy-9Z-octadecenoic acid, and bacterial-derived histamine, modulate distal airway immune responses through epigenetic, receptor-mediated, and immune trafficking mechanisms. Particular emphasis is placed on the role of diet as a key upstream regulator of gut microbiota composition and metabolic function. Finally, we evaluate experimental and translational studies targeting the gut-lung axis, including dietary modulation, microbiome-targeted interventions such as fecal microbiota transplantation, and emerging postbiotic approaches. Collectively, current evidence indicates that gut microbial composition and metabolic function are critical determinants of respiratory immune homeostasis. Targeting the gut-lung axis through nutrition- and microbiome-based strategies offers a promising avenue for the prevention and precision treatment of allergic asthma.}, }
@article {pmid42124058, year = {2026}, author = {Quattrini, S and Galeazzi, T and Monachesi, C and Palpacelli, A and Catassi, G and Quatraccioni, C and Annulli, G and Di Sario, A and Cianfruglia, L and Orciani, M and Armeni, T and Faragalli, A and Gesuita, R and Lionetti, ME and Catassi, C and Gatti, S}, title = {The Oxidative Stress Imbalance in Children and Adults with IBD and Associated Factors.}, journal = {Nutrients}, volume = {18}, number = {9}, pages = {}, pmid = {42124058}, issn = {2072-6643}, support = {RF 2018-12366976//Italian Ministry of Health/ ; D-ECCO grant 2023//European Crohn's and Colitis Organisation/ ; }, mesh = {Humans ; *Oxidative Stress ; Male ; Female ; Adult ; Child ; *Inflammatory Bowel Diseases/blood/metabolism ; Adolescent ; Antioxidants/metabolism ; Biomarkers/blood ; Thiobarbituric Acid Reactive Substances/metabolism ; Middle Aged ; Young Adult ; Glutathione/blood ; Advanced Oxidation Protein Products/blood ; Reactive Oxygen Species/blood ; Case-Control Studies ; Age Factors ; }, abstract = {Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total antioxidant capacity (ferric-reducing ability of plasma (FRAP)), reactive species (ROS), oxidative products (advanced oxidation protein products (AOPPs) and thiobarbituric acid reactive substances (TBARSs)), and antioxidant defenses (glutathione, GSH and intracellular activity of the main antioxidant enzymes) were evaluated. Correlations between OS markers, clinical features, disease characteristics, and inflammatory indices were explored. Results: Eighty-two IBD patients (67.5% in clinical remission) and 73 healthy subjects were enrolled. IBD children showed significant FRAP reduction compared to controls and IBD adults (p < 0.0001), increased AOPPs and reduced GSH compared to controls (p < 0.0001 and p = 0.0011, respectively), higher total GSH (p = 0.020), and lower TBARSs (p = 0.023) compared to IBD adults. In the pediatric group, FRAP was significantly reduced in those with IBD and increased in older subjects and males, while AOPP levels were positively affected by increasing age. In the total IBD cohort, higher FRAP was associated with male gender, increasing age, overweight, and mesalazine therapy. The diagnosis of Ulcerative Colitis was associated with lower FRAP and AOPP levels compared to Crohn's disease. Increased fecal calprotectin significantly decreased the total antioxidant capacity. Conclusions: The antioxidant system shows significant differences in IBD compared to controls, particularly in the pediatric group. The observed pediatric-adult pattern may suggest age-related differences in oxidative balance, but these findings should be interpreted with caution, given the modest sample size. Clinical Trial Registration Number: NCT04513015.}, }
@article {pmid42124415, year = {2026}, author = {Wang, X and Sun, Y and Liu, M and He, Z and Cao, W and Liu, W}, title = {[Role of Gut Mycobiome in Lung Cancer Immunotherapy: Mechanisms, Challenges and Translational Prospects].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {29}, number = {3}, pages = {200-207}, pmid = {42124415}, issn = {1999-6187}, mesh = {Humans ; *Lung Neoplasms/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy ; *Mycobiome ; Animals ; Translational Research, Biomedical ; }, abstract = {Lung cancer is one of the most common malignancies with the highest morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of patients with advanced lung cancer, but more than half of patients derive limited benefit. The gut microbiota can regulate tumor immunity and ICIs efficacy via the gut-lung axis. Although accounting for a small proportion, the gut mycobiome exerts key immunomodulatory effects, yet relevant research lags far behind that of bacteria. This review systematically summarizes the clinical association between the gut mycobiome and lung cancer, clarifies the potential mechanisms by which the mycobiome and its metabolites influence ICIs efficacy through immune regulation, metabolic modulation, and cross-kingdom interactions, and summarizes potential strategies including dietary intervention, fecal microbiota transplantation, and fungal targeting. It provides theoretical support for establishing mycobiome-based predictive models, developing precise interventions, and improving the efficacy of ICIs. .}, }
@article {pmid42125246, year = {2026}, author = {Hjørne, AP and Moretti, CH and Greiner, TU and Procházková, N and Roager, HM and Mortensen, MS and Bäckhed, F and Licht, TR and Laursen, MF}, title = {Intestinal transit time phenotype is not transferred through gut microbiota transplantation.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e21064}, pmid = {42125246}, issn = {2167-8359}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Female ; Mice ; Humans ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Gastrointestinal Transit/physiology ; Phenotype ; Feces/microbiology ; Germ-Free Life ; }, abstract = {Intestinal transit time (TT) varies considerably between healthy individuals and affects gut microbiota composition and activity. Whether differences in the gut microbiota composition also affect the TT is not well elucidated. In this study, we conducted two animal experiments to explore causality between the gut microbiota and TT. In the first experiment, we transplanted two groups of female germ-free (GF) Swiss-Webster mice with fecal material from two healthy human donors with fast and slow TT phenotypes. Following transplantation with human feces, we observed a decrease in TT for both groups of GF recipient mice (from 300 min to 167 min, 95% CI: ±45; and from 369 vs 205 min, 95% CI: ±52) corresponding to reductions of approximately 45% in each group, supporting previous findings that the mere presence of a gut microbiota reduces TT. However, we found no differences in TT between the two recipient groups. In the second experiment, we transplanted two groups of female GF C57Bl/6J mice with cecal material from two different conventional C57Bl/6J mouse donor groups treated with the TT-increasing drug loperamide or a saline vehicle. Again, no differences in TT were observed between the two recipient groups. These findings indicate that either the transferred microbiota did not engraft effectively, or that gut microbiota composition itself is not the principal driver of inter-individual TT variation.}, }
@article {pmid42125443, year = {2026}, author = {Guaraná, JB and de Freitas, SH and Lanchotte, C and Araki, J and Cruz, RJ and Galvão, FHF}, title = {Anorectal Transplantation: Current Overview and Translational Perspectives.}, journal = {Journal of the anus, rectum and colon}, volume = {10}, number = {2}, pages = {189-198}, pmid = {42125443}, issn = {2432-3853}, abstract = {Anorectal transplantation (ART) belongs to the emerging field of vascularized composite allotransplantation. Researchers have studied this procedure experimentally for over two decades as a strategy to restore anal function in patients with severe fecal incontinence and permanent colostomy. These conditions significantly impact the quality of life and pose a global public health issue. This narrative review provides a comprehensive analysis of anorectal transplantation research, covering experimental studies in animal models, and ex vivo investigations. It examines and compares different surgical techniques, considering both procedural effectiveness and functional recovery. These experiments indicate that ART can be successfully performed from a technical standpoint. Ex vivo studies demonstrate acceptable surgical times, and studies in animal models confirm graft viability and functional restoration. Future research should refine surgical techniques, investigate neural regeneration mechanisms, and develop immunosuppressive protocols to advance the field toward clinical application. ART holds the potential to completely change the treatment of severe anorectal dysfunction and permanent colostomy, offering a definitive solution to these irreversible conditions.}, }
@article {pmid42126928, year = {2026}, author = {Song, J and He, J and Liang, Z}, title = {Sucralose Exposure During Pregnancy Elevates Gestational Diabetes Risk via Gut Microbiota-Metabolic Axis in Mice.}, journal = {Journal of diabetes research}, volume = {2026}, number = {1}, pages = {e8638903}, pmid = {42126928}, issn = {2314-6753}, support = {GZY-KJS-ZJ-2025-037//Joint TCM Science &amp; Technology Projects of National Demonstration Zones/ ; ZDFY2022-4XB101//4&#x2009;+&#x2009;X Clinical Research Project of Women's Hospital, School of Medicine, Zhejiang University/ ; 82571935//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Pregnancy ; Female ; *Gastrointestinal Microbiome/drug effects ; *Diabetes, Gestational/metabolism/chemically induced/microbiology ; *Sucrose/analogs &amp; derivatives/adverse effects ; Mice ; Dysbiosis/chemically induced ; *Prenatal Exposure Delayed Effects ; Feces/microbiology ; Mice, Inbred C57BL ; Blood Glucose/metabolism/drug effects ; *Sweetening Agents ; Insulin Resistance ; }, abstract = {Sucralose, a widely used nonnutritive artificial sweetener, has gained increasing popularity during pregnancy due to its low-calorie properties. The influence of sucralose on gestational diabetes mellitus (GDM) risk via alterations in gut microbiota composition is not yet well understood. This study sought to explore how gestational sucralose exposure influences GDM development in mice through gut microbiota dysbiosis, impaired intestinal barrier, and metabolic disorders. As an exploratory extension, we also preliminarily assessed early growth in offspring. In our experimental design, pregnant mice were administered sucralose solution to evaluate GDM incidence. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis. To establish causality, gut microbiota from sucralose-exposed pregnant mice was transplanted into control pregnant mice to assess subsequent GDM development and alterations in fecal 16S rRNA profiles. Additionally, we monitored postpartum glucose metabolism in sucralose-treated pregnant mice and tracked offspring body weight changes. Our results demonstrated that sucralose exposure significantly increased GDM incidence, accompanied by higher glucose levels and diminished insulin sensitivity. Furthermore, sucralose administration caused significant gut microbiota imbalance. It reduced beneficial taxa like Prevotellaceae UCG-001 and Lachnospiraceae UCG-001 while increasing the proinflammatory taxon Parasutterella. These changes strongly correlated with key fecal metabolites, including 5-aminopentanoic acid. Notably, maternal sucralose consumption during pregnancy also affected offspring body weight. These findings collectively indicate that gestational sucralose exposure elevates GDM risk in mice through the gut microbiota-metabolism axis, providing critical scientific evidence regarding the safety of low-calorie sweeteners in clinical applications during pregnancy.}, }
@article {pmid42127421, year = {2026}, author = {Li, Y and Yuan, Q and Yang, Y and Wang, L and Han, Q and Yang, Y and Zhang, J and Wei, H and Yin, Y and Tao, S and Yin, J}, title = {Gut microbiota control host lipid deposition through HDAC9-driven PPARγ acetylation.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrag109}, pmid = {42127421}, issn = {1751-7370}, abstract = {The healthy gut microbiota communities play a complex and significant role in lipid absorption and deposition, leading to multiple health benefits. Here, we confirmed an impaired absorption and deposition function in germ-free pigs and mice, which was partially reversed after human fecal microbiota transplantation. By integrating single-cell data from adipose tissue, we identified HDAC9 as a key regulator, marked by the presence of a population of small mature adipocytes exhibiting high HDAC9 and low PPARγ expression in germ-free pigs. HDAC9 deficiency of preadipocytes drove FABP4/5-mediated lipid deposition by directly targeting PPARγ expression and acetylation modification. Finally, we verified the interaction between gut microbiota and host HDAC9/PPARγ/FABP4/5 signaling cascade might be microbial receptors (ie, Dectin1 or TLRs)-dependent rather than microbial metabolites. Altogether, our study uncovers the gut microbiota-HDAC9-PPARγ axis as a key regulator of adipocyte function and lipid deposition, offering a potential therapeutic target for lipid-related metabolic diseases.}, }
@article {pmid42128051, year = {2026}, author = {Rondeau, LE and Da Luz, BB and Haas, D and Muppidi, P and Wang, X and Dang, R and Rueda, G and Nardelli, A and De Palma, G and Sokol, H and Bercik, P and Caminero, A}, title = {Dietary Tryptophan Enhances Aryl Hydrocarbon Receptor Activation and Reduces Colitis Through Microbial Metabolism.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101811}, doi = {10.1016/j.jcmgh.2026.101811}, pmid = {42128051}, issn = {2352-345X}, abstract = {BACKGROUND &amp; AIMS: Disrupted microbial tryptophan metabolism and impaired aryl hydrocarbon receptor activation are implicated in inflammatory bowel disease pathogenesis. However, strategies to restore this pathway through diet or microbial modulation remain poorly defined. This study investigates how dietary tryptophan and human and mouse microbiota modulate metabolism, aryl hydrocarbon receptor activation, and intestinal inflammation in preclinical models.<br><br>METHODS: Gnotobiotic mice colonized with microbiota of varying complexity or human fecal microbiota from patients with ulcerative colitis and healthy controls were used to assess the impact of microbiota and dietary tryptophan supplementation on aryl hydrocarbon receptor activation and colitis severity. Chemically induced and spontaneous colitis models were investigated.<br><br>RESULTS: Inflammatory bowel disease fecal samples showed reduced aryl hydrocarbon receptor activation compared with healthy controls, and fecal microbiota transplantation into germ-free mice demonstrated that impaired aryl hydrocarbon receptor is microbiota-dependent. Mice colonized with minimal microbiota had impaired microbial tryptophan metabolism, lower aryl hydrocarbon receptor activation, and worsened colitis severity compared with those colonized with complex microbiota. Dietary tryptophan supplementation in conventional and ulcerative colitis-humanized mice enhanced microbial production of aryl hydrocarbon receptor agonists, restored aryl hydrocarbon receptor activation, and reduced colitis severity in an aryl hydrocarbon receptor-dependent manner. Cocolonization with a tryptophan-metabolizing bacterium, Clostridium sporogenes, further improved tryptophan metabolism and colitis severity in mice with impaired microbial tryptophan metabolism.<br><br>CONCLUSIONS: Microbial tryptophan metabolism is critical for determining intestinal inflammation. Dietary tryptophan supplementation restores microbial metabolic pathways, mitigates colitis severity in preclinical models, and may address key metabolic deficiencies in patients with inflammatory bowel disease with impaired tryptophan metabolism. This study demonstrates the therapeutic potential of targeting microbial metabolism with diet in inflammatory bowel disease management.}, }
@article {pmid42128395, year = {2026}, author = {Cho, E and Lee, JH and Hong, JT and Kwon, KS and Shin, YW}, title = {Fecal microbiota transplantation for marked colonic dilatation.}, journal = {The Korean journal of internal medicine}, volume = {41}, number = {3}, pages = {560-562}, pmid = {42128395}, issn = {2005-6648}, }
@article {pmid42129837, year = {2026}, author = {Wang, MZ and Du, ZB and Xu, WQ and Xie, YH and Wang, LL and He, XX and Wang, YH and Zheng, HY and Yao, YL and Song, YB and Lin, ZN and Lin, YC}, title = {Butyrate-producing gut bacteria restrain PBAT microplastic-triggered brain microglial lipotoxicity via a microbiota-butyrate-mTORC1-ISR relay along the gut-brain axis.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03869-1}, pmid = {42129837}, issn = {1742-2094}, support = {82273667//the National Natural Science Foundation of China/ ; 82574139//the National Natural Science Foundation of China/ ; 3502Z202573032//the Natural Science Foundation of Xiamen, China/ ; 2023XAKJ0101024//the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory/ ; 2022Y4009//the Industry-University-Research Cooperation Project of Fujian Science and Technology Plan/ ; FJHYF-L-2025-04-008//the Fujian Province Special Fund Project for Promoting High-Quality Development of Marine and Fishery Industries/ ; 20720250004//the Fundamental Research Funds for the Central Universities/ ; S202210384407//the XMU Undergraduate Innovation and Entrepreneurship Training Programs/ ; }, abstract = {Eco-friendly poly(butylene adipate-co-terephthalate) (PBAT) is widely marketed as biodegradable, yet the neurotoxicity of derived PBAT microplastics (PBAT-MPs) and their underlying mechanisms remain poorly characterized. Here we identify a previously unrecognized "gut microbiota-butyrate-neuro-lipid" axis linking intestinal PBAT-MPs exposure to hippocampal microglial lipotoxicity and cognitive impairment. By integrating fecal microbiota transplantation (FMT) with multi-omics analyses, we demonstrate that orally administered PBAT-MPs preferentially accumulate in the colon, impair epithelial barrier integrity, deplete butyrate-associated taxa, including Muribaculaceae and Alloprevotella, and enrich Escherichia-Shigella. Butyrate depletion elevates systemic lipopolysaccharide (LPS) levels and, via the gut-brain inflammatory route, activates mTORC1-integrated stress response (ISR) signaling in microglia. Consequently, microglia acquire a lipotoxic phenotype characterized by transcriptional up-regulation of DGAT- and ACSL-dependent lipid droplet (LD) biogenesis genes, accumulation of toxic lipids and inflammatory mediators, synaptic stripping, and memory loss. In vivo butyrate supplementation in PBAT-MP-exposed mice alleviates hippocampal pathology, normalizes microglial lipid accumulation, suppresses neuroinflammation, reduces ceramide levels, and improves cognitive performance. Mechanistically, butyrate inhibits mTORC1, attenuates eIF2α-ATF4-dependent ISR signaling, and represses DGAT/ACSL-dependent LD biogenesis, whereas microglial Rptor overexpression abolishes these protective effects, identifying mTORC1 as an upstream metabolic checkpoint. Collectively, our findings establish the microbiota-butyrate-mTORC1-ISR relay as a core driver of PBAT-MPs-induced neurotoxicity and highlight restoration of butyrate signaling as a promising microbiota-based strategy for preventing microplastic-induced brain lipotoxic injury.}, }
@article {pmid42130360, year = {2026}, author = {Li, Y and Niu, HS and Lu, XL and Li, XC and Xiao, M and Wang, Y and Yang, SJ and Guo, YY and Sun, Y}, title = {[Fecal microbiota transplantation attenuates gastrointestinal inflammation in murine acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation by inhibiting RIPK1/RIPK3-mediated necroptosis].}, journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics}, volume = {28}, number = {5}, pages = {598-606}, pmid = {42130360}, issn = {1008-8830}, mesh = {Animals ; *Receptor-Interacting Protein Serine-Threonine Kinases/physiology ; *Graft vs Host Disease/therapy/etiology ; *Necroptosis ; Mice ; Mice, Inbred BALB C ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Fecal Microbiota Transplantation ; Male ; Acute Disease ; Transplantation, Homologous ; Female ; Gastrointestinal Microbiome ; Protein Kinases ; }, abstract = {OBJECTIVES: To investigate the molecular mechanism by which fecal microbiota transplantation (FMT) alleviates gastrointestinal inflammation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine acute graft-versus-host disease (aGVHD).<br><br>METHODS: A murine aGVHD model after allo-HSCT was established, and BALB/c mice were randomly assigned to blank control, bone marrow transplantation, aGVHD model, and FMT treatment groups (n=6 per group). Disease severity was assessed by histopathology. Expression of receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was evaluated by immunohistochemistry. Protein levels of RIPK1, RIPK3, MLKL, phosphorylated RIPK1 (p-RIPK1), and phosphorylated MLKL (p-MLKL) were determined by Western blotting. Plasma regenerating islet-derived protein 3 alpha (Reg3&#x3b1;) was measured by enzyme-linked immunosorbent assay. The intestinal microbiota was profiled by 16S rRNA gene sequencing.<br><br>RESULTS: Compared with the aGVHD model group, the FMT group showed higher relative abundances of Firmicutes and Bacteroidetes and a lower relative abundance of Proteobacteria; body weight loss was markedly attenuated, and survival time was prolonged. Alpha-diversity indices (Simpson, Pielou, Shannon) increased in the FMT group (P<0.05). Intestinal pathology scores, expression of RIPK1, RIPK3, and MLKL, protein levels of RIPK1, RIPK3, MLKL, p-RIPK1, and p-MLKL, and plasma Reg3&#x3b1; levels were significantly reduced in the FMT group versus the aGVHD model group (all P<0.05).<br><br>CONCLUSIONS: FMT may attenuate gastrointestinal inflammation in aGVHD by restoring intestinal microbial balance and inhibiting the RIPK1/RIPK3-mediated necroptosis pathway.}, }
@article {pmid42130461, year = {2026}, author = {Tian, M and Wang, D and Zhang, C and Fan, J and Li, W and Liu, X and Shi, J}, title = {Gut Microbiota Dysbiosis Drives Early Alzheimer's Pathogenesis via Microglial TREM2/SYK/NF-κB Signaling Axis.}, journal = {ACS chemical neuroscience}, volume = {17}, number = {11}, pages = {2190-2202}, doi = {10.1021/acschemneuro.6c00173}, pmid = {42130461}, issn = {1948-7193}, mesh = {Animals ; *Alzheimer Disease/metabolism/microbiology ; *Microglia/metabolism ; *Membrane Glycoproteins/metabolism ; *Receptors, Immunologic/metabolism ; *Syk Kinase/metabolism ; *Gastrointestinal Microbiome/physiology ; *NF-kappa B/metabolism ; Signal Transduction/physiology ; Mice ; *Dysbiosis/metabolism ; Mice, Transgenic ; Fecal Microbiota Transplantation ; Male ; Humans ; Neuroinflammatory Diseases/metabolism ; }, abstract = {Gut microbiota dysbiosis is implicated in Alzheimer's disease (AD), but causal evidence and mechanisms linking it to microglial dysfunction remain unclear. This study aimed to determine whether gut microbiota drives neuroinflammation and cognitive impairment via the microglial TREM2/SYK signaling axis in early AD. Using six-month-old APP/PS1 mice, fecal microbiota transplantation (FMT) was performed between AD and wild-type mice. Cognitive function, gut microbiota composition (16S rRNA sequencing), serum metabolites, hippocampal neuroinflammation, microglial polarization, and TREM2/SYK/NF-κB pathway activity were assessed. BV2 microglial cells were treated with Aβ oligomers, a TREM2 agonist, or a SYK inhibitor for mechanistic validation. AD mice exhibited cognitive decline, reduced microbial diversity (e.g., decreased Bacteroidetes and Lactobacillus), and altered circulating metabolites, including decreased butyrate and elevated LPS. Their hippocampi exhibited heightened glial activation, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and a shift toward pro-inflammatory activation markers (M1-associated). At the molecular level, TREM2 expression was downregulated, whereas SYK phosphorylation and NF-κB activation were enhanced, concomitant with synaptic protein loss. Critically, FMT from healthy donors reversed these abnormalities and improved cognition, whereas AD microbiota induced mild pathology in wild-type mice. In vitro, TREM2 activation or SYK inhibition attenuated Aβ-induced M1 polarization and cytokine release in microglia. Gut microbiota dysbiosis promotes early AD pathogenesis by dysregulating the microglial TREM2/SYK/NF-κB pathway, thereby driving neuroinflammation and synaptic dysfunction. Targeting this microbiota-signaling axis may offer novel therapeutic strategies.}, }
@article {pmid42130741, year = {2026}, author = {Long, J and Zhao, J and Gu, X and Huang, C}, title = {Post-transplant diabetes mellitus after kidney transplantation: pathogenesis, risk factors, and management strategies.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1829579}, pmid = {42130741}, issn = {1664-2392}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; Risk Factors ; *Postoperative Complications/etiology/therapy ; *Diabetes Mellitus/etiology/therapy ; Gastrointestinal Microbiome ; Immunosuppressive Agents/adverse effects ; }, abstract = {Post-transplant diabetes mellitus (PTDM) affects 7-39% of kidney transplant recipients and substantially worsens cardiovascular, infectious, and allograft outcomes. Although PTDM shares core pathophysiological features with type 2 diabetes-peripheral insulin resistance and impaired β-cell secretion-its etiology is fundamentally shaped by immunosuppressive therapy. Calcineurin inhibitors suppress insulin gene transcription via NFAT inhibition and exacerbate lipotoxicity; corticosteroids drive hepatic gluconeogenesis and impair GLUT4-mediated glucose uptake; and mTOR inhibitors reduce β-cell mass through mTORC1-dependent mechanisms. Chronic NF-κB/JNK-driven inflammation further amplifies insulin resistance and promotes β-cell apoptosis. Beyond these established mechanisms, we propose a unifying "gut-immune-metabolic axis" in which immunosuppression-induced gut microbiota dysbiosis-characterized by depletion of short-chain fatty acid-producing taxa (Roseburia, Faecalibacterium prausnitzii) and Akkermansia muciniphila-drives intestinal barrier dysfunction, endotoxemia, impaired FXR/TGR5-mediated GLP-1 secretion, and TMAO-associated metabolic inflammation, collectively perpetuating glucose dysregulation. Risk stratification integrates non-modifiable factors (advanced age, African American/Hispanic/South Asian ethnicity, TCF7L2 polymorphisms, autosomal dominant polycystic kidney disease) with modifiable determinants (pre-transplant dysglycemia, obesity, hypomagnesemia, hepatitis C and cytomegalovirus infections, acute rejection, and diuretic use). Diagnosis requires OGTT-centered assessment per the 2024 International Consensus guidelines, with cautious interpretation of HbA1c during the early post-transplant period. Management encompasses personalized immunosuppression (corticosteroid minimization, tacrolimus trough levels <10 ng/mL, and belatacept-based regimens in high-risk patients), structured lifestyle interventions, and emerging pharmacotherapies-particularly SGLT2 inhibitors and GLP-1 receptor agonists-which offer cardiometabolic benefits beyond glycemic control. Microbiome-targeted strategies, including prebiotics, probiotics, and fecal microbiota transplantation, represent a conceptually compelling frontier warranting prospective investigation. This framework reframes PTDM as a multi-hit, immunometabolic syndrome and provides a translational roadmap toward precision prevention and improved long-term transplant outcomes.}, }
@article {pmid42131202, year = {2026}, author = {Sivamaruthi, BS and Kesika, P and Chaiyasut, C and Ragu Varman, D}, title = {Microbiome driven modulation of neurotransmitters: implications for neurotransmission and mood disorders.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1750377}, pmid = {42131202}, issn = {1664-302X}, abstract = {The human gut microbiome has emerged as a crucial regulator of neurophysiological processes by engaging with the central nervous system (CNS) via the microbiota-gut-brain (MGB) axis. One of the most significant ways gut microorganisms influence brain functions is by altering the levels of neurotransmitters. A significant relationship exists between microbial activity and mood, behavior, and cognition. Gut microorganisms can make or break down bioactive substances like serotonin, dopamine, γ-aminobutyric acid (GABA), glutamate, acetylcholine, and histamine. These microbial modulations influence precursor availability, receptor sensitivity, synaptic signaling dynamics, and neuroimmune modulation, thereby indirectly shaping neurotransmission within central circuits. These neurochemical effects, particularly involving serotonergic, dopaminergic, GABAergic, and glutamatergic pathways, are mediated through microbial metabolites such as short-chain fatty acids (SCFAs), alterations in tryptophan metabolism, immune system activation, vagal nerve transmission, and the control of the hypothalamic-pituitary-adrenal (HPA) axis. Changes in the composition of the microbiome have been frequently linked to mood disorders, such as depression, anxiety, bipolar disorder, and schizophrenia. The current review integrates findings from preclinical and clinical studies on microbiome-related neurotransmitter modulation, emphasizing novel therapeutics such as probiotics, prebiotics, fecal microbiota transplantation, and dietary alterations. Unlike previous reviews that primarily focus on microbiome composition or therapeutic interventions such as probiotics and fecal microbiota transplantation, this review adopts a neurotransmitter-centered framework, integrating microbial regulation of serotonergic, dopaminergic, GABAergic, glutamatergic, cholinergic, and histaminergic systems with the pathophysiology of mood disorders. Connecting microbiota-driven modulation of neurochemistry to mental outcomes offers a promising adjunctive avenue for mood disorder management, pending rigorous mechanistic and clinical validation.}, }
@article {pmid42131305, year = {2026}, author = {Toto, F and Cardile, S and Scanu, M and Marzano, V and Petito, V and Masi, L and Puca, P and Giorgio, V and Alterio, T and Diamanti, A and De Angelis, P and Lopetuso, LR and Scaldaferri, F and Putignani, L and Del Chierico, F}, title = {Ecological patterns of the gut mycobiome and microbiome in ulcerative colitis across life stages.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1769892}, pmid = {42131305}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology ; *Mycobiome ; *Gastrointestinal Microbiome ; Adult ; Child ; Male ; Female ; *Fungi/classification/genetics/isolation &amp; purification ; Bacteria/classification/genetics/isolation &amp; purification ; Middle Aged ; Young Adult ; Adolescent ; Dysbiosis/microbiology ; Metagenome ; Child, Preschool ; Age Factors ; Aged ; Feces/microbiology ; }, abstract = {INTRODUCTION: Age-related variations in the gut microbial communities may influence immune regulation and inflammatory processes in inflammatory bowel diseases (IBD). However, distinguishing age effects from differences in clinical characteristics remains challenging.<br><br>METHODS: We investigated life-stage-associated patterns of the gut microbiome and mycobiome while accounting for clinical heterogeneity between paediatric and adult ulcerative colitis (UC) populations. We analysed 73 targeted metagenomes of bacteria and 69 targeted metagenomes of fungi from 26 paediatric and 47 adult patients with UC. Microbial diversity metrics and multivariate analyses were applied to evaluate community variation, and mucosal immune markers were assessed by ELISA. Clinical variables, including disease activity, duration, and treatment exposure, were considered when interpreting age-related microbial differences.<br><br>RESULTS: Fungal communities exhibited higher richness in adults and formed distinct age-related clusters in beta-diversity analyses, whereas bacterial composition remained largely comparable across age groups. Children were enriched in inflammation-associated fungi (Saccharomycetes, Aureobasidium, Cladosporium) and depleted in taxa commonly linked to gut health (Clavispora, Vishniacozyma, Betamyces). Stratification by life stage identified young adults as displaying the most pronounced dysbiosis, characterised by Basidiomycota/Ascomycota and Firmicutes/Bacteroidota ratios, and reduced Faecalibacterium prausnitzii abundance. Age-associated immune patterns were observed, with lysozyme levels increasing across life stages, correlating with sIgA, and positively associating with F. prausnitzii, although declining with increasing disease severity.<br><br>DISCUSSION: Age-related variation was more evident in fungal than bacterial communities, suggesting that host developmental and immunological factors contribute to mycobiome configuration beyond clinical imbalance alone. Together, these findings indicate that life stage is linked to ecological variation of the gut mycobiome and mucosal immune responses in UC, while bacterial communities appear primarily shaped by disease-related factors. The transition from childhood to adulthood may represent a critical window of host-fungal interaction relevant for age-tailored microbiome-based strategies.}, }
@article {pmid42131376, year = {2026}, author = {Prosty, C and Desormeau, B and Lee, TC and McDonald, EG}, title = {Diagnosis, treatment, and prophylaxis of Clostridioides difficile infections: A cross-sectional survey of Canadian clinicians.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {11}, number = {1}, pages = {37-50}, pmid = {42131376}, issn = {2371-0888}, abstract = {BACKGROUND: A recent international survey of clinician practices in the management of Clostridioides difficile infections (CDIs) identified numerous areas of practice heterogeneity. The degree of practice variability within Canada is unknown.<br><br>METHODS: Data from Canadian participants of an international survey of clinician CDI practices were extracted. Practice alignment with the Association of Medical Microbiology and Infectious Disease (AMMI) Canada CDI treatment guidelines was assessed. CDI practices were compared across provinces using the Fisher exact test with a simulated P value.<br><br>RESULTS: A total of 112 responses were obtained from eight provinces. Vancomycin (85.3% for first episode), vancomycin pulse and taper (P-T) (61.8% and 32.4% for first and second recurrences, respectively), and fecal microbiota transplant (32.4% for third recurrence) were preferred treatment strategies. Practice alignment with the AMMI Canada CDI guidelines for the treatment of recurrences was low (range 23.5%-32.4%, depending on the recurrence number). With respect to secondary CDI prophylaxis during antibiotic reexposure, there were interprovincial differences in the perceived indication (P = .03), whether to prescribe at all (P < .001), and duration of prophylaxis (P = .004). There was significant clinician support (>50%) for randomized clinical trials testing treatment strategies for recurrent episodes and for secondary prophylaxis.<br><br>CONCLUSION: Despite the availability of national guidelines, we found significant heterogeneity in practice across Canada, often not aligned with guideline recommendations. These findings underscore the need for a platform trial comparing treatment strategies and a trial to establish the efficacy of secondary prophylaxis.}, }
@article {pmid42132238, year = {2026}, author = {Roostaei, G and Riahi, T and Nikfar, S and Abdollahi, M}, title = {Harnessing the immune system in lung cancer: emerging role of the microbiome.}, journal = {Expert review of clinical immunology}, volume = {22}, number = {5}, pages = {557-574}, doi = {10.1080/1744666X.2026.2661805}, pmid = {42132238}, issn = {1744-8409}, mesh = {Humans ; *Lung Neoplasms/immunology/therapy/microbiology ; Animals ; Immunotherapy/methods ; *Microbiota/immunology ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics ; *Gastrointestinal Microbiome/immunology ; }, abstract = {INTRODUCTION: The microbiome has emerged as a critical regulator of tumor biology and immune response in lung cancer. Once considered sterile, the lung is now recognized to harbor a diverse microbiome that interacts with the gut-lung axis to shape inflammation, immune evasion, and therapeutic outcomes.<br><br>AREAS COVERED: This study reviews current evidence linking microbiome composition and function to lung cancer development and response to immune checkpoint inhibitors (ICIs). We explore mechanisms of microbial influence on host immunity, identify key taxa associated with treatment outcomes, and summarize therapeutic strategies such as fecal microbiota transplantation, probiotics, postbiotics, dietary changes, antibiotics, and engineered live biotherapeutics. The literature search was performed across multiple databases and sources, including PubMed, Scopus, Embase, and clinical trial registries, up to August 2025, focusing on both preclinical and clinical studies related to lung cancer, immunotherapy, and microbiome-targeted interventions.<br><br>EXPERT OPINION: Microbiome research is redefining precision oncology by presenting new biomarkers and therapeutic targets. Although early-phase trials show potential to improve ICI efficacy, implementation is limited by donor variability, methodological differences, and biosafety issues. Standardized protocols, mechanistic studies, and biomarker-driven patient selection will be crucial to incorporating microbiome modulation into routine lung cancer treatment.}, }
@article {pmid42132696, year = {2026}, author = {Zhou, Z and Pan, X and Ni, J and Lou, Z and Shen, Y and Jiang, S and Dong, X and Wang, F and Chen, Y and Li, L}, title = {Akkermansia muciniphila ameliorates acute liver injury aggravated by MASLD-associated dysbiosis via daidzein/PPAR-α/NF-κB signaling.}, journal = {Food &amp; function}, volume = {17}, number = {10}, pages = {4717-4728}, doi = {10.1039/d6fo01338d}, pmid = {42132696}, issn = {2042-650X}, mesh = {Animals ; NF-kappa B/metabolism ; Mice ; *Isoflavones/metabolism ; *PPAR alpha/metabolism ; *Dysbiosis/microbiology ; Signal Transduction ; Humans ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Probiotics/pharmacology ; Gastrointestinal Microbiome ; Akkermansia ; }, abstract = {Existing evidence indicates that pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) confers susceptibility to acute liver injury (ALI). Nevertheless, the underlying mechanism prompting ALI risk in such a condition is not fully uncovered yet. Gut dysbiosis has been well-documented in MASLD patients which prompts us to hypothesize that gut dysbiosis may serve as a contributing factor and a regulatory target to ALI susceptibility. A case-control study was performed and the increased risk of ALI in MASLD patients was verified. Mice pretreated with MASLD mouse/patient-derived fecal microbiota transplantation (FMT) demonstrated worsened ALI after D-GalN/LPS injection. We identified significant gut dysbiosis with decreased microbial α-diversity, beneficial genus Lactobacillus, and increased potentially harmful bacteria Campylobacter and Helicobacter. Probiotic Akkermansia muciniphila (A. muciniphila) was reported to improve gut dysbiosis. Thus, we tested the effect of A. muciniphila on ALI mice pretreated with MASLD mouse-derived FMT. A. muciniphila significantly ameliorated the worsened ALI and improved gut dysbiosis. Transcriptomic analysis revealed that A. muciniphila restored the impaired liver PPAR-α signaling, alleviating the aggravated NF-κB signaling and downstream inflammation response in the liver. Specifically, A. muciniphila restored the decreased abundance of the PPAR-α agonist daidzein in the colon, thereby restoring PPAR-α activation and inhibiting NF-κB signaling in the liver. Daidzein is also capable of ameliorating ALI aggravated by MASLD-associated dysbiosis, accompanied by PPAR-α activation and NF-κB inhibition. Our findings revealed that gut dysbiosis in MASLD increased the risk of ALI. A. muciniphila exhibited preventive potential for MASLD patients to reduce ALI risk. Daidzein/PPAR-α/NF-κB signaling is important to maintain host resistance to hepatoxic challenge.}, }
@article {pmid42134452, year = {2026}, author = {Sharma, AK and Akhtar, MS and Orayj, K and Farooqui, S and Khan, A and Sharma, G}, title = {Microbial dysbiosis in metabolic disorders: linking epigenomic regulation and pathological mechanisms.}, journal = {Drug discovery today}, volume = {31}, number = {4}, pages = {104698}, doi = {10.1016/j.drudis.2026.104698}, pmid = {42134452}, issn = {1878-5832}, abstract = {Microbial dysbiosis critically contributes to metabolic disorders by altering host-microbiome interactions and disrupting metabolic homeostasis. This review highlights how dysbiosis-derived metabolites, including short-chain fatty acids (SCFA) and trimethylamine-N-oxide (TMAO), modulate epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA expression in key metabolic tissues. These epigenomic changes impair insulin signaling, lipid metabolism, and inflammatory responses. We further explore the potential of microbial-epigenetic biomarkers for early diagnosis of metabolic disease. Moreover, we assess emerging microbiome-based therapies including prebiotics, SCFA supplementation, and fecal microbiota transplantation for their ability to reverse epigenetic dysregulation. Understanding the microbiome-epigenome-metabolism axis may enable precision diagnostics and targeted interventions for obesity, type 2 diabetes, and related disorders.}, }
@article {pmid42134502, year = {2026}, author = {Li, T and Jiang, M and Chen, L and Dong, H and Yu, J and Chen, J and Wang, X}, title = {A neutral polysaccharide from the pulp of Trichosanthes kirilowii Maxim mitigates constipation through microbiota-dependent activation of brain-gut axis.}, journal = {Journal of ethnopharmacology}, volume = {368}, number = {}, pages = {121845}, doi = {10.1016/j.jep.2026.121845}, pmid = {42134502}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Constipation/drug therapy/chemically induced/microbiology/physiopathology ; Male ; *Polysaccharides/pharmacology/isolation &amp; purification/therapeutic use ; *Trichosanthes/chemistry ; Mice ; Fecal Microbiota Transplantation ; *Brain-Gut Axis/drug effects ; Diphenoxylate ; }, abstract = {Trichosanthes kirilowii Maxim, known as "Gualou" in traditional Chinese medicine, has been extensively utilized to cure various diseases. Nevertheless, the precise mechanism through which TKPW, a neutral polysaccharide isolated from the pulp of Trichosanthes kirilowii Maxim by water elution, alleviates constipation remains to be fully elucidated.<br><br>AIM OF THE STUDY: To investigate the efficacy of TKPW in alleviating constipation in mice and to clarify the mechanisms.<br><br>MATERIALS AND METHODS: TKPW was isolated, structurally characterized, and evaluated for its anti-constipation effect in diphenoxylate-induced mice. Fecal parameters, biochemical markers, gut microbiota were analyzed, and the microbiota's role was substantiated using a fecal microbiota transplantation (FMT) trial.<br><br>RESULTS: TKPW was characterized as a heteropolysaccharide with average molecular weight of 12.431&#xa0;kDa, featuring a backbone of &#x3b1;-D-Glcp-(1&#x2008;&#x2192;&#x2008;5)-Araf-(1&#x2008;&#x2192;&#x2008;6)-&#x3b1;-D-Galp-(1&#x2008;&#x2192;&#xa0;6)-&#x3b1;-D-Glcp-(1&#xa0;&#x2192;&#xa0;. High-dose TKPW (TKPW-H) treatment significantly improved fecal output, gastrointestinal transit rate, and colonic morphology in constipated mice. Concurrently, pro-inflammatory cytokine levels were markedly diminished by TKPW-H, alongside a significant increase in tight-junction protein expression. Additionally, TKPW-H selectively promoted excitatory enteric neurotransmitters and suppressed inhibitory ones. TKPW-H resulted in a significant suppression of colonic vasoactive intestinal peptide receptor 1 (VIPR1) expression, accompanied by a concurrent upregulation of 5-hydroxytryptamine receptor 4 (HTR4). Importantly, TKPW-H enhanced the relative abundance of beneficial bacteria, elevated the fecal concentrations of short-chain fatty acids (SCFAs), and activated the cerebral receptors (GPR41, GPR43 and GPR109a). FMT from TKPW-treated donors reproduced the anti-constipation effects.<br><br>CONCLUSION: TKPW supplementation alleviates constipation through modulation of the microbiota-brain-gut axis, underscoring its potential as a prebiotic therapeutic agent.}, }
@article {pmid42135927, year = {2026}, author = {Li, Z and Li, P and Peng, T and Zhou, X and Liu, Y and Ai, C and Xiao, N and Song, S and Lei, X and Liu, J and Wang, W and Zhou, P and Li, Z and Liu, Z and Dai, X and Zhang, Z and Li, T}, title = {Indole-3-carboxaldehyde from Limosilactobacillus reuteri targets the DUSP1/ERK/NOX2/ROS axis to enhance the bactericidal activity of macrophages and protects against sepsis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2671382}, pmid = {42135927}, issn = {1949-0984}, mesh = {*Limosilactobacillus reuteri/metabolism/chemistry ; Animals ; *Macrophages/drug effects/immunology/metabolism/microbiology ; Humans ; *Sepsis/microbiology/prevention &amp; control/immunology/metabolism ; Mice ; *Dual Specificity Phosphatase 1/metabolism/genetics ; Male ; Reactive Oxygen Species/metabolism ; *Indoles/pharmacology/metabolism ; *NADPH Oxidase 2/metabolism/genetics ; Female ; Disease Models, Animal ; Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Middle Aged ; }, abstract = {The gut microbiota plays a critical regulatory role in the pathogenesis of sepsis, yet the immunomodulatory mechanisms of Limosilactobacillus reuteri (L. reuteri) and its metabolites in sepsis remain to be fully elucidated. This study found that the abundance of intestinal L. reuteri was significantly reduced in patients with bacterial sepsis and showed a negative correlation with disease severity. In a mouse model of sepsis induced by cecal ligation and puncture, fecal microbiota transplantation and live bacterial supplementation further confirmed that live L. reuteri effectively attenuated sepsis progression. Integrated metabolomic and network pharmacological analysis identified indole-3-carboxaldehyde (IAld), a metabolite derived from L. reuteri, which enhances macrophage bactericidal function and alleviates sepsis-associated organ damage. Mechanistically, IAld directly targets DUSP1 in macrophages, inhibits its phosphatase activity, thereby promoting ERK phosphorylation, upregulating NOX2 expression, stimulating reactive oxygen species production, and ultimately enhancing bacterial clearance. Notably, circulating IAld levels in septic patients were significantly inversely correlated with SOFA score, APACHE II score, and arterial lactate levels, and IAld safely enhanced the bactericidal function of human macrophages in vitro. This study is the first to systematically demonstrate that L. reuteri and its metabolite IAld exert a protective effect against sepsis through the DUSP1/ERK/NOX2/ROS axis, providing novel mechanistic insights and potential therapeutic targets for immunometabolic intervention in sepsis.}, }
@article {pmid42136241, year = {2026}, author = {Singh, R and Monika,  and Mazumder, R and Mazumder, A and Singh, M and Majee, C and Padhi, S and Das, S}, title = {Chronic Inflammation (A Silent Killer) - Molecular Mechanisms and Emerging Therapeutic Approaches.}, journal = {Current drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113894501450885260409050432}, pmid = {42136241}, issn = {1873-5592}, abstract = {Chronic inflammation is a dysregulated and persistent immune response that underlies numerous serious health conditions, like heart problems, diabetes, nerve damage, cancer, or conditions where the body attacks itself. Recently, scientists have gained a better understanding of how molecules such as cytokines and chemokines, along with dysregulated immune cells, contribute to excessive oxidative stress and impaired healing processes. New tools now help identify this condition as early as possible through biomarkers, advanced laboratory techniques, integrated data approaches, and smart sensors that track biological changes in real time. However, despite this knowledge, effective strategies for early prevention and long-term treatment remain limited. Daily habits, particularly anti-inflammatory dietary patterns, regular physical activity, and stress management, play a critical role in reducing the risk of disease. Emerging therapies, including inflammasome inhibitors, cytokine-targeted biologics, immunometabolic modulators, and specialized pro-resolving mediators, may restore immune homeostasis rather than merely suppressing symptoms. Additionally, microbiome-targeted interventions-such as probiotics, prebiotics, bacteriophage therapy, and fecal microbiota transplantation-are increasingly being recognized as potential strategies to modulate systemic inflammation. Daily habits, especially eating patterns that fight inflammation, walking regularly, or handling stress, are critically important for lowering the chances of illness. Chronic inflammation is a complex, multifactorial process; therefore, its effective management requires integrated efforts in basic research, therapeutic innovation, and population- level healthcare strategies. Innovations in personalized medicine, AI-based analytics, digital health technologies, and microbiome science are poised to significantly enhance diagnostic and therapeutic approaches. Sustained cross-disciplinary collaboration will be critical in mitigating the worldwide impact of chronic inflammatory disorders and improving long-term health outcomes.}, }
@article {pmid42136267, year = {2026}, author = {Saraswati, BD and Wicaksono, AW and Valles, SL and Poeggeler, B and Singh, SK}, title = {Exploring the Gut Microbiome as a Promising Frontier in Alzheimer's Disease Therapy.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X444975260408044214}, pmid = {42136267}, issn = {1875-6190}, abstract = {Alzheimer's Disease (AD) is a major global health challenge, particularly in ageing populations, and current therapies offer limited modification of disease progression. Emerging evidence indicates that the gut microbiome contributes to AD pathogenesis through metabolic, immune, and neuroendocrine mechanisms. Microbial metabolites, including Short-Chain Fatty Acids (SCFAs), bile acids, and trimethylamine-N-oxide (TMAO), regulate neuronal signalling and blood-brain barrier integrity, and dysbiosis has been linked to amyloid-β (Aβ) accumulation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, and synaptic dysfunction. Host genetic factors, particularly APOE ε4 and immune-regulatory variants such as TREM2 and CD33, further influence microbial composition and susceptibility to metabolite-driven pathology. This review provides a deeper synthesis of current evidence by integrating findings across multi-omics studies and identifying key unresolved issues in the microbiome-AD field. The discussion evaluates whether microbiome alterations act as early initiators or downstream consequences of neurodegeneration, examines sources of heterogeneity in microbiome-targeted interventions, and considers how inter-individual variability in host genetics and microbial ecology may inform precision therapeutics. Conceptual frameworks presented here, including a two-phase dysbiosis trajectory and a metabolite "tipping-point" network, aim to reconcile conflicting results and support the development of testable mechanistic hypotheses. Microbiome-directed strategies, such as probiotics, prebiotics, dietary modulation, faecal microbiota transplantation, and antiviral therapies, demonstrate promise but require rigorous mechanistic validation and methodological standardisation. Continued advancement in longitudinal, genotype-stratified, and multi-omics research will be essential for translating microbiome science into clinically actionable approaches. Overall, current evidence positions the gut microbiome as a compelling frontier for the development of personalised, diseasemodifying strategies in AD.}, }
@article {pmid42136277, year = {2026}, author = {Saxena, V and Singh, V and Sanskriti, }, title = {Translational Perspectives on Anti-Inflammatory Interventions for Neurodegenerative Disorders: Evidence from Gut-Brain Axis.}, journal = {Central nervous system agents in medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715249430752260407050033}, pmid = {42136277}, issn = {1875-6166}, abstract = {The Gut-Brain Axis (GBA) has a complex role in chronic neuroinflammation, which is increasingly connected to neurodegenerative diseases (NDDs) such as Multiple Sclerosis (MS), Parkinson's Disease (PD), and Alzheimer's Disease (AD). Through neuronal, endocrine, and immunological pathways, the GBA enables twoway communication between the gastrointestinal tract and the central nervous system. According to recent research, the pathophysiology of neuroinflammatory responses in NDDs may be significantly influenced by gut dysbiosis, increased intestinal permeability, and modified microbial metabolites, such as Short-Chain Fatty Acids (SCFAs) and polyphenols. This study summarizes preclinical and clinical data supporting several anti- inflammatory approaches targeting GBA. Probiotics and fecal microbiota transplantation are two examples of microbiota-based treatments that have demonstrated promise in reducing neuroinflammatory responses and enhancing cognitive performance. Mediterranean and polyphenol-rich diets are among the dietary therapies that show promise in modifying the composition of microorganisms, lowering pro-inflammatory signaling, and enhancing neuroprotection. Through microbiota regulation, pharmacological substances such as curcumin, resveratrol, and SCFA mimetics also have anti-neuroinflammatory benefits. However, a number of translational challenges still exist, including limitations in animal models, a lack of standardized therapies, and inter-individual microbiome heterogeneity. In order to provide precise, GBA-targeted therapies, future views place a strong emphasis on integrating multi-omics, artificial intelligence, and personalized medicine. This study highlights a new therapeutic approach to treating neurodegeneration by examining the translational potential of anti- inflammatory therapies targeting GBA. It also emphasizes the necessity of strong clinical studies to confirm these findings.}, }
@article {pmid42136299, year = {2026}, author = {Xia, B and Wu, S and Yu, W and Lü, Y}, title = {Research Progress on Intervention Strategies Targeting the Gut-Brain Axis in Alzheimer`s Disease.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273431295251201140053}, pmid = {42136299}, issn = {1996-3181}, abstract = {As the most common neurodegenerative disease in the world, Alzheimer's Disease (AD) is characterized by a complex pathogenesis and a lack of effective treatments. In recent years, breakthroughs in the Gut-Brain Axis (GBA) theory have provided a new direction for AD intervention. Studies have shown that AD patients commonly exhibit gut dysbiosis, accompanied by decreased Short-Chain Fatty Acid (SCFA) levels, endotoxin leakage, and increased systemic inflammation, which accelerate cognitive decline via neuroinflammation, Aβ deposition, and synaptic dysfunction. Based on this, intervention strategies targeting the GBA have emerged as a focus of research for slowing down the pathological process of AD. In this study, we systematically summarize the mechanisms linking gut microbiota dysbiosis to AD pathology. This includes the roles of metabolites (e.g., SCFA, LPS, and TMAO) in modulating neuroinflammation and Blood-Brain Barrier (BBB) permeability, as well as the critical involvement of vagal nerve pathways in gut-brain signaling. We further explored the potential of probiotics to improve cognitive function by restoring microbial homeostasis, enhancing anti-inflammatory effects, and elevating neurotrophic factor levels; dietary interventions (e.g., the Mediterranean and MIND diets) to reduce AD risk by modulating microbial composition and metabolic activity; and Fecal Microbiota Transplantation (FMT) to reduce Aβ plaque deposition and mitigate neuroinflammation. Despite promising findings, challenges persist, including discrepancies between animal models and human subjects, individual variability in microbiota composition, and an incomplete understanding of underlying mechanisms. In the future, it will be necessary to combine multiple technologies to develop personalized intervention protocols and optimize clinical translation processes, providing a theoretical basis for the precise treatment of AD.}, }
@article {pmid42137352, year = {2026}, author = {Gong, Y and Ma, X and Wang, L and Zhang, P and Liu, T and Li, Y and Dong, W}, title = {Gut microbiota orchestrates bone homeostasis: a multi-pathway network from intestine to skeleton.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1767726}, pmid = {42137352}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Homeostasis/physiology ; Animals ; *Bone and Bones/metabolism/physiology ; *Osteoporosis/microbiology/metabolism ; *Intestines/microbiology/physiology ; Probiotics ; }, abstract = {Osteoporosis (OP), a widespread metabolic bone condition characterized by diminished bone mass and compromised microarchitecture, poses a significant global health challenge. The gut microbiota (GM) regulates bone homeostasis through the "gut-bone axis," and this review consolidates its diverse mechanisms. GM-derived metabolites directly/indirectly modulate osteoclast/osteoblast activity. GM also regulates systemic immunity to influence the RANKL/OPG pathway and mediates endocrine signals. Furthermore, it modulates intestinal barrier integrity to facilitate mineral/vitamin absorption and interacts with the nervous system to form the "microbiota-gut-brain-bone" axis. GM imbalance, resulting from factors such as aging, hormonal shifts, or dietary habits, promotes the progression of OP through the perturbation of these networks. This review evaluates the therapeutic potential of GM-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, and underscores the GM as a pivotal therapeutic target, emphasizing that future therapeutic strategies for OP must incorporate the interconnected GM-bone axis for efficacious prevention and treatment.}, }
@article {pmid42138670, year = {2026}, author = {Khanna, S and Allegretti, JR and Hashash, JG and Feuerstadt, P}, title = {AGA Clinical Practice Update on Management of Clostridioides difficile Infection in Inflammatory Bowel Disease: Expert Review.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2026.03.008}, pmid = {42138670}, issn = {1528-0012}, abstract = {DESCRIPTION: Clostridioides difficile infection (CDI) remains a significant driver of disease flares and poor outcomes in patients with inflammatory bowel disease (IBD), leading to increased hospitalization, intensified or failed therapy, and higher surgical rates. Compared with the non-IBD population, patients with IBD face greater CDI risk and severity and higher recurrence risk, creating clinical dilemmas when considering antibiotic selection and the timing or necessity of IBD-related therapy adjustments. Emerging evidence highlights microbiota-based therapies such as unapproved fecal microbiota transplantation or US Food and Drug Administration-approved donor-derived therapies as a promising therapeutic avenue for recurrent CDI in patients with IBD, reflecting a growing emphasis on microbiome-directed interventions. This review examines the evolving literature, considering the diagnosis and management strategies and offering pragmatic guidance to optimize outcomes for patients with IBD challenged by concomitant CDI and recurrent CDI.<br><br>METHODS: This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. These practical Best Practice Advice statements were drawn from a review of the best available published evidence, including existing clinical studies, systematic reviews and practice guidelines, and expert opinion. Because a formal systematic review was not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. The focus is on the management of both CDI and IBD in patients with underlying IBD who develop CDI. Best Practice Advice Statements BEST PRACTICE ADVICE 1: In patients with IBD who have new or worsening diarrhea, CDI should be excluded, especially among those with colonic involvement, as they are at increased risk of CDI. Clinicians should consider and treat CDI in patients with end ileostomy or ileo-anal pouch anastomosis with worsening diarrhea. BEST PRACTICE ADVICE 2: In patients with IBD and suspected CDI, a multistep toxin-based assay should be used for diagnostic evaluation. BEST PRACTICE ADVICE 3: In patients with IBD and recent CDI who have been treated successfully with antibiotics, recurrent diarrhea should prompt retesting for CDI. BEST PRACTICE ADVICE 4: In patients with IBD who develop an initial episode of CDI, clinicians should preferentially use fidaxomicin or use vancomycin if fidaxomicin is unavailable or cost-prohibitive. Metronidazole should not be used. BEST PRACTICE ADVICE 5: Clinicians should strongly consider hospitalization for patients with IBD and CDI who demonstrate features of severe colitis or systemic toxicity (eg, more than 6 bowel movements per day, severe abdominal pain, marked leukocytosis, hemodynamic instability, or other evidence of sepsis). BEST PRACTICE ADVICE 6: When selecting an immunosuppressive therapy to treat IBD, no class or mechanism of action has a differential risk of CDI and, therefore, clinicians should choose the therapy that is best to treat the IBD. BEST PRACTICE ADVICE 7: In patients with IBD and acute CDI, concurrent treatment of IBD is critical and clinicians should continue therapy with the required immunosuppressive therapies (ie, immunomodulators, biologics, or small molecules). Steroids can also be used if deemed necessary while CDI is treated with antibiotics. BEST PRACTICE ADVICE 8: Clinicians should consider endoscopic evaluation for IBD activity and exclusion of concomitant cytomegalovirus infection if symptoms persist 48-72 hours after initiation of treatment for CDI. BEST PRACTICE ADVICE 9: Clinicians may consider loperamide in patients with improving inflammation and infection but ongoing diarrhea. BEST PRACTICE ADVICE 10: Clinicians should offer microbiome-based therapies (eg, fecal microbiota, live-jslm, fecal microbiota spores, live-brpk, or unapproved fecal microbiota transplantation) to patients with IBD with at least 1 recurrence of CDI to prevent future infection. BEST PRACTICE ADVICE 11: In patients with IBD, clinicians should not advise probiotics for primary or secondary prevention of CDI. BEST PRACTICE ADVICE 12: In patients with IBD and a history of CDI who are receiving systemic antibiotics, clinicians may consider oral vancomycin prophylaxis as secondary prevention.}, }
@article {pmid42138826, year = {2026}, author = {Chen, X and Shen, M and Zhang, R and Huang, Z and Niu, H and Yu, Q and Chen, Y and Pan, X and Rong, L and Wen, H and Yang, J and Xie, J}, title = {Sulfated Cyclocarya Paliurus Polysaccharide Sorchestrates the Gut Microbiome to Mobilize a Host-Derived 12-HEPE Against Ulcerative Colitis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e75681}, doi = {10.1002/advs.75681}, pmid = {42138826}, issn = {2198-3844}, support = {2023YFF1104001//National Key Research and Development Program of China/ ; 82460642//National Natural Science Foundation of China/ ; }, abstract = {Despite extensive evidence supporting the therapeutic potential of natural product-derived compounds in Ulcerative colitis (UC), their precise mechanisms have yet to be fully elucidated. In this study, structurally modified Cyclocarya paliurus polysaccharide (CP) derivatives were evaluated in a dextran sulfate sodium (DSS)-induced UC mouse model. Among the variants tested, sulfated Cyclocarya paliurus polysaccharide (SCP) emerged as the most therapeutically potent. SCP administration markedly attenuated colitis severity, as evidenced by relieved disease symptoms and reinforced intestinal barrier function. Mechanistically, SCP restored gut microbial homeostasis by enriching beneficial Bacteroidetes and enhancing short-chain fatty acids (SCFAs) production. This remodeled microbial ecosystem orchestrates the upregulation of host-derived 12-hydroxyeicosapentaenoic acid (12-HEPE), which exerts anti-inflammatory effects via direct inhibition of Toll-like receptor 4 (TLR4) signaling. The gut microbiota's functional relevance was substantiated by fecal microbiota transplantation and antibiotic-mediated exhaustion studies. Notably, the therapeutic benefits of 12-HEPE were abrogated upon co-administration of a TLR4 agonist, confirming its target specificity. Elevated serum 12-HEPE levels were observed in a human UC cohort, implying a potential compensatory immunoregulatory response. Our findings elucidate a novel microbiota-host interaction axis wherein SCP alleviates UC by modulating the gut microbiota to enhance endogenous 12-HEPE production, thereby suppressing TLR4-mediated inflammation.}, }
@article {pmid42140492, year = {2026}, author = {Corcione, S and Benech, N and Kuijper, E}, title = {Microbiome science at a turning point: from descriptive ecology to clinical decision making in infectious diseases.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {32}, number = {7}, pages = {1050-1051}, doi = {10.1016/j.cmi.2026.05.017}, pmid = {42140492}, issn = {1469-0691}, }
@article {pmid42141775, year = {2026}, author = {Zhou, F and Wang, L and Zhao, Y and Hu, C and Meng, Y and Fan, J and Fraser, WD and Baillargeon, JP and Ouyang, F and Lye, SJ and Dennis, CL and Shen, J and Wu, Y and Huang, H}, title = {Antenatal depressive symptoms impair offspring neurodevelopment by inducing maternal gut microbiota dysbiosis during pregnancy.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2672188}, pmid = {42141775}, issn = {1949-0984}, mesh = {Female ; Pregnancy ; Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; *Depression/microbiology/complications ; Fecal Microbiota Transplantation ; Adult ; Case-Control Studies ; *Pregnancy Complications/microbiology/psychology ; Prospective Studies ; Butyrates/metabolism ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; *Prenatal Exposure Delayed Effects ; Feces/microbiology ; Infant ; Brain/growth &amp; development/metabolism ; *Neurodevelopmental Disorders/etiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The effects of maternal antenatal depression (AND) across different stages of pregnancy on offspring neurodevelopment remain poorly understood, and the underlying microbiota-related mechanisms are largely unknown. In a multicenter prospective cohort of 2053 pregnant women, we found that elevated depressive symptoms at any trimester were significantly associated with delayed infant neurodevelopment. Using a nested case‒control design with 16S rRNA sequencing of 504 maternal fecal samples, we identified a consistent reduction of butyrate-producing bacteria and disruption of amino acid metabolism in women with AND symptoms - features that correlated with poorer infant cognitive outcomes. To establish causality, fecal microbiota transplantation (FMT) from women with AND symptoms was administered to germ-free dams, resulting in impaired intestinal barrier integrity, heightened neuroinflammatory signaling, and altered polyunsaturated fatty acid and amino acid metabolism in fetal brains at E18.5, leading to postnatal cognitive deficits in the offspring. Remarkably, maternal butyrate supplementation partially rescued these molecular and neurodevelopmental abnormalities. Together, these findings reveal a mechanistic link between maternal mood, gut microbial ecology, and fetal brain development, and identify the maternal gut microbiota and its metabolites as potential therapeutic targets to prevent the intergenerational effects of antenatal depression.}, }
@article {pmid42145753, year = {2026}, author = {Wu, Y and Yan, H and Li, P and Liu, Y and Leng, J and Cui, Y and Lv, X and Pang, L and Zang, N}, title = {Bridging the gaps: the gut-lung axis and microbial metabolites in the pathogenesis and treatment of pulmonary fibrosis.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1817835}, pmid = {42145753}, issn = {2296-858X}, abstract = {Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by structural damage to the lung parenchyma, excessive deposition of extracellular matrix (ECM), and irreversible decline in lung function. Current pharmacological treatments cannot effectively reverse fibrosis, highlighting an urgent need for novel therapeutic targets. Recently, the gut-lung axis and its bidirectional communication have received increasing attention for their roles in PF progression. Metabolites derived from gut microbiota, including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, lipopolysaccharides (LPS), and trimethylamine N-oxide, regulate immune responses, modulate signaling pathways, influence epigenetic modifications, and maintain intestinal barrier integrity, thereby exerting bidirectional effects on PF. Protective metabolites primarily inhibit fibroblast activation and collagen deposition, whereas pathological metabolites promote fibrosis by inducing inflammatory responses and oxidative stress. Potential therapeutic strategies targeting the gut-lung axis include fecal microbiota transplantation (FMT), probiotic and dietary interventions, and Traditional Chinese Medicine (TCM). However, clinical applications face challenges such as donor standardization, immunological safety, and consistency of therapeutic efficacy. Critical limitations remain, including reliance on acute-injury animal models that inadequately represent the chronic, irreversible nature of human PF. Translating findings across distinct PF subtypes requires caution, as their genetic architectures, immune landscapes, and microbiome interactions may differ considerably. Additionally, the causal relationship between microbial dysbiosis and fibrosis remains unclear, and clinical translation currently lacks stratified intervention strategies based on biomarkers. Future research should prioritize large-scale longitudinal cohort studies, integrated multi-omics analyses, organoid models, and gut-lung chip platforms to identify key effector molecules and therapeutic targets, ultimately facilitating precise clinical interventions targeting the gut-lung axis.}, }
@article {pmid42146050, year = {2026}, author = {Huang, X and Yang, X and Yu, Y and Huang, J and Tao, W and Yu, R}, title = {Bibliometric analysis of human microbiota-associated animal model (2005-2025).}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1777297}, pmid = {42146050}, issn = {1664-302X}, abstract = {BACKGROUND: The research on human microbiota-associated (HMA) animal models is an important tool for studying the human microbiome and holds great potential for elucidating disease mechanisms and microbe-based therapeutic interactions. However, a systematic bibliometric assessment of this field has been limited.<br><br>METHODS: This study employed bibliometric methods, retrieving relevant publications published between 2005 and 2025 from the Web of Science Core Collection, Scopus, and PubMed, and visualizing the data with VOSviewer and CiteSpace.<br><br>RESULTS: The analysis revealed a continuous upward trend in the number of publications on this topic. The United States and its research institutions contributed the most and maintained close collaborations with multiple countries. The majority of the articles appeared in journals such as Gut Microbes, Microbiome, and Proceedings of the National Academy of Sciences of the United States of America (PNAS). Keyword and highly-cited reference analyses focused on the application of these models in investigating disease mechanisms and therapeutic exploration, particularly for metabolic, gastrointestinal, oncological, and neurodegenerative diseases. In addition, the impact of modeling factors such as diet and host genetics on the models has also attracted attention.<br><br>CONCLUSION: HMA animal models have become a core platform linking clinical and basic microbiology research, demonstrating unique advantages in recapitulating disease-associated microbial features and phenotypes. Nevertheless, because these models are essential for testing causal links between microbiota and disease, methodological standardization and procedural refinement are needed to enhance reproducibility and clinical applicability.}, }
@article {pmid42146068, year = {2026}, author = {Xie, X and Yan, W and Gan, C and Xiong, W and Huang, Y and Lin, L and Lei, X and Ke, W and Chai, Y and Tang, H and Zhu, H}, title = {Tongxie Yaofang ameliorates IBS-D by targeting the gut microbiota-derived tryptophan metabolites and AhR signaling axis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1786701}, pmid = {42146068}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: Tongxie Yaofang (TXYF) is a classic prescription for IBS-D with liver depression and spleen deficiency, with its therapeutic mechanisms requiring further elucidation. This study investigated the modulatory effects of TXYF on the gut microbiota and microbiota-derived metabolism in an IBS-D rat model to elucidate the underlying mechanisms.<br><br>METHODS: HPLC was employed to identify the main components of TXYF. An IBS-D rat model was replicated using a triple-factor approach that combined neonatal maternal separation, chronic restraint stress, and oral gavage of Sennae folium decoction. To elucidate the mechanisms underlying the effects of TXYF on IBS-D, the gut microbiota was assessed by 16S rRNA sequencing, and microbial metabolites were profiled via untargeted metabolomics. Furthermore, key regulatory factors were examined by immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting. Finally, fecal microbiota transplantation (FMT) was performed to validate the pathogenic role of the microbiota and the therapeutic potential of TXYF.<br><br>RESULTS: TXYF significantly alleviated IBS-D symptoms in rats, including diarrhea and abdominal pain, and improved both depressive-like behavior and intestinal barrier function. Treatment with TXYF increased the abundance of Bifidobacterium in the gut microbiota and promoted the microbial-related metabolic conversion of tryptophan (TRP) to 5-hydroxyindoleacetic acid (5-HIAA), indole-3-acetic acid (IAA), tryptamine, 5-hydroxytryptamine (5-HT), and 2-oxindole. These metabolites activated the aryl hydrocarbon receptor (AhR) signaling pathway, thereby inhibiting MLC phosphorylation and decreasing MLCK expression, and ultimately restoring intestinal barrier function. Furthermore, the FMT experiment demonstrated that the microbiota from TXYF-treated rats significantly ameliorated IBS-D by activating the AhR signaling pathway.<br><br>CONCLUSION: TXYF may alleviate IBS-D symptoms and restore barrier function by increasing the abundance of Bifidobacterium, restoring tryptophan metabolism, and activating the AhR pathway.}, }
@article {pmid42148715, year = {2026}, author = {Li, ZP and Hu, Y and Chen, L and Cheng, J and Huang, YF and Huang, WF and Yi, LT}, title = {Fungicide Chlorothalonil Exposure Induced Intestinal Impairment via the Microbiota/Sphinganine/Ferroptosis Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {21}, pages = {16606-16621}, doi = {10.1021/acs.jafc.6c01962}, pmid = {42148715}, issn = {1520-5118}, mesh = {Animals ; *Nitriles/toxicity ; Mice ; *Fungicides, Industrial/toxicity ; *Ferroptosis/drug effects ; NF-E2-Related Factor 2/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; *Sphingosine/analogs &amp; derivatives/metabolism ; Male ; *Intestines/drug effects/microbiology ; Oxidative Stress/drug effects ; Bacteria/isolation &amp; purification/classification/genetics/drug effects/metabolism ; Humans ; Mice, Inbred C57BL ; }, abstract = {Chlorothalonil is linked to gastrointestinal toxicity, but its underlying mechanisms remain unclear. This study investigated the chlorothalonil-induced intestinal injury in mice. Histological analysis showed epithelial damage and goblet cell depletion. Chlorothalonil disrupted the gut microbiota, including the depletion of Lactobacillus and the enrichment of Enterococcus. Untargeted metabolomics revealed a reduction in sphinganine, which is associated with oxidative stress and ferroptosis. Molecular analysis indicated ferroptosis activation via the Keap1/Nrf2 pathway, evidenced by decreased glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression. Prussian blue staining and transmission electron microscopy confirmed iron deposition and mitochondrial injury, hallmark features of ferroptosis. Fecal microbiota transplantation confirmed dysbiosis as a driver of injury, while ferrostatin-1 treatment partially rescued the pathological phenotype. These findings demonstrate that chlorothalonil causes microbiota dysbiosis and decreases sphinganine, which inactivates Nrf2 signaling and results in ferroptosis. Our study provides new mechanistic insights into the toxicological mechanisms of chlorothalonil.}, }
@article {pmid42148776, year = {2026}, author = {Guo, J and Xiang, Z-w and Hu, F-f and Zhang, S-x and Han, W-j and Ding, X and Wang, X and Ye, M-l and Chen, J-h and Rao, T and Wu, L-l and Lian, G-h and Zhang, W and Huang, Y and Chen, Y}, title = {Turicibacter sanguinis is a candidate gut microbial pathobiont that promotes metabolic dysfunction-associated steatohepatitis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0029226}, doi = {10.1128/msystems.00292-26}, pmid = {42148776}, issn = {2379-5077}, abstract = {UNLABELLED: Emerging evidence points to the gut microbiota's involvement in metabolic dysfunction-associated steatohepatitis (MASH), yet the specific causative microbes remain largely unidentified. This study aimed to identify and functionally characterize candidate microbial pathobionts to MASH progression. Differentially abundant microbes were identified by 16S rRNA sequencing in a choline-deficient, L-amino acid-defined, high-fat diet MASH model, validated in other animal MASH models and in public clinical metagenomic data sets, then screened for consistently altered gut taxa. A candidate underwent functional validation via directed oral administration in mice. Mechanisms were explored through bile acid profiling by UHPLC-MS/MS and FXR signaling analysis by qPCR and immunohistochemistry. Additionally, fecal samples from MASH patients before and after treatment were analyzed to correlate microbial abundance with treatment response. Turicibacter sanguinis was consistently enriched in all MASH models and public data sets, with abundance correlating positively with liver injury markers. Its increased abundance exacerbated steatosis, inflammation, and fibrosis in healthy and diseased mice. Mechanistically, Turicibacter sanguinis altered bile acid composition, thereby increasing conjugated and decreasing unconjugated species, and inhibited hepatic FXR signaling, accompanied by suppressed SHP and elevated CYP7A1 and SREBP1c expression, which is consistent with enhanced bile acid synthesis and lipid accumulation. Futhermore, after pharmacotherapy, reduced Turicibater sanguinis levels correlated positively with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) improvements. In conclusion, Turicibacter sanguinis is a clinically relevant microbial pathogen that exacerbated MASH by inducing bile acid dysregulation and suppressing FXR signaling, highlighting its potential as a candidate biomarker for disease monitoring and motivating future evaluation of targeted microbiome interventions.<br><br>IMPORTANCE: Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health problem with limited treatment options. Although the gut microbiome has been implicated in MASH, the specific bacterial strains that directly drive disease progression remain largely unknown. This study identified Turicibacter sanguinis as a candidate gut microbial pathobiont that promotes MASH, demonstrating its significant enrichment in both animal models and patient samples. By disrupting hepatic metabolic signaling, this bacterium promotes bile acid synthesis and exacerbates liver fat accumulation, inflammation, and fibrosis. Following effective treatment, its abundance decreased significantly in patients. These findings indicate that Turicibacter sanguinis holds promise as a potential target for developing novel microbiome-based diagnostic and therapeutic approaches for MASH.}, }
@article {pmid42149263, year = {2026}, author = {Sorensen, N and Buntzen, S and Pedersen, L and Thorlacius-Ussing, O}, title = {Efficacy and safety of freshly collected autologous adipose tissue for complex anal fistulas in non-IBD patients: a prospective cohort study.}, journal = {Techniques in coloproctology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10151-026-03297-6}, pmid = {42149263}, issn = {1128-045X}, abstract = {BACKGROUND: Complex cryptoglandular anal fistulas present a treatment challenge, with many surgical options associated with recurrence, variable healing rates, and risk of incontinence. Freshly collected autologous adipose tissue (FCAAT) has been proposed as a minimally invasive, one-step alternative. This study aimed to assess clinical healing and clinical improvement and to evaluate the safety of the procedure.<br><br>METHODS: This prospective cohort study included 31 patients without inflammatory bowel disease (IBD) with complex single-tract cryptoglandular anal fistulas treated with FCAAT between May&#xa0;2019 and December 2023 and followed until August 2024. The surgical procedure involved liposuction, processing of adipose tissue,&#xa0;closure of the internal opening, and local injection along the fistula tract in a one-step procedure. Primary outcomes were clinical healing and clinical improvement; secondary outcomes were adverse events.<br><br>RESULTS: The patient cohort presented with advanced disease. Median disease duration was 20&#xa0;months, and one-third of patients had undergone previous attempts at surgical closure. Clinical healing was achieved in 23 patients (74%), with an additional four patients (13%) demonstrating clinical improvement. Five of 27 responders (19%) healed more than 3&#xa0;months post-procedure. Common adverse events included proctalgia in 8 patients (22%), donor site pain 5 (14%), and minor graft site hematomas in 4 (11%). One Clavien-Dindo&#xa0;IIIa event (graft site bleeding) was managed with a single suture; all other complications were minor and resolved conservatively.<br><br>CONCLUSION: FCAAT is a safe and effective one-step treatment for complex anal fistulas in non-IBD patients, offering a high healing rate with predominantly minor complications. A delayed effect was observed in some patients.}, }
@article {pmid42151161, year = {2026}, author = {Wang, Y and Hou, Q and Lv, X and Liu, J and Wang, H and Zhao, Y and Tong, H and Liu, Y and Du, J and Yang, X and Wu, S and He, S and Yang, X}, title = {Inorganic nitrogen metabolic reprogramming of the gut microbiome drives fecal microbiota transplantation in ulcerative colitis.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-73290-y}, pmid = {42151161}, issn = {2041-1723}, support = {32172776//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Although fecal microbiota transplantation (FMT) shows promise for ulcerative colitis (UC), its clinical success appears to be contingent upon the degree of donor microbiota engraftment. Using an LD50-based ecological model, our study reveals that inorganic nitrogen utilization capacity (IN-uc) critically determines gut microbial assembly in high oxidative stress environments, which significantly influences microbial engraftment outcomes. Building on this mechanistic insight, we engineer a probiotic-metabolite consortia designed to synergistically increase IN-uc in the gut ecosystem. We find that PM-mix14 alleviates oxidative stress-mediated colonization barriers of donor microbiota by catalyzing the conversion of excess reactive nitrogen species through multi-step reactions, promotes L-glutamate biosynthesis and ATP production, thereby ensuring greater similarity in the structure and function of the recipient microbiota to those of the donor. In multiple male murine models of colitis, PM-mix14 supplementation during FMT significantly improves microbial engraftment fidelity, which is correlated with increased anti-inflammatory responses and attenuated colonic pathology. Network meta-analysis of multiple clinical datasets further substantiates the prognostic value of donor gut microbial IN-uc in UC remission. Our findings establish the gut microbial IN-uc as an ecological driver of microbiota engraftment and present a rationally designed microbial therapy that optimizes FMT efficacy through targeted metabolic reprogramming.}, }
@article {pmid42152659, year = {2026}, author = {He, L and Huang, Y and Feng, S and Li, H and Zhang, Z and Wu, J and Huang, S and Fong, LM and Wu, K and Li, Z and Wu, F}, title = {Gut Microbiota-Targeted Therapies for Major Depressive Disorder: Mechanisms, Clinical Evidence, and Future Directions.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X432808251117075147}, pmid = {42152659}, issn = {1875-6190}, abstract = {Major Depressive Disorder (MDD) severely impairs individuals' physical and mental health, imposing substantial burdens on families and society. The pathogenesis of MDD remains elusive, but it is hypothesized to involve genetics, central neurotransmitter imbalance, hypothalamic- pituitary-adrenal (HPA) axis hyperactivity, and gut microbiota dysbiosis, among other factors. Antidepressants, which primarily address central neurotransmitter imbalances, are the first-line treatment; however, approximately half of patients exhibit suboptimal responses to conventional therapies. In recent years, attention has been drawn to specific alterations in gut microbiota composition observed in patients with severe depression. Animal studies have demonstrated that fecal transplantation from MDD patients to rodents can induce depressive-like behaviors, whereas fecal transplantation from healthy individuals may reverse such changes. Based on these findings, gut microbiota-targeted interventions have been progressively investigated in subclinical and clinical settings, including probiotic supplementation, fecal microbiota transplantation, and dietary modifications (such as the Mediterranean diet and ketogenic diet). These interventions may offer significant therapeutic effects with minimal side effects and high acceptability, providing new hope for patients with treatment-resistant depression. However, critical parameters such as optimal treatment regimens, dosages, and intervention durations remain unstandardized, and their underlying mechanisms and specific efficacy are still unclear. This review comprehensively evaluates existing clinical studies, focusing on the design of intervention protocols, therapeutic outcomes, adverse effects, and potential mechanisms of action, with the aim of providing guidance for future research.}, }
@article {pmid42152807, year = {2026}, author = {Jing, M and Chen, X and Jiang, M and Fang, H and Zhu, X and Jin, X and Jiao, Y and Hou, N and Gong, W and Liu, A}, title = {Microbial and Metabolic Correlates of Endometrial Dysfunction in Polycystic Ovary Syndrome: A Translational Study.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1471-0528.70266}, pmid = {42152807}, issn = {1471-0528}, support = {//Hangzhou Joint Fund of the Zhejiang Provincial Natural Science Foundation of China/ ; //Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; }, abstract = {OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit a substantially increased risk of miscarriage, yet the underlying mechanisms remain inadequately understood. This study aimed to investigate whether specific gut microbial dysbiosis and metabolic disturbance are associated with and may potentially contribute to endometrial dysfunction and adverse pregnancy outcomes in women with PCOS.<br><br>DESIGN: Prospective cohort study integrated with mechanistic experiments.<br><br>SETTING: Women's Hospital, School of Medicine, Zhejiang University, China (2022-2024).<br><br>POPULATION: A total of 110 women with PCOS and 110 age- and body mass index-matched controls were enrolled.<br><br>METHODS: We performed 16S rRNA and metagenomic sequencing of gut microbiota, with untargeted and targeted serum metabolomics. Functional validation was conducted using primary human endometrial stromal cells and a PCOS rat model intervened with Parabacteroides merdae (P. merdae) supplementation or faecal microbiota transplantation.<br><br>MAIN OUTCOME MEASURES: Gut microbiota composition, serum metabolites, endometrial senescence markers, and pregnancy outcomes.<br><br>RESULTS: Women with PCOS exhibited significantly higher miscarriage rates than controls, accompanied by a marked depletion of P. merdae abundance and elevated serum levels of branched-chain amino acids, particularly isoleucine. Exogenous isoleucine induced cellular senescence in human endometrial stromal cells in a dose-dependent manner. Restoration of P. merdae levels in the PCOS rat model resulted in decreased serum isoleucine levels, amelioration of the senescent endometrial phenotype, and reduction in the fetal resorption rate.<br><br>CONCLUSIONS: These findings suggest that P. merdae depletion and the concurrent accumulation of isoleucine may be associated with endometrial senescence and elevated risk of miscarriage, suggesting the possible involvement of a gut microbiota-metabolite pathway in PCOS-related reproductive dysfunction. These results also provide a mechanistic basis for future translational investigations.}, }
@article {pmid42154122, year = {2026}, author = {Desai, V and Ancil, S and Gupta, R and Kang, M and Bhadada, SK and Sharma, AK and Jearth, V and Rana, SS}, title = {Incidence and Determinants of Pancreatic Insufficiency After Acute Necrotizing Pancreatitis: A Prospective Study.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {42154122}, issn = {1573-2568}, abstract = {BACKGROUND AND AIM: Acute necrotizing pancreatitis (ANP) is associated with pancreatic parenchymal necrosis and may lead to exocrine and endocrine dysfunction. However, the natural course and determinants of pancreatic functional impairment remain incompletely defined. We prospectively evaluated the pancreatic exocrine and endocrine function in patients with ANP and attempted to identify associated risk factors.<br><br>METHODS: Patients aged 18-80&#xa0;years with ANP defined by the&#xa0;Revised Atlanta Classification&#xa0;were enrolled and prospectively followed for 6&#xa0;months. Exocrine function was assessed using fecal elastase-1 (FE-1), and endocrine function was evaluated using fasting glucose, postprandial glucose, HbA1c, and homeostatic model assessment of insulin resistance (HOMA-IR). Clinical severity, etiology, anatomic distribution of necrosis, infected necrosis, and interventions were analyzed as predictors of dysfunction.<br><br>RESULTS: Thirty patients completed 6-month follow-up. At 6&#xa0;months, exocrine insufficiency occurred in 40% of patients (mild 16.7%, severe 23.3%). Endocrine dysfunction was observed in 30% of patients, including diabetes mellitus (6.7%) and prediabetes (23.3%). Necrosis involving the pancreatic head was significantly associated with exocrine insufficiency (p&#x2009;=&#x2009;0.003). Moderately severe acute pancreatitis independently predicted exocrine dysfunction (p&#x2009;=&#x2009;0.01). No clinical or radiologic factor predicted endocrine insufficiency.<br><br>CONCLUSION: Exocrine insufficiency appears to be relatively common following ANP, with a possible association observed in patients with moderately severe disease and head-dominant necrosis; however, these findings require further validation. Endocrine dysfunction was observed in approximately one-third of patients, but no consistent predictors were identified in this cohort.}, }
@article {pmid42154370, year = {2026}, author = {Benekos, K and Katsanos, A and Laspas, P and Panos, GD and Vagiakis, I and Fousekis, FS and Luca, R and Zhou, B and Kostoulas, C and Georgiou, I and Katsanos, KH and Skondra, D and Konstas, AG}, title = {An Update and Overview of the Ocular and Extraocular Microbiome and Its Impact on Ophthalmic Care.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, pmid = {42154370}, issn = {1865-8652}, abstract = {The microbiome has been described as the last human "organ" and is currently the topic of great research interest worldwide. The application of culture-independent methods, like 16S ribosomal next-generation sequencing, has offered researchers the opportunity to identify bacterial populations that were impossible to detect previously using conventional culture methods. Further standardization of these new approaches to characterizing the microbiome is desirable. The present review discusses the mounting evidence suggesting that alterations in the microbiome and microbial metabolites, such as short-chain fatty acids in the gut, mouth, and ocular surface, may play a key role in the pathogenesis of ocular pathologies such as ocular surface disease, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy. Clarifying the probable role of the microbiome in ocular diseases would not only offer valuable insights into pathogenesis but could also enable the development of novel therapeutic approaches. As yet, microbial-based therapeutic applications in ophthalmology are limited. Nevertheless, recently emerging strategies utilizing probiotics and prebiotics, or even fecal transplantation to regulate microbiome composition, offer promising research avenues for developing future innovative therapies for ocular diseases. Further studies employing standardized methodological protocols are needed to ensure the reproducibility of results and to eventually unlock the precise links between the microbiome and the eye.}, }
@article {pmid42155010, year = {2026}, author = {Kim, JS and Loe, A and Ma, SF and Ranjan, P and Lipinski, JH and Mikhail, SG and Gurczynski, SJ and Zhou, X and Huffnagle, GB and Downward, JE and Metcalf, JD and Falkowski, N and Stringer, KA and Dickson, RP and Huang, Y and Moore, BB and Martinez, FJ and Murray, S and Noth, I and O'Dwyer, DN}, title = {Gut microbiota associate with disease severity and survival in idiopathic pulmonary fibrosis.}, journal = {American journal of respiratory and critical care medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajrccm/aamag249}, pmid = {42155010}, issn = {1535-4970}, abstract = {RATIONALE: Gut microbiota modify immunity. Dysregulated immunity plays a key role in the pathogenesis of IPF. However, the role of gut microbiota in IPF pathogenesis is unknown.<br><br>OBJECTIVES: Determine associations between gut microbiota, disease severity and lung transplant-free survival in IPF.<br><br>METHODS: Gut microbiota from patients enrolled in the CleanUP-IPF trial were characterized using fecal swab samples (n&#x2009;=&#x2009;411). CleanUP-IPF investigated the clinical efficacy of long-term anti-microbials in IPF. 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing were performed to comprehensively profile gut microbial communities. Associations between baseline microbiota with disease severity, transplant-free survival, and treatment heterogeneity were analyzed using principal component analysis, multivariate generalized linear models, additive models and Cox regression models.<br><br>MEASUREMENTS AND MAIN RESULTS: Gut microbiota composition varied significantly with sex, age, and proton pump inhibitor use. Gut microbial diversity and community composition were significantly associated with impaired gas exchange (percent predicted (pp) DLCO). Several genera including the Lachnospiraceae unclassified genus were associated with improved transplant-free survival (HR 0.34 95% CI 0.14-0.87, P&#x2009;=&#x2009;.02) in patients not assigned to anti-microbial treatment. Patients with a higher abundance of the Lachnospiraceae unclassified genus exposed to long term co-trimoxazole had worse survival (HR 6.09 95% CI 1.36-27.27, P&#x2009;=&#x2009;.02). Survival in pirfenidone treated patients was significantly associated with a higher abundance of the gut Lachnospiraceae unclassified genus.<br><br>CONCLUSIONS: In exploratory post-hoc analysis, gut microbiota correlated with disease severity, associated with treatment heterogeneity and transplant-free survival in patients with IPF.}, }
@article {pmid42156770, year = {2026}, author = {Chernova, VO and Ng, RW and Yang, L and Ip, M and Corcione, S and Benech, N and van Prehn, J and Kuijper, EJ and Contarino, MF}, title = {Safety and efficacy of faecal microbiota transplantation in Parkinson's disease.}, journal = {NPJ Parkinson's disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41531-026-01376-x}, pmid = {42156770}, issn = {2373-8057}, support = {NL1903//Stichting ParkinsonFonds/ ; }, abstract = {The gut microbiota may influence Parkinson's disease's (PD) pathophysiology. Faecal Microbiota Transplantation (FMT) may therefore improve symptoms. We reviewed five randomized controlled trials (RCT), three cohort studies, one case series, and two single case reports (total of 236 subjects). FMT methods varied (donor selection, FMT preparation method, pre-treatment, administration). Mild, self-limiting gastrointestinal symptoms were the most common adverse events (AEs). Constipation improved consistently after FMT. Motor and non-motor outcomes were heterogeneous, with improvements mainly reported in uncontrolled studies. One RCT demonstrated motor improvement at 8-12 weeks, another only after one year, while others showed no significant changes. In most RCTs, changes fell within or just beyond the minimal clinically important differences (MCID). Five studies reported taxonomic shifts, most consistently increased within the phylum Firmicutes. Large, well-designed RCTs with optimized FMT protocol for patient selection, FMT preparation and delivery, and donor selection are needed to determine whether FMT can affect PD symptoms or disease progression.}, }
@article {pmid42157185, year = {2026}, author = {Wu, R and Teng, X and Cai, Y and Liu, Y and Zhang, W and Li, Z and Fan, J}, title = {Integrated multi-matrix metabolomics reveals gut microbiota-driven systemic metabolic alterations and therapeutic remodeling by fecal microbiota transplantation in autism spectrum disorder.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08217-8}, pmid = {42157185}, issn = {1479-5876}, support = {ZX-KYXM2025001//Autism Research Special Fund of Zhejiang Foundation for Disabled Persons/ ; }, abstract = {BACKGROUND: Gut dysbiosis is deeply implicated in the pathophysiology of autism spectrum disorder (ASD); however, the mechanisms by which fecal microbiota transplantation (FMT) regulates host systemic metabolic homeostasis remain incompletely understood. Specifically, this study aims to address three core objectives: (1) to characterize the paired fecal and urinary metabolic signatures of ASD; (2) to map the microbiota-metabolite interaction networks; and (3) to evaluate the longitudinal metabolic remodeling effects of FMT. Through these objectives, we seek to elucidate the pathological mechanisms from a systems biology perspective.<br><br>METHODS: We employed a multi-omics strategy, integrating 16&#xa0;S rRNA sequencing with untargeted metabolomics on paired fecal and urinary samples from children with ASD (n&#x2009;=&#x2009;33) and healthy controls (HCs) (n&#x2009;=&#x2009;27). Furthermore, we conducted an exploratory longitudinal evaluation of the metabolic remodeling effects of FMT in a subset of patients (n&#x2009;=&#x2009;7) using paired samples collected at baseline and 3 months post-treatment.<br><br>RESULTS: We observed consistent metabolic dysregulation across both gut and peripheral matrices in children with ASD. These alterations were characterized by specific molecular signatures: impaired lipid metabolism (depletion of lysophosphatidylcholine [LPC] 18:2), downregulated cholinergic signaling (reduced methacholine), and the accumulation of neuroactive toxins (elevated tetraethylammonium [TEA]). Integrated multi-omics analysis correlated these metabolic deviations with a reduced abundance of beneficial commensals, such as Faecalibacterium. Preliminary data from the FMT intervention demonstrated a potential reversal of these metabolic phenotypes toward a healthy baseline, with trends indicating targeted restoration of core metabolic markers including LPC 18:2 and methacholine.<br><br>CONCLUSIONS: This study reveals that FMT may exert neuroprotective effects by ameliorating lipid metabolic defects and replenishing precursors of the cholinergic anti-inflammatory pathway (CAP). These findings delineate an ASD-specific gut-kidney metabolic axis, providing a preliminary theoretical basis for precision ASD treatment strategies targeting the microbiota-metabolism axis.}, }
@article {pmid42157525, year = {2026}, author = {Aware, C and Woods, C and Khodakivskyi, P and Dwivedi, AK and Zuckerman, A and Govindarajan, M and Ivanich, K and Yu, W and Cui, J and Gu, Z and Goun, E and Ericsson, AC and Zafonte, R and Balchandani, P and Lin, AL}, title = {Stroke-induced gut microbiome dysbiosis accelerates Alzheimer's disease progression.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {}, number = {}, pages = {271678X261449017}, pmid = {42157525}, issn = {1559-7016}, abstract = {Stroke survivors face an elevated risk of developing Alzheimer's disease (AD), yet the biological mechanisms linking these conditions remain poorly defined. Here, we show that a stroke-induced gut microbiome is a key driver of AD-related pathology. Fecal microbiota transplantation (FMT) from stroke patients into young triple-transgenic Alzheimer's disease (3xTg-AD) mice accelerated tau phosphorylation, increased neuroinflammation, and disrupted metabolic homeostasis in both the brain and gut, compared with FMT from healthy donors. Mice receiving stroke-derived microbiota exhibited persistent, donor-specific dysbiosis and broad metabolic reprogramming involving redox balance, nucleotide metabolism, and energy pathways in cecal contents and brain tissue. These metabolic disturbances were accompanied by widespread and region-specific transcriptional changes revealed by single-cell spatial transcriptomics, including glial activation, impaired neuron-glia communication, and dysregulation of mitochondrial, amyloid-processing and inflammatory pathways across cortical and hippocampal regions. Collectively, these findings identify post-stroke gut dysbiosis as a mechanistic contributor to heightened neurodegenerative vulnerability and AD risk, highlighting the gut-brain axis as a potentially modifiable target for preventing post-stroke dementia.}, }
@article {pmid42158036, year = {2026}, author = {Maung Myint, T and Hand, J and Lowe, A and Kotton, CN and Chen, SC and Beardsley, J and Teixeira-Pinto, A and Wong, G and Chan, S}, title = {Management of Norovirus Infection in Solid Organ Transplant Recipients: A Scoping Review.}, journal = {Transplantation direct}, volume = {12}, number = {6}, pages = {e1944}, pmid = {42158036}, issn = {2373-8731}, abstract = {BACKGROUND: Norovirus infection causes significant morbidity in solid organ transplant (SOT) recipients, yet few treatments are available, and evidence for efficacy is sparse. In this scoping review, we identify and evaluate potential interventions for managing norovirus infections in SOT recipients.<br><br>METHODS: We searched electronic databases from inception to July 6, 2025. Eligible studies were analyzed for participants' characteristics, intervention types, and reported outcomes.<br><br>RESULTS: After screening 245 abstracts, 58 studies were included (1 randomized controlled trial, 27 cohort studies, 5 case series and 25 case reports), mainly from the United States. Transplant types included kidney (n&#x2005;=&#x2005;36), liver (n&#x2005;=&#x2005;12), cardiac (n&#x2005;=&#x2005;12), pulmonary (n&#x2005;=&#x2005;7), pancreas (n&#x2005;=&#x2005;6), small bowel (n&#x2005;=&#x2005;7), and multiorgan (n&#x2005;=&#x2005;13) transplants. The most frequently reported primary outcome was resolution of gastrointestinal (GI) symptoms. Interventions were diverse: immunosuppression modification (n&#x2005;=&#x2005;14), nitazoxanide (n&#x2005;=&#x2005;6), IVIG (n&#x2005;=&#x2005;3), oral immunoglobulin (n&#x2005;=&#x2005;10), combination of these (n&#x2005;=&#x2005;19), fecal transplant (n&#x2005;=&#x2005;2), supportive management (n&#x2005;=&#x2005;4), and others not classified (n&#x2005;=&#x2005;5). Limited quality evidence for the resolution of gastrointestinal symptoms was reported for immunosuppression modification (n&#x2005;=&#x2005;7/14), nitazoxanide (n&#x2005;=&#x2005;4/6), IVIG (n&#x2005;=&#x2005;2/3), oral immunoglobulin alone (n&#x2005;=&#x2005;10/10), fecal transplant (n&#x2005;=&#x2005;2/2), supportive treatment (n&#x2005;=&#x2005;4/4), and a combination of treatments (n&#x2005;=&#x2005;10/19). A lack of clinical improvement was described in 13 of 58 studies.<br><br>CONCLUSIONS: A wide range of interventions has been used to manage norovirus infections in SOT recipients; however, the evidence is limited to observational studies, and the findings are uncertain. High-quality randomized controlled trials are needed to establish treatment efficacy and safety.}, }
@article {pmid42158204, year = {2026}, author = {Chen, C and Zhu, L and Huang, Y and Wang, YY and Kong, L and Lu, S and Shang, X}, title = {Gut microbiota-intestinal barrier crosstalk: mechanistic advances, disease relevance, and public health implications.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1777910}, pmid = {42158204}, issn = {2296-2565}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Public Health ; *Intestinal Mucosa/microbiology ; }, abstract = {BACKGROUND: The intestinal barrier is a critical interface between the host and the external environment, and growing evidence indicates that bidirectional crosstalk between the gut microbiota and the intestinal barrier is a key determinant of intestinal and systemic health. Disruption of this interaction has been implicated in the development of multiple chronic non-communicable diseases, including inflammatory, metabolic, neurodegenerative, and immune-mediated conditions. However, previous reviews have often examined gut microbiota or intestinal barrier dysfunction separately, with less emphasis on their bidirectional interaction as an integrated mechanistic and public health framework.<br><br>OBJECTIVE: This review aims to synthesize current mechanistic advances in gut microbiota-intestinal barrier crosstalk, evaluate its relevance across major disease domains, and examine its potential implications for chronic disease prevention and public health practice. In particular, this review highlights the gut microbiota-intestinal barrier axis as a unifying framework linking microbial metabolism, mucosal homeostasis, systemic inflammation, and prevention-oriented health strategies.<br><br>METHODS: We conducted a structured review of recent studies published between 2019 and 2025 in PubMed, Scopus, and Web of Science, with emphasis on both foundational and emerging evidence. The review focused on microbiota-derived metabolites, epithelial junction integrity, mucosal immune regulation, disease-associated barrier dysfunction, and microbiota-targeted interventions. Evidence from mechanistic, preclinical, and clinical studies was integrated to identify major advances, translational opportunities, and current limitations in the field.<br><br>RESULTS: Current evidence indicates that gut microbiota regulate intestinal barrier integrity through metabolites such as short-chain fatty acids (SCFAs), indole derivatives, and bile acids, which influence tight junction expression, mucin production, epithelial repair, and mucosal immune balance. Conversely, barrier dysfunction may promote microbial translocation, endotoxemia, and chronic low-grade inflammation, thereby contributing to diseases such as inflammatory bowel disease, type 2 diabetes, metabolic-associated fatty liver disease, and neurodegenerative or neuropsychiatric disorders. Microbiota-targeted interventions, including prebiotics, probiotics, dietary approaches, and fecal microbiota transplantation, have shown potential to restore barrier-related homeostasis. However, the current evidence remains constrained by heterogeneity in study design, incomplete causal validation, inconsistent clinical outcomes, and limited standardization of intervention strategies, all of which restrict clinical translation and large-scale public health implementation.<br><br>CONCLUSION: The gut microbiota-intestinal barrier axis is an important determinant of health and disease and may represent a promising target for future prevention-oriented strategies. By integrating mechanistic evidence with disease relevance, translational limitations, and public health perspectives, this review provides a more coherent framework for understanding microbiota-barrier crosstalk. Future research should prioritize causal validation, standardized methodologies, and equitable implementation pathways to support the development of scalable preventive and therapeutic strategies.}, }
@article {pmid42159494, year = {2026}, author = {García-Vidal, C and Gallardo-Pizarro, A and Aiello, TF and Kwon, M and Salavert, M and Pitart, C and Suarez-Lledó, M and Soriano, A and Mensa, J}, title = {Antibiotic therapy in febrile neutropenia in haematological patients: current considerations and future challenges.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {}, number = {}, pages = {}, doi = {10.37201/req/165.2026}, pmid = {42159494}, issn = {1988-9518}, abstract = {The management of febrile neutropenia (FN) in oncohematological patients is undergoing a paradigm shift driven by a deeper understanding of patients' pathophysiological heterogeneity, the increasing speed and accuracy of microbiological diagnostics, the emergence of new antibiotics, and the incorporation of predictive artificial intelligence (AI) as a tool to support clinical decision-making. Our objective is to provide an updated and comprehensive overview of the factors influencing antibiotic treatment in FN. We propose that its management should be based on three essential pillars. First, accurate risk stratification for bacterial infection. Second, ensuring that patients receive appropriate empirical antibiotic therapy, tailoring the initial choice according to the results of surveillance cultures from oropharyngeal and/or fecal microbiota. Finally, prioritizing antibiotic choices that preserve intestinal microbiota eubiosis as much as possible. Reducing colonization and overgrowth of facultative aerobic/anaerobic flora (Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Enterococcus spp.) while preserving strict anaerobic flora decreases the risk of bacterial translocation and complications such as graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or loss of CAR-T functionality. This decision model, grounded in objective criteria, aims to balance the need for effective empirical coverage with responsible antibiotic use.}, }
@article {pmid42159959, year = {2026}, author = {Zhang, Z and Jiang, F and Li, Z and Lin, L and Qi, B and Han, D and Ran, C and Mao, S and Wang, J and Zhou, Z and Wang, M and Li, J and Wang, G and Kang, S and Zhang, T}, title = {Animal gut microbes and microbiomes in the 21st century and beyond.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {42159959}, issn = {1869-1889}, abstract = {Animal gut microbiomes-comprising bacteria, archaea, fungi, viruses, and protozoa-are fundamental to host evolution, physiology, and ecosystem resilience. This review synthesizes 21st-century advances in their diversity, spatiotemporal dynamics, and functional roles across the animal kingdom. Although high-throughput metagenomics has transformed the field, major biases remain: most studies still focus on domesticated vertebrates and fecal samples, leaving substantial "microbial dark matter" in wild hosts, invertebrates, and non-bacterial domains unexplored. We highlight how gut microbiomes mediate adaptation to environmental extremes, including hypoxia, temperature stress, and toxins, and how industrialization disrupts these communities, contributing to biodiversity loss and disease risk. We further integrate eco-evolutionary theory, multi-omics, and spatial modeling to clarify cross-kingdom interactions and functional networks. Finally, we discuss translational applications-including probiotics, fecal microbiota transplantation (FMT), phage therapy, and synthetic consortia-and emphasize the need for global collaborative initiatives, artificial intelligence (AI)-driven discovery, and standardized databases to unlock the full potential of animal gut microbiomes for biodiversity conservation, climate resilience, and planetary health in the coming decades.}, }
@article {pmid42160026, year = {2026}, author = {Zhao, M and Hou, J and Wang, J and Zhu, X and Zou, A and Wang, Y and Liu, Z and Xianyu, Y}, title = {Food-Derived Biohybrid Probiotic Extracellular Vesicles for Synergistic Therapy of Inflammatory Bowel Disease.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e73858}, doi = {10.1002/smll.73858}, pmid = {42160026}, issn = {1613-6829}, support = {LZ26B050002//Natural Science Foundation of Zhejiang Province/ ; 2025C02124//"Pioneer" and "Leading Goose" R&amp;D Program of Zhejiang/ ; 82470544//National Natural Science Foundation of China/ ; 2026YFE0214400//National Key Research and Development Program of China/ ; }, abstract = {Inflammatory bowel disease is a chronic gastrointestinal disorder characterized by persistent intestinal inflammation, microbiota dysbiosis, and impaired mucosal barrier function. Conventional treatments, including pharmacological agents, biologics, and fecal microbiota transplantation, are limited by adverse effects, immune suppression, recurrence, and low patient acceptance. In this study, food-derived probiotic extracellular vesicles (EVs) from Lactiplantibacillus plantarum with dietary polysaccharide (chitosan) and polyphenol (tannic acid) are developed as a synergistic therapeutic strategy for inflammatory bowel disease. The engineered biohybrid with dual-functional coating confers gastrointestinal stability and colon-targeted delivery, while scavenging reactive oxygen species and preserving the intrinsic microbiota-regulating properties of probiotic EVs. Multi-omics approach reveals correlations among microbial community shifts, short-chain fatty acids, oxidative stress modulation, inflammatory cytokine profiles, and disease severity indices. This work provides a promising approach and reveals the synergistic mechanisms of engineered probiotic EVs in reshaping gut microbiota, modulating metabolic networks, and improving the inflammatory microenvironment for the treatment of inflammatory bowel disease.}, }
@article {pmid42161263, year = {2026}, author = {Ni, M and Junker, K and Liu, Y and Fan, Y and Li, Y and Qiao, W and Zhang, XS and Ksiezarek, M and Mead, EA and Tourancheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Davey, LE and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {6}, pages = {1033-1049.e8}, pmid = {42161263}, issn = {1934-6069}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *Gastrointestinal Microbiome/genetics/drug effects ; Anti-Bacterial Agents/pharmacology ; *Adaptation, Physiological/genetics ; DNA Methylation ; Fecal Microbiota Transplantation ; Infant ; *Bacteria/genetics/drug effects ; Metagenomics ; Probiotics ; Feces/microbiology ; Akkermansia ; }, abstract = {The human microbiome continuously adapts to variations in diet and host physiology. Epigenetic phase variation (ePV) mediated by bacterial DNA methylation can generate phenotypic heterogeneity within clonal populations. ePVs have been characterized in human pathogens, but their roles in commensals remain unclear. Here, we cataloged ePVs in infant and adult gut microbiomes, revealing genome-wide and site-specific ePV in response to antibiotics and fecal microbiota transplantation. Long-read metagenomics revealed genome-wide ePV mediated by structural variations of DNA methyltransferases. Analysis of public short-read metagenomic datasets further revealed a high prevalence of genome-wide ePVs in the human microbiome. Site-specific ePVs were identified and associated with antibiotics or probiotic engraftment. Focusing on an Akkermansia muciniphila isolate, we find a specific ePV regulating mucC, a gene of unknown function but whose heterologous expression enhances bacterial tolerance to antibiotics via a bet-hedging strategy. Thus, epigenetic modifications are used by gut bacteria to adapt to fluctuating environments.}, }
@article {pmid42162499, year = {2026}, author = {Gu, R and Li, J and Qi, J and Sun, R and Wu, H and Jin, B}, title = {Odoribacter laneus protects intestinal barrier by bile acid-FXR axis in acute pancreatitis.}, journal = {AMB Express}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13568-026-02071-z}, pmid = {42162499}, issn = {2191-0855}, support = {2023YP44//the Cultivation Foundation of The Second Hospital of Shandong University/ ; }, abstract = {Odoribacter laneus (O. laneus) is a promising probiotic. Acute pancreatitis (AP) is an acute abodominal disease accompanied by intestinal barrier dysfunction and gut dysbiosis. However, the effects of O. laneus in AP remain unexplored. We established AP model of C57BL/6 mice. Western blotting and immunohistofluorescence were used to detect the expression of intestinal tight junction proteins and FXR/NLRP3 pathway. The changes of gut microbiota and bile acids (BAs) were analyzed by 16 S rRNA gene and targeted metabolomics sequencing. The fecal microbiota transplantation (FMT) was used to investigate the role of gut microbiota in O. laneus treatment. O. laneus effectively reduced systemic inflammation, pancreatic damage, and intestinal barrier dysfunction in AP mice. We observed significant enrichment of pathogens along with depletion of second BAs (7-KDA) in AP mice, and these alterations were reversed by O. laneus. FMT experiment showed that the protective roles of O. laneus depended on gut microbiota. O. laneus ameliorated AP via activating intestinal FXR and inhibiting NLRP3 inflammasome in vivo. In vitro and vivo studies showed that 7-KDA protected AP. Taken together, O. laneus could mitigate AP-induced intestinal barrier dysfunction by reversing the disorderd gut microbiota, BAs metabolism, and modulating FXR/NLRP3 pathway.}, }
@article {pmid42162728, year = {2026}, author = {Suresh, G and Nath, M and Tiwari, A and Halder, N and Chawla, R and Velpandian, T}, title = {Gut microbiome dysbiosis in uveitis - mechanistic insights and emerging therapeutic strategies.}, journal = {Experimental eye research}, volume = {270}, number = {}, pages = {111073}, doi = {10.1016/j.exer.2026.111073}, pmid = {42162728}, issn = {1096-0007}, abstract = {Recent studies have suggested the existence of a gut-eye axis, thus bringing the role of gut microbiota (GM) in the development of ocular inflammation in uveitis into focus. The proposed mechanisms for GM dysbiosis-induced uveitis include molecular mimicry, increased intestinal permeability by disruption of barrier integrity, immunomodulation, and alterations. Data from observational clinical studies indicate distinctive microbial signatures associated with uveal inflammation. Based on these findings, novel therapeutic modalities targeting the GM, such as antibiotics, probiotics, prebiotics, fecal microbiota transplantation, biologics, and dietary interventions have been proposed. While initial studies have shown promising results, there is limited clinical evidence supporting their therapeutic efficiency in the management of uveitis. The complexity and diversity of the GM, along with the lack of controlled clinical trials pose a significant challenge to the development of targeted therapeutics. Additionally, further studies are needed to elucidate the molecular mechanisms linking GM dysbiosis and ocular inflammation for developing specific biomarkers for diagnosis, as well as personalized GM-targeted patient interventions.}, }
@article {pmid42162772, year = {2026}, author = {Aumpan, N and Watanabe, J and Yuan, Y and Kanno, T and Leontiadis, GI and Chan, FKL and Moayyedi, P}, title = {Fecal Microbiota Transplantation for Symptom Improvement in Patients With Irritable Bowel Syndrome: Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2026.04.039}, pmid = {42162772}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) could improve symptoms of irritable bowel syndrome (IBS) in some previous trials. We updated a prior meta-analysis of randomized controlled trials (RCTs) determining this issue.<br><br>METHODS: We searched CENTRAL, MEDLINE, and Embase (via Ovid) from inception to February 20, 2026, to identify potential studies. We included RCTs that reported the proportion of patients with IBS symptDom improvement assessed between 4 and 24 weeks after FMT. For primary outcome, we estimated risk ratios (RR) of proportion of patients with IBS symptoms not improved. Data were pooled using a random effects model. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.<br><br>RESULTS: Thirteen RCTs involving 693 patients were eligible for this review. For the intention-to-treat analysis, FMT may reduce IBS symptoms at 12 weeks compared with placebo, but the evidence is very uncertain (RR of symptom not improved with FMT compared with placebo = 0.72; 95% confidence interval [CI], 0.50-1.03). However, in the per-protocol analysis, FMT was statistically significant at improving symptoms (RR, 0.67; 95% CI, 0.46-0.97). Overall adverse events were not different in both groups (RR, 0.98; 95% CI, 0.75-1.29). The subgroup analysis reported IBS symptom improvement using a single dose of FMT (RR, 0.62; 95% CI, 0.41-0.93), and when IBS was diagnosed by Rome IV criteria (RR, 0.38; 95% CI, 0.17-0.86).<br><br>CONCLUSIONS: This systematic review suggested there was very low certainty of evidence that FMT improved IBS symptoms. FMT was effective in some subgroup analyses and in the overall per-protocol analysis, but this needs to be interpreted with caution. (Registration number: PROSPERO CRD420251086189.).}, }
@article {pmid42164024, year = {2026}, author = {Hariyanto, TI}, title = {From dysbiosis to decolonization: The emerging role of fecal microbiota transplantation in antimicrobial resistance.}, journal = {Infectious medicine}, volume = {5}, number = {2}, pages = {100253}, pmid = {42164024}, issn = {2772-431X}, }
@article {pmid42164832, year = {2026}, author = {Kumar, A and Krishan, B and Dhiman, S and Sharma, A and Thadiyan, V and Azmi, W}, title = {Beyond antibiotics: innovative and translational strategies to overcome antimicrobial resistance.}, journal = {3 Biotech}, volume = {16}, number = {6}, pages = {201}, pmid = {42164832}, issn = {2190-572X}, abstract = {The rapid rise of antimicrobial resistance demands therapeutic strategies that extend beyond conventional antibiotics. However, most existing reviews describe emerging alternatives without systematically linking their mechanistic advances to translational readiness and clinical implementation barriers. This review addresses this gap by integrating evidence across multiple beyond-antibiotic approaches, including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, nanotechnology-enabled delivery systems, anti-virulence agents, host-directed immunotherapies, microbiome modulation (engineered probiotics and fecal microbiota transplantation), and drug-repurposing or combination therapies. The principal contribution of this synthesis is a comparative framework that maps mechanisms of action, engineering innovations, and translational evidence across these diverse strategies. Advances such as peptidomimetics, engineered phages, and nanoparticle carriers that enhance stability, targeting, and therapeutic efficacy are highlighted, along with synergistic strategies including phage-antibiotic and CRISPR-nanocarrier combinations. The review further identifies major barriers limiting clinical translation, including delivery efficiency, toxicity and ecological concerns, large-scale production challenges, cost, inconsistent clinical outcomes, and regulatory fragmentation for biologics and live therapeutics. To facilitate clinical implementation, the study proposes a translational roadmap emphasizing standardized evaluation assays, physiologically relevant infection models, integrated rapid diagnostics, and regulatory frameworks tailored for emerging antimicrobial platforms, thereby supporting the development of sustainable therapies for the post-antibiotic era.}, }
@article {pmid42166227, year = {2026}, author = {Kaushik, K and Sharma, M and Sharma, R and Reza, A and Sharma, G and Panwar, S and Nagraik, R and Negi, P and Sharma, A}, title = {Gut microbiota: The hidden hallmark of aging.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2026.02808}, pmid = {42166227}, issn = {1588-2640}, abstract = {Aging is the natural process of changes that are accumulated over time and are responsible for the ever-increasing susceptibility to diseases and death. Extensive research has been done to understand the role of gut microbiota in aging, however, limited progress has been made. Thus, considering the need of the hour we have tried to give a new perspective to this body of research by delving deep into all major factors that are associated with gut microbiome and aging. This review presents a holistic view of the relation between gut microbiome and aging starting from hallmarks of aging and evolution of gut microbiome over lifespan to intricate mechanisms like inflammaging, immunosenescence, gut-brain axis, mitochondrial dysfunction, nutrient imbalance and cardiac implications. In addition, it highlights different therapies like fecal microbiota transplantation, omics and metabolomics studies, and gut modulation therapies that show a promising future towards regulation of gut microbiota for aging interventions. More importantly, this review is an addition to the existing literature which advocates gut microbiome as an additional hallmark of aging, summarising the known status of the research in this field, contributing to developing gut microbiota targeted healthy aging.}, }
@article {pmid42166402, year = {2026}, author = {Peta Martinez, NA and Reinoso Arnaldi, M and Santiago-Rodriguez, TM and Rodriguez-Fernandez, IA}, title = {Microbiota-Based Interventions Differentially Rescue Gut and Social Behavior Phenotypes in Drosophila with Kdm5 Deficiency.}, journal = {Developmental neuroscience}, volume = {}, number = {}, pages = {1-32}, doi = {10.1159/000552681}, pmid = {42166402}, issn = {1421-9859}, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a lifelong neurological and developmental disorder that is often accompanied by gastrointestinal (GI) issues. The bidirectional communication system known as the gut microbiota-brain axis may help explain how GI dysfunction contributes to neurological symptoms. Loss-of-function mutations in the histone demethylases KDM5A, KDM5B or KDM5C are found in patients with intellectual disability and ASD. Here, we use a genetically tractable Drosophila model of loss-of-function of the ASD-associated chromatin regulator Kdm5 to investigate how host genetic disruption influences gut microbial composition and social behavior. Previous studies using a Drosophila Kdm5 loss-of-function (Kdm5LOF) revealed gut microbial dysbiosis, reduced abundance of Lactiplantibacillus plantarum, and impaired social behavior. While L. plantarum supplementation rescued intestinal abnormalities, it did not restore social behavior.<br><br>METHODS: We evaluated multiple microbiota-based interventions, including probiotic supplementation with Lactiplantibacillus plantarum, Lactobacillus helveticus, their combination, and fecal microbiota transplantation (FMT), to determine their capacity to modulate gut microbial composition and behavior in adult Kdm5LOF flies. Gut bacterial abundance was quantified using colony-forming unit (CFU) assays and full-length 16S rRNA gene sequencing. Social behavior was assessed using the social distance assay, while anxiety-like behavior and locomotion were evaluated using the open field test. Gut-specific Kdm5 knockdown was used to assess tissue-specific contributions to microbiota and behavioral phenotypes.<br><br>RESULTS: Kdm5 deficiency resulted in reduced abundance of culturable Lactobacillus, Acetobacter, and Enterobacter species, accompanied by impaired social behavior. L. plantarum supplementation restored gut microbial abundance in both whole-body Kdm5LOF and gut-specific Kdm5 knockdown models but did not significantly rescue social behavior. In contrast, L. helveticus significantly improved social interaction in Kdm5LOF flies despite minimal effects on gut bacterial abundance, revealing a dissociation between microbial restoration and behavioral outcomes. Gut-specific Kdm5 knockdown phenocopied both microbial and social defects observed in Kdm5LOF mutants. Notably, FMT from healthy donors partially restored Lactobacillus abundance, reshaped gut microbial community structure, and partially improved social behavior in Kdm5LOF recipient flies.<br><br>CONCLUSIONS: Together, these findings identify Kdm5 as a key regulator of gut microbial viability and social behavior and demonstrate that microbiota-based interventions exert strain- and phenotype-specific effects. Our results reveal that restoration of microbial abundance alone is insufficient to rescue social behavior and highlight the importance of functional host-microbe interactions in gut-brain communication. This work establishes Drosophila as a tractable platform for dissecting epigenetic regulation of microbiota-behavior relationships in the context of disruption of an ASD-associated gene and for studying microbiota-based modulation of host physiology and behavior. All experiments were conducted in adult flies, and thus these findings reflect post-developmental effects of Kdm5 disruption.}, }
@article {pmid42167887, year = {2026}, author = {Cui, D and Zhou, Y and Zhou, Y and Ge, R and Mao, H and Mathesh, M and Han, L and Yang, W and Yan, F}, title = {Gut microbiota dysbiosis and metabolic alterations in rheumatoid arthritis: a barrier to periodontal repair.}, journal = {RMD open}, volume = {12}, number = {2}, pages = {}, pmid = {42167887}, issn = {2056-5933}, mesh = {Animals ; *Dysbiosis/metabolism/etiology ; *Arthritis, Rheumatoid/metabolism/etiology/microbiology/pathology ; *Gastrointestinal Microbiome ; Rats ; Male ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Arthritis, Experimental/metabolism ; Rats, Sprague-Dawley ; Metabolomics/methods ; X-Ray Microtomography ; RNA, Ribosomal, 16S/genetics ; Bone Regeneration ; Biomarkers ; }, abstract = {OBJECTIVE: To investigate the impact of rheumatoid arthritis (RA) on periodontal healing and the underlying mechanisms.<br><br>METHODS: Mandibular periodontal bone defect (PBD) and collagen-induced arthritis (CIA) models were established in male Sprague-Dawley rats aged 6 weeks, assigned to four groups: control (CON), CIA, PBD and CIA+PBD. Periodontal repair was evaluated at 1, 3 and 6 weeks. To examine the contribution of gut microbiota, pseudo-germ-free rats with PBD received 3-week faecal microbiota transplantation (FMT) from either healthy or CIA donors. Arthritis severity was assessed by paw thickness and arthritis index, while bone microarchitecture was examined by micro-CT and histology. Gut microbiota and metabolites were analysed using 16S ribosomal RNA high-throughput sequencing and untargeted metabolomics.<br><br>RESULTS: CIA was found to significantly impair periodontal bone healing and suppress osteogenesis-related markers, including runt-related transcription factor 2 and alkaline phosphatase. Compared with CON rats, CIA and PBD, CIA+PBD groups exhibited gut microbial dysbiosis and metabolic alterations, particularly in arachidonic acid and tryptophan pathways. FMT from CIA donors further increased osteoclast numbers and delayed bone regeneration. Furthermore, gut-derived factors from CIA animals were associated with increased macrophage expression of pro-inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-1 beta.<br><br>CONCLUSION: Overall, RA-related gut microbiota dysbiosis and metabolic disturbances are linked to impaired periodontal healing, potentially through enhanced inflammatory responses. This study highlights a microbiome-immune-metabolic axis that may influence periodontal regeneration in RA.}, }
@article {pmid42168337, year = {2026}, author = {Tao, M and Liu, Y and Guo, H and Gao, S and Wang, Y and Yan, X and Zhu, Y}, title = {The role of the gut microbiota in radiation enteritis: from mechanistic insights to therapeutic applications.}, journal = {Communications biology}, volume = {9}, number = {1}, pages = {}, pmid = {42168337}, issn = {2399-3642}, support = {BK20250559//Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)/ ; 82403008//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024M762749//China Postdoctoral Science Foundation/ ; }, mesh = {*Gastrointestinal Microbiome/radiation effects ; Humans ; *Enteritis/microbiology/therapy/etiology ; *Radiation Injuries/microbiology/therapy ; Dysbiosis/microbiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Radiotherapy/adverse effects ; }, abstract = {Radiation enteritis (RE) is a severe adverse reaction after abdominal and pelvic radiotherapy, with a complicated pathogenesis and no effective treatment. Although gut microbiota dysbiosis was reported to play a critical role in RE, related molecular characteristics and intervention strategies have not been extensively summarized. In this review, the mechanisms of RE, including injury to intestinal stem cells, damage to the vascular endothelium, reshaped immune microenvironment, and mucosal barrier dysfunction, are discussed. In addition, radiation-induced gut microbiota dysbiosis is characterized by decreased abundance of beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium bifidum, and increased abundance of detrimental bacteria such as Escherichia-Shigella and Enterococcus. Beneficial and detrimental bacteria affect the development of RE by regulating inflammatory signaling pathways such as NF-κB and JAK/STAT3, and through their metabolites such as bile acids and short-chain fatty acids. Accordingly, several microbiome-targeted therapeutic strategies, including antibiotic administration, dietary interventions, fecal microbiota transplantation, probiotic administration and engineered bacteria, have been developed to mitigate RE. However, some challenges still remain for these therapeutic strategies. The goal of this review is to highlight the crucial role of gut microbiota dysbiosis in the pathogenesis of RE, thereby accelerating the development of individualized microbial therapies against this disease.}, }
@article {pmid42168694, year = {2026}, author = {Sahu, P and Satapathy, T}, title = {The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Microbiome Interactions and Therapeutic Targets.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {42168694}, issn = {1867-1314}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multifactorial condition in which the gut-liver axis plays a central pathogenic role. While a large body of literature has described associations between gut microbiota alterations and MASLD, a critical synthesis of the mechanistic pathways linking microbial activity to liver injury remains lacking. This review specifically focuses on gut-derived microbial metabolites as key mediators of disease progression. We examine how short-chain fatty acids, bile acids, lipopolysaccharide (LPS), trimethylamine-N-oxide (TMAO) and microbially derived ethanol influence hepatic lipid metabolism, inflammation and fibrogenesis through defined molecular pathways, including FXR signaling, TLR4 activation and immune-metabolic crosstalk. Importantly, we highlight inconsistencies in human microbiome studies, limitations in establishing causality and the challenges in translating preclinical findings into effective therapies. Although microbiome-targeted interventions such as probiotics, bile acid modulators and fecal microbiota transplantation show promise, their clinical efficacy remains variable due to interindividual heterogeneity and lack of mechanistic precision.By integrating current mechanistic evidence with translational insights, this review identifies critical knowledge gaps and proposes future directions for metabolite-focused therapeutic strategies. A more precise understanding of gut-derived signaling pathways will be essential to move from associative microbiome research toward targeted and personalized interventions in MASLD.}, }
@article {pmid42168704, year = {2026}, author = {Zhang, X and Mallick, H and Rahnavard, A}, title = {Meta-analytic microbiome target discovery for immune checkpoint inhibitor response in advanced melanoma.}, journal = {Communications medicine}, volume = {6}, number = {1}, pages = {}, pmid = {42168704}, issn = {2730-664X}, support = {2109688//National Science Foundation (NSF)/ ; 2109688//National Science Foundation (NSF)/ ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors have transformed melanoma therapy, yet only a subset of patients achieve durable responses. Gut microbes have been linked to response, but reported biomarkers vary across studies. We aim to identify reproducible microbial features and test their generalizability across cohorts and treatment settings.<br><br>METHODS: We reprocessed stool metagenomic sequencing data from 15 melanoma cohorts (763 samples from 484 individuals), including 12 cohorts treated with immune checkpoint inhibitors alone and 3 trials combining immune checkpoint inhibitors with fecal microbiota transplantation. Using a unified analysis pipeline, we profiled microbial species, metabolic pathways, and biosynthetic gene clusters, and analyzed their associations with treatment response using Tweedie regression, random-effects meta-analysis, and multimodal integration with leave-one-dataset-out validation.<br><br>RESULTS: Here, we show that responders in immune checkpoint inhibitor-only cohorts are enriched for several short-chain fatty acid-producing commensals, whereas non-responders show higher abundance of taxa associated with disrupted gut communities. In fecal microbiota transplantation plus immune checkpoint inhibitor trials, response associates with distinct communities and shifts in amino-acid, nucleotide and cofactor metabolism. Across cohorts, multiview prediction models repeatedly select gene clusters linked to antimicrobial peptides and surface polysaccharides, but cross-study discrimination remains modest.<br><br>CONCLUSIONS: Microbiome signatures of response are treatment-context dependent and are not captured by a single universal species. These harmonized findings prioritize microbial taxa and functions for mechanistic studies and future microbiome-informed interventions.}, }
@article {pmid42169007, year = {2026}, author = {Lu, Y and Rong, X and Wei, L and Yang, J and Zhang, K and Tan, Y and Zhao, N and He, X and Lu, C and Li, L}, title = {Baicalein mitigates epithelial barrier impairment and microbiota dysbiosis in allergic asthmatic mice via the gut‑lung axis.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {}, pmid = {42169007}, issn = {1749-8546}, support = {ZB2025013//The Fundamental Research Funds for the Central public welfare research institutes/ ; CI2023C065YLL//Scientific and technological innovation project of China Academy of Chinese Medical Sciences/ ; 102160222020040009016, 160202001000210007//Scientific Research Facility Special Foundation for Operation and Maintenance/ ; }, abstract = {BACKGROUND: Allergic asthma (AA) may result in repeated episodes of chest constriction and coughing. In its most serious manifestations, it can cause death by asphyxiation. Currently, no efficacious therapeutic interventions exist to avert or counteract these serious outcomes. Baicalein (BAI) is a core quality marker of the traditional Chinese medicine Scutellaria baicalensis, but the mechanism of its oral action remains unclear.<br><br>OBJECTIVE: Assess the therapeutic efficacy of BAI in AA mice models and investigate its mechanism of action.<br><br>STUDY DESIGN AND METHODS: Evaluate the efficacy of BAI on ovalbumin-induced AA mice. To assess alterations in the pulmonary and gut microbial communities, 16S rRNA sequencing was employed. The integrity and restoration of the lung and intestinal epithelial lining were evaluated via immunohistochemistry. Furthermore, gas chromatography-mass spectrometry quantified fecal levels of short-chain fatty acids (SCFAs) in AA mice, and flow cytometry was used to analyze the content of ILC2 cells in colon tissue. Finally, the role of beneficial bacteria and their metabolites in inhibiting AA was further confirmed through fecal microbiota transplantation (FMT).<br><br>RESULTS: Oral BAI effectively alleviated AA-related lung epithelial damage and microbiota dysbiosis, while elevating the production of the tight junction proteins. Moreover, BAI mitigated colonic epithelial damage, inhibited ILC2s activation in the colon, enriched the abundance of gut probiotics capable of producing SCFAs, especially Akkermansia muciniphila (A. muciniphila), and increased the content of SCFAs such as propionic acid in feces. The FMT experiment conducted after gavage with broad-spectrum antibiotics confirmed that BAI mediated reversal of microbial dysbiosis plays a key role in the treatment of AA, significantly increasing the expression of GPR41 mRNA in colon tissue and inhibiting the activation of ILC2s.<br><br>CONCLUSION: The potential prebiotic BAI mitigates AA via targeting A. muciniphila and its metabolites, which consequently inhibits epithelial damage and type 2 immune activation.}, }
@article {pmid42171840, year = {2026}, author = {Yu, Y and Tian, M and Sun, S and Wang, H and Qin, M and Gao, Y and Jia, X and Gao, Q and Jiang, F}, title = {Fecal Microbiota Transplantation from Exercise-Preconditioned Mice Attenuates Post-stroke Cognitive Impairment by Preserving Gut and Blood-Brain Barrier Integrity.}, journal = {Neurochemical research}, volume = {51}, number = {3}, pages = {}, pmid = {42171840}, issn = {1573-6903}, support = {2108085MH252//Natural Science Foundation of Anhui Province/ ; 2023AH040288//Natural Science Research Program for Universities in Anhui Province/ ; 2024byfy004//the Science and Technology Programme of Bengbu Medical University/ ; No. 82070265//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Blood-Brain Barrier/metabolism ; *Fecal Microbiota Transplantation/methods ; *Physical Conditioning, Animal/physiology ; *Cognitive Dysfunction/therapy/etiology ; *Gastrointestinal Microbiome/physiology ; Male ; Mice ; Mice, Inbred C57BL ; *Stroke/complications ; }, abstract = {Exercise preconditioning reduces post-stroke cognitive impairment (PSCI), but the contribution of the gut microbiota (GM) to barrier protection remains unclear. We examined whether exercise-preconditioned GM contributes to PSCI improvement and preservation of gut and blood-brain barrier (BBB) integrity. Mice were preconditioned with 4 weeks of voluntary wheel running prior to stroke induction. We assessed cognitive function, GM composition, fecal short-chain fatty acid (SCFA) levels, inflammation, and gut-blood-brain barrier (BBB) integrity. Then, we used fecal microbiota transplantation (FMT) to evaluate how GM contributes to the benefits of voluntary exercise. Our results showed that exercise remodeled the GM composition and elevated SCFAs levels. Also, exercise suppressed systemic, colonic, and neuroinflammation, enhanced the barrier-related protein (Occludin, Claudin-5, and ZO-1) levels, maintained barrier integrity, and alleviated cognitive dysfunction after ischemic stroke. FMT from exercised mice partially reproduced the cognitive and anti-inflammatory benefits. SCFA levels were associated with reduced inflammatory markers and increased expression of barrier-related proteins. The findings suggest that exercise preconditioning is associated with coordinated preservation of gut and BBB integrity and improved cognition after stroke. Moreover, FMT from exercised mice conferred partial protection against PSCI.}, }
@article {pmid42171841, year = {2026}, author = {Gómez-Montañez, E and Rojas-Salazar, YL and Rojas-Salazar, JG}, title = {Microbiome in Gastrointestinal Tumors: Implications in Oncogenesis and Therapeutic Response : Microbiome in Gastrointestinal Tumors.}, journal = {Current oncology reports}, volume = {28}, number = {1}, pages = {}, pmid = {42171841}, issn = {1534-6269}, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/therapy/pathology ; *Gastrointestinal Microbiome ; *Carcinogenesis ; *Dysbiosis/microbiology ; Tumor Microenvironment ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: To provide an updated overview of the role of the human microbiome in the initiation, progression, and therapeutic response of gastrointestinal tumors, emphasizing molecular, immunological, and metabolic mechanisms, as well as its potential as a target for novel therapeutic strategies.<br><br>RECENT FINDINGS: Emerging evidence demonstrates that microbiome dysbiosis contributes to carcinogenesis across gastrointestinal malignancies, including colorectal, gastric, hepatic, and pancreatic cancers. Microbial-derived metabolites, such as short-chain fatty acids and secondary bile acids, modulate key signaling pathways involved in cell proliferation, apoptosis, and genomic stability. In addition, the microbiome influences the tumor microenvironment and immune responses, shaping variability in treatment outcomes. Both preclinical and clinical studies have shown that microbiome composition affects the efficacy and toxicity of chemotherapy and immunotherapy. Notably, specific microbial signatures are being explored as non-invasive biomarkers for early detection and prognostic stratification, while microbiome modulation strategies, such as diet, probiotics, antibiotics, and fecal microbiota transplantation, have demonstrated potential to enhance therapeutic response. The bidirectional interaction between the microbiome and the host plays a central role in gastrointestinal tumorigenesis and treatment response. Although this field holds significant promise for precision oncology, its clinical translation remains limited by interindividual variability, methodological heterogeneity, and insufficient longitudinal evidence. Future efforts should focus on standardization, validation of microbiome-based biomarkers, and integration of multi-omics and artificial intelligence approaches to enable clinically actionable applications.}, }
@article {pmid42171928, year = {2026}, author = {Bi, Q and Zhang, L and Wan, H and Zhang, J}, title = {Harnessing the gut microbiota to enhance immune checkpoint inhibitor efficacy: from mechanistic insights to clinical translation.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {}, pmid = {42171928}, issn = {1573-4978}, support = {HUST: 32500006//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; Tumor Microenvironment/immunology/drug effects ; Fecal Microbiota Transplantation/methods ; Immunotherapy/methods ; Translational Research, Biomedical ; }, abstract = {Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 pathways have revolutionized cancer therapy, yet their efficacy is frequently limited by primary or secondary resistance. Emerging evidence underscores the gut microbiota as a decisive regulator of ICI therapeutic outcomes. This review systematically delineates the multi-dimensional mechanisms through which the microbiota modulates anti-tumor immunity, specifically focusing on the molecular remodeling of immune signaling by microbial metabolites such as short-chain fatty acids (SCFAs) and bile acids, cross-reactive immunity driven by antigenic molecular mimicry, and the spatial restructuring of the tumor microenvironment mediated by the gut-tumor axis. Clinically, fecal microbiota transplantation (FMT) has demonstrated the potential to reverse ICI resistance, while the development of live biotherapeutic products (LBPs) and precise prebiotic combinations offers a standardized path for niche-specific intervention. Despite these advances, critical challenges persist, including the biological mismatch in cross-species animal models, the context-dependency arising from individualized microbial signatures, and the cognitive gap in the temporal dynamics of microbe-drug interactions. Deciphering the non-linear correlation between microbial succession and host immune response will be essential for integrating microbiota-driven strategies into personalized oncology frameworks.}, }
@article {pmid42172084, year = {2026}, author = {Oliveira, JM and Luxo, C and Matos, AM}, title = {Human Polyomaviruses of Clinical Relevance: Modes of Transmission and Associated Pathologies.}, journal = {Reviews in medical virology}, volume = {36}, number = {3}, pages = {e70166}, doi = {10.1002/rmv.70166}, pmid = {42172084}, issn = {1099-1654}, support = {//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Polyomavirus Infections/transmission/virology/pathology/diagnosis ; *Polyomavirus/pathogenicity/classification/genetics/physiology/isolation &amp; purification ; Seroepidemiologic Studies ; Clinical Relevance ; }, abstract = {Polyomaviruses are non-enveloped viruses with double-stranded circular DNA genome. Currently, 13 members of the Polyomaviridae family have been classified as human polyomavirus (HPyVs). Despite high seroprevalence values have been reported for the majority of the HPyVs worldwide, the main mode of transmission remains to be elucidated, and simple and common routes, such as faecal-oral and respiratory have been suggested. In general, HPyVs are responsible for asymptomatic primary infection, followed by asymptomatic lifelong persistent infection. In situations of severe immunosuppression, viral reactivation of some HPyVs may occur and result in the development of associated clinical manifestations. JCPyV is the causative agent of Progressive Multifocal Leukoencephalopathy, BKPyV is associated with nephropathy among kidney transplant recipients, MCPyV with Merkel Cell Carcinoma and TSPyV with Trichodysplasia spinulosa. The association of certain HPyVs with severe diseases, in addition to the high seroprevalence of the majority of HPyVs, emphasises the need to address various knowledge gaps that still exists in the natural history of these viruses, including the transmission routes and the pathogenic mechanisms. The present review summarises current information on HPyV transmission routes and associated diseases, including diagnosis and available treatment options, highlighting the need for further studies.}, }
@article {pmid42172181, year = {2026}, author = {Gomes, JV and Ribeiro, SPO and Nascimento, GMCD and Santos, DOD and Paula, DJG and Lima, SCS and Simão, TA}, title = {The human microbiome in cancer: Not just a sidekick anymore.}, journal = {Genetics and molecular biology}, volume = {49Suppl 1}, number = {Suppl 1}, pages = {e20250236}, pmid = {42172181}, issn = {1415-4757}, abstract = {The human microbiome is increasingly recognized as a dynamic element in cancer biology. Studies across breast, prostate, lung, colorectal, and cervical tumors reveal that microbial communities influence carcinogenesis, immune regulation, and treatment outcomes. When the balance of these microorganisms is altered, inflammation becomes chronic, metabolism is disrupted, and signaling pathways such as NF-κB, IL6-STAT3, and β-catenin are activated. Bacterial metabolites and genotoxins, including colibactin and bile acids, may damage DNA and reshape the epigenetic landscape. Distinct microbial profiles have been linked to prognosis and to patient responses to chemotherapy and immunotherapy. The presence of beneficial taxa, such as Akkermansia muciniphila and Ruminococcus, has been associated with improved response to immune checkpoint inhibitors. At the same time, antibiotic-induced depletion of gut microbiome can reduce therapeutic efficacy. Strategies that help restore microbial balance, including probiotics, dietary interventions, and fecal microbiota transplantation, are being explored as complementary therapies. Although methodological differences and contamination remain challenges, the growing body of evidence indicates that the microbiome is a measurable and modifiable component of tumor ecosystems with strong potential for diagnostic, prognostic, and therapeutic applications in precision oncology.}, }
@article {pmid42172659, year = {2026}, author = {Liu, C and Yin, X and Yuan, X}, title = {Gut microbiota dysbiosis and osteoporosis: pathogenesis and novel intervention strategies.}, journal = {Future microbiology}, volume = {21}, number = {7}, pages = {657-668}, pmid = {42172659}, issn = {1746-0921}, mesh = {Humans ; *Osteoporosis/microbiology/therapy/etiology ; *Dysbiosis/therapy/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; Intestinal Barrier Function ; Bone Remodeling ; }, abstract = {Osteoporosis represents a major global public health challenge, with current pharmacological treatment often limited by substantial side effects. Recent research identifies the gut-bone axis as a key regulatory pathway linking gut microbiota to bone metabolic homeostasis. This review synthesizes findings from PubMed, Web of Science, and Scopus (up to March 2026) to elucidate how gut microbiota dysbiosis drives osteoporosis pathogenesis through interconnected mechanisms: aberrant immune modulation, altered microbial metabolites, impaired nutrient absorption, endocrine disruption, and systemic inflammation stemming from intestinal barrier failure. Consequently, these pathways disrupt the delicate balance of bone remodeling. Based on these insights, we outline novel microbiota-targeted therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, natural bioactive compounds, traditional Chinese medicine, and nanomaterials. These interventions aim to prevent and manage osteoporosis by reshaping the intestinal microecology via multi-target modulation. Future endeavors should prioritize in-depth mechanistic exploration, personalized precision interventions, and enhanced clinical translation to integrate these strategies into comprehensive osteoporosis care frameworks.}, }
@article {pmid42172982, year = {2026}, author = {Yan, S and Zhang, Y and Fan, Q and Jia, W and Dai, Y and Li, X and Lu, S and Sheng, Y and Sun, S and Lin, R and Tang, Y and Zhao, C}, title = {Evodiamine targets ZO-1 to ameliorate cholestatic liver disease: Intestinal homeostasis as the core mediator of gut-liver axis repair and bile acid metabolism remodeling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {157}, number = {}, pages = {158288}, doi = {10.1016/j.phymed.2026.158288}, pmid = {42172982}, issn = {1618-095X}, mesh = {Animals ; Homeostasis/drug effects ; Male ; *Zonula Occludens-1 Protein/metabolism ; *Bile Acids and Salts/metabolism ; Liver/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; *Quinazolines/pharmacology ; *Cholestasis/drug therapy/metabolism ; Gastrointestinal Microbiome/drug effects ; Intestines/drug effects ; Fecal Microbiota Transplantation ; Disease Models, Animal ; *Liver Diseases/drug therapy/metabolism ; }, abstract = {BACKGROUND: Cholestatic liver disease (CLD) is a complex and multifactorial chronic disorder that requires a systematic and integrative management. Evodiamine (EVO), a natural alkaloid derived from Evodiae Fructus, has demonstrated significant therapeutic potential in ameliorating digestive diseases. However, the beneficial effects of EVO on CLD and the underlying mechanisms remain poorly understood.<br><br>OBJECTIVE: This study aims to elucidate the mechanisms through which EVO modulates the progression of CLD, with a particular focus on the regulation of gut-liver axis homeostasis.<br><br>METHODS: The therapeutic efficacy of EVO in bile duct ligation (BDL)- and &#x3b1;-naphthyl isothiocyanate (ANIT)-induced CLD rat models was systematically evaluated. An integrative approach combining network pharmacology with multi-omics analyses (transcriptomic, metagenomic sequencing, targeted bile acid metabolomics) was employed to identify significantly altered molecular networks. Fecal microbiota transplantation (FMT) was conducted to validate the functional role of gut microbiota in the hepato-intestinal protective effects. Direct molecular targets as well as the functional validation were confirmed through molecular docking, pull-down assays, surface plasmon resonance and cellular thermal shift assay.<br><br>RESULTS: EVO achieved significant synchronous hepato-intestine protection in both CLD rats: it markedly ameliorated hepatic injury and hepatic fibrosis, downregulated pro-inflammatory cytokine levels, while preserving intestinal barrier integrity and alleviating intestinal inflammation. Mechanistically, EVO exerted these protective effects by directly targeting the tight junction protein ZO-1 and enhancing its expression and stability. Furthermore, EVO restored intestinal microbial homeostasis, corrected dysregulated BA metabolism-specifically normalizing deoxycholic acid (DCA) levels. FMT experiments demonstrated that the synchronous hepato-intestinal beneficial effects of EVO were partially mediated by gut microbiota.<br><br>CONCLUSION: EVO exerts a protective effect against CLD by directly targeting ZO-1 to strengthen intestinal barrier function, thereby restoring gut microbial balance and rebalancing BAs metabolism (especially DCA levels) in the gut-liver axis. This study uncovers a novel ZO-1-dependent mechanism of EVO in CLD, highlighting EVO as a promising candidate for the treatment of CLD and providing new insights into gut-liver axis-targeted therapies.}, }
@article {pmid42173875, year = {2026}, author = {Nie, X and Li, Q and Tao, Z and Xu, Y and Li, B and Xie, J and Nie, S}, title = {Faecalibacterium prausnitzii-derived extracellular vesicles ameliorate experimental colitis through regulating barrier immunity and gut microbiota.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00897-2}, pmid = {42173875}, issn = {2396-8370}, support = {SKLF-ZZB-202543//State Key Laboratory of Food Science and Resources, Nanchang University/ ; 20242BAB21031//Natural Science Foundation of Jiangxi/ ; 20232BCD44003//Technological Project of Jiangxi Province/ ; }, abstract = {Ulcerative colitis (UC) is closely linked to intestinal barrier dysfunction and gut dysbiosis. Bacterial extracellular vesicles (bEVs) act as key mediators of bacteria-host crosstalk, with great potential in regulating host health. Recent studies have shown that EVs derived from gut commensal bacteria offer therapeutic advantages in treating UC. Herein, we explored the therapeutic effect of Faecalibacterium prausnitzii-derived EVs (PEVs) in DSS-induced colitis mice. Results showed PEVs significantly improved intestinal barrier damage, restored Th17/Treg balance and alleviated gut dysbiosis. Further fecal microbiota transplantation (FMT) confirmed that feces from PEVs-treated mice transferred beneficial effects to recipient colitis mice. Collectively, our findings indicate that commensal gut microbiota-derived nanovesicles have the potential to serve as candidates for UC treatment.}, }
@article {pmid42173912, year = {2026}, author = {Huang, Y and Hu, Y and Zhao, Y and Li, Y and Liu, Y and Wang, M and Wang, Q and Hu, H}, title = {Ulcerative colitis-driven gut dysbiosis exacerbates periodontal bone loss through the gut-oral axis /Th17/Treg imbalance.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01015-6}, pmid = {42173912}, issn = {2055-5008}, support = {gzwkj2025-445//the Science and Technology Fund of Guizhou Provincial Health Commission(gzwkj2025-445)/ ; QKHJC-MS[2026]895//Guizhou Provincial Science and Technology Programme/ ; 17zy-002//Outstanding Young Talent Project of Zunyi Medical University/ ; HZ[2024]340//the Zunyi Science and Technology Program/ ; }, abstract = {Ulcerative colitis (UC) and periodontitis, both microbial dysbiosis-driven chronic inflammatory disorders, coexist and mutually exacerbate, but the causal mechanisms remain unclear. Using ligature-induced periodontitis plus DSS-colitis mice, we found UC doubles alveolar bone loss, heightens systemic inflammation, oxidative stress, and osteoclastogenesis. 16S rRNA and LC-MS metabolomics showed UC enriches oral pathogens, depletes gut Firmicutes, expands Bacteroides, and correlates with suppressed amino-acid/bile-acid biosynthesis. Fecal microbiota transplantation (FMT) from DSS donors into antibiotic-pretreated periodontitis-prone mice replicated aggravated bone loss, systemic inflammation, gut-barrier leakage, and Th17/Treg imbalance, while healthy-donor FMT protected. GC-MS revealed 35-60% reductions in acetate, propionate, and butyrate; keystone taxa Parabacteroides and Muribaculum inversely correlated with SCFAs and host inflammatory genes. Collectively, UC-driven gut dysbiosis is a transmissible causal factor that simultaneously remodels oral and intestinal biofilms, erodes epithelial barriers, and amplifies osteoclastic bone resorption. SCFAs-producing microbes or supplementation may be potential therapeutics for UC-associated periodontitis patients.}, }
@article {pmid42174754, year = {2026}, author = {Chen, Y and Zhao, J and Zhao, J and Chen, Q and Dong, S and Jia, S and Zhao, Y and Hao, D and Yin, Y and Lin, S and Chen, Y and Zhuang, Y and Peng, H}, title = {Effects of fecal microbiota transplantation and probiotics on the gut microbiome in antibiotic-treated septic patients: A pilot randomized controlled trial.}, journal = {Virulence}, volume = {17}, number = {1}, pages = {2668764}, pmid = {42174754}, issn = {2150-5608}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/administration &amp; dosage/therapeutic use ; *Fecal Microbiota Transplantation ; Pilot Projects ; Male ; Middle Aged ; Female ; *Sepsis/therapy/microbiology/drug therapy ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; Aged ; Prospective Studies ; Critical Illness ; Dysbiosis/therapy ; Treatment Outcome ; Feces/microbiology ; Adult ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Broad-spectrum antibiotics, essential for sepsis management in critically ill patients, cause significant gut dysbiosis. Restoring gut microbiota may improve outcomes, but the efficacy of interventions like fecal microbiota transplantation (FMT) and probiotics in this setting remains underexplored. This study aims to evaluate the feasibility and potential efficacy of FMT versus probiotics on gut microbiome restoration and inflammatory markers in critically ill, antibiotic-treated sepsis patients. In this single-center, prospective, exploratory pilot RCT, 40 sepsis patients were were randomized 2:1:1 to: Control (n = 20, antibiotics treatment), Probiotics (n = 10, antibiotics treatment combined one week of probiotics), and FMT (n = 10, antibiotics treatment combined one week of FMT) groups. Gut microbiota composition was analyzed using 16S rDNA sequencing, and clinical inflammatory markers were assessed at baseline, one week, and two weeks post-treatment. FMT significantly mitigated antibiotic-induced reductions in microbial diversity. At 2 weeks, the FMT group exhibited higher alpha-diversity (Chao1 index, p = 0.0125; Shannon/Simpson trends p = 0.06) compared to Control and Probiotics groups. FMT increased beneficial Bacteroides abundance and reduced Enterobacteriaceae. BugBase analysis revealed FMT significantly lowered pathogenic potential of gut microbiota (p = 0.021). Donor-recipient analysis showed FMT shifted recipient microbiomes toward donor enterotype. This study provides preliminary evidence that FMT, but not the probiotic regimen, effectively restores gut microbiome diversity and composition, reduces pathogenic potential, and may improve clinical outcomes in critically ill sepsis patients after broad-spectrum antibiotics. This study was registered on ClinicalTrials.gov (NCT05578196).}, }
@article {pmid42177552, year = {2026}, author = {Zou, F and Wu, Z and Wang, S and Xu, M and Xia, P and Hu, Y and Fang, T and Hu, P and Huang, C and Deng, F}, title = {Microbiota-derived butyrate inhibits colonic epithelial pyroptosis and mitigates DSS-induced colitis via interacting with aryl hydrocarbon receptor.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08264-1}, pmid = {42177552}, issn = {1479-5876}, support = {82470586//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intestinal barrier defects cause antigen translocation and immune dysregulation. The pyroptosis of colonic epithelial cells (CECs) disrupts the colonic barrier, and its inhibition might be a therapeutic approach for ulcerative colitis (UC), but the mechanisms are not fully understood.<br><br>METHODS: A DSS-induced UC model was established to assess the level of colonic epithelial cell pyroptosis. 16S rDNA sequencing and LC&#x2012;MS/MS were applied to screen potential candidate bacterial species and metabolites. The roles of target metabolites were evaluated in vivo using GSDMD-knockout mice. FHC cells treated with LPS&#x2009;+&#x2009;ATP were used as a cellular model of pyroptosis, and the underlying molecular mechanism was explored mainly by siRNA transfection and lentivirus infection.<br><br>RESULTS: We found that DSS-treated mice exhibited increased levels of pyroptosis in the colon. Fecal microbiota transplantation (FMT) significantly suppressed mucosal inflammation and CEC pyroptosis, accompanied by increased levels of butyrate-producing bacteria and butyrate in feces. Butyrate treatment alleviated DSS-induced colitis in mice. Moreover, GSDMD knockout mitigated DSS-induced colitis in mice, whereas a butyrate intervention failed to further ameliorate colitis in GSDMD-knockout mice. Mechanistically, we found that butyrate significantly inhibited LPS&#x2009;+&#x2009;ATP-induced pyroptosis by activating its receptor, aryl hydrocarbon receptor (AhR), in FHC cells, while silencing AhR suppressed this effect. The overexpression of cGAS in FHC increased the level of pyroptosis, whereas the administration of butyrate inhibited the activation of the cGAS-STING pathway. Treatment with a cGAS inhibitor significantly reversed the increase in pyroptosis caused by AhR knockdown in pyroptotic FHC cells.<br><br>CONCLUSIONS: Gut microbiota-derived butyrate levels were increased after FMT. Butyrate suppressed the proinflammatory cGAS-STING-NF-&#x3ba;B signaling axis via AhR to inhibit CEC pyroptosis and thereby alleviate UC.}, }
@article {pmid42177905, year = {2026}, author = {Liu, T and Wang, H and Lu, D and Yan, C and Hang, F and Ma, B and Meng, X}, title = {Emodin inhibits the formation of gallstones by affecting the intestinal flora and expression of hepatic HIF1α.}, journal = {International immunopharmacology}, volume = {183}, number = {}, pages = {116878}, doi = {10.1016/j.intimp.2026.116878}, pmid = {42177905}, issn = {1878-1705}, mesh = {Animals ; *Emodin/pharmacology/therapeutic use ; *Gallstones/drug therapy/prevention &amp; control/microbiology/metabolism ; Mice, Inbred C57BL ; *Liver/metabolism/drug effects ; Mice ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Male ; *Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {BACKGROUND: Gallstone disease is a prevalent digestive disorder worldwide; however, current therapeutic approaches remain limited. Emodin, a natural anthraquinone compound, exerts diverse biological effects including anti-inflammatory activity and metabolic regulation. To elucidate the mechanism by which emodin inhibits gallstone formation, we conducted in vivo experiments, multi-omics analysis, and network pharmacology.<br><br>METHODS: Six-week-old C57BL/6 mice were used to establish an in vivo model with emodin intervention. Fecal microbiota transplantation (FMT), 16S rRNA gene sequencing, and serum metabolomics sequencing were employed to investigate the effects of emodin on gut microbiota and serum metabolites. Network pharmacology was applied to predict the regulatory effects of emodin on liver-related genes, which were further verified by fundamental experiments. The correlations between gut microbiota, serum metabolites, and liver genes were explored. Statistical analysis was performed using GraphPad Prism 9.0.<br><br>RESULTS: The medium dose of emodin (30&#xa0;mg/kg) showed the optimal inhibitory effect on gallstones formation. Emodin reshaped the intestinal flora structure in mice with gallstones and increased the abundance of Limosilactobacillus reuteri (L. reuteri) in vivo. By elevating serum tauroursodeoxycholic acid (TUDCA) levels in mice, emodin downregulated the expression of hepatic HIF1&#x3b1; and upregulated the expression of AQP8.<br><br>CONCLUSIONS: Emodin inhibited gallstone formation in mice through two complementary mechanisms. First, emodin modulated the gut microbiota to promote the proliferation of L. reuteri; second, it increased serum TUDCA levels, thereby regulating the HIF1&#x3b1;-AQP8 pathway to alleviate cholestasis. In addition, we speculate that L. reuteri may elevate serum TUDCA content via several indirect pathways.}, }
@article {pmid42178721, year = {2026}, author = {Schulze, K and Goldschmidt, I and Melk, A and Boehne, M and Woltemate, S and Ballmaier, M and Kleiner, S and Lehmann, E and Kramer, M and Vital, M}, title = {Altered SIgA-targeting of gut microbiota is associated with long-term dysbiosis in pediatric solid organ transplant recipients.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2675078}, pmid = {42178721}, issn = {1949-0984}, mesh = {Humans ; *Dysbiosis/microbiology/immunology/etiology ; *Gastrointestinal Microbiome ; Child ; Male ; Female ; *Immunoglobulin A, Secretory/immunology/genetics ; *Transplant Recipients ; Tacrolimus/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification ; Adolescent ; Immunosuppressive Agents/adverse effects/therapeutic use ; *Organ Transplantation/adverse effects ; Feces/microbiology ; Child, Preschool ; Liver Transplantation/adverse effects ; }, abstract = {The composition of the gut microbiota (GM) is altered in solid organ transplantation (SOT) recipients, where the degree of dysbiosis is associated with long-term survival and is believed to be influenced by immunosuppression therapy. At the interface stands secretory (S)IgA, however, little is known about its role in governing dysbiosis in the context of SOT. We performed quantitative metagenomic analyses of the GM accompanied by SIgA sequencing in 48 pediatric SOT recipients (age = 10.6 ± 4.7 y) receiving either heart (n = 11), kidney (n = 10) or liver transplantation (n = 27), and compared the results to age-matched healthy controls (HC, n = 16). We confirmed compositional and functional dysbiosis in SOT recipients, with the degree of dysbiosis being associated with tacrolimus (TAC) levels. Overall, SOT recipients exhibited higher SIgA levels than HC, along with an increased percentage of bacteria targeted and altered target spectra. Furthermore, altered SIgA responses were associated with the degree of dysbiosis. A mechanistic model connecting immunosuppression, GM composition and SIgA-targeting is proposed, suggesting that GM dysbiosis in SOT recipients is mediated by the immune system through the SIgA response; direct drug-mediated effects on fecal communities were not observed in in vitro experiments. Our study provides new insights into factors that contribute to persisting dysbiosis in SOT recipients.}, }
@article {pmid42178957, year = {2026}, author = {Ciesielski, P and Zaniewska, M and Waliszewski, M and Dziewa, N and Kołodziejczak, M}, title = {Treatment for full-thickness rectal prolapse using the abdominal access: An evaluation of 94 cases.}, journal = {Polski przeglad chirurgiczny}, volume = {98}, number = {2}, pages = {8-12}, doi = {10.5604/01.3001.0055.5841}, pmid = {42178957}, issn = {2299-2847}, mesh = {Humans ; *Rectal Prolapse/surgery ; Female ; Middle Aged ; Male ; Treatment Outcome ; Prospective Studies ; Adult ; Aged ; *Digestive System Surgical Procedures/methods ; Surgical Mesh ; }, abstract = {Introduction: Full-thickness rectal prolapse (FTRP) is a multifactorial disease that can be treated with different surgicaltechniques. There is still no standard surgical procedure, and the selection of the surgical technique is based on the individualassessment and the experience of the surgeon. The benefits to patients should focus on repair of bowel prolapse, reduction ofconstipation, and an improvement in pelvic floor muscle insufficiency.Aim: Aim of this study was to evaluate clinical and functional outcomes after abdominal surgery for FTRP in a prospective single- -center observational study.Materials and methods: Between 2016 and 2022, a total of 94 consecutive patients (46.2 18.2 years) underwent abdominal surgery due to FTRP using an abdominal approach. They were operated on with ventral mesh rectopexy (VMR) (55 pts.) or resection and suture rectopexy - Frykman-Goldberg procedure (FG) (39 pts.). Before and after the surgery, clinical and functional outcomes were measured. The follow-up period ranged from 1 to 6 years (mean: 26 months).Results: At last follow-up, constipation occurred in 27.6% of VMR and 31.3% of FG patients (p = 0.754; calculated among patients with available postoperative constipation status). The Wexner incontinence score was significantly better in the VMR group (1.0 2.1 vs. 3.6 5.0, p = 0.009). There were no differences in the EQ5D indices between the groups (1.7 2.0 vs. 2.4 2.8, p = 0.257).Conclusions: Both surgical procedures revealed comparable rates of recurrence and complications. While QoL was similarbetween groups, VMR yielded a significantly greater improvement in the Wexner incontinence score.}, }
@article {pmid42180552, year = {2026}, author = {Chen, Y and Wei, X and Yi, X and Jiang, DS}, title = {Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.}, journal = {Acta pharmaceutica Sinica. B}, volume = {16}, number = {5}, pages = {2711-2729}, pmid = {42180552}, issn = {2211-3835}, abstract = {Degenerative diseases are a group of medical conditions characterized by the progressive and irreversible deterioration of cells, tissues, and organs over time. Emerging evidence highlights the alteration and functions of the gut microbiome in the development of degenerative diseases. Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated as a pivotal factor in the regulatory effect of the gut microbiome on degenerative diseases. Moreover, gut metabolites, particularly short-chain fatty acids and trimethylamine N-oxide, are closely related to iron overload, redox imbalance, and lipid peroxidation. Recently, microbiome-based therapies, such as fecal microbiota transplantation, have been considered novel therapeutic strategies. In this review, we focus on degenerative diseases and explore the interactions between the gut microbiome and ferroptosis, aiming to provide new insights into the underlying mechanisms and clinical implications.}, }
@article {pmid42181429, year = {2026}, author = {Lopez Garri, S and Lingier, P and Dassonville, M and Tulelli, B}, title = {Long-Term Quality of Life and Functional Outcomes in Patients With Anorectal Malformations: A Retrospective Multicenter Study in Brussels, Belgium.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e107561}, pmid = {42181429}, issn = {2168-8184}, abstract = {Introduction Anorectal malformations (ARMs) are congenital conditions requiring surgical correction. Despite surgical intervention, patients often experience persistent fecal and urinary dysfunction, significantly impacting their quality of life (QoL). This multicenter retrospective study aimed to assess QoL in ARM patients, identify factors influencing QoL deterioration, and propose improved management strategies. Methods We retrospectively analyzed data from 39 ARM patients who underwent surgery between 1999 and 2019 at two Belgian hospitals. Patients completed the Hirschsprung's Disease Anorectal Malformation Quality of Life Questionnaire (HAQL). We also reviewed their medical records. Descriptive statistical analysis was performed. Results At a median follow-up of 106 months, functional outcomes showed high rates of constipation (87%), fecal incontinence (54%), and fecal soiling (87%). Fecal incontinence was more prevalent in patients with bulbar rectourethral and recto-vesical fistulas. Postoperative complications occurred in 72% of patients, primarily in those with high ARMs, and correlated with increased constipation and abdominal pain. Management gaps were observed: only 47% of constipated patients and 56% of incontinent patients underwent anorectal manometry, and only 50% of constipated patients utilized physiotherapy. QoL assessment revealed persistent digestive functional disorders and physical symptoms across age groups, which improved with age. However, emotional and body image issues persisted into adulthood. Conclusion Patients with ARMs frequently experience significant functional digestive disorders and impaired QoL. Suboptimal management, particularly regarding the use of anorectal manometry and physiotherapy, contributes to these challenges. A long-term, multidisciplinary follow-up is crucial. This follow-up should include systematic dietary support, perineal rehabilitation, and targeted interventions guided by anorectal manometry to improve QoL in this population.}, }
@article {pmid42181890, year = {2026}, author = {Gamal, NK and Fakhry, R and Hatem, Y and Rashed, E and Marzouk, R and Bukr, AKM and Akawi, N and George, MY}, title = {Neurodegeneration at the crossroads: the gut-brain axis and blood-brain barrier in Parkinson's disease - a review.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1813134}, pmid = {42181890}, issn = {1663-9812}, abstract = {Parkinson's disease (PD), which is one of the most common neurodegenerative illnesses, involves abnormal deposition of α-Synuclein and loss of dopaminergic neurons in the substantia nigra. Beyond this, there is increasing evidence that the gut-brain axis (GBA) and blood-brain barrier (BBB) interfere in disease initiation and progression. Dysbiosis of the gut microbiota affects the intestine and the BBB, allowing microbial metabolites and proinflammatory mediators to enter the CNS, causing neuroinflammation and neurodegeneration. Studies show that α-Synuclein pathology can originate in the gut and reach the brain via the vagus nerve. This review summarizes the connections among GBA, BBB, and PD, focusing on oxidative damage, inflammatory cascades, decreased expression of tight junction proteins, and signaling pathways such as TLR4/MyD88/NF-κB. In addition, we discuss therapeutic strategies that target the microbiota-BBB axis, such as probiotics, fecal microbiota transplantation, natural compounds (e.g., piperine, anethole, polymannuronic acid, Paeonia lactiflora), and stem cell therapy, which have demonstrated neuroprotective potential in animal models. Overall, the literature emphasizes the importance of restoring gut homeostasis and BBB integrity, and suggests that getting this axis right may offer novel opportunities for PD treatment. Future research is crucial to validate the efficacy of this approach clinically and to develop tailored therapies to prevent or delay PD progression.}, }
@article {pmid42182017, year = {2026}, author = {Li, J and Qiu, X}, title = {Neurodevelopmental disorders and the gut microbiome: insights into ADHD and tic disorders.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1779746}, pmid = {42182017}, issn = {1664-302X}, abstract = {This review examines the relationship between tic disorders (TD), attention deficit hyperactivity disorder (ADHD), and the gut microbiota within the framework of the gut-brain axis. We summarize current evidence on the clinical characteristics and neurobiological features of TD and ADHD, and discuss how genetic susceptibility, environmental exposures, and dietary factors may interact with gut microbial composition. We further review studies comparing the gut microbiota of affected individuals and healthy controls, with attention to recurrent taxa-level findings, functional hypotheses, and emerging microbiome-targeted interventions such as probiotics and fecal microbiota transplantation. Importantly, most available human studies remain associative rather than mechanistic, and cross-study comparability is limited by heterogeneity in sequencing approaches, cohort characteristics, medication exposure, and dietary control. Overall, current findings support the gut microbiota as a relevant component of neurodevelopmental disorders such as ADHD and TD, while highlighting the need for larger longitudinal and mechanistic studies to clarify causality and therapeutic potential.}, }
@article {pmid42182071, year = {2026}, author = {Qin, R and Yu, P and Wang, H and Zhou, J and Gong, R and Duan, Y and Jia, H and Xie, M and Zhou, Y and Hu, J}, title = {Gut-bone axis crosstalk: Microbiota-driven immune-metabolic-neural networks in bone disorders and precision interventions.}, journal = {Journal of orthopaedic translation}, volume = {58}, number = {}, pages = {101126}, pmid = {42182071}, issn = {2214-031X}, abstract = {UNLABELLED: The gut microbiota regulates bone metabolism via a complex gut-bone axis involving short-chain fatty acids (SCFAs), immune modulation, and neuroendocrine signals. However, the precise mechanisms remain unclear, and microbiota-targeted interventions (probiotics, prebiotics, fecal microbiota transplantation) are not yet optimized for clinical use. This review systematically synthesizes the immune-metabolic-neural interaction network within the gut-bone axis, highlighting non-linear crosstalk among SCFAs, bile acids, tryptophan derivatives, immune cells (macrophages, Treg/Th17), and vagus nerve signaling. We critically assess translational hurdles, including heterogeneous study designs, confounding factors, and lack of causal evidence. Based on this network perspective, we propose a framework for future research that prioritizes multi-omics approaches, stratified interventions, and rigorous trials. This synthesis advances understanding of how gut dysbiosis drives bone disorders and paves the way for precision skeletal medicine.<br><br>This review identifies microbial markers for risk stratification of bone metabolic disorders and discusses SCFA-based strategies and fecal microbiota transplantation (FMT) in conditions including osteoporosis, impaired fracture healing, rheumatoid arthritis, and glucocorticoid-associated osteonecrosis. It provides testable hypotheses for large-scale randomized controlled trials (RCTs), directly supporting translation of microbiome research into clinical practice for bone disorders.}, }
@article {pmid42182110, year = {2026}, author = {Zhang, Z and Holton, M and Ferrer, DM and Tripp, AD and Richter, A and Dixit, PD and Urtecho, G}, title = {Metagenome-scale Modeling to Assess Microbiome Metabolic Complementarity for Precision Microbiota Transplantation Therapies.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {42182110}, issn = {2692-8205}, abstract = {Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable, in part because existing computational models do not fully capture the metabolic compatibility between donor and recipient communities. Here, we present a metagenome-scale metabolic modeling framework that quantifies metabolic niche complementarity between donor and recipient microbiomes to predict transplantation outcomes. Using MICOM-derived community metabolic models, we show that donor taxa whose metabolic flux profiles are more dissimilar from the recipient community engraft at significantly higher rates in both murine and human FMT cohorts. In a human IBS trial, metabolic models accurately predicted post-FMT community composition via leave-one-out cross-validation and recapitulated disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to demonstrate a platform for personalized donor screening. This screen identified super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition, as quantified by a flux-derived ecological network balance index that strongly predicted engraftment potential. This framework provides a mechanistic, scalable tool for rational donor-recipient matching that could guide personalized microbiome-based therapies.}, }
@article {pmid42183070, year = {2026}, author = {Dou, M and Xu, J and Ye, X and Liu, J and Shi, L}, title = {Fecal Microbiota Transplantation From Healthy Donors Reduces Glycemic Variability in Streptozotocin-Induced Diabetic Rats via Enhanced Hepatic Glycogen Synthesis.}, journal = {International journal of endocrinology}, volume = {2026}, number = {}, pages = {8852077}, pmid = {42183070}, issn = {1687-8337}, abstract = {BACKGROUND: Blood glucose fluctuations in patients with brittle diabetes have been a problem for clinicians. A recent study found that transplanting the intestinal flora of healthy people to patients with brittle diabetes can improve their blood glucose fluctuations. However, the underlying mechanism remains unclear.<br><br>METHODS: Streptozotocin-induced diabetic rats were assigned to receive fecal microbiota transplantation (FMT) from healthy donors or to remain untreated, while normal rats received FMT from brittle diabetes donors or remained untreated. Groups included the normal control group (NC group), the diabetic group (DM group), normal rats with FMT from brittle diabetic patients (NC-DMFMT group), and diabetic rats with FMT from normal individuals (DM-NCFMT group). Blood glucose variability, rat liver glucokinase, and glycogen levels, as well as intestinal short-chain fatty acid content, were detected in each group of rats. Gut microbiota composition was analyzed using 16S rDNA sequencing.<br><br>RESULTS: Compared with the standard deviation of blood glucose (SDBG) (1.664&#x2009;&#xb1;&#x2009;0.427&#x2009;mmol/L) in the NC group, that of the DM group (6.879&#x2009;&#xb1;&#x2009;1.475&#x2009;mmol/L) was higher. However, the DM-NCFMT group reduced SDBG (4.387&#x2009;&#xb1;&#x2009;0.619&#x2009;mmol/L) vs. the DM group (p < 0.05). Hepatic glycogen (27.57&#x2009;&#xb1;&#x2009;5.254&#x2009;mg/L) was lower in the DM group than in the NC group (55.48&#x2009;&#xb1;&#x2009;9.467&#x2009;mg/L) but increased in the DM-NCFMT group (37.59&#x2009;&#xb1;&#x2009;1.283&#x2009;mg/L) vs. the DM group. The abundance of Bifidobacteria in the DM group was decreased compared to that in the NC group. In contrast, Bifidobacterium abundance in the DM-NCFMT group increased after standard human flora transplants (p < 0.05). Correlation and stepwise regression analysis indicated that Bifidobacteria reduced SDBG partly by promoting hepatic glycogen synthesis, with an effect share of 23.01%.<br><br>CONCLUSION: Normal individual fecal microbiota transplantation improves glucose variability in DM rats, potentially mediated by enhanced hepatic glycogen synthesis.}, }
@article {pmid42183271, year = {2026}, author = {Zhang, H and Zhang, K and Liu, J and Luo, H}, title = {Multidimensional exploration of the relationship between gut microbiota and colorectal cancer: focus on clinical tumorigenesis and treatment.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1807247}, pmid = {42183271}, issn = {1664-3224}, mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology/etiology/immunology/metabolism/pathology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; *Carcinogenesis ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The gut microbiota has received considerable attention in the field of colorectal cancer (CRC) research in recent years. In this review, we have explored the multifaceted relationship between the gut microbiota and CRC progression and treatment. The composition, distribution, and normal physiological functions of the gut microbiota have been summarized, along with the association between gut dysbiosis and CRC based on the body of evidence from animal experiments and clinical studies. In addition, we have discussed the mechanisms through which specific microbial configurations or microbiota-derived metabolites may contribute to colorectal carcinogenesis, including genotoxic effects, inflammation, and immune dysregulation. The impact of the gut microbiota on the efficacy of chemotherapy, radiotherapy, and immunotherapy, and new treatment strategies based on the gut microbiota, such as probiotic intervention, prebiotic application, and fecal microbiota transplantation have also been explored. Despite some promising outcomes, the specific carcinogenic microorganisms have not been identified, and it is challenging to distinguish association from causation, determine the influence of individual differences, and translate the research to clinical applications. In the future, more rigorous longitudinal studies, gnotobiotic models with defined microbial communities, and mechanistic interventional studies are needed to strengthen causal inference, and provide practical guidance for CRC prevention and treatment. Beyond summarizing reported associations, this review proposes a microbiota-immune-metabolism-therapy axis by integrating tumorigenic mechanisms, immune contexture, and treatment responsiveness into a single translational framework.}, }
@article {pmid42184295, year = {2026}, author = {Wong, SH}, title = {The human microbiome at translational crossroads: an ecological and causal perspective.}, journal = {Singapore medical journal}, volume = {67}, number = {5}, pages = {279-287}, pmid = {42184295}, issn = {2737-5935}, mesh = {Humans ; *Translational Research, Biomedical ; Probiotics/therapeutic use ; *Microbiota ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ecology ; }, abstract = {The human microbiome has emerged as a central focus of biomedical research, driven by interest in its translational potential for chronic diseases. Although compelling associations link microbial alterations to gastrointestinal, metabolic, neuropsychiatric and systemic conditions, successful clinical translation remains limited. This perspective contends that the principal barrier is not biological relevance but the application of reductionist thinking to an inherently complex ecological system, compounded by an incomplete understanding of causality. This review examines the gradient of causal confidence across gut-organ axes, from established roles in digestive disorders to less established distal associations, as well as highlights the epistemological challenges underlying microbiome research. A critical appraisal of current strategies, including probiotics, live biotherapeutics and faecal microbiota transplantation, suggests that progress requires ecological reasoning, causal rigour and systems-level integration. Moving from association to intervention demands approaches that account for host-microbiome complexity rather than oversimplified microbial targeting.}, }
@article {pmid42184718, year = {2026}, author = {El-Sehrawy, AAMA and Soleimani Samarkhazan, H}, title = {The silent pharmacist: Harnessing the gut microbiome to improve therapy in hematologic malignancies.}, journal = {Translational oncology}, volume = {70}, number = {}, pages = {102833}, pmid = {42184718}, issn = {1936-5233}, abstract = {The gut microbiome, a complex ecosystem of microorganisms, is now recognized as a key determinant of drug efficacy and toxicity, giving rise to the field of pharmacomicrobiomics. This review decodes the profound influence of the gut microbiome on treatment outcomes for hematologic malignancies. We explore the tripartite mechanistic pathways through which gut microbes act: the direct enzymatic biotransformation of chemotherapeutic agents, the indirect immunomodulation of systemic and anti-tumor responses, and the preservation of mucosal barrier integrity to prevent devastating complications like graft-versus-host disease (GVHD). The manuscript details how the microbiome interacts with specific drug classes, from conventional chemotherapies like cyclophosphamide to cutting-edge immunotherapies like immune checkpoint inhibitors and CAR-T cells, shaping their clinical success. Furthermore, we discuss the translational potential of targeting this "silent pharmacist" through fecal microbiota transplantation, next-generation probiotics, and dietary interventions. Finally, we highlight the main translational opportunities, current limitations, and future clinical priorities for integrating microbiome science into hematology, paving the way for more personalized and improved cancer care.}, }
@article {pmid42186662, year = {2026}, author = {Mueller, MK and Rousseau, SR and Hark, GM and Shaffer, LR and Rizvanović, BF and Nuelle, JAV}, title = {The Role of the Gut Microbiota in Functional Recovery after Peripheral Nerve Injury: A Narrative Review.}, journal = {Orthopedic reviews}, volume = {18}, number = {}, pages = {162156}, pmid = {42186662}, issn = {2035-8164}, abstract = {INTRODUCTION: While researchers have previously pointed to the peripheral nervous system as a method of transportation for the gut microbiota metabolites to distant organs, researchers have more recently studied the impact of gut microbiota on the peripheral nerves. The purpose of this review was to synthesize the literature on how modulation of the gut microbiota impacts functional recovery following peripheral nerve injury.<br><br>METHODS: Electronic searches were conducted in Ovid/Medline and PubMed to identify articles that discuss gut microbiome interventions following peripheral nerve injury in sciatic nerve chronic constriction injury or crush injury animal models and the effects on peripheral nerve regeneration and functional recovery.<br><br>RESULTS: Twelve articles met inclusion criteria; all were prospective studies in animal models. Four interventions were identified by the twelve studies, including probiotics, antibiotics, intermittent fasting, and naturopathic compounds. Probiotic treatment and dietary interventions targeted at modulating the gut microbiota improved histological, sensory, and motor outcomes following peripheral nerve injury. While antibiotic treatment negatively impacted recovery after peripheral nerve injury, co-treatment with probiotics or reconstitution of the gut microbiota through fecal microbiota transplantation was able to rescue these negative effects.<br><br>CONCLUSION: Alterations in the gut microbiota, whether induced by antibiotics, probiotics, intermittent fasting, or dietary interventions, impact functional recovery, neuropathic pain, and inflammatory processes. However, future research should focus on identifying the specific microbial taxa responsible for neuroregenerative effects and developing standardized protocols for probiotic treatment to optimize improvement in peripheral nerve recovery after injury.}, }
@article {pmid42187072, year = {2026}, author = {John, JM and Manjarres, Z and Zulkifly, NI and Plumb, AN and Pratt, ML and Sadler, KE}, title = {Male-specific analgesic effects of minocycline in sickle cell disease are mediated by microglia and the microbiome.}, journal = {Pain}, volume = {167}, number = {7}, pages = {1683-1695}, doi = {10.1097/j.pain.0000000000004008}, pmid = {42187072}, issn = {1872-6623}, mesh = {Animals ; *Minocycline/therapeutic use/pharmacology ; Male ; *Microglia/drug effects ; *Anemia, Sickle Cell/complications/drug therapy ; Female ; Mice ; Mice, Transgenic ; *Microbiota/drug effects/physiology ; *Sex Characteristics ; Disease Models, Animal ; *Analgesics/therapeutic use/pharmacology ; Hyperalgesia/drug therapy ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Over 50% of individuals with sickle cell disease (SCD) experience chronic pain that is phenotypically distinct from their acute, vaso-occlusive crisis pain. Chronic SCD pain is commonly managed with opioid-based drugs that are associated with unwanted side effects, incomplete pain relief, and-in this population-accessibility issues. Thus, new treatments for chronic SCD pain are desperately needed. Here, we examined the analgesic efficacy of acute minocycline treatment in transgenic SCD mice. Sickle cell disease mice exhibit gut dysbiosis and chronic inflammation. Therefore, we hypothesized that minocycline would provide robust analgesia in this model given the drug's antibiotic and anti-inflammatory properties, respectively. Six days of minocycline treatment reversed chronic mechanical hypersensitivity only in male SCD mice. We identified 2 potential mechanisms underlying these sex-specific effects. First, we observed increased microgliosis only in the dorsal horn of male SCD mice. Minocycline treatment had opposite effects on microglial number in male and female SCD spinal cords. Second, minocycline treatment altered the gut microbiota in a sex-specific fashion; fecal microbiota transplant (FMT) from minocycline-treated female SCD mice induced widespread pain in recipients, whereas FMT from minocycline-treated male SCD mice did not. In summary, these experiments highlight novel sex-specific mechanisms of minocycline analgesia and support future exploration of minocycline use for SCD pain management, but only in male patients.}, }
@article {pmid42188905, year = {2026}, author = {Yao, Y and Yang, Z and Xie, T and Zhang, Y and Huang, F and Meng, C and Wu, Y}, title = {Multi-Omics Analyses of the Gut Microbiota and Metabolism in Cats with Different Body Conditions and the Effects of Fecal Microbiota Transplantation.}, journal = {Veterinary sciences}, volume = {13}, number = {5}, pages = {}, pmid = {42188905}, issn = {2306-7381}, abstract = {Obesity is increasingly recognized in domestic cats and is associated with metabolic disturbances such as insulin resistance and dyslipidemia. The gut microbiota is considered an important regulator of host metabolism, yet its role in feline obesity remains unclear. In this study, a multi-omics approach was used to investigate gut microbiota composition and metabolic profiles in cats with different body conditions and to evaluate the effects of fecal microbiota transplantation (FMT) on the feline gut microbiota and overall metabolism. In Experiment 1, twenty-four cats were classified as obese, normal, or lean, and their gut microbiota and serum metabolites were analyzed. In Experiment 2, fecal microbiota from obese or lean donors were transplanted into recipient cats. Although overall microbial diversity and community structure did not differ significantly among groups, Coriobacteriaceae and Collinsella were enriched in obese cats, whereas Enterobacteriaceae-related taxa were more abundant in normal-weight cats. Serum metabolomics revealed alterations mainly related to amino acid and antioxidant metabolism, including O-acetylcarnitine, glutathione, and tryptophan metabolism. FMT shifted the recipient gut microbial communities toward their respective donor profiles (obese or lean) but did not significantly affect body weight or routine serum biochemical parameters during the experimental period. These findings suggest that gut microbiota remodeling may influence metabolic processes prior to detectable phenotypic changes in cats.}, }
@article {pmid42192549, year = {2026}, author = {Zhang, L and Quan, J and Nie, L and He, S and Lin, Y and Liu, X and Zhang, Y and Zhuang, L and Jia, C and Li, M and Wang, Q and Duan, L}, title = {Electroacupuncture prevents CUMS induced depressive-like behaviors by inhibiting microglia-mediated synaptic pruning induced by gut dysbiosis.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {}, pmid = {42192549}, issn = {1749-8546}, support = {82305383//National Natural Science Foundation of China/ ; 2023KQNCX017//Ordinary Universities Youth Innovative Talents Project of Guangdong Province Department of Education/ ; 20241088//Project of Guangdong Provincial Administration of Chinese Medicine/ ; 2024A04J4161, 2024A03J0354//Science and Technology Planning Project of Guangzhou/ ; }, abstract = {RATIONALE: Electroacupuncture (EA) has been widely used for depression treatment. Microbiota-gut-brain (MGB) axis plays a vital role in regulating emotional behaviors. However, the potential role of MGB axis in EA-mediated protective effects remains unclear.<br><br>METHODS: The protective effects of EA in chronic unpredictable mild stress (CUMS) induced mice were evaluated, and the gut microbiota and metabolic profiles were analyzed. Fecal microbiota transplantation (FMT) was utilized to explore the role of MGB axis in the protective effects of EA. Analyses related to synaptic pruning mediated by microglia were conducted to explore the molecular mechanisms.<br><br>RESULTS: In this study, EA treatment prevented depressive-like behaviors in CUMS mice. Mechanistically, EA ameliorated CUMS-induced gut microbiota dysbiosis and inflammation, and partially restored gut microbial metabolism, particularly affecting the abundance of Alistipes and taurine metabolism. Furthermore, EA significantly reduced systemic and hippocampal inflammation. It also attenuated aberrant synaptic pruning in the hippocampus. Moreover, FMT from CUMS mice induced depressive-like behaviors, gut inflammation and microglia-mediated aberrant synaptic pruning, whereas FMT from EA-treated donors exerted protective effects against these impairments.<br><br>CONCLUSION: Collectively, our findings suggest that EA prevented CUMS-induced depression-like behaviors and support the involvement of the MGB axis in its protective effects.}, }
@article {pmid42192558, year = {2026}, author = {Aggad, WS and Ghosh, R and Almohaimeed, HM and Mohammedsaleh, ZM and Saleh, FM and Almars, AI and Jyothi, SR and Panigrahi, R and Kumer, A and Dhara, B}, title = {Exosome-mediated gut-brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives-A narrative review.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70226}, pmid = {42192558}, issn = {2576-2095}, support = {PNURSP2026R213//Princess Nourah Bint Abdulrahman University/ ; }, abstract = {The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut-brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut-brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood-brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut-brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.}, }
@article {pmid42193296, year = {2026}, author = {Pinton, P}, title = {Microbiome-Based Therapies in Ulcerative Colitis: Mechanisms, Clinical Evidence, and a Precision-Medicine Framework.}, journal = {Biomedicines}, volume = {14}, number = {5}, pages = {}, pmid = {42193296}, issn = {2227-9059}, abstract = {Microbiome-based therapies are reshaping the therapeutic landscape for ulcerative colitis (UC), offering new avenues for disease management beyond conventional immunomodulatory and biologic treatments. UC remains a chronic, relapsing condition with significant unmet clinical needs, as many patients fail to achieve sustained remission or experience adverse effects with current therapies. The gut microbiome has emerged as a central contributor to UC pathogenesis, influencing epithelial barrier integrity, immune homeostasis, and metabolic signaling. Interventions such as fecal microbiota transplantation (FMT) and defined microbial consortia have demonstrated proof-of-concept efficacy in early-phase clinical trials, each leveraging distinct mechanistic strategies. FMT, as a broad ecological intervention, restores microbial diversity and functional redundancy, potentially addressing multiple pathogenic mechanisms simultaneously. In contrast, defined consortia enable precise targeting of specific metabolic and immunological pathways, including short-chain fatty acid production, bile-acid remodeling, epithelial barrier reinforcement, immune modulation, and succinate degradation. Recent clinical evidence suggests that consortia with broader mechanistic coverage may achieve more consistent biological activity than narrowly focused designs. This review synthesizes mechanistic and clinical insights across broad and defined microbial consortia, integrates evidence from randomized controlled trials and early-phase LBP studies, and outlines a precision-medicine framework to guide therapy selection. We highlight the importance of aligning therapeutic mechanisms with patient-specific microbial, metabolic, and immune profiles, and discuss future directions including biomarker-guided stratification, hybrid consortia, and adaptive trial designs. Advancing both broad and defined approaches, while incorporating ecological principles, mechanistic understanding, and patient stratification, will be essential to realizing the full therapeutic potential of microbiome-based therapies in UC.}, }
@article {pmid42193302, year = {2026}, author = {Marchitto, SA and Abbatecola, G and Zeidan, RS and Morgan, L and Calvani, R and Picca, A and Schlögl, M and Tosato, M and Leeuwenburgh, C and Anton, SD and Landi, F and Marzetti, E and Cacciatore, S}, title = {The Gut-Muscle Axis in Sarcopenia: Mechanisms, Evidence Gaps and Translational Challenges.}, journal = {Biomedicines}, volume = {14}, number = {5}, pages = {}, pmid = {42193302}, issn = {2227-9059}, support = {D1.2024//Universit&#xe0; Cattolica del Sacro Cuore/ ; D1.2025//Universit&#xe0; Cattolica del Sacro Cuore/ ; N/A//Centro Studi Achille e Linda Lorenzon/ ; P30 AG028740/AG/NIA NIH HHS/United States ; 2022YNENP3//Ministero dell'universit&#xe0; e della ricerca/ ; }, abstract = {Sarcopenia is an age-related skeletal muscle disorder characterized by reduced muscle mass, strength, and physical performance, as well as increased risk of disability, hospitalization, and mortality. Emerging evidence suggests that gut microbiota alterations may contribute to muscle decline via a microbiota-gut-muscle axis, acting as a context-dependent modulator rather than a primary causal driver. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut dysbiosis to sarcopenia. Preclinical studies show that microbiota modulation (e.g., antibiotics, probiotics, prebiotics, postbiotics, fecal microbiota transplantation) affects muscle mass, strength, and metabolism through pathways including inflammation, mitochondrial dysfunction, altered short-chain fatty acid production, and impaired anabolic signaling. In humans, observational studies associate lower microbial diversity and reduced short-chain fatty acid-producing taxa with poorer muscle outcomes, but findings are heterogeneous and non-causal. Interventional trials remain limited and characterized by small sample sizes, with effects more consistent for functional outcomes than muscle mass. Overall, the gut microbiota represents a modifiable contributor within the complex biology of sarcopenia. Future studies should integrate microbiome profiling and multi-omics approaches within well-designed clinical trials to identify responder phenotypes and define the role of microbiota-targeted strategies within multimodal interventions.}, }
@article {pmid42194001, year = {2026}, author = {Zhao, Z and Wang, J and Wu, Z and Ye, L and Wang, J and Wang, Y and Zhao, Y and Zhang, H and Luo, C and Tong, J}, title = {Integrated Multi-Omics Analysis Explores the Protective Effects and Potential Mechanisms of Pulsatilla chinensis on Canine Antibiotic-Associated Diarrhea.}, journal = {Biomolecules}, volume = {16}, number = {5}, pages = {}, pmid = {42194001}, issn = {2218-273X}, support = {32272904//National Natural Science Foundation of China/ ; 32373086//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Dogs ; *Diarrhea/chemically induced/drug therapy/veterinary/prevention &amp; control/metabolism ; Multiomics ; *Anti-Bacterial Agents/adverse effects ; *Pulsatilla/chemistry ; Metabolomics ; *Plant Extracts/pharmacology/chemistry ; Cytokines ; }, abstract = {Diarrhea is a common gastrointestinal disorder in animals, often worsened by antibiotic use. Pulsatilla chinensis (PC) is traditionally used for gastrointestinal issues, but its bioactive constituents and mechanisms remain unclear. This study investigated the preventive effects of PC in a canine model of antibiotic-associated diarrhea using an integrated multi-omics approach. LC-MS identified key constituents of PC, including anemoside B4, berberine, stigmasterol, and quercetin. In silico analyses predicted that stigmasterol and quercetin target EGFR and AKT1, modulating inflammation and epithelial repair via PI3K-Akt and IL-17 signaling pathways. In vivo, treatment with PC significantly reduced serum pro-inflammatory cytokines such as TNF-α and IL-6 and elevated immune markers including IgG and IgA compared to the control group. Furthermore, 16S rRNA analysis revealed that PC restored gut microbial diversity, reflected by increased Sobs and Chao1 indices, enriched beneficial Lactobacillus, and decreased the abundance of inflammation-associated taxa such as Proteobacteria, Desulfobacterota, and Escherichia-Shigella. These findings suggest that PC suppresses inflammation and remodels the gut microbiome, providing a mechanistic basis for its use as an herbal alternative to antibiotics. Future studies should include fecal microbiota transplantation and targeted metabolomics to establish causality and optimize therapeutic strategies.}, }
@article {pmid42194897, year = {2026}, author = {Lau, WL and Li, W and Sumida, K and Kalantar-Zadeh, K}, title = {The Role of Diet and Gut Microbiome in CKD Progression and Therapy.}, journal = {Journal of clinical medicine}, volume = {15}, number = {10}, pages = {}, pmid = {42194897}, issn = {2077-0383}, abstract = {There is a bidirectional relationship between chronic kidney disease (CKD) and an altered gut microbiome, with gut-derived uremic toxins contributing to cardiovascular-kidney-metabolic effects. In this review, we summarize the interplay between diet, the intestinal microbiota and systemic sequelae including CKD progression, cardiovascular morbidity and cognitive decline. We discuss the current state of knowledge regarding microbiota-modulating therapies that have the potential to delay CKD complications such as plant-dominant diets, oral adsorbents, prebiotics/probiotics, fecal microbiota transplantation and exercise.}, }
@article {pmid42197000, year = {2026}, author = {Shehata, F and Dwyer, KM and McGee, SL and Rivera, LR}, title = {Gut Microbiome Dysbiosis in Metabolic Syndrome: Current Evidence and Emerging Perspectives.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, pmid = {42197000}, issn = {2072-6643}, mesh = {Humans ; *Metabolic Syndrome/microbiology/therapy ; *Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Synbiotics/administration &amp; dosage ; }, abstract = {The gut microbiota plays a crucial role in human metabolism, and disruptions to its composition, particularly reductions in bacterial diversity, have been increasingly associated with the development of metabolic syndrome (MetS). MetS encompasses a constellation of interrelated metabolic risk factors, including central obesity, insulin resistance, dyslipidemia, and hypertension, which collectively elevate the risk of cardiovascular and cerebrovascular disease. A comprehensive understanding of the mechanisms underlying MetS is therefore critical for the development of effective preventive and therapeutic strategies. Complex interactions between the gut microbiota and host metabolic pathways are mediated by multiple factors, including microbial metabolites, inflammatory signaling, and host immune responses. This narrative review characterizes the clinical manifestations of MetS and alterations in gut microbiota composition, characterized by an overrepresentation of potentially pathogenic taxa and a concomitant decline in beneficial microbial species. In addition, we discuss current and emerging approaches to microbiota modulation, including prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, and evaluate their potential roles in the prevention and management of MetS. We identify critical evidence gaps and propose research priorities for evidence-based clinical strategies for MetS management and prevention.}, }
@article {pmid42197001, year = {2026}, author = {Lupu, VV and Nedelcu, AH and Miron, I and Anton, SC and Sasaran, MO and Frasinariu, OE and Jechel, E and Bozomitu, LI and Chisnoiu, T and Anton, CR and Marginean, CO and Morariu, ID and Mihai, CM and Anton, E and Lupu, A}, title = {Early Gut Microbiota and Neurodevelopmental Trajectories: Implications for Pediatric Neuropsychiatric Vulnerability-A Narrative Review.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, pmid = {42197001}, issn = {2072-6643}, mesh = {Humans ; Neurodevelopment ; *Gastrointestinal Microbiome/physiology ; *Neurodevelopmental Disorders/microbiology ; Dysbiosis/microbiology ; Child ; Brain/growth &amp; development ; Probiotics ; Prebiotics/administration &amp; dosage ; Neuronal Plasticity ; }, abstract = {Neurodevelopment is a dynamic and multifactorial process, critical in the early stages of life, involving the formation of neural networks, the establishment of synapses, and the maturation of cognitive, social and emotional circuits. In this context, the gut microbiome emerges as an essential regulator of neurodevelopment, exerting influences through multiple biochemical and immunological mechanisms that define the "gut-brain axis". The microbiota modulates neurodevelopment by regulating neurotransmitters (serotonin, dopamine, GABA), the production of microbial metabolites, including short-chain fatty acids, the modulation of inflammatory cytokines, and vagal signaling to the central nervous system. Recent evidence highlights the role of microbiota in modulating microglia, synaptogenesis, dendritic maturation, and neuronal plasticity, emphasizing how these processes are influenced by microbial activity rather than providing a comprehensive treatise on plasticity itself. Gut microbiota disturbances, or dysbiosis, have been associated with various neuropsychiatric and neurodevelopmental disorders, contributing to cognitive, behavioral, and emotional dysfunctions. This article summarizes, in a narrative manner, the main dysbiosis patterns identified in these disorders and the biological mechanisms by which the microbiome influences neuronal development and function, including immune-neuronal interactions, metabolomic modulation, and neuroendocrine signaling. Finally, emerging directions of intervention aimed at adjusting the microbial profile, such as dietary adjustment, the use of probiotics, prebiotics, symbiotics, and fecal microbiota transplantation, are presented with the aim of positively influencing neurodevelopment and preventing or ameliorating associated dysfunctions. This review emphasizes the need for longitudinal, rigorous, and controlled clinical trials to validate the efficacy of microbiota modulation strategies and to substantiate their integration into individualized pediatric management protocols.}, }
@article {pmid42197004, year = {2026}, author = {Wang, M and Lyu, Y and Zhang, J and Wang, Y and Yang, Y and Mao, YH}, title = {FMT from Exercise and Konjac Glucomannan Preconditioned Donors Rescues Antibiotic-Induced Dysbiosis with Enhanced Ecological Restoration in Mice.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, pmid = {42197004}, issn = {2072-6643}, support = {2023ZDZX2035; 2024ZDZX2061//Guangdong Scientific Research Platform and Projects for the Higher-educational Institution (Key Area Project)/ ; SL2024A04J01093//the Guangzhou Fundamental and Applied Research/ ; No.82030098//National Natural Science Foundation of China/ ; S202410585045 and 202410585015//the College Students Innovation and Entrepreneurship Training Program/ ; 2023A1515010004//the Guangdong Basic and Applied Basic Research Foundation/ ; }, mesh = {Animals ; *Dysbiosis/therapy/chemically induced/microbiology ; *Fecal Microbiota Transplantation/methods ; *Mannans/pharmacology ; *Anti-Bacterial Agents/adverse effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; Male ; *Physical Conditioning, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Although antibiotics have a wide range of applications in medical clinical practice and possess significant clinical value, their inevitable contribution to gut microbiome dysbiosis warrants attention. Our previous research has confirmed that the combined intervention of exercise and konjac glucomannan (KGM) has a better regulatory effect on gut dysbiosis in mice compared with individual interventions.<br><br>METHODS: This study aims to further investigate whether this effect can be transmitted through fecal microbiota transplantation (FMT), and to compare the recovery effects of autologous FMT (a-FMT), fecal microbiota transplantation after exercise combined with KGM intervention (EK-FMT), and combinative intervention with exercise and KGM (EXE-KGM) on gut microbiome dysbiosis. Sample sizes ranged from five to six animals.<br><br>RESULTS: The results showed that the a-FMT group recovered &#x3b1; diversity the fastest, including Chao, Shannon, and Simpson indices(p < 0.05), within 2 weeks after transplantation when compared with the CTL group. At the end of the experiment, the Bray-Curtis distance of the a-FMT group was closest to the CTL group, while the EXE-KGM group had delayed recovery, there was no significant difference between the EK-FMT group and the EXE-KGM group. Metagenomic analysis and metabolomics analysis indicated that the arginine synthesis and metabolism pathways (KEGG: map00471, map00473, arginine biosynthesis) played a core role in the restoration of the microbiota.<br><br>CONCLUSIONS: The results of this experiment indicate that EK-FMT group can partially transfer the regulatory effects of combined exercise and KGM intervention, a-FMT accelerates the recovery speed of the gut microbiome and arginine metabolism may play an important role in it. This finding provides a theoretical basis and practical direction for special populations to receive special donor fecal treatment.}, }
@article {pmid42197026, year = {2026}, author = {Alsinani, Y and Rostamkhani, F and Shirvani, H}, title = {Exercise and the Gut Microbiome: From Mechanisms to Clinical Applications.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, pmid = {42197026}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Exercise/physiology ; Fatty Acids, Volatile/metabolism ; }, abstract = {Background/Objectives: The gut microbiome is a critical regulator of host metabolism, immunity, and the gut-brain axis. Exercise is a promising non-pharmacological modulator of microbial ecology, yet human evidence remains heterogeneous and the translational gap persists. This narrative review synthesizes mechanisms, human and animal evidence, and future directions for the exercise-gut microbiome axis. Methods: PubMed, Scopus, Web of Science, and SID were searched for articles published between January 2000 and February 2025. Keywords included exercise, physical activity, gut microbiome, gut microbiota, short-chain fatty acids, and gut-muscle axis. From 218 initial records, 89 original studies (47 human, 42 animal) met inclusion criteria and were critically appraised. Results: Exercise modulates the gut microbiome via splanchnic hypoperfusion, hyperthermia, altered transit time, and immune-mediated barrier regulation. Moderate-intensity continuous training consistently increases alpha diversity and enriches butyrate-producing taxa (Faecalibacterium prausnitzii, Roseburia hominis) and mucin-degrading Akkermansia muciniphila. High-intensity interval training transiently increases intestinal permeability in untrained individuals but, following adaptation, stimulates butyrate production via lactate cross-feeding metabolism-a recent breakthrough. Effects are transient and reversible upon detraining. Animal models establish causality through fecal microbiota transplantation; human randomized controlled trials demonstrate modest, intensity-dependent, and highly individualistic responses. Emerging evidence supports the gut-muscle axis in sarcopenia and personalized exercise prescription guided by microbiome profiling. Conclusion: Exercise shows promise as a low-cost modulator of the gut microbiome for enriching health-associated taxa and improving metabolic outcomes. Definitive evidence linking exercise-induced microbial shifts to enhanced athletic performance in humans remains lacking. Future research requires diet-controlled randomized controlled trials with ≥12-week interventions, shotgun metagenomics, and mechanistic validation of the gut-muscle axis in humans.}, }
@article {pmid42197071, year = {2026}, author = {Jing, Y and Bai, X and Ji, Y and Zhai, Z and Zhao, Y and Hao, Y}, title = {Fecal Microbiota Transplantation from Toddler Donors Ameliorated DSS-Induced Colitis in Mice by Reshaping Gut Microbiota.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, pmid = {42197071}, issn = {2072-6643}, support = {No. 2022YFF1100105//the National Key R&amp;D Program of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/chemically induced/microbiology ; *Gastrointestinal Microbiome ; Dextran Sulfate ; Mice ; Male ; Disease Models, Animal ; Humans ; Colon/pathology/microbiology ; Mice, Inbred C57BL ; Dysbiosis/therapy ; Feces/microbiology ; Intestinal Barrier Function ; Cytokines/metabolism ; }, abstract = {Background/Objectives: Gut microbiota dysbiosis is a key driver of inflammatory bowel disease (IBD), and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy. In this study, we investigated the protective effects of toddler-derived FMT against colitis and elucidated the underlying mechanisms. Methods: Firstly, fecal microbiota from healthy toddlers was transplanted into antibiotic-pretreated mice, establishing stable colonization between days 14 and 21 post-transplantation. Results: In a dextran sulfate sodium-induced colitis model, FMT significantly ameliorated colitis symptoms, including reduced disease activity index and restored colon length. Toddler-derived FMT improved the intestinal barrier by preserving goblet cell density and enhancing MUC2 expression. Meanwhile, colonic inflammation was alleviated by FMT, which suppressed pro-inflammatory cytokines, reduced CD4[+] T cell counts, and associated with downregulation of JAK/STAT-related transcripts. 16S rRNA sequencing revealed that FMT remodeled the gut microbiota by enriching beneficial genera, including Bacteroides, Parabacteroides, Blautia, and Akkermansia, which correlated positively with colon length and negatively with inflammatory markers. Conclusions: These findings provided a theoretical foundation that toddler-derived microbiota represents a potential donor source for FMT in IBD.}, }
@article {pmid42197467, year = {2026}, author = {Bartocci, B and Del Gaudio, A and Murgiano, M and Papa, A and Cammarota, G and Gasbarrini, A and Scaldaferri, F and Lopetuso, LR}, title = {Emerging Role of Gut Microbiota in Modulating Response to Therapies in IBD.}, journal = {Microorganisms}, volume = {14}, number = {5}, pages = {}, pmid = {42197467}, issn = {2076-2607}, abstract = {The gut microbiota is increasingly recognized as a key contributor in the pathogenesis and progression of inflammatory bowel disease (IBD). Compared with healthy individuals, patients with IBD show marked dysbiosis, characterized by reduced microbial diversity, an expansion of facultative anaerobes such as Proteobacteria, and a depletion of obligate anaerobes within the Firmicutes phylum. These changes have been implicated in the perpetuation of intestinal inflammation, disruption of mucosal immune homeostasis, and altered metabolic functions, further underscoring the microbiota's relevance in IBD pathophysiology. However, microbiota-driven insights have not yet been consistently translated into therapeutic stratification or clinical decision-making. A major challenge lies in the complex and dynamic interplay between the gut microbiota and various treatment modalities, including conventional immunosuppressants, biologics, and small-molecule inhibitors. While accumulating evidence suggests that IBD treatments may modulate microbial composition and function, it remains unclear whether these changes represent a direct pharmacological effect or are secondary to inflammation control. Additionally, there is a lack of comparative data on microbiota profiles associated with differential responses to various therapeutic classes, limiting the implementation of microbiota-informed precision medicine. In this review, we synthesize current evidence on the association between gut microbiota composition and treatment outcomes, focusing on biologic agents and small-molecule therapies. Furthermore, we discuss the potential of microbiota-targeted strategies, such as fecal microbiota transplantation (FMT) and precision probiotics, in enhancing therapeutic response. A deeper understanding of host-microbe interactions could enable a more personalized and effective approach to IBD management.}, }
@article {pmid42198436, year = {2026}, author = {Zou, Y and Hu, RT and Yu, Q and Rao, PL and Cui, HY and Wei, WJ and Cai, X and Li, HK and Shen, YH}, title = {Liuweidihuang Pill Attenuates Early Bleomycin-Induced Pulmonary Fibrosis in Mice and Is Associated with Gut Microbiome.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, pmid = {42198436}, issn = {1424-8247}, support = {ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; }, abstract = {Background: Pulmonary fibrosis (PF) is a chronic, progressive lung disease with limited treatment options. Liuweidihuang pill (LDP), a classical formula for kidney-yin deficiency, has been reported to have anti-inflammatory and anti-oxidative activities, suggesting potential relevance to PF. Purpose: This study evaluated whether LDP attenuates bleomycin-induced PF in mice and whether gut microbiota remodeling may contribute to its protective effects. Methods: Mice received intratracheal bleomycin followed by LDP gavage. Lung pathology was assessed by hematoxylin-eosin (HE) and Masson staining. Inflammatory cytokines, hydroxyproline (HYP), and α-SMA were measured. LDP and LDP-containing serum were profiled by UPLC-MS. The gut microbiota was analyzed using 16S rDNA sequencing. To further explore whether microbiota-related changes were associated with the protective phenotype, fecal microbiota transplantation (FMT) and probiotic VSL#3 intervention were performed. In addition, LDP-containing serum was tested in a TGF-β1-induced EMT model in A549 cells. Results: LDP reduced lung index, inflammatory infiltration, interstitial fibrosis, α-SMA expression, HYP content, and pro-inflammatory cytokine levels in bleomycin-treated mice. These effects were accompanied by gut microbiota remodeling and transcriptomic changes related to inflammation, metabolism, and fibrosis. VSL#3 partially reproduced the protective phenotype, whereas FMT showed limited efficacy. LDP-containing serum had a limited inhibitory effect on EMT inhibited EMT in vitro, suggesting that systemic host responses may contribute to the in vivo effect. Conclusions: LDP attenuated early bleomycin-induced PF and was associated with reduced inflammation and gut microbiota remodeling. These findings suggest a possible role for microbiota-host interactions in LDP-associated protection; however, causal directionality, key active effectors, and protein-level pathway validation remain unresolved.}, }
@article {pmid42198457, year = {2026}, author = {Pastras, P and Aggeletopoulou, I and Psalti, V and Triantos, C}, title = {Gut Microbiota in Irritable Bowel Syndrome and Inflammatory Bowel Disease: Differences in Pathophysiology, Biomarkers, and Treatment Implications.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, pmid = {42198457}, issn = {1424-8247}, abstract = {Alterations in the intestinal microbiota have been implicated in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, their biological significance and therapeutic implications differ substantially between the two conditions. Although dysbiosis is a common feature, the mechanisms by which alterations in the microbiota contribute to disease pathophysiology and clinical expression are distinct. Some pathways are more prominent in IBS (e.g., the gut-brain axis), whereas others are more prominent in IBD (e.g., reduced microbial diversity). Equally important are pathways that appear to play a role exclusively in IBD [e.g., Adherent-invasive Escherichia coli (AIEC) and Paneth cells], as well as others that seem to be specific to IBS (e.g., mast cell activation). In IBD, microbiota changes are primarily linked to immune dysregulation, mucosal barrier impairment, and inflammation-driven pathways, whereas in IBS, they are mainly associated with functional disturbances mediated by neuroimmune signaling and microbial metabolites. Furthermore, several microbiome-associated biomarkers differ between these two diseases, and some are already assessed by international guidelines. Although the microbiota plays a key role in IBS and IBD pathophysiology, microbiome-based treatments remain limited, especially in IBD. There are clinically available treatments in IBS (e.g., rifaximin, low-FODMAP diet), but in IBD, only the probiotic VSL#3 is guideline-approved in ulcerative colitis pouchitis prophylaxis. Nevertheless, the dynamic nature of the microbiota continues to support the investigation of already studied (e.g., probiotics, fecal microbiota transplantation) and potential novel therapeutic approaches at the research level. The aim of this review is to compare the gut-microbiota-related pathophysiological pathways and biomarkers between IBS and IBD, to summarize the microbiome-related medications that have already been studied in both diseases, and to suggest new potential therapeutic options based on the gut microbiota.}, }
@article {pmid42198975, year = {2026}, author = {Zhang, J and Bai, J and Ren, X and Ye, X and Tan, M and Yang, Y and Li, L and Fu, Z}, title = {[Fecal microbiota transplantation inhibits colonic tumor growth in mice by suppressing the TLR4/MyD88/NF-κB signaling pathway].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {46}, number = {5}, pages = {1139-1148}, pmid = {42198975}, issn = {1673-4254}, mesh = {Animals ; Myeloid Differentiation Factor 88/metabolism ; *Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Mice ; Signal Transduction ; *Colonic Neoplasms/therapy ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Transforming Growth Factor beta1/metabolism ; Cell Line, Tumor ; Killer Cells, Natural ; Male ; }, abstract = {OBJECTIVES: To explore the effects of fecal microbiota transplantation (FMT) on immune function and tumor inhibition in mice.<br><br>METHODS: C57BL/6N mice were divided into blank control group, tumor bearing model group, and FMT intervention group (n=6). In the latter two groups, the mice bearing subcutaneous MC38 colon cancer cell xenografts were treated with daily gavage of normal saline or 0.1 mL of bacterial suspension. The changes in tumor mass and volume were recorded, and peripheral blood natural killer (NK) cell counts and NKG2A and NKG2D receptor expressions were analyzed using flow cytometry; serum lipopolysaccharide (LPS) levels were measured with ELISA. The binding ability of NF&#x2011;&#x3ba;B to the TGF&#x2011;&#x3b2;1 gene promoter was analyzed with JASPAR. The mRNA and protein expressions of TLR4, MyD88, NF&#x2011;&#x3ba;B, TGF&#x2011;&#x3b2;1, perforin and granzyme in the tumor tissues were detected using RT qPCR and Western blotting, and the changes in gut microbiota were analyzed using 16S high throughput sequencing.<br><br>RESULTS: FMT significantly reduced tumor mass and volume in the tumor-bearing mice. Peripheral CD3&#x207b;NK1.1&#x207a; cell counts were significantly decreased in the tumor-bearing mice regardless of FMT treatment, which, however, reversed the increase of CD3[-]NKG2A[+] cells and reduction of CD3[-]NKG2D[+] cells and reduced serum LPS levels in the mouse models. Molecular docking and JASPAR analysis confirmed LPS-TLR4 binding (binding energy: -13.1 kcal/mol) and identified NF-&#x3ba;B binding sites on TGF&#x2011;&#x3b2;1 promoter. FMT downregulated mRNA and protein expressions of TLR4, MyD88, NF&#x2011;&#x3ba;B and TGF&#x2011;&#x3b2;1 and upregulated perforin and granzyme mRNA expressions in the xenografts. FMT also restored gut microbiota diversity and composition, and reversed the increase of Proteobacteria and decrease of Lactobacillus murinus in the tumor-bearing mice.<br><br>CONCLUSIONS: FMT modulates the relative abundances of intestinal Proteobacteria and Lactobacillus murinus in tumor-bearing mice, and inhibits tumor growth by suppressing the TLR4/MyD88/NF&#x2011;&#x3ba;B signaling axis, down-regulating TGF-&#x3b2;1 expression, and promoting NK cell activation.}, }
@article {pmid42199152, year = {2026}, author = {Zhang, W and Song, Y and Li, C and Luo, Y and Shao, M and Guo, F and Wei, F and Fan, X and Guo, W and Xu, F and Sang, Y and Zhang, D and Zhou, Y and Wang, L and Kang, Z and Yang, Y and Song, C and Liu, Y and Ma, X and Wang, J and Li, C and Ma, S and Zhao, L and Qin, Z and Xing, G and Zhao, Q and Li, J and Song, S and Zhao, D and Huang, T and Wang, Q and Zhao, Y and Qin, G}, title = {Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota-Dependent Manner.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e17222}, doi = {10.1002/advs.202517222}, pmid = {42199152}, issn = {2198-3844}, support = {82170839//National Natural Science Foundation of China/ ; U23A20414//National Natural Science Foundation of China/ ; 82470876//National Natural Science Foundation of China/ ; 82300930//National Natural Science Foundation of China/ ; 251111311500//Key Research and Development Program of Henan Province/ ; 242300421272//Natural Science Foundation of Henan Province/ ; LHGJ20230200//Henan Joint Construction Program/ ; SBGJ202301006//Science and Technology Research Project of Henan Province/ ; }, abstract = {Canagliflozin reduces albuminuria in patients with diabetic kidney disease (DKD) beyond its glucose-lowering effect, but the mechanisms remain unclear. We analyzed 85 patients treated with canagliflozin and 85 controls over 26 weeks to explore whether the gut microbiome and its metabolites contribute to renoprotection. Canagliflozin remodeled the gut microbiota, notably enriching Roseburia intestinalis and increasing plasma melibiose levels. In mice, canagliflozin alleviated glomerular endothelial injury and albuminuria. Similar effects were replicated by fecal microbiota transplantation, Roseburia intestinalis, or melibiose administration. Mechanistically, melibiose bound to and activated glyoxalase 1, reduced methylglyoxal, and suppressed the AGE-RAGE pathway, preserving glomerular endothelial integrity. Furthermore, oral melibiose precursor supplementation reduced albuminuria in patients with early-stage DKD. These findings suggest the involvement of a gut-kidney axis in the renoprotective effects of canagliflozin and indicate that melibiose may serve as a potential therapeutic strategy for DKD.}, }
@article {pmid42201625, year = {2026}, author = {Akram, F and Zainab, S and Shabbir, I and Haq, IU}, title = {Gut microbiota and cancer immunotherapy: from dysbiosis to personalized immune checkpoint blockade optimization.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {42201625}, issn = {1874-9356}, abstract = {Cancer has become one of the most prominent causes of death worldwide due to its increasing mortality rate. Immune checkpoint blockade therapy is an effective regimen for tumor control. Still, it faces challenges, including primary resistance and interindividual variations, thereby directing the field towards a new era of immunotherapy adjuncts. Recent studies have shown that the microbiota of cancer patients influences the outcomes of ICB (immune checkpoint blockade) therapy through microbiome-immune system crosstalk. Homeostatic commensal microbial consortia aid in combating tumors by enhancing immunity, whereas dysbiotic microbes facilitate cancer development by mediating immunosuppression. Microbiota modulation via microbiome-targeted interventions, including fecal microbiota transplantation or washed microbiota transplantation from responders, biotic supplements, and dietary modifications, can convert primary resistance to durable responses and thus augment immunotherapy responsiveness in cancer treatment. This review discusses the dual nature of microbiota in mediating the development and treatment of cancer, its crucial role in shaping ICB therapy responsiveness, and the identification of microbial biomarkers into a refined Discovery-Validation-Clinical (DVC) pipeline linked to multi-omics profiling and personalized microbiome-modulation interventions for ICB therapy optimization. In addition, it presents the translational clinical decision framework that highlights patient stratification, intervention timing, and implementation barriers to support clinical translation. Ultimately, the gut microbiome emerges as a "force multiplier" of cancer ICB therapy, thereby enabling microbiome-guided precision oncology and strengthening a roadmap toward personalized cancer care.}, }
@article {pmid42202865, year = {2026}, author = {Hoel, ME and Gimenez, AR and Elbe, A and Horecka, K and Alvarez, E and Lashnits, E}, title = {Oral fecal microbial transplant for parvovirus in the outpatient setting: a randomized controlled trial to evaluate a practical and low-cost intervention.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-7}, doi = {10.2460/javma.26.01.0051}, pmid = {42202865}, issn = {1943-569X}, abstract = {OBJECTIVE: To evaluate commercially available oral capsules providing fecal microbial transplant (FMT) as a practical option for adjunctive treatment of canine parvovirus (CPV) in an outpatient setting. We hypothesized that treatment with FMT capsules would improve survival and hasten resolution of clinical signs compared to placebo.<br><br>METHODS: This blinded, randomized controlled trial evaluated oral FMT capsules in shelter dogs with CPV treated with an outpatient protocol (September 2022 to August 2024). Eligible dogs were randomized to receive adjunctive FMT or placebo, with 3 dosing regimens assessed. The primary outcome was time to recovery; secondary outcomes included survival, escalation to ICU, and resolution of clinical signs.<br><br>RESULTS: 101 dogs were enrolled, of which 52 were in the control group and 49 received FMT. Dogs that survived without escalation to ICU-level care in both the control (n = 42) and FMT groups (32) had a median duration to recovery of 5 days (P = .872). There was a 94% (49 of 52) survival rate in the control group compared to 82% (40 of 49) for the group receiving FMT (P = .051); there was no significant difference in survival between groups when controlling for age or weight (OR, 3.18; 95% CI, 0.74 to 17.28; P = .139).<br><br>CONCLUSIONS: There was no evidence that oral FMT capsules hastened recovery or improved short-term survival rate in an outpatient setting. Future work is needed to determine whether oral FMT has negative effects in dogs with CPV.<br><br>CLINICAL RELEVANCE: This study provides evidence that oral FMT treatment may not be helpful in the outpatient treatment of CPV.}, }
@article {pmid42203970, year = {2026}, author = {Ning, K and Chen, Y and Yang, X and Dou, X and Liu, S and Wang, DE and Niu, Y and Xu, H}, title = {Gut microbiota alteration contributes to bone marrow mesenchymal stem cells connexin43 response to high-fat diet induced obesity in mice.}, journal = {International journal of obesity (2005)}, volume = {}, number = {}, pages = {}, pmid = {42203970}, issn = {1476-5497}, abstract = {BACKGROUND/ OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) contribute to controlling adipose tissue homeostasis and may be a potential target for obesity therapy. Since lack of connexin43(Cx43) in mesenchymal stem cells (MSCs) is known to combat high-fat diet (HFD)-induced adiposity. Also, HFD is a well-known risk factor for gut microbiota dysbiosis. Here we attempt to address the interaction between HFD, gut microbiota, and Cx43 deficiency in BMSCs during the development of obesity.<br><br>METHODS: BMSC-specific Cx43 knockout (Prrx1-Cre;Cx43[flox/flox](cKO)) and control littermate (Cx43[flox/flox](flox))mice were fed a regular chow diet or a HFD for 8 weeks. Cecal microbiome composition was assessed by 16S ribosomal RNA (rRNA) sequencing, and further analyzing correlation between gut microbiota and obesogenic parameters. Moreover, transplantation fecal microbiota was used to probe the salutary effect of BMSC Cx43.<br><br>RESULTS: HFD fed cKO mice notably altered cecal microbiome composition as proved by a distinctively clustered separation from flox mice. Concomitantly, Allobaculum induced by HFD was strongly correlated positively with body weight, glucose intolerance, and adipose mass. The recipients with gut microbiota from cKO mice displayed anti-obesity phenotype as the donors.<br><br>CONCLUSIONS: Gut microbiota alteration may be one main reason for the salutary effect of BMSC Cx43 knockout on body adiposity.}, }
@article {pmid42204443, year = {2026}, author = {Henriksen, IW and Hansen, CHF and Koch, J and Sørensen, DB and Nielsen, DS and Bartholdy, C and Hansen, AK}, title = {A Refined Method for Fecal Microbiota Transplantation Using Nutella.}, journal = {Clinical and translational science}, volume = {19}, number = {6}, pages = {e70576}, pmid = {42204443}, issn = {1752-8062}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods/adverse effects/instrumentation ; Mice, Inbred BALB C ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; Administration, Oral ; Female ; }, abstract = {Fecal microbiota transplantation (FMT) in mice is an evolving research field, often employing oral gavage, which can be stressful and harmful for the animals and time-consuming for technicians. Voluntary intake methods, such as delivery in Nutella, have successfully been used for drug administration in mice and may likewise be a promising tool to refine traditional FMT techniques. Nutella-based FMT may improve animal welfare, reduce workload, and enhance animal safety without compromising microbiota engraftment rates. This study compared microbiota engraftment after mouse-to-mouse FMT in antibiotic-treated BALB/c mice using three methods: oral gavage, pipette delivery, and voluntary intake of a Nutella-inoculum mixture. Feces collected before and after FMT were analyzed using GridION Nanopore 16S rRNA gene amplicon sequencing. Nutella-based FMT showed similar engraftment rates as traditional methods i.e., oral gavage and pipette delivery. Oral gavage delivery resulted in greater variability and divergence from the donor composition compared to pipette delivery. Notably, the oral gavage group had the highest number of genera differing from the donor. Single-dose FMT restored microbial diversity in one study, while it was less effective in another, suggesting to add a second dose of FMT. Nutella-based FMT appears to be an efficient, reproducible, and less stressful alternative to forced-feeding methods, warranting further exploration.}, }
@article {pmid42204557, year = {2026}, author = {Preetam, S and Bora, J and Porna Dutta, S and Talukdar, N and Rustagi, S and Thapliyal, S and Malik, S and Choudhary, N and Kumar, D and Kondaveeti, SB}, title = {Role of gut microbiota in cancer modulation: molecular mechanisms and emerging therapeutic strategies.}, journal = {Infectious agents and cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13027-026-00767-2}, pmid = {42204557}, issn = {1750-9378}, abstract = {The gut microbiota exerts profound effects on host physiology, immunity, and disease susceptibility, with growing evidence implicating its role in cancer initiation, progression, and therapy response. Dysbiosis and microbial-derived metabolites contribute to oncogenesis by modulating epithelial signalling, immune regulation, and systemic inflammation. This review synthesises current knowledge on the crosstalk between the gut microbiome and cancer, spanning molecular mechanisms, site-specific malignancies, and treatment outcomes. We discuss how microbial pathways, including NF-κB, STAT3, Wnt/β-catenin, and inflammasome activation, shape tumour biology, and how microbiota profiles correlate with cancer risk and progression in colorectal, gastric, liver, breast, gynaecological, and pulmonary cancers. Furthermore, we highlight the microbiome's impact on responses to chemotherapy, radiotherapy, and immunotherapy. Finally, we evaluate therapeutic strategies targeting the microbiota, from conventional dietary and probiotic interventions to cutting-edge approaches such as faecal microbiota transplantation, engineered bacterial strains, and microbiome-based biomarkers. Understanding these complex interactions offers novel opportunities to integrate microbiome science into precision oncology.}, }
@article {pmid42204645, year = {2026}, author = {Zhao, N and Wu, L and Peng, S and Yang, H and Song, Y and Zhang, Y and Ding, L}, title = {Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.}, journal = {Biomarker research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40364-026-00930-2}, pmid = {42204645}, issn = {2050-7771}, support = {82303235//National Natural Science Foundation of China/ ; 2025SF-YBXM-358//Key Research and Development Projects of Shaanxi Province/ ; 2025JC-YBQN-1236//Natural Science Basic Research Program of Shaanxi Province/ ; NUHSRO/2023/005/Startup/3//NUS STARTUP grant/ ; MOH-OFIRG24jan-0001, MOH-OFIRG23jul-0007 and MOH-OFIRG21nov-0007//NUS-NJU Research Collaboration Fund 2025, OF-IRG grant from National Medical Research Council/ ; NRF, CRP28-2022RS-0001//CRP grant from National Research Foundation/ ; }, abstract = {The gut microbiome plays a critical role in shaping host immunity and profoundly affects the efficacy of cancer immunotherapy. Accumulating evidence suggests that interventions designed to alter the microbial community, including fecal microbiota transplantation, probiotics, and engineered bacteria, can reprogram the tumor-immune microenvironment and enhance clinical efficacy. This Review provides a comprehensive overview of the molecular and cellular mechanisms through which the gut microbiota influences antitumor immunity, and it highlights recent clinical studies evaluating these interventions. We further examine inherent challenges, including inter-individual variability in microbial composition, difficulties in achieving stable and durable colonization, technical barriers in delivery, and potential safety concerns associated with immune activation or off-target effects. Finally, we discuss future directions for translating microbiome-targeted therapies into oncology, emphasizing the need for mechanistic insight, standardized protocols, rigorous evaluation, and integration with precision immunotherapy strategies to optimize therapeutic outcomes.}, }
@article {pmid42205476, year = {2026}, author = {Pollicardo, C and Gotta, F and Bottino, P and Vay, D and Pizzo, V and Scaglione, S and Pontarollo, G and Novi, M and Boatti, L and Mignone, F and Melioli, G and Rapallo, F and Rocchetti, A}, title = {Defining reference values for the gut microbiota in a Southern European population.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1766733}, pmid = {42205476}, issn = {2235-2988}, mesh = {Humans ; Reference Values ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; High-Throughput Nucleotide Sequencing ; Fecal Microbiota Transplantation ; Europe ; Sequence Analysis, DNA ; Male ; Female ; DNA, Bacterial/genetics ; European People ; Adult ; }, abstract = {INTRODUCTION: The clinical implementation of gut microbiota analysis requires the definition of reliable reference values derived from standardized and certified methodologies applied to a population representative of the intended clinical setting.<br><br>METHODS: In this study, 250 fecal samples were analyzed using a CE-certified 16S rRNA bacterial profiling assay for taxonomic characterization across multiple bacterial levels. Sequencing reads were quality-filtered and aligned against the RDP database (release 11, update 5); only sequences with &#x2265;80% alignment coverage and &#x2265;97% similarity were retained.<br><br>RESULTS: The resulting taxonomic distributions were first compared with data previously obtained from a similar population, revealing only minor differences. As an additional validation, comparative analyses were performed with data from a clinical study on fecal microbiota transplantation (FMT). Donor profiles were highly consistent with those obtained in the present study, whereas pre-transplant samples showed marked deviations from the reference ranges; post-transplant profiles progressively converged toward them.<br><br>DISCUSSION: Although the limited sample size precludes accurate assessment of rare taxa (<0.1% relative abundance), the use of a single Next-Generation Sequencing (NGS) platform and the focus on a Southern European population characterized by the Mediterranean diet allowed the establishment of the first set of gut microbiota reference values derived from a certified in-vitro diagnostic workflow. These data represent an essential step toward the integration of gut microbiota testing into clinical laboratory practice, enabling standardized interpretation of microbiota imbalance and supporting targeted medical interventions aimed at restoring microbial equilibrium.}, }
@article {pmid42205579, year = {2026}, author = {Liu, Y and Gong, J and Wang, W and Li, X and Jia, H and Wang, R and Sun, Q and Zhang, R and Zhang, Y and Huang, L}, title = {The effects of filtration and centrifugation on the gut microbiota in fecal microbiota transplantation preparation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1768356}, pmid = {42205579}, issn = {1664-302X}, abstract = {BACKGROUND: The preparation method of fecal microbiota suspensions is crucial for reliable fecal microbiota transplantation research. However, current protocols vary significantly in processing parameters, potentially compromising the comparability of studies. Systematic comparisons of how different preparation techniques affect the microbial community are still lacking.<br><br>METHODS: Fresh fecal samples from nine adult volunteers were processed via filtration and centrifugation at various speeds. Microbial viability was assessed via live/dead staining and colony forming unit enumeration. 16S rDNA sequencing was performed to analyze bacterial diversity and taxonomic composition.<br><br>RESULTS: The microbial composition and functional potential did not differ between the filtration alone group and the fresh fecal group, and filtration resulted in the lowest bacterial mortality. Mortality increased with increasing centrifugation speed. Centrifugation selectively affected the abundance of some genera (e.g., Delftia and Acinetobacter). High-speed supernatants presented markedly lower OD600 values than low-speed supernatants did, and differential centrifugation visibly reduced the amount of debris.<br><br>CONCLUSION: Filtration alone best preserved fecal microbial viability, composition and functional potential. Centrifugation enrichment becomes selective at high speeds. Differential centrifugation offered superior impurity removal. The preparation strategy should be tailored to the research or therapeutic goal.}, }
@article {pmid42206183, year = {2026}, author = {Wang, Z and Cui, H and Huang, H and Zhang, P and Yin, L and Luo, G and Li, Q and Zhang, Y and Meng, L and Chang, W and Li, X and Yang, X and Ye, J}, title = {Therapeutic effect of Tripterygium hypoglaucum (H. Lév.) Hutch. extract on psoriasis-like skin inflammation correlated with gut microbiota homeostasis in mice.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1822819}, pmid = {42206183}, issn = {1663-9812}, abstract = {BACKGROUND: Tripterygium hypoglaucum (H. Lév.) Hutch. (THH) exerts anti-inflammatory and immunosuppressive effects against psoriasis. However, the extent to which and the mechanisms by which it ameliorates psoriasis-like dermatitis through modulation of the gut microbiota-metabolite axis remain unclear.<br><br>METHODS: This study investigated the therapeutic effects and underlying mechanisms of THH in a murine model by employing 16S rRNA gene sequencing, intestinal metabolomic profiling, fecal microbiota transplantation (FMT), and co-housing experiments.<br><br>RESULTS: Our results demonstrated that THH treatment significantly decreased PASI scores, alleviated epidermal hyperplasia and skin inflammation, and reversed IMQ-induced gut dysbiosis by restoring the Firmicutes/Bacteroidota ratio and modulating the abundance of beneficial and pathogenic bacteria. Metabolomic analysis revealed that THH normalized multiple metabolic pathways disturbed by IMQ, including arachidonic acid metabolism, sphingolipid metabolism, and primary bile acid biosynthesis. Correlation analyses further revealed significant associations among the altered gut microbiota, key metabolic pathways, and psoriasis-related phenotypic indices. Moreover, FMT from THH-treated mice conferred significant anti-psoriatic efficacy. Similarly, co-housing experiments resulted in the alleviation of skin lesions, reduction of spleen weight, and downregulation of inflammatory cytokines.<br><br>CONCLUSION: These findings demonstrate that THH attenuates psoriasis-like dermatitis partly by reshaping gut microbiota composition and regulating key metabolic pathways, supporting a potential gut-targeted therapeutic strategy for psoriasis.}, }
@article {pmid42206375, year = {2026}, author = {Wang, J and Xu, J and Mai, H and Niu, G and Wu, S and Zhang, X and Zhu, J and Aschner, M and Meng, Q and Chen, R}, title = {Microplastic Exposure Aggravates Cardiomyopathy Under Hemodynamic Stress Through the Gut-Heart Axis.}, journal = {Circulation}, volume = {}, number = {}, pages = {}, doi = {10.1161/CIRCULATIONAHA.126.079820}, pmid = {42206375}, issn = {1524-4539}, abstract = {BACKGROUND: Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplored. This study investigates the effects of BPF on the cardiovascular system and intestinal barrier.<br><br>METHODS: Germ-free mouse models and fecal microbiota transplantation techniques were used to confirm the role of gut microbiota in BPF-induced cardiovascular injury. Untargeted metabolomics and spatial metabolomics were used to identify the in vivo metabolic products of BPF. Single-cell sequencing was used to identify which cardiac cell types were damaged by BPF exposure.<br><br>RESULTS: BPF was detected in 90.5% of 285 human urine samples (median, 1.16 ng/&#x3bc;g creatinine). BPF exposure induced cardiomyocyte hypertrophy, cardiac dysfunction, and intestinal barrier damage, effects contingent on the presence of gut microbiota. Metabolomic analysis identified the microbial conversion of BPF to N-acetylputrescine (NAP). Mechanistically, we found that BPF stimulated intestinal epithelial cells to secrete spermidine/spermine N1-acetyltransferase 1 (Sat1), which catalyzed this conversion. Furthermore, NAP impaired the intestinal barrier by disrupting the Golgi-mitochondria axis and caused cardiac hypertrophy by activating the p53 pathway and inhibiting glycolysis in cardiomyocytes. Supplementation with Akkermansia muciniphila or its metabolite tryptophol mitigated BPF-induced cardiac and intestinal injuries by downregulating the Sat1-NAP axis. Clinical analysis further showed elevated serum NAP levels in patients with inflammatory bowel disease, positively correlating with cardiac injury markers.<br><br>CONCLUSIONS: BPF disrupts intestinal barrier function through microbial metabolism involving the tryptophol/Sat1 pathway, leading to NAP production. NAP damages intestinal organelles and enters circulation, inducing cardiac p53 activation and hypertrophy. This study delineates a novel gut microbiota-Sat1-NAP pathway underlying BPF-induced cardiotoxicity, offering new insights for risk assessment and therapeutic intervention.}, }
@article {pmid42208345, year = {2026}, author = {Lauriola, M and Dejongh, S and Steigert, S and Zadora, W and Valkenburg, S and Augustijns, P and Glorieux, G and Oswald, S and Farré, R and Meijers, B}, title = {Kidney dysfunction regulates gut transporters.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {200}, number = {}, pages = {119581}, doi = {10.1016/j.biopha.2026.119581}, pmid = {42208345}, issn = {1950-6007}, mesh = {Animals ; Humans ; Caco-2 Cells ; Male ; *Renal Insufficiency, Chronic/metabolism/microbiology/physiopathology ; *Kidney/physiopathology/metabolism ; Gastrointestinal Microbiome/physiology ; Female ; Rats ; *Colon/metabolism/microbiology ; Uremic Toxins/metabolism ; Middle Aged ; *Membrane Transport Proteins/metabolism/genetics ; Aged ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism/genetics ; }, abstract = {BACKGROUND: The gut-kidney axis is crucial in chronic kidney disease (CKD). As kidney function declines, uremic toxins accumulate in plasma, and gut dysbiosis, oxidative stress, and inflammation arise, potentially affecting the expression of proteins involved in absorption, distribution, metabolism, and excretion (ADME). We aimed to determine the colonic expression of ADME proteins in CKD and explore modulatory mechanisms.<br><br>METHODS: RNA and protein expression of key gut transporters, enzymes and receptors were determined in colon biopsies from 17 patients with CKD and 12 healthy volunteers using RNA sequencing and targeted mass spectrometry. In parallel, we induced CKD in rats by 5/6th nephrectomy, and we administered an antibiotic cocktail to assess differences when depleting the gut microbiome. Caco-2 cells exposed to human serum or fecal water derived from CKD patients were used to elucidate modulatory mechanisms.<br><br>RESULTS: CKD downregulated the colon efflux transporter proteins P-gp (apical), MRP3 (basolateral) and BCRP (apical) (BCRP only in patients not undergoing hemodialysis). P-gp downregulation was mediated by aromatic gut microbiome-derived uremic toxins in patients, consistently with in vitro observation that P-gp was downregulated in Caco-2 cells exposed to CKD serum. In CKD rats' colon, Mdr1a was downregulated, and Bcrp was upregulated only when antibiotics were administered, indicating the gut microbiome influences P-gp and BCRP in CKD.<br><br>CONCLUSIONS: We confirmed kidney-gut crosstalk, highlighting how uremic environment and gut dysbiosis consequent to CKD impact gut transport physiology. P-gp and BCRP can be downregulated via gut microbiome metabolites, thus shedding light on the importance of therapies targeting microbial activity.}, }
@article {pmid42211136, year = {2026}, author = {Rashidi, A and Minot, SS and Lee, SJ and Hill, GR and Podlesny, D}, title = {Cohesive modules of engraftment in fecal microbiota transplantation.}, journal = {iScience}, volume = {29}, number = {6}, pages = {116025}, pmid = {42211136}, issn = {2589-0042}, abstract = {While single-strain probiotics fail to address community-level microbiota injuries in dysbiosis-related conditions and fecal microbiota transplantation (FMT) produces unpredictable communities, a middle-ground approach has emerged. This approach involves using small consortia of species, combining the precision of single-strain probiotics and the holistic approach intrinsic to FMT. The species selection in this oligomicrobial strategy is typically proprietary or based on studies linking single species to disease or health. To advance this approach, we developed the concept of cohesive modules of engraftment (CME) and a workflow for their identification from FMT trials. CMEs represent small donor microbiota subsets that engraft as units (modularity), while maintaining their original composition (cohesiveness). In benchmarking, we identified >200 highly cohesive CMEs (2-5 species) in 5 FMT trials and found evidence for cross feeding as a mechanism for CME integrity. Due to their predictable post-treatment compositions, CMEs deserve investigation as potential ingredients of future therapeutic microbial consortia.}, }
@article {pmid42211453, year = {2026}, author = {Fei, Y and Mao, P and Fan, B}, title = {Mapping the gut microbiota-diabetic peripheral neuropathy research landscape: a bibliometric analysis of emerging trends and translational frontiers.}, journal = {Frontiers in endocrinology}, volume = {17}, number = {}, pages = {1815280}, pmid = {42211453}, issn = {1664-2392}, mesh = {Animals ; Humans ; *Bibliometrics ; *Diabetic Neuropathies/microbiology/therapy ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; *Translational Research, Biomedical/trends ; }, abstract = {BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes the most prevalent chronic complication of diabetes mellitus, affecting approximately 50% of patients throughout their disease course. Accumulating evidence indicates that gut microbiota (GM) dysbiosis plays a pivotal role in DPN pathogenesis via the gut-brain axis. However, a comprehensive bibliometric analysis delineating the intellectual landscape and evolutionary trajectory of this rapidly advancing research domain remains absent.<br><br>METHODS: Publications pertaining to gut microbiota and DPN were systematically retrieved from the Web of Science, PubMed, and Scopus databases (spanning 2010-2025). CiteSpace 6.4.R1 was employed to perform co-occurrence, clustering, timeline, burst detection, and co-citation analyzes, thereby visualizing the field's intellectual structure and developmental trends.<br><br>RESULTS: A total of 133 publications met the inclusion criteria, exhibiting exponential growth after 2018 with an average annual increase of 35.7%. Keyword analysis identified core research clusters centered on GM, neuropathic pain, the gut-brain axis, and therapeutic interventions such as fecal microbiota transplantation (FMT), traditional Chinese medicine, and causal inference methodologies like Mendelian randomization. Burst detection analysis revealed a temporal shift from foundational concepts (e.g., "oxidative stress", "inflammation") toward interventional strategies (e.g., "fecal microbiota transplantation", "traditional Chinese medicine") and causal inference approaches (e.g., "Mendelian randomization"). Co-citation analysis highlighted seminal contributions, including clinical trials demonstrating FMT efficacy and animal studies elucidating the role of microbial metabolites such as butyrate.<br><br>CONCLUSION: This study presents the inaugural bibliometric analysis of the GM-DPN research field. The domain is transitioning from establishing associative links to elucidating causal mechanisms and evaluating targeted interventions. Keyword trend analysis underscores a convergence toward a multi-mechanistic gut-brain axis model. Future research priorities derived from the literature encompass clinical translation, multi-omics integration, and personalized therapeutic strategies.}, }
@article {pmid42213471, year = {2026}, author = {George, M and Negi, L and Maan, M}, title = {A Gutsy Move? Microbiome Reset With Fecal Microbiota Transplant Brings Remarkable Turnaround in Severe Alcohol-Associated Hepatitis: A Case Report.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {49}, number = {3}, pages = {163-178}, pmid = {42213471}, issn = {1538-9766}, }
@article {pmid42214222, year = {2026}, author = {Qiao, Y and Zhang, X and Wu, F and Wang, Y and Wu, Y and Zhang, Y and Cheng, W and Bu, F and Miao, Y and Wang, Y and Huo, X and Wang, J and Ma, X}, title = {Wedelolactone alleviates rheumatoid arthritis by gut microbiota-dependent immunomodulation and p53-mediated inhibition of fibroblast-like synoviocytes.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {157}, number = {}, pages = {158297}, doi = {10.1016/j.phymed.2026.158297}, pmid = {42214222}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Synoviocytes/drug effects ; *Arthritis, Rheumatoid/drug therapy ; *Tumor Suppressor Protein p53/metabolism ; Mice ; Humans ; Arthritis, Experimental/drug therapy ; *Coumarins/pharmacology ; Fibroblasts/drug effects ; Immunomodulation/drug effects ; Male ; Mice, Inbred DBA ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and a parallel dysbiosis of the gut microbiota. Wedelolactone (WL), a natural bioactive compound, exhibits potent anti-inflammatory and immunomodulatory activities; however, its therapeutic potential in RA is unknown.<br><br>PURPOSE: This study aimed to evaluate the potential effect of WL on RA and explore its underlying mechanism.<br><br>METHODS: The anti-arthritic activity of WL was assessed in wild-type and antibiotic&#x2011;treated (ABX) collagen&#x2011;induced arthritis (CIA) mice in vivo and in human rheumatoid-arthritis synovial fibroblasts (MH7A) cells and murine rheumatoid-arthritis fibroblast-like synoviocytes (RA-FLS) cells in vitro. Additionally, fecal microbiota transplantation (FMT), 16S rDNA sequencing, intestinal barrier integrity assays, splenic and colonic Th17/Treg analyses and targeted metabolomics of short-chain fatty acids (SCFAs) were performed to clarify its microbiota-directed actions. Finally, RNA-seq coupled with chemical inhibition and genetic knockdown with siRNA were employed to explore its effect on the hyperproliferation of synoviocytes.<br><br>RESULTS: WL attenuated RA symptoms in CIA mice as evidenced by delayed disease onset, decreased joint swelling, less bone invasion and lower cumulative incidence. WL also reduced the Th17/Treg cell ratio in the spleen and colon and improved the intestinal barrier by inhibiting colonic inflammation and up-regulating tight junction proteins ZO-1 and Occludin. Concomitantly, WL reversed the RA-induced dysbiosis of gut microbiota and markedly elevated SCFAs levels, thereby restoring intestinal barrier integrity and re-establishing Th17/Treg homeostasis. FMT significantly ameliorated arthritis, further verifying the role of the gut microbiota-joint axis in the anti-arthritic effect of WL. However, FMT only partially mimicked the efficacy of WL, which was comparable to that of WL in ABX mice, indicating an additional microbiota-independent pathway. Additionally, WL directly inhibited the proliferation and migration of both MH7A and RA-FLS cells and induced G0/G1 cell cycle arrest. Transcriptomic profiling revealed that WL up-regulated p53-pathway genes including MDM2 and CDKN1A. Subsequently, pharmacologic blockade and genetic knockdown of the p53 axis abolished WL-induced decreases in cell viability and EdU positive cells and reversed the up-regulation expression of CDKN1A and HMOX1. Mechanistically, WL directly bound to p53, disrupted the p53-MDM2 interaction, suppressed p53 ubiquitination and proteasomal degradation, thereby stabilizing and upregulating p53 expression.<br><br>CONCLUSION: WL mitigated CIA in mice by modulating gut microbiota-SCFAs-Th17/Treg axis and inhibiting proliferation of RA-FLS via p53 pathway. The findings provide the pre-clinical foundation for the development of WL as an anti-RA agent.}, }
@article {pmid42214386, year = {2026}, author = {Sun, H and Dulencin, A and Kirn, TJ and Vo, J and Liachko, I and Rao, D and Manzano-Santana, J and Patel, E and Looi, C and Horton, DB and Barrett, E and Weidner, M and Bachmann, G and Panettieri, RA and Connor, BA and Rogova, M and Nagy-Szakal, D and Couto-Rodriguez, M and Kotwal, S and Wu, Q and Simon, J and Blaser, MJ and Dominguez Bello, MG}, title = {Autologous fecal microbiota transplantation restores the infant gut microbiome and metabolome after antibiotics: a case report.}, journal = {mBio}, volume = {}, number = {}, pages = {e0071126}, doi = {10.1128/mbio.00711-26}, pmid = {42214386}, issn = {2150-7511}, abstract = {UNLABELLED: Antibiotic exposure during infancy disrupts gut microbiome assembly during a critical developmental window. Strategies to restore these ecosystems remain limited. In the REPAIR trial (NCT06609980), eight infants were followed longitudinally; two received amoxicillin for otitis media, and one subsequently underwent autologous fecal microbiota transplantation (aFMT) using stool collected prior to antibiotic exposure. Shotgun metagenomics, Hi-C-assisted resistome profiling, and untargeted metabolomics were performed on samples collected before and after antibiotics. Amoxicillin treatment was associated with displacement of community structure, enrichment of antibiotic resistance genes (ARGs), and altered fecal metabolites, including short-chain fatty acids, bile acids, acylcarnitines, bilirubin derivatives, tricarboxylic acid (TCA) cycle metabolites, and amino acids. In the non-restored infant, microbiota composition and ARG profiles remained persistently altered during follow-up, accompanied by sustained metabolic divergence. In contrast, the aFMT-treated infant demonstrated convergence toward pre-antibiotic community structure, directional restructuring of ARG carriers -including reduction of β-lactam and tetracycline resistance genes- and metabolite profiles trending toward the pre-antibiotic baseline across analytical platforms. Although limited to a case-based comparison, these findings provide integrated ecological and functional evidence that aFMT may promote recovery following antibiotic perturbation during early-life microbiome development and support the rationale for larger controlled clinical trials.<br><br>IMPORTANCE: Antibiotic exposure in early life disrupts the developing gut microbiome during a critical window of host-microbe interaction. However, the extent to which these disturbances resolve naturally, or can be actively reversed, remains unclear. In this study, we use longitudinal sampling in infants to examine microbiome recovery following antibiotics, with and without autologous fecal microbiota transplantation (aFMT). We show that antibiotic exposure leads to coordinated disruptions in microbial composition, antibiotic resistance genes, and metabolic profiles. While partial recovery spontaneously occurs over time, faster and more extensive restoration toward the pre-antibiotic state is observed following aFMT. These findings provide insight into the ecological dynamics of microbiome reassembly in early life and highlight the potential of using controlled perturbations to understand microbiome resilience.<br><br>CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT06609980.}, }
@article {pmid42214571, year = {2026}, author = {Han, EJ and Kim, DH and Ahn, JS and Choi, YJ and Chung, HJ}, title = {Gut-derived commensal bacteria attenuate corticosterone-induced depressive-like behavior via regulation of oxidative stress and mitochondrial apoptotic signalling.}, journal = {Pharmacological research}, volume = {230}, number = {}, pages = {108269}, doi = {10.1016/j.phrs.2026.108269}, pmid = {42214571}, issn = {1096-1186}, abstract = {Chronic stress and sustained glucocorticoid exposure disrupt intracellular signaling networks that regulate mitochondrial function and neurotrophic support, thereby increasing vulnerability to depressive disorders. Among these alterations, redox imbalance and mitochondrial dysfunction contribute to impairment of neuronal survival pathways, including TrkB-ERK-CREB-BDNF signaling. However, upstream biological modulators of these stress-responsive processes remain incompletely understood. Here, we investigated whether gut-derived commensal bacteria function as modulators of neuronal signaling under chronic stress conditions. Using a fecal microbiota transplantation (FMT)-based behavioral stratification approach, we identified Intestinimonas butyriciproducens and Parabacteroides merdae as species depleted in mice with increased depressive-like immobility. Functional validation showed that both strains attenuated oxidative stress, reduced intracellular reactive oxygen species, and suppressed mitochondrial apoptotic signaling in neuronal cells, accompanied by restoration of TrkB-ERK-CREB signaling and increased brain-derived neurotrophic factor expression. In a chronic corticosterone model, oral administration of these strains reduced depressive-like behavior and restored hippocampal BDNF levels. Collectively, these findings demonstrate that defined commensal bacteria act as biological modulators of intracellular signaling pathways, including redox balance and mitochondrial function, thereby preserving neurotrophic signaling. This study provides evidence linking specific commensal taxa to modulation of neuronal signaling under chronic stress conditions.}, }
@article {pmid42214609, year = {2026}, author = {Yuan, S and Lin, L and Liu, J and Lin, Q and Wang, S and Wu, J and Xu, D and Liu, Y and Lee, JY and Qiu, L}, title = {Treadmill exercise attenuates neuroinflammation in APP/PS1 mice via gut microbiota remodeling: Evidence from fecal microbiota transplantation.}, journal = {Life sciences}, volume = {400}, number = {}, pages = {124500}, doi = {10.1016/j.lfs.2026.124500}, pmid = {42214609}, issn = {1879-0631}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Physical Conditioning, Animal/physiology ; Mice ; *Gastrointestinal Microbiome/physiology ; *Neuroinflammatory Diseases/therapy ; Male ; *Alzheimer Disease/therapy/microbiology ; Amyloid beta-Protein Precursor/genetics ; Mice, Transgenic ; Disease Models, Animal ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Inflammation ; Lipopolysaccharides/metabolism ; Dysbiosis ; }, abstract = {Alzheimer's disease is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, lipopolysaccharide (LPS) translocation, and neuroinflammation. However, it is unclear whether exercise-induced gut microbiota remodeling causally contributes to the neuroprotective effects of exercise in AD. Herein, APP/PS1 mice underwent 12 weeks of treadmill exercise, and fecal microbiota transplantation (FMT) was used to determine whether exercise-related benefits could be transferred to the recipient mice. Behavioral performance was assessed using the Morris water maze and open-field test. Gut microbial profiles were analyzed by 16S rDNA sequencing. Intestinal barrier integrity was evaluated using histology, AB-PAS staining, and tight-junction protein expression, while plasma and brain LPS levels were measured by enzyme-linked immunosorbent assay. Neuroinflammation was examined with immunofluorescence and Western blotting. It was found that treadmill exercise improved spatial learning, memory, and anxiety-like behavior in APP/PS1 mice. These benefits were partly reproduced in recipients of microbiota from exercised donors. Exercise also restored gut microbial diversity and composition, increased the abundance of taxa including Dubosiella and UBA1819, alleviated colonic injury, enhanced mucus secretion, upregulated ZO-1, Occludin, and Claudin-1, and reduced plasma and brain LPS levels. In parallel, exercise and FMT from exercised donors decreased brain TLR4 expression, attenuated microglial and astrocytic activation, and suppressed TLR4/NF-κB signaling and downstream inflammatory cytokines. These findings indicate that treadmill exercise alleviates neuroinflammation in APP/PS1 mice, at least in part, through gut microbiota remodeling, improved intestinal barrier integrity, and reduced LPS-driven inflammatory signaling.}, }
@article {pmid42215979, year = {2026}, author = {Li, X and Zhang, X and Yuan, S and Zhang, J}, title = {The gut-lung axis in ARDS: beyond microbial translocation.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-026-03752-w}, pmid = {42215979}, issn = {1465-993X}, support = {82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2025ZD01902600//Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, abstract = {The gut-lung axis has emerged as a pivotal pathway in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Disruption of the intestinal barrier, a common event in critical illness, facilitates the systemic dissemination of live microbiota, their pathogen-associated molecular patterns (PAMPs), and bioactive metabolites. This process critically depends on the integrity of the gut vascular barrier (GVB). The GVB is the endothelial layer underlying the gut epithelium. It serves as the final gatekeeper, restricting microbial products from entering the systemic circulation. Concurrently, intestinal immune cells, such as γδ T cells and innate lymphoid cells (ILCs), migrate to the lungs and amplify the inflammatory cascade. Emerging evidence links regulated cell death, especially pyroptosis, necroptosis, and ferroptosis, to disruption of both gut and lung barriers, fueling a self-amplifying cycle of organ injury. This review synthesizes current evidence on the cellular, molecular, and metabolic mechanisms underlying gut-derived lung injury. Furthermore, we critically evaluate several emerging gut-targeted therapeutic strategies aimed at restoring microbial homeostasis and mitigating ALI/ARDS, including fecal microbiota transplantation (FMT), probiotics, synbiotics, and mesenchymal stem cell (MSC) therapy. Deciphering the gut-lung dialogue holds promise for developing novel treatments for this devastating condition.}, }
@article {pmid42218119, year = {2026}, author = {Fessler, JL and Olm, MR and Engleman, EG and Sonnenburg, JL}, title = {Integration of donor microbiota following FMT correlates with anti-PD-1 response in melanoma.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-73465-7}, pmid = {42218119}, issn = {2041-1723}, support = {R21CA290426//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Fecal microbiota transplantation (FMT) has shown promise in improving anti-PD-1 therapy in melanoma, but the underlying microbial features remain poorly defined. We performed a strain-resolved metagenomic meta-analysis across three independent FMT plus anti-PD-1 melanoma trials (n = 41). Across cohorts, therapeutic benefit was linked to successful integration of donor microbiota, rather than increased diversity or engraftment of specific species. Responders acquired more donor-derived strains, exhibited greater post-FMT similarity to their donor, and maintained a more stable microbiome. Following FMT, non-responders' microbiomes showed greater taxonomic instability, larger fluctuations in estimated microbial load, and increased abundance of pathogen-associated secretion system genes, whereas responders showed enrichment for microbial functions involved in community-level metabolism and communication. Finally, shifts in tumor-infiltrating immune profiles tracked with clinical outcomes and microbiome changes. Together these findings highlight that distinct patterns of microbiome restructuring, including stable community transitions and altered functional capacity, are associated with anti-PD-1 response following FMT.}, }
@article {pmid42218700, year = {2026}, author = {Zhang, Y and Wang, Y and Yang, Y and Mei, H and Liu, X and He, Y and Qin, S and Feng, B}, title = {Gut-Liver Axis Failure in Critical Alcohol-Associated Liver Disease: From ICU Secondary Hits to Microbiome-Targeted Therapy.}, journal = {Mediators of inflammation}, volume = {2026}, number = {1}, pages = {e3968719}, pmid = {42218700}, issn = {1466-1861}, support = {82460373//National Natural Science Foundation of China/ ; 82560382//National Natural Science Foundation of China/ ; HZ (2025) 312//Zunyi Science and Technology Bureau, China/ ; HZ (2023) 366//Zunyi Science and Technology Bureau, China/ ; HZ (2025) 172//Zunyi Science and Technology Bureau, China/ ; QZYY-2024-137//Guizhou Administration of Traditional Chinese Medicine/ ; gzwkj2024-310//Guizhou Provincial Health Commission/ ; MTyk2024-55//Kweichow Moutai Hospital Research Project/ ; HZ202411//Traditional Chinese Medicine Hospital of Zunyi Medical and Pharmaceutical College/ ; }, mesh = {Humans ; Intensive Care Units ; *Liver Diseases, Alcoholic/therapy/microbiology/metabolism ; *Liver/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Intestinal Barrier Function ; Fecal Microbiota Transplantation ; Dysbiosis ; }, abstract = {Alcohol-associated liver disease (ALD) can progress to critical illness phenotypes requiring intensive care, including severe alcohol-associated hepatitis, acute decompensation, and alcohol-associated acute-on-chronic liver failure (ACLF). In these patients, short-term outcomes are driven less by the burden of fibrosis alone than by systemic inflammation, immune dysfunction, infection, and multiorgan failure. At the core of this process is gut-liver axis failure, which links alcohol-induced dysbiosis and intestinal barrier disruption to microbial translocation, hepatic innate immune activation, and systemic inflammatory amplification. In the intensive care unit (ICU), secondary hits such as broad-spectrum antibiotics, acid suppression, parenteral nutrition, shock, sedatives or opioids, and mechanical ventilation may further exacerbate these mechanisms and disturb microbial ecology and barrier integrity. Microbiome-targeted therapies (probiotics, postbiotics, and fecal microbiota transplantation) are biologically plausible. However, current evidence is mainly derived from non-ICU or relatively stable ALD populations. Therefore, their use in critically ill patients requires strict safety boundaries, including severe barrier disruption, invasive devices, uncontrolled infections, and profound immune dysfunction. This narrative review synthesizes the pathophysiological continuum from gut barrier failure to systemic inflammation and multiorgan dysfunction in critical ALD, with particular emphasis on ICU-specific secondary hits, safety-aware microbiome modulation, and future phenotype-informed precision strategies.}, }
@article {pmid42218858, year = {2026}, author = {Sun, Y and Xie, D and Fu, H and He, M and Li, J and Wu, C and Pan, S}, title = {Harpagide alleviates sepsis-induced acute respiratory distress syndrome via gut microbiota modulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {157}, number = {}, pages = {158329}, doi = {10.1016/j.phymed.2026.158329}, pmid = {42218858}, issn = {1618-095X}, mesh = {Animals ; *Respiratory Distress Syndrome/drug therapy/etiology/microbiology ; *Sepsis/complications/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Humans ; Scrophularia/chemistry ; Mice, Inbred C57BL ; Disease Models, Animal ; *Iridoid Glycosides/pharmacology ; Fecal Microbiota Transplantation ; *Pyrans/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Lung/drug effects ; }, abstract = {BACKGROUND: Sepsis-associated acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in critically ill patients, with limited therapeutic options beyond supportive care. The gut-lung axis is critical in sepsis pathogenesis, yet effective targeting strategies remain scarce. Harpagide (HPG), an iridoid glycoside from Scrophularia ningpoensis, exhibits anti-inflammatory properties, but whether it protects against sepsis-induced ARDS through gut microbiota modulation remains unexplored.<br><br>METHODS: Sepsis-induced ARDS was established using the cecal ligation and puncture (CLP) model. Gut microbiota dependency was assessed via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). Ffar2[-/-] mice were used to verify receptor necessity. Microbial composition and SCFAs were analyzed by 16S rRNA sequencing and GC-MS. Lung signaling was assessed by RNA-seq, Western blot, and RT-qPCR. Plasma SCFAs were quantified in sepsis-induced ARDS patients (n = 12) and healthy controls (n = 12) by LC-MS/MS.<br><br>RESULTS: HPG significantly improved survival, attenuated lung injury, and suppressed cytokine storm in septic mice. These effects were abolished by ABX but transferable via FMT, confirming microbiota dependency. HPG enriched acetate-producing taxa, elevating fecal and plasma acetate. Transcriptomic analysis revealed simultaneous suppression of NF-&#x3ba;B signaling and excessive IFN-&#x3b3;/STAT1 activation. HPG-mediated protection was completely abrogated in Ffar2[-/-] mice, and exogenous sodium acetate recapitulated these effects in a Ffar2-dependent manner. Clinically, plasma acetate was significantly depleted in ARDS patients and correlated with disease severity.<br><br>CONCLUSIONS: HPG alleviates sepsis-induced ARDS by reshaping gut microbiota to boost acetate production, which activates FFAR2 to orchestrate immune reprogramming via NF-&#x3ba;B and IFN-&#x3b3;/STAT1 pathways, offering a novel microbial-metabolic therapeutic strategy.}, }
@article {pmid42219603, year = {2026}, author = {Coiffard, B and Brodovitch, A and Mège, JL and Bardin, N and Cassir, N}, title = {IgM/IgA-Enriched Immunoglobulins: a Key to Breaking the Cycle of Clostridioides difficile Infection Recurrences in Patients with Hypogammaglobulinemia?.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiag291}, pmid = {42219603}, issn = {1537-6613}, abstract = {We present the case of a 57-year-old woman with secondary hypogammaglobulinemia who experienced Clostridioides difficile infection, with repeated recurrences despite transient clinical responses to standard therapies, including repeated fecal microbiota transplantation. Following the replacement of intravenous immunoglobulin supplementation with IgM/IgA-enriched immunoglobulin, no recurrence of CDI was observed during the 24-month follow-up period.}, }
@article {pmid42220281, year = {2026}, author = {de Bruijn, CMA and Oorthuys, AOJ and Zeevenhooven, J and Davids, M and Levels, JHM and Vlieger, AM and Herrema, H and Nieuwdorp, M and Benninga, MA}, title = {Feasibility and efficacy of fecal microbiota transplantation in adolescents with refractory irritable bowel syndrome: A randomized clinical pilot trial.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70459}, pmid = {42220281}, issn = {1536-4801}, support = {//Stichting Dioraphte/ ; //For Wis(h)dom Foundation/ ; 09150182010020/ZONMW_/ZonMw/Netherlands ; 015.017.050//Aspasia Premium/ ; 09150182010020/ZONMW_/ZonMw/Netherlands ; }, abstract = {OBJECTIVES: To assess the feasibility and efficacy of fecal microbiota transplantation (FMT) in adolescents (16-21 years) with refractory irritable bowel syndrome (IBS).<br><br>METHODS: Randomized controlled pilot trial. Thirty-two patients were included and randomized to receive two allogeneic or autologous FMTs. At baseline and after 6 weeks, two allogeneic or autologous FMTs were administered via a nasoduodenal tube. Feasibility outcomes included dropout rate. Clinical efficacy was evaluated by the proportion of responders (&#x2265;50 points reduction in total score of the IBS severity-scoring-system) at 12, 24, and 48 weeks follow-up. Secondary outcomes included health-related quality of life (QoL), depression and anxiety scores, and school/work absenteeism.<br><br>RESULTS: One patient (3%) withdrew after randomization, due to lack of effect after the first FMT. Response rates 12 weeks after allogeneic and autologous FMTs were 40% and 38% (p&#x2009;=&#x2009;0.886). At 24 weeks, significantly more patients responded after allogeneic FMTs (60% vs. 25% autologous, p&#x2009;=&#x2009;0.048), without significant differences at 48 weeks (60% vs. 50%, p&#x2009;=&#x2009;0.576). Total QoL score was significantly better after allogeneic than autologous FMTs at 12, 24, and 48 weeks (p&#x2009;=&#x2009;0.028, p&#x2009;=&#x2009;0.007, p&#x2009;=&#x2009;0.011). In the allogeneic FMTs group, school/work absenteeism was 7% at 24 weeks (vs. 41% autologous, p&#x2009;=&#x2009;0.037).<br><br>CONCLUSIONS: Allogeneic FMTs were feasible and resulted in high response rates and better QoL compared to autologous FMTs. These results provide preliminary evidence for the use of allogeneic FMTs in adolescents with refractory IBS.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03074227 (https://clinicaltrials.gov/study/NCT03074227?id=NCT03074227&amp;rank=1).}, }
@article {pmid42220621, year = {2026}, author = {Kaiser Junior, RL and Piron-Ruiz, L and Tomiatti, RZ and De Castro, MLS and Quadros, LG and Ruiz, MA}, title = {Clinical Remission of Crohn's Disease and Closure of a Rectovaginal Fistula After Autologous Non-Myeloablative Hematopoietic Stem Cell Transplantation.}, journal = {International medical case reports journal}, volume = {19}, number = {}, pages = {550993}, pmid = {42220621}, issn = {1179-142X}, abstract = {BACKGROUND: Crohn's Disease is a chronic, heterogeneous, recurrent and remitting inflammatory bowel disease that can affect any part of the digestive system. To date there is no cure for this disease. Clinical treatment aims to reestablish a balance and avoid crises that are common in an immune-mediated disease that promotes intestinal dysregulation. Anti-inflammatory medications, corticosteroids, immunosuppressants and biologics are part of the therapeutic arsenal for the disease. Obstructions, strictures and intestinal fistulas are complications that require repeat surgery in most patients. Fistulas in the anal or perianal regions are common with rectovaginal fistulas being a serious and complex complication that is difficult to control. Autologous hematopoietic stem cell transplantation can be employed for select patients with severe, refractory autoimmune diseases that have failed to respond adequately to conventional treatments.<br><br>CASE PRESENTATION: A 31-year-old Brazilian patient underwent several unsuccessful perianal surgeries for a complex rectovaginal fistula during her twelve years with active Crohn's Disease. Stool elimination was mostly through the vagina as she had rectal stenosis. Consequently, rectal amputation and permanent colostomy implantation were recommended but refused by the patient. Instead, she underwent a non-myeloablative autologous hematopoietic stem cell transplantation. Four years later, she is without active disease, with no manifestation of a rectovaginal fistula. Previous descriptions of rectovaginal fistula closure with hematopoietic stem cell transplantation were not found in a review of the literature.<br><br>CONCLUSION: For patients who refuse radical surgery, the presence of a fistula is not a contraindication for hematopoietic stem cell transplantation. The procedure provided progressive improvement not only with apparent cure of the Crohn's disease but with no manifestation of the rectovaginal fistula four years after the transplantation.}, }
@article {pmid42220936, year = {2026}, author = {Elbeltagi, YM and Abd Rab El Rasool, AO and Elkashlan, AM and Al-Beltagi, M}, title = {Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.}, journal = {World journal of clinical pediatrics}, volume = {15}, number = {2}, pages = {117274}, pmid = {42220936}, issn = {2219-2808}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits.<br><br>AIM: To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD.<br><br>METHODS: Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I [2] to quantify heterogeneity.<br><br>RESULTS: Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I [2] approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-&#x3b1; autoantibodies.<br><br>CONCLUSION: The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.}, }
@article {pmid42221399, year = {2026}, author = {Al Jnainati, M and Govindarajan, A and Tyagi, S and Iltaf, M and Al Jnainati, J and Ayoub, M and Shadab, HA}, title = {Harnessing Microbiome Therapy to Treat Metabolic Syndrome.}, journal = {AACE endocrinology and diabetes}, volume = {13}, number = {3}, pages = {463-472}, pmid = {42221399}, issn = {3050-9157}, abstract = {BACKGROUND/OBJECTIVE: Metabolic syndrome, a global health crisis marked by insulin resistance, obesity, and dyslipidemia, necessitates novel therapeutic approaches beyond conventional symptom management. Emerging research highlights the gut microbiome as a pivotal modulator of metabolic health, with dysbiosis-characterized by reduced microbial diversity and proinflammatory shifts-implicated in disease pathogenesis. This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.<br><br>CASE REPORT: This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.<br><br>DISCUSSION: Fecal microbiota transplantation transfers beneficial microbiota to enhance insulin sensitivity, while probiotics and synbiotics modulate inflammation, strengthen gut barrier integrity, and stimulate metabolic regulators like glucagon-like peptide-1 and short-chain fatty acids. Mechanistically, these therapies mitigate systemic inflammation, improve glucose/lipid homeostasis, and reduce intestinal permeability linked to endotoxin translocation. Clinical trials report improved glycemic control, lipid profiles, and weight management, underscoring their multitargeted potential. However, challenges such as donor variability, lack of standardized protocols, and long-term safety concerns hinder widespread application. Personalized approaches, informed by machine learning and microbial biomarkers, alongside innovations in Clustered Regularly Interspaced Short Palindromic Repeats-based engineering and encapsulation technologies, may address these limitations.<br><br>CONCLUSION: Despite promising outcomes, rigorous large-scale trials and interdisciplinary collaboration are essential to validate efficacy, optimize delivery, and ensure ethical compliance. In conclusion, microbiome therapies represent a paradigm shift in treating metabolic syndrome by targeting root causes, yet translating preclinical success into clinical practice demands further innovation and evidence-based standardization.}, }
@article {pmid42221483, year = {2026}, author = {Yang, H and Liu, S and Chen, X and Yin, C and Xiao, L and Xu, W and Lv, S and Xie, L and Yin, C}, title = {Gut microbiota-associated immunomodulation contributes to the protective effects of fluvastatin against endometriosis in a mouse model, accompanied by increased Akkermansia muciniphila abundance.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1762444}, pmid = {42221483}, issn = {1664-302X}, abstract = {BACKGROUND: Endometriosis (EMs) is a chronic inflammatory disease characterized by tumor-like growth behavior and limited therapeutic options. Increasing evidence suggests that gut microbiota may contribute to EMs progression by promoting chronic inflammation and immune dysregulation. Fluvastatin, a lipid-lowering agent, exhibits anti-inflammatory, anti-tumor, and immunomodulatory effects and has also been reported to influence microbial homeostasis. However, the relationship among fluvastatin treatment, gut microbiota, and EMs progression remains unclear. This study aimed to investigate this relationship.<br><br>MATERIALS AND METHODS: A mouse model of EMs was established by autologous uterine tissue transplantation, followed by oral fluvastatin administration for 3 weeks. Lesion growth, inflammatory responses, and immune characteristics were evaluated by histology, quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry. Gut microbiota involvement was assessed using antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT). Microbial composition was analyzed by metagenomic sequencing. The role of Akkermansia muciniphila was evaluated by direct oral supplementation.<br><br>RESULTS: Fluvastatin significantly reduced the volume and mass of ectopic lesions and decreased the mRNA expression of pro-inflammatory cytokines. It was also associated with changes in macrophage polarization-related markers and reduced abnormal activation of splenic immune cells. Antibiotic-induced gut microbiota depletion attenuated the protective effects associated with fluvastatin treatment, whereas FMT from fluvastatin-treated mice partially transferred similar protective changes. Metagenomic analysis revealed that fluvastatin reshaped gut microbiota composition and increased the abundance of Akkermansia muciniphila. Moreover, oral supplementation with Akkermansia muciniphila attenuated EMs progression and was associated with anti-inflammatory and immune-related changes similar to those observed after fluvastatin treatment.<br><br>CONCLUSION: These findings suggest that the protective effects associated with fluvastatin treatment are accompanied by changes in gut microbiota composition, including increased abundance of Akkermansia muciniphila. Gut microbiota may contribute to the beneficial effects of fluvastatin in EMs. These results support the potential value of microbiota-informed therapeutic strategies for EMs.}, }
@article {pmid42221532, year = {2026}, author = {Mishra, AK and Mishra, A and Vikal, A and Singh, H and Y Thajudeen, K and Khan, G and Ahmed, MM}, title = {Fecal microbiota transplant and its usefulness in hepatic disorders: a systematic review.}, journal = {Therapeutic advances in gastroenterology}, volume = {19}, number = {}, pages = {17562848261452504}, pmid = {42221532}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic approach aimed at restoring gut microbial balance through the transfer of stool from healthy donors. It has gained significant attention for its role in managing gut dysbiosis-associated disorders, particularly hepatic diseases.<br><br>OBJECTIVE: This systematic review evaluated the therapeutic efficacy and clinical potential of FMT in the management of liver-related conditions, including recurrent Clostridium difficile infection (CDI), non-alcoholic fatty liver disease, liver cirrhosis, and hepatic encephalopathy.<br><br>DESIGN: A systematic review of existing literature was conducted to assess the clinical outcomes, mechanisms, and challenges associated with FMT in hepatic disorders.<br><br>DATA SOURCES AND METHODS: Relevant studies were identified from peer-reviewed scientific databases, focusing on clinical trials, observational studies, and experimental research investigating the role of FMT in gut dysbiosis and liver disease. Data were analyzed to evaluate efficacy, underlying mechanisms, and safety considerations.<br><br>RESULTS: FMT demonstrated high efficacy in recurrent CDI, with cure rates exceeding 80%-90%. In hepatic disorders, FMT was associated with improved microbial diversity, enhanced gut barrier integrity, and reduced systemic inflammation, contributing to better liver function and clinical outcomes. However, variability in donor selection, potential safety risks, and regulatory limitations remain significant challenges.<br><br>CONCLUSION: FMT represents a promising therapeutic strategy in hepatology, underscoring the critical role of the gut-liver axis. Advances such as synthetic microbiota and personalized microbiome-based therapies may further optimize its safety and efficacy, paving the way for innovative, microbiome-centered interventions in liver disease management.}, }
@article {pmid42221589, year = {2026}, author = {Song, D and Gao, H and Wang, T and Wei, Q and Liu, A and Ren, J}, title = {Gut microbiota dysbiosis-induced chronic inflammation as a driver of atherosclerosis: cellular crosstalk and host-microbe interactions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1789194}, pmid = {42221589}, issn = {2235-2988}, mesh = {Animals ; Humans ; *Atherosclerosis/immunology/microbiology/therapy ; *Dysbiosis/complications/immunology/microbiology/therapy ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *Host Microbial Interactions/immunology ; *Inflammation/immunology/microbiology/therapy ; Intestinal Barrier Function/immunology ; Methylamines/metabolism ; }, abstract = {Gut microbiota dysbiosis is increasingly recognized as an upstream contributor to chronic low-grade inflammation and atherosclerosis (AS). Disruption of microbial homeostasis may impair intestinal barrier integrity, increase exposure to pro-inflammatory microbial products and metabolites, and reduce protective metabolites such as short-chain fatty acids (SCFAs), thereby activating innate immune signaling and sustaining vascular inflammation. Current evidence indicates that gut dysbiosis promotes atherosclerosis mainly through three interconnected processes: metabolite imbalance, barrier dysfunction with microbial translocation, and systemic immune reprogramming. Clinical studies have linked gut-derived biomarkers, particularly trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS)-related signals, to atherosclerotic burden and adverse cardiovascular outcomes, while experimental studies using fecal microbiota transplantation, probiotics, antibiotics, and gene-deficient models support a contributory role of the gut-immune-vascular axis. Emerging interventions, including dietary modulation, pharmacological repurposing, and microbiome-targeted therapies, may attenuate gut-derived chronic inflammation and offer new strategies for AS prevention and treatment. However, heterogeneity across studies and the limited causal evidence in humans warrant cautious interpretation. Overall, gut dysbiosis-driven chronic inflammation represents a biologically meaningful and potentially modifiable pathway in atherosclerosis.}, }
@article {pmid42225253, year = {2026}, author = {Singh, L and Bhullar, G and Shaik, S and Ganesh, V and Kesani, H and Rai, M}, title = {Gut Feeling: Microbiota as a Hidden Regulator of Hypertension.}, journal = {The Journal of nutrition}, volume = {156}, number = {7}, pages = {101623}, doi = {10.1016/j.tjnut.2026.101623}, pmid = {42225253}, issn = {1541-6100}, abstract = {Emerging evidence identifies the gut microbiota as a key regulator of blood pressure (BP) through its role in metabolizing dietary substrates into bioactive compounds that influence vascular, immune, and neurohumoral pathways. This review synthesizes recent mechanistic, preclinical, and clinical evidence linking gut microbial dysbiosis to hypertension, with particular emphasis on nutrition-dependent microbial metabolism and its translational implications. Experimental studies demonstrate that depletion of short-chain fatty-acid (SCFA)-producing bacteria and enrichment of proinflammatory and trimethylamine-producing taxa contribute to endothelial dysfunction, immune activation, and renin-angiotensin-aldosterone system dysregulation. Fecal microbiota transplantation and germ-free animal models provide causal evidence that hypertensive microbiota can directly elevate BP. Human multiomics and metabolomic studies further show that microbial functional capacity and metabolite production, rather than taxonomic composition alone, are strongly associated with hypertensive phenotypes and therapeutic responsiveness. Importantly, dietary interventions, including high-fiber diets, resistant starch, and the Dietary Approaches to Stop Hypertension diet, modulate microbial composition and enhance SCFA production, providing a mechanistic basis for their antihypertensive effects. Microbiota-drug interactions have also emerged as a novel determinant of antihypertensive treatment efficacy. Collectively, these findings support a metabolite-centered framework in which diet-microbiota interactions influence BP regulation. Targeting the gut microbiota through nutritional and microbiome-based strategies represents a promising adjunctive approach for hypertension prevention and personalized management. However, large-scale longitudinal and interventional human studies are needed to establish causality and optimize microbiota-targeted therapies.}, }
@article {pmid42225309, year = {2026}, author = {Wang, W and Niu, X and Li, S and Cheng, B and Cheng, L and Yang, C and Xu, X and Chang, S and Wang, C and Liu, S}, title = {Efavirenz Mitigates Dyslipidemia and Attenuates Ulcerative Colitis through Gut Microbiota Modulation.}, journal = {ACS infectious diseases}, volume = {12}, number = {6}, pages = {2136-2148}, doi = {10.1021/acsinfecdis.6c00330}, pmid = {42225309}, issn = {2373-8227}, mesh = {Alkynes ; Animals ; *Benzoxazines/pharmacology/administration &amp; dosage/therapeutic use ; Cyclopropanes ; Humans ; *Dyslipidemias/drug therapy/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Colitis, Ulcerative/drug therapy/microbiology ; Male ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; HIV Infections/drug therapy ; Rats, Sprague-Dawley ; Oxidoreductases Acting on CH-CH Group Donors ; }, abstract = {Antiretroviral therapy (ART) is central to controlling human immunodeficiency virus (HIV) infection, yet it is frequently associated with dyslipidemia, a condition linked to the exacerbation of ulcerative colitis (UC) in people living with HIV (PLWH). The underlying mechanisms of ART-induced dyslipidemia and its contribution to UC progression remain incompletely understood. Here, we demonstrate that efavirenz (EFV), a widely used non-nucleoside reverse transcriptase inhibitor, mitigates ART-induced dyslipidemia and ameliorates UC symptoms. Our in vitro investigations reveal that palmitic acid (PA)-induced inflammation in human normal colorectal mucosal cells (FHCs) is mediated by the activation of the Akt phosphorylation pathway, triggered by the accumulation of 7-dehydrocholesterol (7-DHC), a substrate of 7-dehydrocholesterol reductase (DHCR7). While EFV did not directly modulate this inflammatory cascade in FHCs, in vivo studies using a high-fat diet (HFD)-induced dyslipidemia rat model demonstrated that EFV significantly attenuated elevated lipid levels and improved DHCR7 expression in dextran sulfate sodium (DSS)-induced UC tissues. Notably, fecal microbiota transplantation (FMT) from EFV-treated rats to HFD-fed recipients reduced dyslipidemia and restored DHCR7 expression, thereby suppressing 7-DHC-driven Akt phosphorylation and inflammatory responses in UC tissues. Our findings suggest a mechanism by which EFV mitigates dyslipidemia and UC progression, mediated through the regulation of lipid metabolism and gut microbiota. These findings provide compelling evidence for the potential of EFV to regulate dyslipidemia and associated comorbidities in HIV-infected individuals.}, }
@article {pmid42227044, year = {2026}, author = {Singh, VK and Gupta, P and Jain, SK and Matreja, PS}, title = {The gut-brain axis in Alzheimer's and Parkinson's diseases: a systematic review of microbiota-derived biomarkers and novel therapeutic approaches.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/13803395.2026.2673084}, pmid = {42227044}, issn = {1744-411X}, abstract = {BACKGROUND: The altered gut microbiota substantially impacts the onset and progression of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most widely studied neurodegenerative conditions. Microbiome-derived metabolites have been increasingly associated with disease onset, progression, and therapeutic targets in neurodegenerative disorders. Exploring the diagnostic and therapeutic implications of gut microbiome-derived biomarkers is critical to advancing our understanding and management of neurodegeneration.<br><br>METHODOLOGY: We systematically reviewed both clinical and preclinical studies published from 2010 to 2025. Studies examining gut microbiota composition, microbial-derived metabolites, or therapeutic interventions targeting the gut microbiome were included. Identification of gut microbiome alterations, discovery of microbial or metabolite-based biomarkers, association with disease onset or progression, and/or therapeutic effects on cognitive, neurological, or inflammatory outcomes were evaluated.<br><br>RESULT: Short-chain fatty acids(SCFAs) such as butyrate and acetate were found to be noninvasive biomarkers in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and Parkinson's disease (PD). Lower SCFA levels correlated with cognitive decline. Diagnostic accuracy improved when SCFA combinations were used, with AUCs ranging from 0.75 to 0.87. Trimethylamine N-oxide(TMAO) levels showed inconsistent associations, with both elevated and reduced levels linked to disease risk. Therapeutic approaches targeting gut microbiota, including probiotics, prebiotics, dietary changes, and fecal microbiota transplantation, demonstrated cognitive benefits and modulation of gut-brain signaling pathways.<br><br>CONCLUSION: Overall, gut-derived biomarkers offer a promising avenue for early diagnosis and novel therapeutic approaches in AD and PD, while acknowledging that evidence in other neurodegenerative diseases remains limited through modulation of the gut-brain axis.}, }
@article {pmid42227494, year = {2026}, author = {Wang, JM and Wang, RQ and Wang, Y and Gao, XY and Liu, SY and Qi, SW and Hu, GL and Li, DL and Zhang, Y and Xu, XK and Feng, HL}, title = {Exploring the Influence of Circadian Rhythm Disorders in Metabolic Syndrome through Gut Microbiota.}, journal = {Combinatorial chemistry &amp; high throughput screening}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113862073482277260412133043}, pmid = {42227494}, issn = {1875-5402}, abstract = {INTRODUCTION: Metabolic syndrome (MetS) is a chronic metabolic disorder whose global prevalence continues to rise, imposing a significant burden on public health. With the development of round-the-clock societies, shift work has become increasingly commonplace. A growing body of epidemiological evidence indicates that circadian rhythm disruption constitutes a predictable risk factor for MetS; however, the precise mechanisms underlying this relationship remain inadequately understood. This study employed golden hamsters as a model to investigate the effects of circadian rhythm disruption simulated by cyclic light (CL) exposure on MetS.<br><br>METHODS: Thirty-three male golden hamsters (7 weeks old, body weight 120-160 g) were randomly assigned to four groups for a 6-week intervention: the Control group (normal light + normal diet, ND), the high-fat diet group (normal light + HFD, to induce a MetS model), the cyclic light group (CL + normal diet, CL), and the CL + HFD group (CL + HFD). Outcome measures included metabolic indicators, hepatic histopathology, and gut microbiota (analyzed via 16S rDNA sequencing).<br><br>RESULTS: The stability of the MetS model was assessed through measurements of body weight, fasting blood glucose, and total cholesterol levels. The results indicated that CL exposure may further aggravate metabolic disorders associated with MetS. Furthermore, it was observed that CL exposure intensified MetS-related disturbances in gut microbiota, evidenced by an increase in &#x3b1;-diversity and distinct separation in &#x3b2;-diversity. CL exposure in the MetS model golden hamsters resulted in a reduced abundance of Bacteroidetes and Weissella, alongside an overgrowth of Helicobacter.<br><br>DISCUSSION: Circadian rhythm disruption is an independent risk factor for MetS. It further exacerbates metabolic indicators by inducing gut microbiota dysbiosis and promoting the growth of harmful bacteria. Future research should integrate functional metabolomics with faecal microbiota transplantation studies to validate causal mechanisms and explore clinical translational value.<br><br>CONCLUSION: Circadian rhythm disruption is an independent risk factor for MetS. It exacerbates the pathological progression of MetS by reducing beneficial bacteria and promoting the growth of harmful bacteria, thereby further damaging its metabolic indicators.}, }
@article {pmid42228606, year = {2026}, author = {Waghmode, S and Viswanathan, R and Koligudde, V and Umare, P and Lavania, M}, title = {Microbial shifts in early life: the pediatric gut microbiome and its role in health and disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2681763}, pmid = {42228606}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Infant ; Prebiotics ; Infant, Newborn ; Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation &amp; purification ; Breast Feeding ; Neurodevelopmental Disorders/microbiology ; Inflammatory Bowel Diseases/microbiology ; }, abstract = {This review explores the pivotal role of the pediatric gut microbiome in shaping early-life development and influencing susceptibility to disease, emphasizing its impact on immune, metabolic, and neurodevelopmental processes. The neonatal period represents a critical window for host-microbiome interactions, beginning at birth when intestinal barrier function is still developing and immune responses remain immature. During this formative stage, rapid microbial colonization and ecological succession are influenced by delivery mode, infant feeding practices, antibiotic exposure, and environmental factors. Beyond bacterial populations, the early-life gut virome composed of bacteriophages and eukaryotic viruses evolves dynamically and contributes to microbial community structure, gene exchange, and immune system maturation. Microbially derived signals and metabolites support the development of mucosal integrity, immune programming, and host microbe equilibrium, with long-term implications for systemic immune function. Breastfeeding fosters the establishment of microbial communities and metabolic profiles associated with immune tolerance, whereas formula feeding and early-life antibiotic use may disrupt normal microbiome development. Alterations in early microbial trajectories have been associated with heightened risk of pediatric conditions, including allergic diseases, obesity, inflammatory bowel disease, and neurodevelopmental disorders. The review further evaluates emerging microbiome-directed strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, considering both their therapeutic promise and current challenges. Collectively, current evidence underscores the early-life gut microbiome as a central determinant of host development and a compelling target for disease prevention strategies.}, }
@article {pmid42229822, year = {2026}, author = {An, X and Li, C and Chai, Y and Wang, H and Yang, L and Qin, L and Soprun, LA and Gavrilova, NY and Wen, Z and Xu, J and Li, Q and Yang, D and Li, W and Guo, J and Li, Y and Wang, N and Yu, H}, title = {Luteolin rescues high-fat diet-induced hippocampal mitochondrial oxidative stress and cognitive decline by regulating gut microbiota-kynurenine-aryl hydrocarbon receptor axis.}, journal = {Free radical biology &amp; medicine}, volume = {253}, number = {}, pages = {427-442}, doi = {10.1016/j.freeradbiomed.2026.06.002}, pmid = {42229822}, issn = {1873-4596}, abstract = {High-fat diet (HFD)-induced gut dysbiosis precipitates hippocampal mitochondrial oxidative stress, a pivotal driver of synaptic failure and cognitive decline. However, the molecular conduits linking intestinal microbial shifts to cerebral redox imbalance remain poorly defined, limiting therapeutic strategies. Here, we show that luteolin attenuates HFD-induced cognitive impairment in association with modulation of the gut microbiota-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) axis and improved mitochondrial redox homeostasis. Luteolin treatment ameliorated HFD-induced memory deficits and metabolic abnormalities in mice, effects that were markedly reduced after gut microbiota depletion and were transmissible via fecal microbiota transplantation. Consistent with this pathway, luteolin suppressed HFD-induced expansion of Proteobacteria (e.g., Escherichia coli), diminished intestinal lipopolysaccharide (LPS) leakage, and normalized colonic indoleamine 2,3-dioxygenase 1 (IDO1) expression. Consequently, luteolin reduced peripheral and hippocampal Kyn accumulation, thereby restricting AhR nuclear translocation and preventing the aberrant transcription of AhR-target genes implicated in mitochondrial respiratory chain disruption. Functionally, luteolin restored hippocampal mitochondrial bioenergetics, attenuated pathological reactive oxygen species (ROS) overload, and preserved synaptic long-term potentiation (LTP). The protective efficacy of luteolin against mitochondrial oxidative insult and cognitive decline was phenocopied by AhR inhibition and abrogated by exogenous Kyn supplementation. Collectively, our findings identify the gut Proteobacteria-Kyn-AhR signaling axis as an important contributor to hippocampal mitochondrial oxidative stress in HFD-challenged brains. Luteolin emerges as a promising microbiota-targeted antioxidant intervention that safeguards cognitive function by rectifying this gut-brain redox relay.}, }
@article {pmid42230119, year = {2026}, author = {Alexander, JL and Mullish, BH and Thomas, L and Weersma, RK and Sokol, H and Roberts, LA and Edwards, LA and Emmanuel, A and Gerasimidis, K and Hall, LJ and Iqbal, TH and Kinross, JM and McIlroy, J and Monaghan, TM and Sergaki, C and Shawcross, DL and Stewart, CJ and Lamb, CA and Williams, HRT and Hansen, R and Hold, G}, title = {Recent advances in our understanding of the gut microbiome: an analysis from the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2026-338252}, pmid = {42230119}, issn = {1468-3288}, abstract = {At around 10 years ago, at the time of the first publication by the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology, recognition of the gut microbiome's importance in health and disease was transitioning from fringe interest towards major global pursuit. A decade on, we appraise the considerable progress made in the field, while acknowledging ongoing challenges. Earlier human work characterising the 16S rRNA gene amplicon signature of particular conditions in small cohorts has been superseded by larger, multicentre studies with extensive metadata. Studies increasingly employ shotgun metagenomics and other 'omic' techniques-coupled with refined bioinformatic tools and disease models-to better characterise perturbation in gut microbiome functionality. The arrival of 'gold standard' pipelines for microbiome analysis and increased mechanistic validation of signals are key developments towards more clinically-translatable outcomes. Novel clinical areas where the gut microbiome has relevance have emerged, including early life and the efficacy of certain treatments (including immune checkpoint inhibitors and vaccination). Enthusiasm for 'microbiome diagnostics and treatments' has grown, but barriers to widespread adoption remain. Faecal microbiota transplant (FMT) is established for treating recurrent Clostridioides difficile infection, with donor-derived 'next generation' FMT products licensed for this condition in certain countries. Beyond FMT, other microbial therapeutic techniques-including nutritional, bacteriophage and probiotic therapies-show promise, but have not fulfilled their high expectations yet. Gut microbiome research is now well-established and shows significant translational potential; the future focus will be translational work to drive its utility in clinical diagnostics, prognostics and therapeutics.}, }
@article {pmid42230351, year = {2026}, author = {Domagała, A and Kiecka, A}, title = {Gut Microbiota and Autoimmune Diseases: The Therapeutic Potential of Probiotics.}, journal = {Current microbiology}, volume = {83}, number = {7}, pages = {}, pmid = {42230351}, issn = {1432-0991}, mesh = {Humans ; *Probiotics/therapeutic use/administration &amp; dosage ; *Autoimmune Diseases/therapy/microbiology/immunology ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, increasing attention has been directed toward the role of gut microbiota in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis (RA), and multiple sclerosis (MS). Numerous studies have shown that gut dysbiosis-an imbalance in the intestinal microbial community-can influence host immune responses by modulating inflammatory pathways, gut barrier integrity, and immune cell function. Patients with T1D, RA, and MS often exhibit a decreased abundance of anti-inflammatory bacteria (e.g., Faecalibacterium prausnitzii) and an overrepresentation of pro-inflammatory taxa (e.g., Prevotella copri). Probiotics and fecal microbiota transplantation have shown therapeutic potential by restoring microbial balance, enhancing short-chain fatty acid production, supporting regulatory T cell function, and suppressing pro-inflammatory Th1 and Th17 responses. Despite promising results, the efficacy and safety of these interventions remain uncertain, especially in immunocompromised individuals. The lack of standardization in probiotic formulations, limited large-scale clinical trials, and unknown long-term effects restrict their widespread application. Moreover, individual variability in microbiota composition and disease phenotype complicates the development of universally effective treatments. Further rigorous research is necessary to better understand the immunological mechanisms involved and to develop safe, personalized, and effective microbiota-based therapeutic strategies. Until then, probiotics and FMT should be considered as adjunctive therapies within comprehensive treatment plans for autoimmune diseases rather than standalone solutions.}, }
@article {pmid42230372, year = {2026}, author = {Ram, E and Carter, D}, title = {Reframing loss of efficacy in sacral neuromodulation: a neurofunctional service model for coloproctology.}, journal = {Techniques in coloproctology}, volume = {30}, number = {1}, pages = {}, pmid = {42230372}, issn = {1128-045X}, mesh = {Humans ; *Electric Stimulation Therapy/methods ; *Fecal Incontinence/therapy ; *Low Anterior Resection Syndrome/therapy ; Lumbosacral Plexus ; Sacrum/innervation ; Treatment Failure ; Treatment Outcome ; }, abstract = {BACKGROUND: Sacral neuromodulation (SNM) is an established therapeutic option for fecal incontinence, low anterior resection syndrome (LARS), and selected bowel dysfunction phenotypes encountered in colorectal practice. Despite durable benefit in many patients, secondary loss of efficacy (LOE) remains a common long-term management problem and is often interpreted primarily through a mechanical lens.<br><br>OBJECTIVE: To refine a conceptual neurofunctional service model for LOE in SNM and to translate it into a more clinically applicable framework for coloproctological practice.<br><br>FRAMEWORK: For the purposes of this paper, LOE is defined as deterioration after a previously effective phase, operationalized by one or more of the following: loss of at least 50% of the initial clinically meaningful benefit; deterioration of five or more points on a validated symptom instrument (Wexner Continence Score, LARS Score, or equivalent), or documented worsening in a structured patient symptom diary; or sustained patient-reported decline over at least two consecutive assessments, after exclusion of technical failure. We propose a structured pathway comprising confirmation of LOE, systematic technical exclusion, minimum neurofunctional reassessment, phenotype-guided reprogramming, predefined reassessment intervals, and explicit thresholds for revision or explantation. Terms such as neuroadaptive drift and phenotype mismatch are presented as explanatory hypotheses rather than established mechanisms.<br><br>CLINICAL IMPLICATIONS: Viewing SNM as a dynamic network-modulating therapy rather than a static device intervention may reduce unnecessary procedural escalation and improve the consistency of long-term management. The proposed model is intended as an implementable service framework for structured follow-up and reprogramming in patients with suspected LOE.}, }
@article {pmid42230754, year = {2026}, author = {Bethlehem, L and Bartu, L and Marke, G and Mar, P and Feldman, S and Eggers, J and Ruprecht, C and Britton, GJ and Aggarwala, V and Bongers, G and Li, Z and Yang, N and Hohmann, EL and Mogno, I and Faith, JJ and Grinspan, A}, title = {15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {42230754}, issn = {1546-170X}, abstract = {Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) but has undefined composition and poor scalability. In vitro manufactured live biotherapeutic products (LBPs) enable both scalability and defined strain composition but with higher manufacturing complexity, resulting in few LBP clinical trials. Here we show how an accessible platform to produce human-grade LBPs could accelerate LBP development. We provide regulatory documentation and manufacturing protocols to facilitate translating microbiome advances to human trials. With this platform, we conducted the first direct comparison of the same bacterial strains from donor-sourced FMT compared to an in vitro manufactured 15-strain LBP drug product, MTC01, for the treatment of rCDI. In a phase 1b randomized controlled trial, 18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low-dose FMT (n = 4), high-dose FMT (n = 5), low-dose MTC01 (n = 4) or high-dose MTC01 (n = 5), with a 5:1 female:male ratio. The primary outcome of safety was met with 10 adverse events across eight patients, evenly spread across MTC01 (five events) and FMT (five events) recipients and no treatment-related adverse events across all four groups. For secondary outcomes of efficacy and engraftment, rCDI was prevented 8 weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients. Strain engraftment was high and durable for both FMT and MTC01 with a dose effect for the LBP. ClinicalTrials.gov: NCT05911997 .}, }
@article {pmid42231156, year = {2026}, author = {Yang, Q and Liang, Y and Liu, J and Jia, R and Li, J and Yan, Z}, title = {Fecal microbiota transplantation from Hezuo pigs alleviates intestinal inflammatory injury in Clostridium perfringens type C-infected piglets via modulation gut microbiota and intestinal barrier.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-05169-3}, pmid = {42231156}, issn = {1471-2180}, support = {23JRRA1422//Natural Science Foundation of Gansu Province/ ; 32460845//National Natural Science Foundation of China/ ; GSARS10//Pig Industry in Gansu Agriculture Research System/ ; 2023-QN-135//Lanzhou Youth Science and Technology Talent Innovation Project/ ; }, abstract = {Clostridium perfringens type C (CpC)-induced piglet diarrhea is a major challenge in the swine industry. This study aimed to investigate the protective effects of fecal microbiota transplantation (FMT) from Hezuo pigs against intestinal injury in Duroc×Landrace×Yorkshire (DLY) suckling piglets infected with CpC. Piglets were divided into two groups, including CpC-challenged control group and FMT-treatment group, which received fecal suspension from Hezuo pigs prior to infection. Morphological, immunological, microbiomic, and metabolomic analyses were conducted after post-infection. The results demonstrated that FMT significantly alleviated jejunal damage, leading to a significant increase in jejunal villus height and a significant decrease in crypt depth (P < 0.01). The intervention elevated the number of goblet cells (P < 0.05) and upregulated the expression of tight junction protein genes Occludin, ZO-1, Claudin-1 and the anti-inflammatory cytokine IL-10, while significantly reducing the levels of pro-inflammatory cytokines TNF-α and IL-6 (P < 0.05). FMT enriched beneficial genera such as Akkermansia, Rothia, Peptococcus, and Proteocatella, and increased the levels of the sphingolipid metabolite ceramide (d18:1/18:0). Correlation analysis further indicated that these microbiota alterations were positively associated with intestinal barrier repair and anti-inflammatory activity, and were strongly correlated with ceramide (d18:1/18:0) levels. In conclusion, FMT mitigates CpC-induced intestinal injury by modulating the gut microbiota and metabolome, thereby enhancing intestinal barrier integrity and regulating inflammatory responses. This study provides theoretical support and practical insights for the application of FMT as a promising microbiome-based strategy to control CpC-associated intestinal diseases in piglets.}, }
@article {pmid42232158, year = {2026}, author = {Wang, H and Shao, S and Peng, Y and Xu, W and Zhang, J and Liu, X and Bian, X and Huang, K and Zhang, X}, title = {Pneumococcal Endopeptidase O Attenuates Colitis by Inhibiting the Macrophage-CCL2 Axis and Reshaping Gut Microbiota.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {601434}, pmid = {42232158}, issn = {1178-7031}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent immune activation and gut microbiota dysbiosis, for which current therapies remain limited by incomplete efficacy and substantial adverse effects. This study aimed to investigate the protective effects of pneumococcal endopeptidase O (PepO) on UC and its potential mechanisms of action.<br><br>METHODS: The efficacy of PepO was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis mouse model. Clinical phenotypes were assessed using the disease activity index (DAI), colon length, histopathological analysis, and inflammatory cytokine levels. Macrophage infiltration and key inflammatory mediators were analyzed via immunofluorescence, flow cytometry, ELISA, and qPCR. Mechanisms were further validated by macrophage depletion using clodronate liposomes and recombinant CCL2 supplementation. In addition, gut microbiota composition was analyzed via 16S rRNA sequencing, and causality was confirmed through antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) experiments.<br><br>RESULTS: PepO administration significantly improved disease activity, colon length, and ameliorated histopathological damage in the mice. Mechanistically, PepO directly inhibited macrophage CCL2 production, reducing macrophage infiltration and the release of pro-inflammatory cytokines in colitis. Additionally, PepO remodelled the gut microbiota and markedly increased the abundance of beneficial bacteria, such as Lactobacillus and Akkermansia. Antibiotic-induced microbiota depletion completely abolished PepO's protective effect, while FMT successfully replicated its protective actions, including suppression of CCL2 expression and macrophage infiltration.<br><br>CONCLUSION: This study shows that PepO exerts potent anti-colitic effects through a dual mechanism involving direct inhibition of the macrophage-CCL2 axis and microbiota-dependent enhancement of gut immune homeostasis.}, }
@article {pmid42232317, year = {2026}, author = {Jakobsen, SS and Kousgaard, SJ and Cold, F and Halkjær, SI and Petersen, AM and Kjeldsen, J and Hansen, JM and Thorlacius-Ussing, O}, title = {The effect of fecal microbiota transplantation on quality of life in patients with chronic pouchitis: a post hoc analysis of the MicroPouch trial.}, journal = {Therapeutic advances in gastroenterology}, volume = {19}, number = {}, pages = {17562848261452497}, pmid = {42232317}, issn = {1756-283X}, abstract = {BACKGROUND: During surgical treatment for ulcerative colitis, an ileal pouch-anal anastomosis is often constructed. Pouchitis, the most common complication after this surgery, substantially reduces patients' quality of life (QoL). In chronic pouchitis, antibiotic treatment often proves ineffective. Fecal microbiota transplantation (FMT) has emerged as a potential treatment for chronic pouchitis.<br><br>OBJECTIVES: To determine the effect of FMT on QoL in patients with chronic pouchitis.<br><br>DESIGN: An exploratory post hoc analysis of data from the MicroPouch trial. A double-blinded, placebo-controlled study comprising a 4-week intervention period and 12-month follow-up.<br><br>METHOD: Thirty patients with chronic pouchitis were randomized 1:1 to receive either FMT or placebo. Treatment was administered by enema once daily for 2&#x2009;weeks, then every other day for the following 2&#x2009;weeks. QoL was assessed using three questionnaires-the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Pouch Dysfunction Score (PDS), and the 36-item Short Form Questionnaire (SF-36)-at baseline and at subsequent follow-ups.<br><br>RESULTS: At the 30-day follow-up, FMT-treated patients showed a significant decrease in QoL from baseline, measured by the SIBDQ (p&#x2009;=&#x2009;0.03). Within the FMT group, the PDS did not change significantly from baseline to day 30 (p&#x2009;=&#x2009;0.36). The placebo group reported higher SF-36 QoL scores at both baseline and day 30 (p&#x2009;=&#x2009;0.02), although neither group showed significant within-group changes over time.<br><br>CONCLUSION: In patients with chronic pouchitis, FMT may temporarily worsen symptoms and reduce QoL, as indicated by three QoL questionnaires showing no improvement or poorer outcomes versus placebo. Trial registration: The study is registered at ClinicalTrials.gov (Trial number NCT04100291), date: 12 September 2019.}, }
@article {pmid42233026, year = {2026}, author = {Hu, N and Yang, Y and Chen, R and Guan, J and Gu, H and Zhang, L and Zhang, X and Wang, X and Zhang, L}, title = {Resveratrol ameliorates intrahepatic cholestasis of pregnancy by modulating the gut-liver axis and FXR-mediated bile acid homeostasis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1819374}, pmid = {42233026}, issn = {1664-3224}, mesh = {Animals ; Female ; *Cholestasis, Intrahepatic/drug therapy/metabolism ; *Resveratrol/pharmacology/therapeutic use ; Pregnancy ; *Bile Acids and Salts/metabolism ; Rats ; Homeostasis/drug effects ; Receptor, Farnesoid X-Activated ; *Pregnancy Complications/drug therapy/metabolism ; *Liver/metabolism/drug effects ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Signal Transduction/drug effects ; Rats, Sprague-Dawley ; }, abstract = {OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder with limited treatment options. This study investigated the therapeutic potential of resveratrol (RES) and its underlying mechanisms, focusing on the gut-liver axis and bile acid metabolism in an estrogen-induced ICP rat model.<br><br>METHODS: Pregnant rats were randomized into Sham, ICP (induced by 17&#x3b2;-estradiol), and ICP+RES (15, 30, 60 mg/kg) groups. Systemic and hepatic inflammation, liver function, histopathology, and intestinal barrier integrity were assessed. Hepatic bile acid profiles were analyzed by UHPLC-MS/MS, and gut microbiota was evaluated by 16S rRNA sequencing. The role of gut microbiota was further examined via fecal microbiota transplantation (FMT) in pseudogerm-free rats. Key proteins in the FXR signaling pathway were analyzed by Western blotting.<br><br>RESULTS: RES treatment dose-dependently alleviated ICP manifestations, including reducing serum levels of total bile acids, total bilirubin, and liver enzymes (AST, ALT, ALP), while mitigating systemic and hepatic inflammation. It also restored intestinal barrier integrity and corrected gut microbiota dysbiosis. FMT from RES-treated donors recapitulated these therapeutic effects in recipient ICP rats. Furthermore, RES reversed the hepatic bile acid imbalance by reducing primary bile acids and increasing beneficial secondary bile acids. Mechanistically, RES upregulated the expression of FXR and its downstream targets, including SHP, BSEP, UGT2B4, and CYP1A1.<br><br>CONCLUSION: RES effectively ameliorated ICP through multi-faceted mechanisms involving the attenuation of inflammation, restoration of gut microbiota and intestinal barrier, and correction of bile acid homeostasis via activation of the FXR signaling pathway. Our findings highlight RES as a promising multi-mechanistic therapeutic candidate for ICP.}, }
@article {pmid42233032, year = {2026}, author = {Zheng, H and Lai, C and Liu, F and Luo, H}, title = {Research landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025).}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1817557}, pmid = {42233032}, issn = {1664-3224}, mesh = {*Immune Checkpoint Inhibitors/adverse effects ; Bibliometrics ; *Colitis/chemically induced/immunology ; Humans ; Animals ; Immunotherapy/adverse effects ; Translational Research, Biomedical ; }, abstract = {BACKGROUND: In recent years, immune checkpoint inhibitors have been widely adopted in cancer therapy. However, their use is frequently associated with the development of colitis. This study employs bibliometric methods to analyze the knowledge structure and current research trends in immune checkpoint inhibitors induced colitis.<br><br>METHODS: A systematic literature search was conducted within the Web of Science Core Collection database. Data analysis and visualization were performed using CiteSpace, VOSViewer, and the Bibliometrix package in R software.<br><br>RESULTS: The present study collated 1,010 papers on ICI-induced colitis from Web of Science Core Collection, encompassing literature from 62 countries/regions, 1,873 institutions, 7,385 authors, and 373 journals. The United States demonstrated leadership in two key metrics: publication volume, with a total of 470 publications, and total citations, with a total of 41,125 citations. The University of Texas MD Anderson Cancer Center produced the highest number of publications (n=83). Wang Yinghong (n=48) emerged as the most prolific author. The Journal for Immunotherapy of Cancer was the most widely disseminated publication in this field (n=60). An analysis of keywords identified research trends beyond ICI, colitis, and irAE, including Ipilimumab, immunotherapy, Nivolumab, melanoma, cancer, and Pembrolizumab.<br><br>CONCLUSION: This study performed a visual analysis of the fundamental knowledge structure underlying immune checkpoint inhibitors mediated colitis. The results indicate that future research should prioritize the exploration of combination therapies, clinical case management strategies, underlying pathogenic mechanisms, fecal microbiota transplantation, and the identification of predictive and diagnostic biomarkers for adverse events.}, }
@article {pmid42234773, year = {2026}, author = {Sakamachi, Y and Wiley, E and Trempus, CS and Jacobs, H and Solis, A and Johnson, CG and Meng, X and Hussain, S and Roselli, A and Lipinski, JH and O'Dwyer, DN and Randall, TA and Malphurs, J and Papas, B and Wu, BG and Li, Y and Kugler, MC and Mehta, S and Scappini, E and Thomas, SY and Li, JL and Zhou, L and Karmaus, PW and Lih, FB and Fessler, MB and McGrath, JA and Gibson, K and Kass, DJ and Gleiberman, A and Andrianova, E and Walts, A and Invernizzi, R and Molyneaux, PL and Yang, IV and Zhang, Y and Kaminski, N and Segal, LN and Schwartz, DA and Gudkov, AV and Garantziotis, S}, title = {Toll-like receptor 5 protects against murine lung fibrosis through reduced dysbiosis, and TLR5 deficiency is associated with human IPF.}, journal = {Science translational medicine}, volume = {18}, number = {852}, pages = {eadw1028}, doi = {10.1126/scitranslmed.adw1028}, pmid = {42234773}, issn = {1946-6242}, mesh = {Animals ; *Toll-Like Receptor 5/metabolism/deficiency ; *Dysbiosis/microbiology ; *Idiopathic Pulmonary Fibrosis/metabolism/microbiology/pathology/genetics/complications ; Humans ; Mice, Inbred C57BL ; Bleomycin ; Lung/pathology/microbiology ; Male ; Mice ; Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.}, }
@article {pmid42235389, year = {2026}, author = {Niu, S and Du, Y and Liu, B and Feng, Z and Wang, G and Li, C and Wang, Y and Sun, Q and Yu, F and Zhou, G and Ba, Y}, title = {Fluoride-induced male reproductive toxicity: Dual-tissue pyroptosis in the gut-testis axis mediated by inflammatory cytokines.}, journal = {Journal of hazardous materials}, volume = {514}, number = {}, pages = {142537}, doi = {10.1016/j.jhazmat.2026.142537}, pmid = {42235389}, issn = {1873-3336}, abstract = {Excessive fluoride impairs male reproductive function, and the gut-testis axis is potentially an important pathway. However, the molecular mechanism remains unclear. This study aimed to investigate whether fluoride damaged the male reproductive system through the gut-testis axis and to identify the molecular pathways involved. We first established in vivo rat models that were treated with sodium fluoride (NaF) and underwent fecal microbiota transplantation (FMT), and then constructed in vitro indirect co-culture models. In NaF-treated rats, our results showed disrupted testicular tissue structure, significantly decreased sperm quality and serum testosterone levels, elevated estradiol, and downregulated expression of tight junction proteins (ZO-1 and Occludin). NaF damaged intestinal physical, chemical, and microbial barriers, characterized by decreased ZO-1, Occludin, and MUC2, increased relative abundances of Firmicutes and Proteobacteria, and elevated intestinal permeability. Higher levels of IL-1β and TNF-α were found in colon, testis, and serum of NaF-treated rats. Transcriptomic analysis revealed significant enrichment of the NF-κB signaling pathway in both the colon and testis. Quantitative analysis and immunofluorescence exhibited the alteration of NF-κB-mediated pyroptosis pathway, with upregulation of Cle-Casp-1, NLRP3, ASC, GSDMD, GSDMD-N in both the colon and testis. The elevation of LDH levels was observed in serum and cell supernatant. Critically, FMT alleviated these damages. Concurrently, in vitro experiments confirmed that NaF induced similar inflammatory responses and pyroptosis, and these effects were mitigated by shikonin. In conclusion, fluoride may impair male reproduction by activating the NF-κB-mediated pyroptosis pathway with the gut-testis axis.}, }
@article {pmid42237172, year = {2026}, author = {Moon, JM and Kim, SE and Kim, J and Cho, YS and Kim, H and Gweon, TG and Kim, KO and Kim, KW and Kim, K and Kim, MC and Moon, HW and Park, SK and Bang, CS and Yang, YJ and Kim, Y and Oh, CK and Lee, YJ and Lee, JG and Chang, JY and Chong, YP}, title = {Clinical Approaches to Clostridioides difficile Infection Management: Insights From a Nationwide Survey of Korean Physicians.}, journal = {Journal of Korean medical science}, volume = {41}, number = {21}, pages = {e150}, pmid = {42237172}, issn = {1598-6357}, support = {HI19C0481/MOHW/Ministry of Health and Welfare/Korea ; HC20C0099/MOHW/Ministry of Health and Welfare/Korea ; }, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; Republic of Korea ; *Clostridium Infections/diagnosis/drug therapy/pathology ; Surveys and Questionnaires ; Clostridioides difficile/isolation &amp; purification ; Metronidazole/therapeutic use ; Vancomycin/therapeutic use ; Nucleic Acid Amplification Techniques ; Physicians ; Diarrhea ; Enterotoxins/analysis ; Bacterial Toxins/analysis ; Practice Patterns, Physicians' ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) remains a significant public health challenge, with variable diagnostic and treatment practices. This study evaluated current clinical practices for CDI diagnosis and management in Korean physicians through a nationwide survey.<br><br>METHODS: An online survey was conducted among physicians treating CDI, including gastroenterologists and infectious disease specialists. The survey covered diagnostic approaches, treatment regimens, and management strategies, including differentiation based on disease severity and recurrence.<br><br>RESULTS: A total of 300 physicians responded. The most commonly reported indication for CDI testing was the occurrence of three or more diarrheal episodes within a 24-hour period. The majority of physicians (69.7%) preferred multiple diagnostic tests, favoring simultaneous testing (90.4%) over a stepwise approach. Preferred tests included nucleic acid amplification test (NAAT) (69%), glutamate dehydrogenase+toxin A/B combined assay (56%) and toxin enzyme immunoassay (EIA) (48%). Single-test users preferred toxin EIA (37.4%) and NAAT (29.7%). Treatment was primarily tailored to severity by 84.1% of physicians. For non-severe CDI, oral vancomycin (50.7%) and metronidazole (29%) were the main treatments, with 88% not recommending hospitalization. Severe CDI was treated with oral vancomycin (45.3%) or intravenous metronidazole in combination (44.9%), often for &#x2265; 14 days. For the first recurrence, 69.3% used oral vancomycin, with 22.6% opting for a tapered/pulsed regimen. Fecal microbiota transplantation use increased from 0.3% initially to 17.6% for multiple recurrences. In CDI with ileus, 64% preferred combination therapy, and 48% used vancomycin enemas. In inflammatory bowel disease patients, 99% underwent CDI testing for worsening diarrhea. Immunomodulators and biologics were continued in 79% and 73% of non-severe cases, respectively, but often paused during severe CDI.<br><br>CONCLUSION: Korean physicians generally follow the recently developed Korean guideline for CDI practice, but certain gaps and inconsistencies in choices were observed in clinical situations. Further efforts are needed to monitor guideline implementation and to analyze gaps between guideline recommendations and real-world clinical practice to optimize CDI management in Korea.}, }
@article {pmid42237178, year = {2026}, author = {Zhang, Q and Khan, I and Lei, E and Chen, H and Tang, X and Ding, L and Hong, M}, title = {The gut-brain-gonad axis mediates salinity adaptation in an invasive turtle: causal evidence from microbiota transplantation and metabolite supplementation.}, journal = {Animal microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s42523-026-00583-4}, pmid = {42237178}, issn = {2524-4671}, abstract = {BACKGROUND: Preliminary studies have shown that salinity stress can impair the differentiation of spermatogonial stem cells (SSC) in red-eared slider (Trachemys scripta elegans) through the gut-brain-gonad axis, thereby affecting their reproductive ability. However, a direct causal link between salinity-induced gut microbiota alterations and reproductive suppression remains unclear. To test the hypothesis that gut microbiota and their metabolites mediate salinity adaptation by modulating the gut-brain-gonad axis, we conducted fecal microbiota transplantation (FMT) and metabolite supplementation experiments.<br><br>RESULTS: Results showed that the FMT group successfully recapitulated the donor's gut microbial profile and exhibited significant changes in intestinal metabolites. Both FMT and GABA supplementation mimicked the reproductive inhibitory phenotype observed under direct salinity stress: altered brain neurotransmitter levels (increased dopamine, decreased serotonin), downregulated expression of reproductive genes (e.g. GnRH1, FSH&#x3b2;), and impaired SSC self-renewal and differentiation in testes, as evidenced by reduced marker gene expression (e.g. PLZF, Stra8) and disrupted testicular histology.<br><br>CONCLUSION: Our findings demonstrate that salinity stress reshapes the gut microbiota and metabolome. This leads to increased inhibitory signaling, notably via GABA, along the gut-brain-gonad axis. Ultimately, this signaling cascade suppresses reproductive function. This study provides novel mechanistic insights into the environmental adaptation strategies of an invasive species and highlights the potential of targeting the microbiome-metabolite axis for developing innovative, environmentally friendly biocontrol approaches against this invasive species.}, }
@article {pmid42237397, year = {2026}, author = {Deiana, M and Veschetti, L and Reynolds, K and Hunt, VL and Padovani, N and Manfredi, M and Vezzelli, E and Rizzi, E and Degani, M and Malerba, G and Ursini, T and Ronzoni, N and Piubelli, C and Buonfrate, D and Tiberti, N}, title = {Molecular characterisation of extracellular vesicles released by Strongyloides stercoralis infective larvae isolated from a clinical sample.}, journal = {Parasites &amp; vectors}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13071-026-07484-0}, pmid = {42237397}, issn = {1756-3305}, support = {MR/W006308/1//GW4 BioMed2 MRC DTP studentship/ ; "Fondi Ricerca corrente-L3P2" to IRCCS Sacro Cuore Don Calabria Hospital//Ministero della Salute/ ; }, abstract = {BACKGROUND: Extracellular vesicles (EVs) represent a key mechanism of host-pathogen crosstalk. Numerous helminth parasites have already been reported to shed EV-like structures carrying biomolecules, including small RNAs (sRNAs), with functional effects on target cells. However, the ability of Strongyloides stercoralis to release EVs has yet to be demonstrated.<br><br>METHODS AND RESULTS: Following the isolation of S.&#xa0;stercoralis infective larvae (iL3s) from faecal samples obtained from a patient with strongyloidiasis, we showed that iL3s maintained in vitro for up to 48 h release EV-like structures. Transmission electron microscopy and nanoparticle tracking analysis highlighted vesicular structures enclosed by a bilayer and with a diameter of 120 nm in range. Small RNA sequencing identified multiple EV-associated sRNA types, including miRNAs, only partly overlapping with the previously described somatic miRNome. Comparative analyses revealed that several EV-associated miRNAs were conserved amongst Strongyloides spp., whereas others appeared specific to S.&#xa0;stercoralis. Prediction analyses indicated that miRNAs and other sRNAs may target human genes associated with the regulation of gene expression and immune response, supporting a potential role in host-parasite interaction.<br><br>CONCLUSIONS: These findings provide the first experimental evidence that S.&#xa0;stercoralis iL3s release EVs carrying regulatory sRNAs and suggest that EV-mediated RNA delivery may represent an additional tool for host-pathogen interaction. More in-depth investigations of these EVs may provide novel insights into the pathophysiology of strongyloidiasis as well as novel targets for clinical applications.}, }
@article {pmid42238434, year = {2026}, author = {Basson, AR and Katz, J and Nguyen, V and Singh, D and Menghini, P and Gomez-Nguyen, A and Sieg, J and Bell, M and Thamma, K and Ponzani, G and Osme, A and Rodriguez-Palacios, A and Cominelli, F}, title = {A Randomized Controlled Trial Comparing Soy-Pea Protein to Animal Protein in Adults with Crohn's Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.20.26353678}, pmid = {42238434}, abstract = {BACKGROUND AND AIMS: Diet plays a critical role in managing Crohn's disease (CD) inflammation. We assessed whether dietary replacement of animal protein (AnimalP) by soy-pea protein (SoyP) decreases the pro-inflammatory potential of gut microbiota and intestinal inflammation in CD patients.<br><br>DESIGN: In an open-label, randomized controlled feeding trial at University Hospitals Cleveland Medical Center, CD participants and healthy controls were randomized (1:1) to a soy-pea or animal protein diet for 7-days. Primary outcomes were the absolute difference (&#x394;d7-d0) in; Crohn's Disease Activity Index (CDAI) score and fecal myeloperoxidase (MPO). Secondary outcomes included fecal calprotectin (FC) and high-sensitivity C-reactive protein (hsCRP). Murine fecal transplantation experiments were performed to determine the inflammatory potential of diet-altered gut microbiota.<br><br>RESULTS: The study randomized 66 participants and 60 were included in the final analysis (n=31 CD, n=29 HC). After 7 days, CD-SoyP participants were more likely than CD-AnimalP to show reductions in HBI (RR=4.68, 95% CI: 1.22-17.98, P=0.009) and fecal MPO (RR=2.30, 95% CI: 1.04-4.85, P=0.032), with a similar directional trend for CDAI (RR=1.52, 95% CI: 0.89-2.58, P=0.135). No participants experienced worsening of CDAI. The rank-based composite CDAI-MPO score was lower in the CD-SoyP vs CD-AnimalP group (median [IQR]: 5 [4-6] vs 8 [7-9]; P=0.012). Stratified analyses showed significant reductions in fecal MPO among CD participants with lower baseline disease activity (CDAI <150; P<0.0001), but not in those with higher activity (P=0.799).<br><br>CONCLUSION: Short-term addition of plant-based soy-pea protein within a controlled diet exerted a beneficial, anti-inflammatory effect in CD, with evidence of greater effects among participants with lower baseline disease activity. ClinicalTrials.gov, Number NCT04065048 .}, }
@article {pmid42239536, year = {2026}, author = {Singh, P and Saravanan, A and Seitz, J and Alkarzon, N and Medugu, N}, title = {A one health perspective on the intestinal microbiome's role in COVID-19 outcomes and recovery.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1763844}, pmid = {42239536}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/microbiology/therapy ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; SARS-CoV-2 ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; Pandemics ; }, abstract = {Emerging infectious diseases, particularly zoonotic ones, remain major global health concerns. The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), highlights the interconnectedness of human, animal, and environmental health within the One Health framework. The intestinal microbiome plays a central role in host immunity and systemic homeostasis, and its disruption has been linked to altered disease severity and recovery patterns in COVID-19. Evidence suggests that SARS-CoV-2 infection induces intestinal dysbiosis, modifies immune signaling, and affects the microbiota-gut-brain axis (MGBA), contributing to neuropsychiatric and metabolic complications. This review synthesizes current findings on the intestinal microbiome's role in COVID-19 pathophysiology and recovery, explores emerging therapeutic strategies including probiotics, prebiotics, and fecal microbiota transplantation, and emphasizes the importance of integrating microbiome research into pandemic preparedness through a One Health approach.}, }
@article {pmid42240365, year = {2026}, author = {Chen, B and Su, Z and Sun, Y and Shao, Z and Yu, X and Jiang, X and Xue, X and Yu, L and Wang, L and Zhao, W and Feng, Y and Ning, K and Zhang, M and Cao, A and Zhang, L}, title = {Gut microbial culturomics identifies autism-associated Shigella and reveals species-level remodeling during fecal microbiota transplantation.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0079726}, doi = {10.1128/spectrum.00797-26}, pmid = {42240365}, issn = {2165-0497}, abstract = {Autism spectrum disorder (ASD) has been repeatedly linked to gut microbiota alterations, yet mechanistic insight remains limited by the scarcity of ASD-specific cultured isolates. Here, we performed large-scale gut microbial culturomics on fecal samples from 41 children with ASD and 12 typically developing (TD) controls, generating 1,724 isolates across six phyla. Longitudinal culturomics profiling was further conducted in 17 ASD children undergoing a 9-week fecal microbiota transplantation (FMT) intervention. All isolates underwent 16S rRNA sequencing and non-redundant clustering to assess species-level diversity, ASD-TD differences, and microbial dynamics associated with clinical response. ASD children harbored a distinct culturable microbiota enriched for Shigella flexneri and Shigella boydii, whereas TD children were enriched in beneficial taxa, such as Bifidobacterium catenulatum subsp. and other health-associated species. Notably, 20 species isolated from ASD children and 20 from TD children were absent from major existing gut microbiota biobanks, thereby expanding the cultivable repertoire. Among FMT participants, clinical responders exhibited increased alpha diversity, progressive enrichment of TD-associated beneficial taxa, such as Bacteroides fragilis, Anaerostipes hadrus, Parabacteroides merdae, and Turicibacter sanguinis, and a marked reduction of ASD-associated Shigella flexneri and Shigella boydii, whereas non-responders showed minimal shifts. Acquisition of TD-enriched strains at week 9 was strongly correlated with clinical improvement, suggesting that species-level ecosystem remodeling may contribute to FMT efficacy. This work establishes one of the first ASD-focused gut microbial culturomics resources, identifies Shigella as a potential ASD-associated taxon, and provides foundational evidence and testable mechanistic hypotheses for future microbiome-based interventions in ASD.IMPORTANCEMost autism spectrum disorder (ASD) microbiome studies rely on sequencing, which identifies associations but lacks live strains needed for mechanistic tests. We cultured 1,724 isolates from ASD and typically developing (TD) children, providing an ASD-focused, strain-level resource. ASD samples showed a significantly higher prevalence of Shigella flexneri. Longitudinal profiling during fecal microbiota transplantation (FMT) showed that clinical responders gained TD-enriched taxa and lost Shigella spp., and these shifts correlated with symptom improvement. This resource enables functional assays and gnotobiotic studies with ASD-relevant strains and provides a foundation for rational microbiome-based interventions.}, }
@article {pmid42240746, year = {2026}, author = {Hu, Z and Yan, J and Wang, X and Liu, Z}, title = {Gut-bone axis in rheumatoid arthritis: microbiota-driven barrier dysfunction, immune crosstalk, and therapeutic strategies.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {7}, pages = {}, pmid = {42240746}, issn = {1572-9699}, support = {2023RC105, 2023KY1235//Medical Health Science and Technology Project of Zhejiang Province/ ; 2024USXH287//Shaoxing University enterprise important horizontal topic/ ; }, mesh = {Humans ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; *Gastrointestinal Microbiome ; Intestinal Barrier Function ; Animals ; Dysbiosis/immunology ; *Bone and Bones/immunology/metabolism ; }, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive bone destruction in which immune dysregulation plays a central role. Recent evidence has highlighted the gut-bone axis as a critical framework linking gut microbiota to skeletal and immune homeostasis. Gut microbiota dysbiosis disrupts intestinal barrier integrity by altering tight junction proteins and increasing intestinal permeability, facilitating microbial translocation and triggering systemic inflammatory responses. Microbiota-derived metabolites, including short-chain fatty acids, bile acids, and tryptophan metabolites, act as key mediators along the gut-bone axis. These metabolites regulate multiple signaling pathways and immune cell functions, particularly by modulating the balance between T helper 17 and regulatory T cells, suppressing B-cell hyperactivation, promoting macrophage M2 polarization, and inhibiting dendritic cell maturation. These actions may contribute to immune homeostasis and bone metabolism associated with RA. This review systematically summarizes the role of gut microbiota dysbiosis, intestinal barrier dysfunction, and microbial metabolites in RA pathogenesis within the framework of the gut-bone axis. Furthermore, microbiota-targeted therapeutic strategies, including probiotics, prebiotics, dietary interventions, fecal microbiota transplantation, and traditional Chinese medicine, are discussed as potential approaches to restore host-microbiota balance. However, most current evidence is derived from preclinical studies, highlighting the need for further clinical validation. Despite these limitations, a deeper understanding of microbiota-driven mechanisms along the gut-bone axis may provide novel insights into RA pathogenesis and facilitate the development of targeted and personalized therapeutic strategies.}, }
@article {pmid42241760, year = {2026}, author = {Wang, G and Chen, Y and Xiao, Y and Sun, M and Li, X and Akhtar, M and You, Y and Zhou, X and Shi, D}, title = {Ostrich-derived Bacillus safensis O-6 enhances broiler growth performance by modulating gut microbiota and protein digestibility.}, journal = {Poultry science}, volume = {105}, number = {9}, pages = {107127}, pmid = {42241760}, issn = {1525-3171}, abstract = {In broiler production, the inefficient utilization of dietary protein limits growth performance and wastes resources. Inspired by the high feed conversion efficiency of ostriches, which may host beneficial digestive microbes, this study investigated whether fecal microbiota transplantation (FMT) from ostriches could confer advantageous traits to broilers, and further sought to isolate and evaluate potential probiotic. In an initial FMT trial involving 54 one-day-old broilers, the FMT group exhibited significantly higher average daily gain (ADG) at 7 and 14 days of age compared to the Ctrl group (P < 0.05). From the fecal samples of ostrich donors, a bacterial strain, Bacillus safensis O-6 (O-6), was isolated and identified as a high producer of both protease and cellulase. In a subsequent feeding trial with 72 one-day-old broilers, supplementation with O-6 (4.74 × 10[7] CFU/mL/day in drinking water) increased the ADG by 7.16% by day 35 (P <0.01). The treatment also significantly enhanced the activities of protease, amylase, and lipase in the small intestine (P < 0.05), elevated serum immunoglobulins A and M (IgA and IgM) (P < 0.01), and improved immune organ indices (Spleen index and Bursa of Fabricius index, P < 0.05). Furthermore, O-6 supplementation significantly enhanced the alpha and beta diversity of the cecal microbiota (P < 0.05). This was accompanied by an enrichment of beneficial bacterial taxa, including Rikenellaceae and Alistipes, alongside a substantial reduction in cecal protein content by 28.23%, indicating improved protein digestibility. These results demonstrate that O-6 is a promising probiotic that enhances broiler growth by improving digestive enzyme activity, immune function, and gut microbiota structure. This study demonstrates that beneficial traits of ostriches can be transferred to broiler chickens through their gut microbiota (probiotics), offering a new avenue for the exploration of avian-derived probiotics.}, }
@article {pmid42242207, year = {2026}, author = {Yasuma-Mitobe, K and Liao, C and Németh, T and Byrne, K and Billips, A and Faustino Ramos, RJJ and Salinas, CN and Chan, E and Perissinoto, M and Adami-Sampson, S and Salman, A and Sidebottom, AM and Plitas, G and Butler, G and Cross, JR and Pamer, EG and Gácser, A and Xavier, JB and Hohl, TM}, title = {Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.05.008}, pmid = {42242207}, issn = {1934-6069}, abstract = {In hematopoietic cell transplant (HCT) patients, intestinal Candida parapsilosis expansion and translocation can cause life-threatening candidemia, yet whether commensal intestinal bacteria prevent Candida expansion remains incompletely defined. Here, we trained a machine learning model on supernatant metabolomic profiles of Lachnospiraceae to identify bacteria-derived inhibitors of fungal growth, identifying valeric and butyric acids as top hits. Fecal samples from HCT patients supported this association, with valeric and butyric acid levels inversely correlating with C. parapsilosis growth. In cell culture and mice, valeric acid inhibited C. parapsilosis growth by increasing intracellular acidification. Administration of glycerol valerate, or free or microencapsulated valeric acid, to release valeric acid along the entire intestinal tract blunted C. parapsilosis growth at murine intestinal sites where valeric acid was detected. Thus, machine learning identified a mechanistic driver of trans-kingdom ecology limiting C. parapsilosis intestinal expansion and may inform strategies to reduce patient risk of candidiasis.}, }
@article {pmid42242653, year = {2026}, author = {Wang, Y and Zhang, J and Hou, X and Guan, T and Gong, J and Lin, J and Zhang, H and Xiao, J and Simal-Gandara, J and Wang, H and Cao, H}, title = {Soluble dietary fiber from Piper sarmentosum Roxb. leaves modulates gut microbiota-derived cis-11-eicosenoic acid to regulate lipid metabolism.}, journal = {International journal of biological macromolecules}, volume = {370}, number = {}, pages = {152887}, doi = {10.1016/j.ijbiomac.2026.152887}, pmid = {42242653}, issn = {1879-0003}, abstract = {Obesity represents a critical global health challenge, significantly elevating risks for major chronic diseases. This underscores the urgent necessity to develop innovative prevention and therapeutic interventions. While Piper sarmentosum Roxb. has demonstrated antidiabetic and antihypertensive properties, its anti-obesity effects and underlying mechanisms remain largely uncharacterized. This study aimed to evaluate the anti-obesity effects of soluble dietary fiber from Piper sarmentosum Roxb. leaves (PSDF) and elucidate its molecular basis. PSDF was characterized as an acidic dietary fiber, predominantly composed of galacturonic acid (55.64%), galactose (21.74%), and arabinose (11.97%), exhibiting a triple-helical conformation and high thermal stability. In diet-induced obese mice, six weeks of PSDF administration significantly ameliorated glucose and lipid metabolic disorders (p < 0.05), an effect associated with modulation of gut microbiota. Untargeted metabolomics identified cis-11-eicosenoic acid (GA) as a key metabolite. In a 3T3-L1 single-cell model, GA treatment did not affect adipocyte differentiation. However, in a co-culture model of 3T3-L1 adipocytes and RAW264.7 macrophages, GA significantly downregulated pro-inflammatory cytokines (IL-1β, TNF-α) and SREBF1 expression, while upregulating anti-inflammatory markers (IL-4, IL-10) and fatty acid oxidation genes (CPT1A, PGC-1α). These results initially suggested that GA may exert anti-obesity effects primarily through modulating inflammation-associated lipid metabolism pathways. Fecal microbiota transplantation (FMT) confirmed both GA elevation and anti-adiposity effects were microbiota-dependent. These findings demonstrated PSDF alleviated lipid accumulation by modulating a gut microbiota-adipose axis centered on GA production, thereby improving inflammation-mediated lipid metabolism. This newly elucidated microbiota-GA axis establishes a theoretical basis for developing PSDF-based soluble dietary fibers into microbiota-focused anti-obesity nutraceuticals.}, }
@article {pmid42243132, year = {2026}, author = {Hu, Y and Zhou, M and Xie, T and Wei, M and Wang, K and Wei, H and Zhang, F and Zhang, Z}, title = {Gut microbiota-associated N-Acetyl-L-leucine mediates fructose-induced hyperuricemia via the P300-URAT1 pathway.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00917-1}, pmid = {42243132}, issn = {2396-8370}, support = {32560551//National Natural Science Foundation of China/ ; 20232BCJ23090//Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province/ ; 2025004//Project of Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Science/ ; }, abstract = {Hyperuricemia (HUA), a metabolic disorder characterized by elevated uric acid (UA), is marked by a rising incidence and trend toward earlier onset, both strongly associated with fructose intake. However, the roles of gut microbiota and their metabolites remain unclear. This study employed a fructose-induced HUA mouse model and fecal microbiota transplantation (FMT) to assess the impact of fructose-altered gut microbiota on the microbial community structure and UA degradation capacity in recipient mice. Non-targeted metabolomics was then utilized to identify key metabolites, and the HUA-inducing effects and underlying mechanisms of the metabolite were further validated. The results confirmed that microbiota from fructose-induced HUA mice promoted HUA development in recipients, significantly increasing the abundance of Bacteroidota and reducing microbial UA degradation ability. Specifically, recipient mice exhibited disordered amino acid metabolism, primarily characterized by elevated N-Acetyl-L-leucine. This metabolite was subsequently shown to induce HUA by promoting UA synthesis through enhanced adenosine deaminase and xanthine oxidase activity, as well as inhibiting UA excretion via upregulation of the reabsorption transporter urate transporter 1 (URAT1) through E1A binding protein p300 (P300) regulation. These results highlight N-Acetyl-L-leucine as a pivotal gut microbiota-associated metabolite in fructose-induced HUA and offer new insights and potential targets for future interventions.}, }
@article {pmid42243298, year = {2026}, author = {Kunevičius, A and Gawlińska, K and Burokas, A and Gawliński, D}, title = {Efficacy of pharmacological and microbiota-based therapies in preclinical models of autism spectrum disorder: a systematic review.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {42243298}, issn = {1476-5578}, support = {2021/43/B/NZ5/02552//Narodowe Centrum Nauki (National Science Centre)/ ; 2023/51/D/NZ5/02090//Narodowe Centrum Nauki (National Science Centre)/ ; }, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition in which pharmacological and microbiota-targeted interventions are emerging as promising therapeutic avenues. Animal models are the main tool to investigate etiology, molecular mechanisms and screening for pharmacological therapies. Methodological differences, outcome measure variability, incomplete reporting, biological confounders, and overgeneralization of the results made evaluating innovative pharmacological agents challenging. These limitations in the field highlight a need for systematic and standardized research to reliably assess and translate pharmacological interventions from ASD animal models to human clinical relevance.<br><br>SUBJECTS: This systematic review synthesized efficacy evidence for pharmacological and microbiota-based therapies across established ASD animal models.<br><br>RESULTS: We identified 52 recent (2010-2025) studies that reported key ASD behavioral outcomes after pharmacological or microbiota-focused treatments. Interventions were grouped into therapeutic classes - including oxytocinergic agents, E/I balance therapeutic targets, metabolic drugs, cannabinoids, purine-based interventions and emerging targets - alongside microbiota-directed strategies such as probiotics, prebiotics, and fecal microbiota transplantation. By integrating effect directions and robustness across models, we identified most potential drug candidates, evaluated the efficacy of novel strategies, and recognized critical translational gaps. The reviewed studies demonstrate that ASD-like behavioral deficits in preclinical models can be modulated through interventions targeting diverse biological systems, including neurotransmission, neuroinflammation, metabolism, and the gut-brain axis.<br><br>CONCLUSIONS: These findings support the multifactorial nature of ASD pathophysiology which arises from a network of interacting systemic processes rather than a single molecular defect. It could explain the limited success of traditionally narrowly targeted interventions and suggest a paradigm shift into a more systemic approach.}, }
@article {pmid42243405, year = {2026}, author = {Su, H and Xu, T and Hu, W and Wang, H and Pei, Z and Lu, W}, title = {A multi-strain biofilm consortium enhances gut microbiota resilience and restores post-antibiotic homeostasis.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {42}, number = {6}, pages = {}, pmid = {42243405}, issn = {1573-0972}, support = {32172216//National Natural Science Foundation of China/ ; JUSRP202504013//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Biofilms/growth &amp; development/drug effects ; *Anti-Bacterial Agents/pharmacology/adverse effects ; Homeostasis/drug effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; Bacteria/classification/drug effects/genetics ; RNA, Ribosomal, 16S/genetics ; *Microbial Consortia/drug effects/physiology ; Dysbiosis ; Specific Pathogen-Free Organisms ; Germ-Free Life ; Feces/microbiology ; Probiotics ; Mice, Inbred C57BL ; }, abstract = {Antibiotics can significantly disrupt gut microbiota homeostasis, reducing microbial diversity and causing dysbiosis associated with health issues. Gut biofilms play a critical role in resilience and stress tolerance of the intestinal ecosystem. Mucosal microbial communities also help restore the gut microbiota after interventions like probiotics, antibiotics, or fecal transplants. Previously, we developed a core bacterial consortium with strong in vitro biofilm-forming and stress-resilient properties, but its colonization ability and in vivo function remained unclear. In this study, we first validated the in vivo biofilm formation of the microbial consortium using a germ-free (GF) mouse model, then introduced single-, dual-, and multi-strain combinations with varying biofilm-forming abilities into specific-pathogen-free mice to assess their potential for recovering antibiotic-disrupted gut microbiota. Our findings indicate that the robust, in vitro-selected consortium continued to form substantial biofilms in GF mouse intestines. 16 S rRNA sequencing showed that, compared to single- or dual-strain treatments, administering the core consortium significantly increased microbial richness and diversity. The gut microbiota of consortium-treated mice more closely resembled healthy controls, suggesting the core consortium has superior potential to restore healthy gut microbiota. Overall, our research demonstrates the core consortium markedly improves gut microbiota resilience to antibiotic-induced disruptions in mice, accelerates restoration of health-associated taxa, and reestablishes gut homeostasis. This approach could transform probiotic interventions from passive supplementation to active ecological engineering, providing a theoretical and experimental basis for next generation of engineered probiotics and microbiome restoration therapies.}, }
@article {pmid42243519, year = {2026}, author = {Lima, AP and Novais, JB and Antunes, AEC and Calgaro, M and Merege-Filho, C and Rezende, DN and Romero, MA and Santo André, HC and Baptista, I and de Sá Pinto, AL and de Cleva, R and Santo, MA and Dantas, WS and Gil, S and Rodrigues, MRC and Artioli, GG and Vitulo, N and Roschel, H and Gualano, B and Nicoletti, CF and Benatti, FB}, title = {Exercise reprograms the gut microbiota to enhance metabolic outcomes after bariatric surgery: a translational, cross-species study.}, journal = {International journal of obesity (2005)}, volume = {}, number = {}, pages = {}, pmid = {42243519}, issn = {1476-5497}, abstract = {BACKGROUND/OBJECTIVES: Exercise training has been associated with metabolic improvements in bariatric patients beyond weight and fat loss, potentially involving modulation of the gut microbiota. We investigated whether exercise-related microbial changes are associated with metabolic adaptations in women undergoing Roux-en-Y gastric bypass (RYGB) by combining a randomized controlled exercise intervention trial in women post-surgery with a human-to-mouse fecal microbiota transplantation (FMT) experiment.<br><br>SUBJECTS/METHODS: Thirty-two women were randomized to RYGB (n&#x2009;=&#x2009;16) or RYGB plus a 6-month exercise training program initiated three months post-surgery (RYGB&#x2009;+&#x2009;ET; n&#x2009;=&#x2009;16), while a lean control group (LEAN; n&#x2009;=&#x2009;16) was evaluated at baseline. Blood and fecal samples were collected before surgery, and at 3 (POST3) and 9 (POST9) months following surgery for biochemical, inflammatory, and microbiota analyses.<br><br>RESULTS: Both surgical groups showed comparable improvements in body composition and inflammation; however, RYGB&#x2009;+&#x2009;ET was associated with greater improvements in HDL, triglycerides, fasting glucose, and fasting insulin. Exercise was also associated with increased gut microbiota &#x3b1;-diversity and shifts in microbial composition, including enrichment of genera previously linked to short-chain fatty acid (SCFA) metabolism and host metabolic health. To explore the potential contribution of these microbial communities, fecal microbiota collected at POST9 were transplanted into 36 high-fat diet-fed female mice, generating recipient groups rRYGB, rRYGB+ET, and rLEAN. Mice receiving RYGB&#x2009;+&#x2009;ET microbiota displayed similar inflammatory status and glucose tolerance, but lower fasting insulin and HOMA-IR, along with partial preservation of intestinal morphology, compared with mice receiving RYGB microbiota.<br><br>CONCLUSIONS: These findings suggest that exercise following bariatric surgery is associated with distinct gut microbial configurations and metabolic improvements, and that exercise-conditioned microbiota may contribute to aspects of host metabolic regulation after surgery.}, }
@article {pmid42243653, year = {2026}, author = {Zhang, YL and Gou, HZ and Li, ZJ and Xi, JH and Wang, XJ and Shang, J and Zhu, D and Ren, LF and Shu, XJ and Zhang, L}, title = {Role of the gut microbiota-bile acid axis in liver fibrosis based on microbiomics and targeted metabolomics.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-05224-z}, pmid = {42243653}, issn = {1471-2180}, support = {ldyyyn2023-87//Fund of the First Hospital of Lanzhou University/ ; 2025B-010//Gansu Provincial University Teachers' Innovation Fund Project/ ; 31960236//National Natural Science Foundation of China/ ; EEMRE202403//Open Fund of Gansu Key Laboratory of Microorganisms for Extreme Environments/ ; 23JRRA1498//Joint Scientific Research Foundation of Gansu Province/ ; 2019-RC-34//Lanzhou Talent Innovation and Entrepreneurship Project/ ; }, abstract = {BACKGROUND: Effective diagnoses and treatments for liver fibrosis (LF) are lacking. The gut microbiota (GM)-bile acid (BA) axis is critically associated with LF development and may represent a potential target for delaying or reversing LF.<br><br>METHODS: We combined fecal microbiomics and BA-targeted metabolomics to characterize the GM-BA axis in rats with carbon tetrachloride (CCl&#x2084;)-induced LF and used fecal microbiota transplantation (FMT) and probiotics (Bifidobacterium quadruple viable tablet solution) to regulate the GM-BA axis to investigate the role of the GM-BA axis in LF and its related mechanisms.<br><br>RESULTS: The GM composition and GM &#x3b2;-diversity differed significantly between the control and model rats. Clostridia and others were significantly increased, whereas Bifidobacteriales and others were significantly decreased in model rats. Serum BA metabolism differed significantly between the groups. The concentrations of 19 BAs were significantly increased in model rats. FMT improved the disordered GM by increasing Bifidobacteriales and others and decreasing Clostridia and others. Probiotics improved the disordered GM by decreasing Clostridia, Lachnospiracea_incertae_sedis and others. FMT and probiotics improved BA metabolism by decreasing BAs such as tauroursodeoxycholic acid (TUDCA). FMT and probiotics were associated with a reduced degree of LF in model rats.<br><br>CONCLUSIONS: The GM-BA axis is strongly associated with LF, and the use of FMT and probiotics may contribute to regulating the GM-BA axis and to alleviating LF.}, }
@article {pmid42243780, year = {2026}, author = {Kim, NH and Lee, JH and Oh, J and Lee, S and Jung, ES and Suh, DH and Kang, HJ and Kim, B and Kim, HS and Kim, H and Yun, INR and Kim, EH and Kim, E and Jeong, JY and Ji, Y and Cho, SY and Lee, SW}, title = {Emphysema severity-associated gut microbiota modulates smoke-induced emphysema: evidence from fecal microbiota transplantation.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-026-03743-x}, pmid = {42243780}, issn = {1465-993X}, support = {2021R1A2C3008021//National Research Foundation of Korea/ ; RS-2023-NR077159//National Research Foundation of Korea/ ; RS-2022-NR067421//Bio&amp;Medical Technology Development Program of the NRF/ ; 2024ER080601//National Institute of Health research project/ ; }, abstract = {BACKGROUND: Cigarette smoking is the key risk factor for chronic obstructive pulmonary disease, but even similar levels of smoking can result in different disease severity. We hypothesize that differences in gut microbiota and metabolites contribute to differences in emphysema severity through the gut-lung axis. In this study, we compared the microbiome and metabolome among non-emphysema, non-severe emphysema and severe emphysema groups. Additionally, the impact of fecal microbiota transplantation from non-emphysema, non-severe emphysema and severe emphysema groups on emphysema were investigated.<br><br>METHODS: A total of 78 participants with a smoking history were included in this study and categorized into three groups: non-emphysema, non-severe emphysema, and severe emphysema. Gut microbiota and metabolites were analyzed, and germ-free mice underwent fecal microbiota transplantation with feces from donors representative of each group prior to smoking exposure.<br><br>RESULTS: Significant differences in gut microbiota and metabolites were observed among the groups, with lower acetic acid levels in patients with severe emphysema, and a greater abundance of Prevotellaceae and Megasphaera in patients without emphysema. Fecal microbiota transplantation from donors with severe emphysema worsened lung pathology in mice subjected to smoking exposure, whereas fecal microbiota transplantation from donors without emphysema attenuated emphysema development.<br><br>CONCLUSIONS: Gut microbiota and metabolites in participants with a smoking history differ according to the presence of emphysema and its severity, and can affect emphysema development. This suggests a role for gut microbiota in lung disease and provides a foundation for exploring gut microbiota as a potential therapeutic target for chronic obstructive pulmonary disease.}, }
@article {pmid42243963, year = {2026}, author = {Zong, J and Luo, Y and Wu, M and Wang, N and Sui, Y and Yang, J and Zhang, B and Li, C and Zhou, X}, title = {Gut microbiota-derived Tryptophanol driven by N-Carbamylglutamate alleviates premature ovarian failure through inhibiting oxidative stress.}, journal = {Journal of ovarian research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13048-026-02152-4}, pmid = {42243963}, issn = {1757-2215}, support = {2023YFD1300501//National Key Research and Development Program of China/ ; 32172726,32272872//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Premature ovarian failure (POF) affects 1-5% of women under 40 years old and is characterized by granulosa cells (GCs) apoptosis and follicular atresia. However, the pathogenesis of POF is complex and lacks effective prevention and treatment strategies. N-carbamylglutamate (NCG), a bioactive substance known for its antioxidant properties; however, whether it can alleviate POF remains unclear.<br><br>METHODS: This study using the cyclophosphamide (Cy)-induced POF mouse model, and demonstrated that NCG, has beneficial effects in alleviating POF symptoms and restoring the intestinal mucosal barrier through gut microbiota-metabolite crosstalk. Integrated 16&#xa0;S rRNA sequencing, untargeted metabolomics, and fecal bacteria transplantation (FMT) experiments revealed that NCG induced restructuring of gut microbial communities, with enrichment of Muribaculum intestinale and concomitant elevation of its associated Tryptophan-derived metabolite, Tryptophanol.<br><br>RESULTS: Mechanistically, Tryptophanol, supplementation alleviated POF by reducing mouse GCs apoptosis and oxidative stress via inhibiting Phosphatidylinositol 3-kinase/ Protein Kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways, thereby restoring ovarian function and fertility, and the efficacy of NCG in alleviating POF relies on promoting Tryptophanol-mediated anti-oxidative stress.<br><br>CONCLUSIONS: Our findings, highlight the "gut microbiota-Tryptophanol-ovary" axis in POF pathogenesis, and propose a potential therapy for NCG to regulate gut microbiota to restore ovarian redox homeostasis to alleviate POF.}, }
@article {pmid42244285, year = {2026}, author = {Chen, Q and Liu, J and Jin, Y and Gu, Y}, title = {[Gut microbiota dysbiosis in type 1 diabetes mellitus: Impacts, mechanisms, and interventions].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {51}, number = {3}, pages = {387-396}, pmid = {42244285}, issn = {1672-7347}, support = {2023ZD0507400 and 2023ZD0507403//the Four Major/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology/therapy/immunology ; *Dysbiosis/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Fatty Acids, Volatile/metabolism ; }, abstract = {Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease whose pathogenesis involves interactions between genetic susceptibility and environmental factors. Gut microbiota dysbiosis may participate in the onset and progression of T1DM. Dysbiosis of the gut microbiota in patients with T1DM is characterized not only by reduced microbial diversity but also by systemic functional disturbances, particularly the depletion of protective metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. These alterations may aggravate pancreatic islet autoimmunity through mechanisms including molecular mimicry, disruption of immune homeostasis, and impairment of intestinal barrier function. Intervention strategies targeting the gut microbiota, such as fecal microbiota transplantation, probiotics, and dietary regulation, have shown potential in delaying disease progression and improving glycemic control in animal models and some clinical trials. However, the heterogeneity of therapeutic efficacy still requires further validation. Future studies should integrate multi-omics technologies with personalized medicine approaches to further elucidate microbiota-host interaction mechanisms, thereby promoting early prediction and precision intervention for T1DM. Regulation of the gut microbiota may become a novel therapeutic target for the prevention and treatment of T1DM and provide new strategies for its management.}, }
@article {pmid42245509, year = {2026}, author = {Wang, Z and Li, L and Dong, Y and Zhang, Y}, title = {The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1820111}, pmid = {42245509}, issn = {1664-302X}, abstract = {The pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is very complex. Recent studies have shown that gut microbiota and their metabolites play a key role in the progression of these diseases. Tryptophan (Trp) is an essential amino acid, which mainly produces a variety of biologically active compounds in the intestine through the metabolism of indole pathway, Kynurenine pathway (KP) and serotonin pathway, including indole derivatives, Kynurenine (KYN) and serotonin (5-HT). These metabolites affect the central nervous system (CNS) through the Microbiota-gut-brain axis (MGBA) and affect CNS in a variety of mechanisms, including immune regulation, neuroprotection and maintenance of intestinal barrier function. They are involved in key pathological processes such as neuroinflammation, oxidative stress and pathological protein aggregation. This paper systematically reviews the mechanism of the role of Trp metabolites derived from gut microbiota in NDDs, and explores their specific roles in AD, PD, Amyotrophic Lateral Sclerosis (ALS) and Huntington's disease (HD), and summarizes the potential therapeutic value of the current pathway strategy. These strategies include nutritional intervention, targeted microbiome therapy [such as probiotic and fecal microbiota transplantation (FMT)], and metabolite-derived drugs. Future research must clarify its dynamic mechanism in the human body, develop relevant biomarkers, and promote personalized prevention and treatment strategies through clinical transformation, so as to provide a new direction for early intervention and treatment of NDDs.}, }
@article {pmid42246001, year = {2026}, author = {Chen, S and Liu, J and Ni, H and Zhu, F and Liu, H and Lin, R}, title = {Gut microbiota and the kidney-gut-skin axis in chronic kidney disease-associated pruritus: mechanisms and therapeutic implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1811786}, pmid = {42246001}, issn = {2235-2988}, mesh = {Humans ; *Pruritus/therapy/etiology/microbiology ; *Renal Insufficiency, Chronic/complications/microbiology/therapy ; Animals ; *Gastrointestinal Microbiome/physiology ; *Skin/microbiology/pathology ; *Kidney/microbiology ; Dysbiosis ; Probiotics/therapeutic use ; }, abstract = {Chronic kidney disease-associated pruritus (CKD-aP) is a highly prevalent and debilitating symptom in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), severely impairing quality of life, sleep quality, mental health, and clinical outcomes. Its pathogenesis is multifactorial and remains incompletely understood, involving chronic inflammation, immune imbalance, abnormal neuro-opioid pathways, mineral metabolism disorders and skin barrier damage. The kidney-gut-skin axis has attracted increasing attention as a novel theoretical framework to elucidate the roles of gut microbiota dysbiosis, gut-derived uremic toxins, intestinal barrier impairment and systemic inflammation in the development of CKD-aP. This review summarizes the traditional pathogenic mechanisms of CKD-aP, reviews recent advances linking gut microbial alterations to pruritus-related pathways, and systematically evaluates gut-targeted and metabolism-targeted interventions, including probiotics, prebiotics, synbiotics, AST-120, fecal microbiota transplantation, phytochemicals, Uremia Clearance Granules, and vitamin D-related strategies. Current evidence is mostly associative and is mainly derived from general CKD/ESKD populations, animal models, and in vitro studies; specific clinical validation in CKD-aP cohorts remains limited. Accordingly, gut microbiome-related mechanisms and interventions remain hypothetical and adjunctive, without established causal relationships or validated standard therapies for CKD-aP. Future studies are required to identify CKD-aP-specific pathological alterations, adopt longitudinal design and multi-omics analysis, conduct mechanistic verification, and perform randomized controlled trials with pruritus as a predefined primary endpoint.}, }
@article {pmid42246158, year = {2026}, author = {Xia, R and Ge, J and Shuai, Y}, title = {The Prebiotic 2'-Fucosyllactose Ameliorates Colitis via an Akkermansia muciniphila-Mediated Prebiotic-Microbiota-Metabolite Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {23}, pages = {17898-17912}, doi = {10.1021/acs.jafc.5c15443}, pmid = {42246158}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Trisaccharides/administration &amp; dosage/metabolism ; *Colitis/microbiology/drug therapy/metabolism ; *Prebiotics/analysis/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; Humans ; Male ; *Akkermansia/metabolism ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; }, abstract = {Recent studies indicate that 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, alleviates inflammatory bowel disease (IBD) by modulating the gut microbiota, yet the underlying mechanisms and key functional bacteria involved remain unclear. This study employed fecal microbiota transplantation and an antibiotic-treated mouse model to investigate the role of 2'-FL-mediated gut microbiota in lipopolysaccharide-induced colitis, with a focus on Akkermansia muciniphila (A. muciniphila). Results demonstrated that 2'-FL intervention significantly enriched A. muciniphila in the gut and promoted the production of short-chain fatty acids (SCFAs). Fecal microbiota transplantation experiments confirmed that 2'-FL-modulated microbiota reshaped the gut ecosystem in recipient mice. Notably, monocolonization with A. muciniphila alone alleviated colitis, while coadministration of 2'-FL synergistically enhanced anti-inflammatory effects and SCFAs production. These findings reveal that 2'-FL operates via a "prebiotic-key bacterium-metabolite" axis, wherein A. muciniphila acts as a mediator to metabolize 2'-FL into SCFAs, orchestrating anti-inflammatory and barrier-protective responses.}, }
@article {pmid42246374, year = {2026}, author = {Pauwels, A and Devolder, L and Falony, G and D'haeseleer, M and Nagels, G and Van Remoortel, A and Derrien, M and D'hooghe, M and Raes, J}, title = {Deconfounded, quantitative microbiome profiling identifies robust multiple sclerosis markers and clinical covariate associations.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2681876}, pmid = {42246374}, issn = {1949-0984}, mesh = {Humans ; *Multiple Sclerosis/microbiology ; *Gastrointestinal Microbiome ; *Bacteria/classification/isolation &amp; purification/genetics ; Biomarkers/blood ; Feces/microbiology ; Female ; Adult ; Male ; Middle Aged ; }, abstract = {Despite a wealth of gut microbiota studies in multiple sclerosis (MS), consistent results are lacking. Here, we study confounder effects and use of quantitative microbiome profiling (QMP) in 228 MS patients (103 untreated) and 2860 population controls (Flemish Gut Flora Project (FGFP)). Total bacterial load was lower in relapsing remitting (RR)MS, while strong fecal moisture effects, indicative of longer transit times, in MS vs. FGFP, were driven by primary progressive (PP)MS. Applying cell count and moisture in deconfounded QMP, we identified 21 differentially abundant genera in MS, with a.o. Lachnobacterium, Blautia enriched, and Clostridium, Bacteroides depleted. Deconfounded QMP across 10 published studies (1065 patients, 874 controls) did not confirm commonly detected markers (Akkermansia, Roseburia), yet lowered Bacteroides, and higher Blautia and Methanobrevibacter emerged as robust MS biomarkers. Lowered butyrate producers (Butyricicoccus, Butyricimonas) merit further investigation. Enterotype stratification linked the low cell count Bacteroides 2 enterotype to low-efficacy DMTs, and the Prevotella enterotype to lower disease severity. Serum glial fibrillary acidic protein (GFAP), a disease progression biomarker, was identified as a covariate of gut microbial variation and inversely correlated with Faecalibacterium and Roseburia abundance in PPMS. Overall, our study provides robust disease markers and emphasizes the importance of QMP and confounder control.}, }
@article {pmid42247160, year = {2026}, author = {Palani Kumar, MK and Iyer, KS and Shahi, SK and Raygoza Garay, JA and Mangalam, A and Dayal, S}, title = {Age and sex dependent shift in murine gut microbiome reveals pathological links to host cardiovascular and metabolic pathways.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {42247160}, issn = {2509-2723}, support = {HL168630/HL/NHLBI NIH HHS/United States ; HL007344/HL/NHLBI NIH HHS/United States ; BX007087//U.S. Department of Veterans Affairs/ ; AI162778//National Institute of Allergy and Infectious Diseases/ ; 18IPA4180014//American Heart Association/ ; P30 ES005605/ES/NIEHS NIH HHS/United States ; 1I01CX002212//Iowa City Veterans Affairs Medical Center/ ; }, abstract = {The gut microbiome undergoes dynamic, sex-dependent changes across the lifespan. However, comprehensive studies examining the combined effects of age and sex are limited. This study investigated both compositional and functional alterations in the gut microbiome of young (4 months, n = 14) and aged (20 months, n = 20) C57BL/6 J mice of both sexes using 16S rRNA gene (V3-V5) sequencing. Microbial community structure and predicted functional profiles were analyzed via QIIME2 and PICRUSt2, with pathway annotation based on MetaCyc. Compared to aged mice, young mice exhibited higher alpha diversity, with the highest increase observed in young females. This sex-specific difference was lost in aged mice. Aging was also associated with an increased Firmicutes-to-Bacteroidetes ratio, and distinct shifts in key taxa, including increased Lactobacillus and Roseburia and reduced Bacteroides and Lachnospiraceae. Functional prediction revealed substantial age-related metabolic shifts, especially in females showing alteration in 45 pathways including upregulation of branched-chain amino acid (BCAA) metabolism, uric acid metabolism, and lipopolysaccharide biosynthesis. To directly link alterations in microbial BCAA metabolism with host metabolic outcomes, fecal abundance of the bacterial BCAA aminotransferase gene (ilvE) was quantified and found to be significantly increased in aged mice. Concurrently, aged mice exhibited higher plasma levels of BCAA, insulin, and random glucose, indicating age-associated metabolic dysregulation. Fecal ilvE abundance associated positively with plasma BCAA levels, and negatively with blood glucose in aged mice, suggesting a link between microbial BCAA metabolism and host glucose homeostasis. Our findings demonstrate that gut microbiome composition and function are influenced by both age and sex. We also showed that these alterations in microbial BCAA metabolism are associated with host metabolic parameters during aging. Our findings underscore the importance of incorporating both age and sex as biological variables in microbiome research and may inform development of age- and sex-specific microbiome-targeted interventions.}, }
@article {pmid42247892, year = {2026}, author = {Yang, W and Chen, J and Zhang, Y and Ma, X and Sun, J and Xia, L and Zeng, J}, title = {From air pollution to lung cancer: Microbiota as a mediator in the malignant transformation of pulmonary nodules.}, journal = {Microbiological research}, volume = {311}, number = {}, pages = {128572}, doi = {10.1016/j.micres.2026.128572}, pmid = {42247892}, issn = {1618-0623}, abstract = {Air pollution contributes to the malignant transformation of pulmonary nodules and the development of lung cancer. Emerging evidence suggests that the lung is not a sterile environment, and that air pollution-induced dysbiosis may alter the composition and diversity of the lung microbiota. This review explores the pathway by which exposure to air pollution may contribute to respiratory tract dysbiosis, which in turn may alter the tumor microenvironment, disrupt immune homeostasis, and ultimately be implicated in the progression of pulmonary nodules. A model of "air pollution-microbiota dysbiosis-immune modulation-PN malignancy" is proposed. Regarding alterations in the tumor microenvironment and immune suppression, the roles of various cytokines (IL-1, IL-6, IFN-γ, TGF-β) and signaling pathways (PI3K/AKT, NF-κB, ERK) and the effects of immune suppression on T cells, natural killer cells, and macrophages were found. Additionally, the "oral-lung axis" contributes to the progression of PD-LC, with Porphyromonas gingivalis identified as a key biomarker and pathogenic driver. Additionally, treatment approaches such as immune checkpoint inhibition, antibiotic therapy, fecal microbiota transplantation, and probiotic therapy have all shown encouraging potential. This review highlights the pivotal role of dysbiosis in the air pollution-PN-LC axis, providing insights into novel pathogenic mechanisms and highlighting microbiota-targeted approaches for lung cancer prevention and treatment.}, }
@article {pmid42248097, year = {2026}, author = {Li, S and Li, Z and Chen, C and Liu, M and Cui, Y and Zhu, X and Wang, Z and Sun, H and Li, D and Liu, B and Shi, Y}, title = {Alfalfa polysaccharides-driven Kineothrix alysoides alleviates deoxynivalenol-induced intestinal injury by regulating macrophage polarization.}, journal = {Journal of hazardous materials}, volume = {514}, number = {}, pages = {142588}, doi = {10.1016/j.jhazmat.2026.142588}, pmid = {42248097}, issn = {1873-3336}, abstract = {Deoxynivalenol (DON), as one of the common mycotoxins, is widely present in crops and poses a significant threat to host health. Alfalfa polysaccharides (APs), as novel prebiotics, exert significant immunoregulatory effects and can modulate gut microbiota (GM). However, it remains unclear whether APs can alleviate DON-induced intestinal injury. In this study, we demonstrated that APs attenuated DON-induced intestinal toxicity by reducing inflammatory responses, maintaining intestinal barrier integrity, and promoting M2 macrophage polarization. Fecal microbiota transplantation (FMT) assays showed that transplantation of DON-disrupted GM into healthy recipient mice recapitulated the intestinal pathological injury induced by DON, whereas transplantation of fecal microbiota from the control and APs-treated groups exerted no adverse effects in mice. APs treatment restored the disrupted GM and significantly upregulated the abundance of Kineothrix alysoides (K. alysoides). Gavage administration of K. alysoides effectively alleviated DON-induced intestinal injury and inhibited M1 macrophage polarization. The beneficial effects of K. alysoides were abolished when macrophages were depleted using clodronate liposomes. Collectively, these results indicate that APs can ameliorate DON-induced intestinal injury by regulating K. alysoides and macrophage polarization, providing an important scientific basis for the future application of APs in food and feed products.}, }
@article {pmid42248125, year = {2026}, author = {Niu, M and Li, J and Huang, J and Qiao, T and Zhang, L and Yin, L and Zhang, K and Yin, L and Zhang, Y and Li, Q and Song, X and Zuo, L and Geng, Z and Song, C and Hu, J}, title = {Dipsacoside B alleviates experimental colitis by reshaping gut microbiota and metabolically regulating the balance of macrophage polarization.}, journal = {International immunopharmacology}, volume = {185}, number = {}, pages = {116947}, doi = {10.1016/j.intimp.2026.116947}, pmid = {42248125}, issn = {1878-1705}, abstract = {Gut dysbiosis-driven macrophage polarization plays a critical role in the pathogenesis of ulcerative colitis (UC). Dipsacoside B (DB), a natural saponin, possesses potential anti-inflammatory properties; however, its influence on mucosal immunity and the gut microbiota remains to be elucidated. To evaluate the therapeutic effects of DB, this study employed a DSS-induced colitis model in C57BL/6 mice, testing three different doses. The role of the gut microbiota was investigated through antibiotic-induced depletion and fecal microbiota transplantation (FMT). Both in vivo and in vitro experiments were carried out to assess intestinal barrier function and immune responses, with the latter involving colonic organoid and Caco-2 cells exposed to macrophage-conditioned media. Further mechanistic insights were gained via integrated 16S rRNA sequencing and untargeted metabolomics. In terms of colitis outcomes, DB exerted dose-dependent relief of symptoms and restored intestinal barrier integrity. At the immune level, DB encouraged macrophages within the lamina propria to transition from an M1 to an M2 phenotype. Importantly, the gut microbiota was essential for these effects, when antibiotics were used to deplete the microbiota, the protective effects of DB were abolished, but its protective effects on the mucosa could be transferred via FMT. Omics analyses pointed to increased Akkermansia and activation of the alpha-linolenic acid (ALA) pathway, accompanied by elevated methyl jasmonate (MeJA). In vitro, MeJA was found to regulate macrophage polarization tipping the balance away from M1 and toward M2 and to preserve tight junctions in epithelial cells exposed to inflammatory stress. Collectively, this work reveals that DB ameliorates UC via microbiota-dependent enrichment of MeJA, a microbiota-associated ALA-derived metabolite. Furthermore, this study demonstrates that MeJA exerts immunomodulatory effects by balancing macrophage polarization, thereby providing a novel strategy for targeted therapeutic interventions in UC.}, }
@article {pmid42248955, year = {2026}, author = {Yan, S and Wang, L and Xu, Y and Zhu, W and Li, N and Chen, Q and Li, L}, title = {An Integrated Dataset of Clinical and Microbial Profiles for Fecal Microbiota Transplantation.}, journal = {Scientific data}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41597-026-07502-x}, pmid = {42248955}, issn = {2052-4463}, support = {YJXYS-C-003//the Program for Research-oriented Physician of Shanghai Tenth People's Hospital/ ; 20234Y0079//the Shanghai Municipal Health Commission Research Project/ ; 21Y11908300//the Shanghai Science and Technology Innovation Action Plan/ ; 2022YFC2010201//the China National Key R&amp; Program during the 13th Five-Year Plan Period/ ; 2022YFA1304101//the National Key R&amp; Program of China/ ; }, abstract = {Functional gastrointestinal disorders (FGIDs) are prevalent and burdensome, yet progress in microbiota-targeted therapies such as fecal microbiota transplantation (FMT) has been hampered by the lack of large-scale, integrated datasets. Current studies are mostly limited in sample size and scope, constraining mechanistic insight and precision application. To address this gap, we established FMTdb, a curated dataset focused on FGID patients treated with FMT. This resource integrates demographic, clinical, and multi-omic microbiota data from 15 rigorously screened long-term donors, 370 FGID recipients, and 2,008 healthy community controls. Longitudinal metadata include donor follow-up and pre- and post-treatment observations of recipients across multiple time points. By providing a multi-layered dataset that connects microbial composition with host response, FMTdb offers a robust platform for biomarker discovery, mechanistic exploration, and the development of personalized microbiota-based interventions for FGIDs.}, }
@article {pmid42249360, year = {2026}, author = {Shao, X and Li, R and Lan, Y and Gao, X and Liu, DZ and Li, R and Niu, J}, title = {Early prediction of sepsis in the ICU: a comparative analysis of multiple machine-learning algorithms using the MIMIC-III database.}, journal = {BMC medical informatics and decision making}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12911-026-03610-1}, pmid = {42249360}, issn = {1472-6947}, support = {LHGJ20240911//Exploration of Beneficial Populations and Mechanism Analysis of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy/ ; }, abstract = {Sepsis is a high-burden, highly heterogeneous clinical challenge that affects up to 30% of ICU patients. Reliable early prediction is essential for timely intervention and improved outcomes. We aimed to develop and validate a machine-learning model for predicting sepsis onset beyond the first 24 h of ICU admission. Data from septic patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Feature selection was performed with the Boruta algorithm. Nine algorithms-XGBoost-DART, Gaussian Naïve Bayes, LightGBM-DART, Random Forest, AdaBoost, Multi-Layer Perceptron (MLP), Support Vector Machine (SVM-RBF), k-Nearest Neighbors (KNN), and Ridge Regression-were trained and comprehensively evaluated with respect to discrimination, calibration, and clinical utility. Class imbalance was addressed using SMOTE on the training set and cost-sensitive learning for applicable algorithms. Among 1,634 ICU patients included (after excluding those meeting Sepsis-3 criteria within the first 24 h), 349 (21.4%) developed sepsis after the 24-hour observation window. AUROCs ranged from 0.794 to 0.881 across the nine models. AUROCs ranged from 0.810 to 0.895 across the nine models. XGBoost-DART achieved the highest AUROC (0.881, 95% CI: 0.854-0.908) along with the best accuracy (0.847), F1-score (0.762), and specificity (0.897). Decision-curve analysis demonstrated that XGBoost-DART delivered the greatest net benefit over the widest range of threshold probabilities, underscoring its strong clinical utility. In summary, machine-learning models provide a reliable tool for early sepsis prediction in the ICU. The XGBoost-DART model, with its outstanding performance, empowers clinicians to identify high-risk patients and initiate timely interventions to reduce mortality.}, }
@article {pmid42249511, year = {2026}, author = {Stahl, S and Widmaier, H and Sakk, V and Nalapareddy, K and Kissmann, AK and Rosenau, F and Mulaw, MA and Haslam, DB and Geiger, H}, title = {Aging of the adaptive immune system affects the gut microbiome and systemic levels of vitamin B6.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {}, pmid = {42249511}, issn = {2049-2618}, support = {GRK 2254 HEIST//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Aging/immunology ; Mice ; *Gastrointestinal Microbiome/immunology ; *Adaptive Immunity ; *Vitamin B 6/blood/metabolism ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/microbiology ; Immunity, Mucosal ; Ileum/immunology/microbiology ; }, abstract = {BACKGROUND: Age-associated dysregulation of the gut microbiota is a hallmark of aging and has been linked to multiple age-related diseases, yet upstream host factors driving these changes remain incompletely defined. Extensive bidirectional crosstalk between gut microbiota and mucosal immunity has been described. Aging is accompanied by a progressive decline in immune function, collectively termed aging-associated immune remodeling (AAIR). AAIR encompasses widespread compositional and functional changes that impair an effective response to pathogens, vaccines, and tissue damage. We examined whether AAIR is an upstream host factor influencing the composition of the microbiome upon aging.<br><br>RESULTS: Hallmarks of AAIR were also present in the ileal lamina propria, including reduced na&#xef;ve CD4[+] and CD8[+] T cell populations and expansion of memory and regulatory T cell subsets. To test whether mucosal AAIR reflects intrinsic aging of the hematopoietic system, we used an HSC transplantation model where young RAG1[-/-] recipients develop an adaptive immune system derived exclusively from either young or aged donor HSC in an otherwise young host environment. Recipients of aged HSCs recapitulated key features of mucosal AAIR, particularly loss of na&#xef;ve T cells, demonstrating that AAIR in the ileal LP is driven at least in part by aged HSCs. Shotgun metagenomic sequencing of fecal samples revealed that ileal AAIR is associated with alterations in gut microbiota. In detail, there was a reduced abundance of taxa associated with the vitamin B6 (VB6) biosynthesis and salvage pathways. Accordingly, VB6 levels in serum were reduced in mice with aged immune systems.<br><br>CONCLUSION: Our findings link AAIR to reduced microbial VB6 pathway abundance and lower systemic VB6 availability, suggesting that immune aging shapes the functional output of the microbiome in ways that diminish its VB6 biosynthetic capacity. This postulates an immune-microbiome-VB6 association that warrants further investigations for therapeutic strategies to increase VB6 levels upon aging. Video Abstract.}, }
@article {pmid42250785, year = {2026}, author = {Wang, M and Yao, Y and Li, Z and Wang, S and Yan, K and Romer, A and Li, S and Zhong, J and Su, P and Li, B and Zhu, H and Li, J}, title = {Hypertension-associated gut dysbiosis drives target organ damage through impaired polyunsaturated fatty acids metabolism and immune activation.}, journal = {Pharmacological research}, volume = {230}, number = {}, pages = {108281}, doi = {10.1016/j.phrs.2026.108281}, pmid = {42250785}, issn = {1096-1186}, abstract = {Hypertension (HTN) is a major risk factor for cardiovascular diseases, with chronic low-grade inflammation emerging as a critical contributor to its development and target organ damage. Emerging evidence implies gut microbiota in blood pressure regulation. However, the long-term impact of patient-derived gut dysbiosis on the chronic progression of HTN remains insufficiently characterized. This study aimed to determine how HTN-associated gut microbiota contributes to sustained blood pressure elevation and target organ damage during long-term colonization, and to elucidate underlying immune-metabolic mechanisms using multi-omics analyses. Fecal microbiota from hypertensive patients or normotensive controls were transplanted into germ-free mice, followed by continuous monitoring for 10 weeks to mimic the long-term adaptive remodeling of humanized microbiota within the host. Temporal dynamics of gut microbiota were assessed by 16S rRNA sequencing. Integrated metabolomic and transcriptomic analyses were performed on intestinal, cardiac, fecal, and serum samples. FMT from hypertensive patients induced sustained systolic blood pressure elevation and structural damage in target organs. HTN-FMT mice exhibited reduced microbial diversity and a dysbiotic signature characterized by enrichment of pro-inflammatory taxa and depletion of beneficial commensals. Metabolomic profiling revealed marked disturbances in polyunsaturated fatty acids metabolism. These metabolic alterations were accompanied by enhanced CD4[+] T cell activation, elevated systemic inflammatory cytokines, and concordant enrichment of interleukin-17 signaling pathways in both intestinal and myocardial transcriptomes. These findings reveal interactions among gut dysbiosis, metabolic imbalance, and immune activation during long-term colonization with HTN-associated microbiota, underscoring the central role of the gut-immune axis in the chronic progression of hypertensive target organ injury.}, }
@article {pmid42250826, year = {2026}, author = {Kinoshita, Y and Sato, W and Ueno, T}, title = {Evaluation of autologous fecal microbiota transplantation for restoring equine gut microbiota after antibiotic-induced dysbiosis.}, journal = {Journal of equine veterinary science}, volume = {165}, number = {}, pages = {106049}, doi = {10.1016/j.jevs.2026.106049}, pmid = {42250826}, issn = {0737-0806}, abstract = {Microbial resilience is important to maintain a healthy gut environment in horses, especially after antibiotic administration, but the efficacies of post-antibiotic recovery strategies remain poorly characterized. We used microbial amplicon sequencing to compare spontaneous recovery, autologous fecal microbiota transplantation (FMT), and probiotic administration in 18 horses following antibiotic-induced dysbiosis. Clinically healthy horses received a combination of cephalothin and minocycline for 5 consecutive days before intervention. Fecal microbial recovery was longitudinally evaluated by using community-level dissimilarity metrics. Antibiotic treatment induced marked dysbiosis in all horses. Autologous FMT resulted in significantly faster recovery toward individual pre-treatment baselines compared with spontaneous recovery (significantly lower dissimilarity at day 3 post-treatment, P < 0.05), whereas the effects of probiotics were only evident in cumulative recovery metrics and not at specific time points. These findings indicate that autologous FMT has the potential to accelerate the recovery of the equine gut microbiota following antibiotic-induced dysbiosis.}, }
@article {pmid42251131, year = {2026}, author = {Cai, J and Wang, M and You, Y and Sun, F and Wang, M and Wang, N and Wang, R and Zhang, K and Ge, R and Wang, H}, title = {AS-IV attenuates nigral NLRP3 inflammasome in a Parkinson's disease mouse model via gut microbiota.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-10415-5}, pmid = {42251131}, issn = {2399-3642}, support = {81601108//National Natural Science Foundation of China (National Science Foundation of China)/ ; ZR2021MH135 and ZR2016HQ14//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; }, abstract = {Astragaloside IV (AS-IV) neuroprotection against rotenone (ROT)-induced Parkinson's pathology was examined via microbiota-gut-brain axis mechanisms. Methods included intraperitoneal AS-IV, fecal microbiota transplantation (FMT) from AS-IV-treated mice, and AS-IV-modulated microbiota transplantation. Substantia nigra dopaminergic neurons/microglia were evaluated by confocal imaging, while NLRP3, caspase-1, IL-1β, and α-synuclein (α-syn) levels were quantified via Western blot. Gut microbiota (16S rRNA sequencing) and striatal metabolites (LC-MS/MS) were analyzed. AS-IV attenuated ROT-induced motor deficits, dopaminergic neuron loss, α-syn overexpression, and NLRP3/caspase-1 activation, while elevating fecal SCFAs and increasing Bacteroidetes/Porphyromonadaceae with reduced Firmicutes. FMT from AS-IV-treated to ROT mice improved motor function, suppressed TH[+] neuron loss, and inhibited microglial/NLRP3 activation. AS-IV-modulated microbiota transplantation upregulated Bacteroidetes, Porphyromonadaceae, Barnesiella, and downregulated Firmicutes, Lactobacillaceae, Lactobacillus, and Desulfovibrio. Crucially, FMT from AS-IV-treated to naïve mice alleviated ROT-induced damage, whereas ROT microbiota transplantation induced rotations and decreased Bacteroidetes, Actinobacteria, Porphyromonadaceae, Sutterellaceae, and Parasutterella. AS-IV reversed these microbial changes. Genus-level microbiota alterations correlated with motor severity. ROT microbiota reduced 5-HIAA, indole-3-carboxaldehyde, thyroxine, and glutathione; AS-IV restored indole-3-carboxaldehyde and thyroxine. AS-IV exerts neuroprotection by suppressing NLRP3 inflammasome activation via gut microbiota remodeling and metabolic regulation through the microbiota-gut-brain axis.}, }
@article {pmid42253950, year = {2026}, author = {Han, X and Guo, XL and Qiu, J}, title = {From gut-reproductive microbiota to ferroptosis: a comprehensive insight into the molecular-pathogenicity of endometriosis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1762013}, pmid = {42253950}, issn = {1664-3224}, mesh = {Humans ; *Ferroptosis ; Female ; *Endometriosis/microbiology/metabolism/etiology/immunology ; Iron/metabolism ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; }, abstract = {Endometriosis (EMS) is a highly heterogeneous chronic gynecological disease characterized by pain, infertility, and relapse, with its etiology and pathogenesis not yet fully elucidated. Traditional theories, including "retrograde menstruation," "implantation theory," and "abnormalities in immune tolerance," struggle to adequately explain the complex lesion behavior, diverse phenotypic characteristics, and accompanying immune-metabolic disorders. In recent years, the key roles of imbalances in the gut and reproductive microbiomes, abnormal iron metabolism, and the newly proposed ferroptosis in the occurrence and development of EMS have gradually gained attention, suggesting that this disease may be a systemic condition involving the interplay of microbial ecology, iron metabolism, and cell death. Existing studies indicate that the gut-reproductive microbiome profoundly influences the body's iron homeostasis and iron load by regulating mucosal immunity, systemic inflammatory responses, and metabolic environments. This, in turn, activates the ferroptosis pathway through iron-dependent lipid peroxidation and cell membrane damage, participating in the formation, maintenance, and inflammatory microenvironment shaping of ectopic lesions. Based on these findings, this article systematically reviews the interactions between gut-reproductive microbiome imbalance and iron metabolism disorders, integrating multi-omics evidence such as microbiome analysis, metabolomics, and iron metabolism/ferroptosis-related molecular markers. It proposes a new pathological mechanism framework of "dysbiosis-iron overload-ferroptosis" incorporating microecological imbalance and ferroptosis into a unified picture of the pathogenesis of EMS. Furthermore, this article discusses potential therapeutic strategies and application prospects surrounding microbiome remodeling (such as probiotics, fecal microbiota transplantation, dietary and lifestyle interventions) and pharmacological targeting of key ferroptosis-related molecules. Through a comprehensive and critical analysis of existing evidence, this review aims to provide a more systematic theoretical framework for the mechanistic research of EMS and offer ideas and directions for future clinical translation of precise classification, individualized intervention, and novel treatment plans.}, }
@article {pmid42253976, year = {2026}, author = {Liu, M and Wang, W and Qian, L}, title = {Microbiota-targeted therapeutic strategies for elderly-onset rheumatoid arthritis: based on the gut-joint axis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1850656}, pmid = {42253976}, issn = {1664-3224}, mesh = {Humans ; *Arthritis, Rheumatoid/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; Animals ; Fecal Microbiota Transplantation ; *Joints/immunology/microbiology ; Immunosenescence ; Age of Onset ; }, abstract = {Elderly-onset rheumatoid arthritis (EORA) presents distinct clinical challenges, including more refractory disease activity, higher comorbidity burden, and increased disability and mortality compared to younger-onset RA. Emerging evidence implicates the gut-joint axis-specifically the synergistic interplay between immunosenescence, inflammaging, and gut microbiota dysbiosis-in the pathogenesis of EORA. This review aims to synthesize current evidence on the role of the gut microbiota in EORA, elucidate the mechanistic links between age-related immune changes and microbial dysbiosis, and evaluate the therapeutic potential of microbiota-targeted interventions, including dietary modifications, nutraceuticals, and fecal microbiota transplantation.}, }
@article {pmid42254003, year = {2026}, author = {Sun, S and Lang, H and Cheng, S and Ren, R and Yao, W and Ma, Y and Nashun, D and Wang, Y and Si, Q}, title = {Gut microbiota in Henoch-Schönlein purpura: from pathogenesis to therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1838103}, pmid = {42254003}, issn = {1664-3224}, mesh = {Animals ; Humans ; *Dysbiosis/complications/immunology/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *IgA Vasculitis/immunology/microbiology/therapy ; Intestinal Barrier Function ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Henoch-Schönlein purpura (HSP), also known as immunoglobulin A vasculitis, is a common systemic vasculitis in children. Although its pathogenesis remains unclear, recent studies suggest that the gut microbiota may play a significant role in its initiation and progression. In patients with HSP, gut microbiota dysbiosis and associated metabolic alterations are linked to impaired intestinal barrier integrity, activation of the innate immune system, and dysregulation of adaptive immune cell subsets; this includes imbalances in the T helper 17 (Th17)/regulatory T (Treg) and follicular helper T (Tfh)/follicular regulatory T (Tfr) axes. These changes may ultimately trigger immunoglobulin A immune complex deposition and dysregulation of the complement system, potentially establishing a positive feedback loop that drives immune-mediated inflammatory injury. Modulation of the gut microbiota has been shown to restore intestinal barrier function and immune homeostasis; this indicates its potential as a therapeutic target. This review summarizes recent research on gut microbiota alterations in patients with HSP, and evaluates its role in the pathogenesis of the condition. It also discusses promising therapeutic strategies, including probiotics and prebiotics, traditional Chinese medicine and its active components, fecal microbiota transplantation, and targeted-release formulations. This review aims to identify potential microbial biomarkers and therapeutic targets for improving the clinical management of HSP.}, }
@article {pmid42254009, year = {2026}, author = {Chen, S and Zhang, C and Liu, X and Zhu, Y and Niu, C and Lv, W}, title = {Pasteurized Akkermansia muciniphila alleviates high-fat diet-induced bone loss via Nr4a1-dependent Treg differentiation.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1833607}, pmid = {42254009}, issn = {1664-3224}, mesh = {Animals ; Diet, High-Fat/adverse effects ; Mice ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Cell Differentiation/immunology ; *Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism/genetics ; Male ; *Probiotics/pharmacology/administration &amp; dosage ; Mice, Knockout ; Osteogenesis ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Obesity ; Akkermansia ; *Bone Resorption/etiology ; Osteoclasts ; Disease Models, Animal ; }, abstract = {BACKGROUND: Obesity, a global epidemic, disrupts bone metabolism via gut microbiota dysbiosis, and probiotic/postbiotic supplementation emerges as a promising intervention. Akkermansia muciniphila (Akk), a next-generation probiotic, exerts metabolic benefits in obesity, yet its effects on bone homeostasis-especially in pasteurized form (pAkk)-and underlying mechanisms remain unclear.<br><br>METHODS: High-fat diet (HFD)-induced obese mice were used to establish bone loss models, with fecal microbiota transplantation to verify gut microbiota's role. Mice were gavaged with live Akk, pAkk, or control for 4 weeks. Bone microarchitecture was assessed via micro-computed tomography (&#x3bc;CT), and bone formation/resorption were detected by histomorphometry, ELISA, and TRAP staining. Flow cytometry, immunofluorescence, and qRT-PCR analyzed regulatory T (Treg) cell differentiation. RNA sequencing identified key genes, and Nr4a1 knockout mice validated the mechanism. Cell coculture confirmed pAkk-induced Tregs' inhibitory effect on osteoclastogenesis.<br><br>RESULTS: Obesity-related gut microbiota induced trabecular bone loss, with reduced intestinal Akk abundance. pAkk (but not live Akk) rescued HFD-induced bone loss, increased bone formation marker (P1NP), decreased resorption marker (&#x3b2;-CTX), and inhibited osteoclast differentiation. pAkk promoted CD4[+]CD25[+]Foxp3[+] Treg differentiation in the intestine and spleen via CD103[+] dendritic cells, and these Tregs suppressed osteoclastogenesis. Transcriptomic and functional validation showed Nr4a1 was upregulated by pAkk and essential for Treg differentiation; Nr4a1 knockout abrogated pAkk's bone-protective effects.<br><br>CONCLUSION: Pasteurized Akkermansia muciniphila alleviates HFD-induced bone loss in obese mice by promoting intestinal and systemic Treg differentiation to inhibit osteoclastogenesis, dependent on the nuclear hormone receptor Nr4a1. Our findings identify pAkk as a promising postbiotic for obesity-related bone loss and uncover a novel Nr4a1/Treg axis linking gut microbiota to bone homeostasis.}, }
@article {pmid42254101, year = {2026}, author = {Khan, SA and Qamar, MA and Ali, T and Omer, MH and Tahir, A}, title = {Reconsidering immunotherapy resistance: the emerging role of the tumor microbiome in head and neck and lung cancers.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {6}, pages = {3812-3814}, pmid = {42254101}, issn = {2049-0801}, abstract = {Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized treatment for non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), yet resistance limits durable responses in many patients. Emerging evidence implicates the intratumoral microbiome - comprising bacteria, fungi, and viruses within tumor tissues - as a key modulator of tumor biology, immune infiltration, and ICI sensitivity, beyond traditional tumor-intrinsic and immune factors. In HNSCC, human papillomavirus (HPV)-negative tumors exhibit higher oncobacteria abundance than HPV-positive ones, with elevated levels linked to worse survival in HPV-positive oropharyngeal cases, suggesting an immunosuppressive tumor microenvironment that may influence ICI outcomes. In NSCLC, intratumoral taxa such as Fusobacterium nucleatum and Bacteroides fragilis promote progression and evasion via immune checkpoint modulation (PD-1/PD-L1), pro-inflammatory pathways (toll-like receptors and cytokines like interleukin-6/tumour necrosis factor-alpha), metabolic reprogramming (PI3K/AKT), and recruitment of suppressive cells (neutrophils and myeloid-derived suppressor cells). Pan-cancer studies show microbial enrichments and compositional shifts in responders versus non-responders to ICI, with metabolites (e.g., lactate and succinic acid) driving M2 macrophage polarization, T-cell suppression, and resistance. The gut-tumor axis further exacerbates refractoriness through systemic dysbiosis and immune alterations. Preclinical models indicate that targeted microbiome interventions - such as fecal microbiota transplantation, specific probiotics (e.g., Bifidobacterium spp. and Akkermansia muciniphila), or selective antibiotics - can restore antitumor immunity, enhance ICI efficacy, and minimize broad dysbiosis risks. Integrating intratumoral microbial profiling into HNSCC and NSCLC clinical trials could refine patient stratification, uncover predictive biomarkers, and accelerate microbiome-directed adjunct therapies, advancing precision oncology and expanding immunotherapy benefits.}, }
@article {pmid42254157, year = {2026}, author = {Arif, L and Abbasi, MM and Raza, AA and Samadi, A}, title = {From microbiome profiling to precision medicine: diagnostic and therapeutic potential in gastrointestinal disorders: current evidence, challenges, and future directions.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {6}, pages = {3348-3359}, pmid = {42254157}, issn = {2049-0801}, abstract = {Gastrointestinal (GI) disorders, affecting millions globally (approximately 1.5 billion people with IBS alone), impose a significant healthcare burden and remain challenging to diagnose and manage. Current approaches are often invasive or symptom based, highlighting an urgent need for more precise and personalized strategies. The gut microbiome may offer novel diagnostic biomarkers and therapeutic targets, potentially transforming patient care. It supports GI and systemic health via metabolism, immune modulation, and neurochemical signaling. The dysbiosis of the gut microbiota contributes significantly to the pathogenesis of various GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colorectal cancer (CRC), and small intestinal bacterial overgrowth. This narrative review critically evaluates the diagnostic potential of microbiome profiling and its clinical applications in developing personalized therapeutic strategies. We examine cutting-edge techniques such as 16S rRNA sequencing, metagenomics, and metabolomics, and discuss how dietary modulation, precision probiotics, and fecal microbiota transplantation are being increasingly used to reshape gut microbial composition. However, it is critical to note that while microbiome alterations show consistent associations with GI diseases, current evidence remains largely observational and associative. To date, no microbiome-based test has achieved regulatory approval or clinical validation as a standalone diagnostic tool for IBD, IBS, or CRC, and therapeutic applications remain investigational with modest clinical benefits in select conditions. Additionally, we highlight the translational challenges of integrating microbiome-based diagnostics into mainstream clinical practice and propose future research imperatives. This review provides a balanced perspective on the promise and challenges of integrating microbiome-based approaches into clinical gastroenterology, while proposing actionable research priorities to guide future investigations toward clinically validated, patient-centered diagnostic, and therapeutic solutions.}, }
@article {pmid42254520, year = {2026}, author = {Zhang, L and Lin, S and Zu, B and Chen, Z and Li, S and Lin, W and Dong, T and Chen, Z}, title = {Safety and efficacy of fecal microbial transplantation for the prevention and treatment of acute graft-versus-host disease: a meta-analysis.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1802260}, pmid = {42254520}, issn = {1664-302X}, abstract = {OBJECTIVE: In recent years, fecal microbiota transplantation (FMT) has been increasingly investigated for the prevention and treatment of acute graft-versus-host disease (aGVHD). Nevertheless, its clinical efficacy remains uncertain. Therefore, this study aims to systematically evaluate the clinical efficacy of FMT in preventing and treating aGVHD.<br><br>METHODS: We systematically searched Cochrane Library, PubMed, Embase, and Web of Science from inception to October 2025 for studies comparing FMT with conventional regimens (corticosteroids and/or immunosuppressants) for aGVHD prevention and treatment. All statistical analyses were performed using RevMan 5.4.1 and Stata 16.<br><br>RESULTS: Six studies involving 262 patients were included. Among them, 85 patients received FMT for aGVHD prevention, 65 received conventional prophylaxis, 68 received FMT for Gastrointestinal aGVHD (GI-aGVHD) treatment, and 44 received conventional treatment for GI-aGVHD. Meta-analysis showed no significant difference in the incidence of aGVHD between the FMT and conventional groups [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 0.10-16.72, p = 0.84]. However, the FMT group demonstrated significantly higher 14-day and 30-day complete response (CR) rates, as well as 14-day clinical response rates, in patients with GI-aGVHD compared to the conventional group (OR = 8.54, 95% CI = 2.49-29.29, p = 0.0007; OR = 8.44, 95% CI = 2.98-23.96, p < 0.0001; OR = 4.66, 95% CI = 1.73-12.55, p = 0.002). No significant differences were observed in the incidence of bacteremia or sepsis between the two groups (OR = 0.37, 95% CI = 0.13-1.01, p = 0.05; OR = 0.38, 95% CI = 0.11-1.33, p = 0.13). Additionally, the abundances of Bacteroides and Bifidobacterium were significantly higher in the FMT group than in the conventional group [standardized mean difference (SMD) = 1.59, 95% CI = 0.15-3.03, p = 0.03; SMD = 1.01, 95% CI = 0.41-1.60, p = 0.0009].<br><br>CONCLUSION: FMT showed favorable effects in improving clinical symptoms of GI-aGVHD and increasing the abundance of beneficial gut bacteria, and no increased risk of bloodstream infection was observed. These findings suggest that, for patients with established GI-aGVHD who may respond poorly to conventional regimens, FMT can serve as an effective adjunctive or salvage treatment. However, no significant advantage was observed for FMT in preventing aGVHD.}, }
@article {pmid42256217, year = {2026}, author = {Yao, G and Pan, X and Chen, F and Yang, L and Zhou, L and Peng, M and Yang, X}, title = {Gut Bacteroidales and AMH/INH-B ratio predict sperm retrieval: mechanistic insights via SCFA-mediated regulation of blood-testis barrier and steroidogenesis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1777930}, pmid = {42256217}, issn = {2235-2988}, mesh = {Male ; Animals ; Humans ; Mice ; *Azoospermia/blood ; *Sperm Retrieval ; *Gastrointestinal Microbiome ; *Blood-Testis Barrier/metabolism ; *Inhibins/blood ; Retrospective Studies ; *Anti-Mullerian Hormone/blood ; Biomarkers/blood ; Testis/metabolism ; Disease Models, Animal ; Spermatozoa ; RNA, Ribosomal, 16S/genetics ; Testosterone/blood ; Adult ; }, abstract = {OBJECTIVE: To establish a non-invasive predictive model for microdissection testicular sperm extraction (micro-TESE) outcomes in FSH-normal non-obstructive azoospermia (NOA) patients by integrating gut microbiota profiling with serum biomarkers.<br><br>METHODS: We conducted a retrospective clinical analysis of 58 men and established a busulfan-induced FSH-normal NOA mouse model. Serum hormone levels (FSH, INH-B, AMH, testosterone) were measured by ELISA, and gut microbiota was analyzed via 16S rRNA sequencing. Testicular histology and ultrastructure were assessed by H&amp;E staining and TEM, while protein expression was evaluated by IHC, IF, and Western blot. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the serum AMH/INH-B ratio for sperm retrieval outcomes.<br><br>RESULTS: In both patients and model mice, serum INH-B, AMH, and the AMH/INH-B ratio were significantly decreased (P&#xa0;<&#xa0;0.01), correlating with severe spermatogenic impairment. Mice exhibited a marked reduction in the abundance of Bacteroidales and Muribaculaceae. Fecal microbiota transplantation (FMT) restored these microbial populations, improved testicular function, and upregulated key proteins involved in proliferation (PCNA, PGK2), blood-testis barrier integrity (ZO-1, Claudin11), and steroidogenesis (StAR, CYP17A1) (P&#xa0;<&#xa0;0.05). Mechanistically, FMT increased serum short-chain fatty acid (SCFA) levels, which served as the chemical messengers correlating directly with the recovery of BTB proteins and steroidogenic enzymes. Clinically, the serum AMH/INH-B ratio showed strong predictive efficacy for micro-TESE outcomes, with an area under the ROC curve (AUC) of 0.92 (95% CI: 0.86-0.98), optimal cut-off value of 0.65, sensitivity of 88.2%, and specificity of 85.7%. The gut Bacteroidales abundance (from mouse data) was mechanistically linked to spermatogenic function, suggesting its potential as a future clinical biomarker pending validation.<br><br>CONCLUSIONS: Our findings elucidate an SCFA-mediated gut-testis axis, highlighting the therapeutic potential of microbiota modulation and providing a novel tool to guide clinical decision-making, potentially reducing unnecessary surgeries in FSH-normal NOA.Additionally, the serum AMH/INH-B ratio serves as a robust non-invasive biomarker for predicting micro-TESE outcomes in FSH-normal NOA, while gut Bacteroidales abundance may represent a complementary mechanistic target for future clinical investigation.}, }
@article {pmid42256221, year = {2026}, author = {Giju, JK and John, S and Sivadas, A and Prabhakar, M and K, K and Sunilkumar, D and Nair, BG and Pal, S and Prakash, V}, title = {From dysbiosis to precision medicine: targeting the microbial-metabolic axis in IBD management.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1826972}, pmid = {42256221}, issn = {2235-2988}, mesh = {Animals ; Humans ; *Dysbiosis/complications/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Intestinal Barrier Function ; Precision Medicine/methods ; *Probiotics/therapeutic use ; Diet Therapy ; Fatty Acids, Volatile/biosynthesis ; Plant Preparations/therapeutic use ; Antimicrobial Peptides/physiology ; Immunomodulation ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition that has a rapidly changing global epidemiology. IBD has been traditionally viewed as a primary immune system dysfunction, but emerging evidence more accurately describes IBD as a perturbance of the intricate balance between host immunity, the intestinal microbiome, and intestinal metabolism. Although genetic and environmental components have long been recognized as contributors, accumulating evidence increasingly highlights the pivotal role of microbial dysbiosis in the pathogenesis of IBD. In patients with IBD, intestinal dysbiosis, which is often characterized by reduced Firmicutes and increased pro-inflammatory bacteria, triggers a cascade of pathogenic events. These pathogenic events include impaired epithelial barrier function, dysregulated immune activation against luminal antigens, and immune reprogramming. Central to these processes are functional changes in microbial metabolism, particularly in pathways involving short-chain fatty acids (SCFAs), bile acids, and redox homeostasis, which critically contribute to the development of chronic mucosal inflammation. The current therapeutic backbone of IBD-including aminosalicylates, biologics, and immunomodulators-largely targets the inflammatory response. However, the challenges such as primary non-response, secondary loss of response, and systemic side effects are often problematic. Consequently, there is an urgent need to develop novel therapeutic and preventive strategies that target the underlying microbial and metabolic causes of the disease rather than modulating immune responses. This review integrates the pathomechanistic implications of the microbiome-metabolic axis in the maintenance of gut homeostasis and its disruption in IBD, with particular emphasis on the global epidemiology of the disease. We further evaluate emerging therapeutic and preventive strategies aimed at restoring the microbiome-metabolic axis, including fecal microbiota transplantation (FMT), probiotic therapy, bacteriophage therapy, and helminth-based therapies. In addition, we explore the potential of advanced approaches such as microbiome engineering and precision genome editing to enable highly personalized therapeutic paradigms. By bridging microbial ecology with clinical pathology, this review highlights the transformative potential of targeting the host-microbiota interface to achieve improved long-term outcomes in IBD.}, }
@article {pmid42257798, year = {2026}, author = {Zhou, AN and Liu, L and Huang, MM and Yang, S and Fei, H}, title = {The microbiota-gut-immunity axis in teleost fish: dual regulatory mechanisms of viral infections and prospects for microbiome-based antiviral strategies.}, journal = {Fish physiology and biochemistry}, volume = {52}, number = {3}, pages = {}, pmid = {42257798}, issn = {1573-5168}, mesh = {Animals ; *Fishes/immunology/microbiology/virology ; *Fish Diseases/immunology/microbiology/virology/therapy ; *Virus Diseases/veterinary/immunology/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/immunology ; Prebiotics ; Probiotics ; }, abstract = {Bacteria and viruses engage in complex synergistic and antagonistic interactions with profound implications for host health, particularly through functional modulation by intestinal and other mucosal (e.g., skin, gill) microbiota. In teleost models, intestinal microbiota demonstrates dual regulatory capacities-either potentiating or suppressing viral infections. However, the mechanistic underpinnings of these interactions remain inadequately explored in aquatic species. This review systematically delineates the dual regulatory pathways (facilitative vs. inhibitory) through which the gut microbiota modulates viral infections in fish. Based on these mechanisms, we propose a novel microbiota-gut-immunity axis framework-defined as the bidirectional communication network linking gut microbial communities, intestinal barrier function, and host systemic immunity-for the development of integrated antiviral interventions. Furthermore, we critically evaluate emerging strategies-including probiotics, prebiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), microalgae, seaweed, and phytoactive compounds-to develop preventive and therapeutic countermeasures. Based on mechanistic insights, probiotics and prebiotics emerge as the most promising candidates for large-scale application, as they directly reshape gut microbial composition and enhance host immunity along the microbiota-gut-immunity axis. In contrast, FMT and herbal medicines, while acting on multiple nodes of the axis, currently face safety and standardization challenges, positioning them as adjunctive therapies. Importantly, these mechanistic insights reveal evolutionarily conserved immune pathways with significant translational potential for human virology.}, }
@article {pmid42258310, year = {2026}, author = {Mehboob, AA and Fatima, R and Kanwal, S and Ali, M and Karim, M and Fatima, S}, title = {Exploring the gut-lung axis in post-liver transplant acute lung injury: A multi-omics approach.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2026.02911}, pmid = {42258310}, issn = {1588-2640}, abstract = {Acute lung injury (ALI) is a significant post-operative complication of liver transplant (LT), with mounting evidence suggesting a role for the gut-lung axis. However, the mechanistic link between gut microbiota dysbiosis and ALI pathogenesis in LT recipients remains poorly understood. This hybrid translational investigation integrates transcriptomic profiling (bulk and single-cell RNA-seq), immune infiltration analysis, fecal microbiota composition (16S rRNA), and predictive functional profiling in ALI vs. non-ALI (NALI) LT patients. Machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to identify key gene biomarkers. Microbiota-host gene correlations and canonical correspondence analysis (CCA) were performed to evaluate multi-omic relationships. ALI patients exhibited reduced gut microbial diversity and increased abundance of Enterococcus and Escherichia-Shigella, alongside a depletion of beneficial taxa (Faecalibacterium, Bacteroides). CXCL3, CD48, and IRAK3 were identified as robust ALI biomarkers (Area Under the Curve >0.83), validated in both serum and Bronchoalveolar Lavage Fluid. These genes correlated positively with pro-inflammatory microbes and immune cell infiltration. Functional prediction revealed enrichment in lipopolysaccharide biosynthesis, Toll-like receptor signaling, and bacterial chemotaxis. CCA confirmed that microbiota variation significantly explained host transcriptomic variance. Our study uncovers a functional gut-lung immunological axis in post-LT ALI. Gut dysbiosis modulates immune gene expression and lung inflammation, suggesting that the microbiome serves as a potential source of diagnostic biomarkers and therapeutic targets in transplant-associated lung injury.}, }
@article {pmid42259000, year = {2026}, author = {Wen, S and Shi, M and He, S and Zhu, Y}, title = {Gut microbiota in blood pressure control: Friend or foe?.}, journal = {Microbiological research}, volume = {311}, number = {}, pages = {128571}, doi = {10.1016/j.micres.2026.128571}, pmid = {42259000}, issn = {1618-0623}, abstract = {Hypertension is a major global public health issue characterized by complex pathogenesis and a high risk of multiple comorbidities. Gut microbes play a crucial role in blood pressure regulation. This review aims to clarify the roles of distinct gut microbiota compositions in regulating blood pressure and to analyze their potential mechanisms of action in hypertension. Gut microbes produce metabolites that regulate the host immune system, metabolic homeostasis, and other physiological processes, including blood pressure. Key microbial metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), have been shown to regulate blood pressure through complex mechanisms. Hypertension disrupts intestinal barrier integrity, allowing inflammatory factors and noxious substances to enter the circulation, creating a vicious cycle between hypertension and gut dysregulation and possibly even inducing other diseases. Current strategies targeting gut microbiota for blood pressure control include fecal microbiota transplantation (FMT) and probiotic supplementation, but further clinical validation of their efficacy and safety is required. In conclusion, the relationship between gut microorganisms and hypertension is intricate and context-dependent, rather than being simply classified as entirely beneficial or detrimental. Future studies should further elucidate the mechanisms of various gut microorganisms regulating blood pressure and explore safer and more effective therapeutic strategies.}, }
@article {pmid42259432, year = {2026}, author = {Hao, L and Li, ZF and Qu, YN and Zhao, FY and Lu, SY and Li, BQ and Zhang, HY and Wang, HQ}, title = {IUPHAR review. Gut microbial metabolites as remote regulators of behavior and neuropsychiatric disease.}, journal = {Pharmacological research}, volume = {230}, number = {}, pages = {108284}, doi = {10.1016/j.phrs.2026.108284}, pmid = {42259432}, issn = {1096-1186}, abstract = {The gut-brain axis has emerged as a fundamental pathway through which gut-derived microbial metabolites exert remote control over brain development, neural circuit function and behavior. This Review synthesizes evidence that key microbial metabolites including short-chain fatty acids, tryptophan derivatives, bile acids and trimethylamine N-oxide modulate neuroimmune, neuroendocrine and synaptic signaling in a context-dependent manner, influencing whether the brain maintains homeostasis or progresses toward pathology. We critically evaluate how these metabolites contribute to the etiology and symptomatology of neurodevelopmental and psychiatric disorders such as autism spectrum disorder, major depressive disorder, anxiety and post-traumatic stress disorder. Causal insights are highlighted by studies demonstrating that fecal microbiota transplantation from affected individuals to rodents transfers core behavioral phenotypes. It is important to note, however, that while FMT and gnotobiotic studies establish causality in animal models, evidence from human studies remains predominantly correlative, and we have explicitly distinguished these evidence tiers throughout. We also explore the translational potential of microbiome-derived biomarkers for diagnosis and the challenges in developing targeted therapeutics, including probiotics, postbiotics and metabolite-sequestering agents. Moving forward, the field should prioritize decoding the contextual determinants of microbial influence and adopt personalized, function-based strategies to effectively modulate the gut-brain metabolic axis for brain health.}, }
@article {pmid42259828, year = {2026}, author = {Yang, X and Li, X and Xu, D and Feng, Y and Guo, Y and Hu, Y}, title = {Faecalibacterium-derived spermidine mediates the amelioration of fatty liver hemorrhagic syndrome by inulin in laying hens.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01037-0}, pmid = {42259828}, issn = {2055-5008}, support = {32402778//National Natural Science Foundation of China/ ; 32372824//National Natural Science Foundation of China/ ; 2022YFA1304201//National Key Research and Development Program of China/ ; 2023TZXD037//Shandong Provincial Key Research and Development Program of China/ ; }, abstract = {Fatty liver hemorrhagic syndrome (FLHS) is a critical disease threatening the laying hen industry. Inulin, a widely used prebiotic, has shown promise in alleviating metabolic disorders, but its role in mitigating FLHS in laying hens is not fully understood. Here, we investigated the effects and underlying mechanisms of inulin-mediated alleviation of FLHS in a high-carbohydrate low-protein diet (HCD)-induced laying hen model. We found that inulin supplementation significantly ameliorated HCD-induced hyperlipidemia, hyperglycemia, hepatic steatosis, liver injury, and oxidative stress. These phenotypic improvements were accompanied by enhanced fatty acid oxidation and suppressed lipid synthesis and inflammation. Microbiota analysis revealed that inulin reshaped the HCD-perturbed cecal microbiota, with Faecalibacterium identified as the only dominant genus substantially depleted by HCD and restored by inulin. Targeted metabolomics showed that inulin elevated cecal spermidine levels, which strongly correlated with Faecalibacterium abundance and improved metabolic traits. Fecal microbiota transplantation (FMT) from inulin-treated donors replicated the protective effects, confirming the causal role of gut microbiota in mediating inulin's anti-FLHS activity. Further mechanistic investigation using the representative species Faecalibacterium prausnitzii demonstrated that inulin enhanced spermidine production through transcriptional activation of the spermidine biosynthetic pathway. Spermidine, in turn, upregulated hepatic ALDH1A2 expression, enhancing retinoic acid synthesis and activating the AMPK-SIRT1 axis, thereby reducing lipid accumulation in hepatocytes. Collectively, these findings establish a novel Faecalibacterium-spermidine-ALDH1A2-retinoic acid-AMPK-SIRT1 axis through which inulin alleviates FLHS, highlighting inulin as a dietary intervention targeting the gut-liver axis and offering novel therapeutic avenues for preventing this disorder in laying hens.}, }
@article {pmid42260597, year = {2026}, author = {Rynikova, M and Gancarcikova, S and Lauko, S and Mudronova, D and Adamkova, P and Janicko, M and Demeckova, V}, title = {Exploring new animal models of ulcerative colitis: evaluating chemical and patient-derived microbial triggers to advance translational relevance.}, journal = {Laboratory animal research}, volume = {42}, number = {1}, pages = {}, pmid = {42260597}, issn = {1738-6055}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with multifactorial aetiology involving genetic, immune, environmental, and microbial factors. Alterations in the gut microbiome are a consistent feature of UC, yet their causal contribution to disease onset and progression remains unresolved. Current animal models rely largely on chemical or genetic induction and fail to capture the complexity of host-microbiome interactions characteristic of human disease. To address this limitation and enhance the translational relevance of preclinical research, this study employed patient-derived microbiota to model UC-associated dysbiosis and investigated its effects alone and in combination with chemical induction.<br><br>RESULTS: We compared three mouse models using different UC-induction triggers: dextran sulphate sodium (DSS), faecal microbiota transplantation (FMT) from a UC patient, and their combination (COMB). DSS and COMB treatments induced marked clinical symptoms, whereas FMT alone caused only mild changes, likely due to the short exposure period. Immunophenotyping revealed distinct immune profiles across all models, with leukocyte and neutrophil infiltration in the colonic mucosa of all groups, demonstrating that the microbiota alone can elicit localized immune activation. Transcriptomic analysis showed that FMT significantly modulated tight junction and mucin gene expression and induced microbiome shifts resembling those observed in human UC. In contrast, DSS triggered a strong pro-inflammatory transcriptional response and reduced microbial diversity, but with compositional changes mostly opposing those seen in UC patients. The COMB model combined features of both approaches - producing clinical symptoms and inflammatory activation similar to DSS and tight junction dysregulation resembling FMT.<br><br>CONCLUSIONS: This study investigated novel experimental models of ulcerative colitis by incorporating patient-derived microbiota as an inducing factor. DSS induced strong clinical and inflammatory responses, FMT primarily altered barrier gene expression and microbiome composition, and their combination merged both inflammatory and epithelial characteristics. These microbiota-based models show promise for more accurately reproducing UC pathophysiology and thereby improving translational relevance. Further optimization is needed, including adjustment of exposure duration and sequence of induction, as well as validation for reproducibility.}, }
@article {pmid42260668, year = {2026}, author = {Wang, Y and Ren, C and Dong, W and Li, Q and Deng, F and Zhao, F and Cheng, Y and Sun, P and Li, H and Wang, Y}, title = {Polygala oligosaccharide esters improve memory disorder by restoring gut microbiota homeostasis through the regulation of the "gut-brain" axis.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {}, pmid = {42260668}, issn = {1749-8546}, support = {[2024SJ327]//the Graduate Practice and Innovation Project of Shanxi Provincial Education Department, China/ ; [X2024SJ017]//the Graduate Innovation and Practice Project of Shanxi University of Chinese Medicine, China/ ; [2023ZYYB2017]//The Shanxi Administration of Traditional Chinese Medicine,China/ ; [2023PY-TH-03]//the Taihang Materia Medica Research and Development Guidance Special Project, China/ ; [2025XK36]//The Traditional Chinese Medicine Pharmacology and Toxicology Discipline Construction Project of Shanxi University of Chinese Medicine,China/ ; [2021-143]//Shanxi Scholarship Council of China/ ; }, abstract = {BACKGROUND: Yuanzhi (Polygala tenuifolia Willd.) possesses the effects of calming the spirit, enhancing intelligence, regulating the heart-kidney connection, eliminating phlegm, and reducing swelling. It is commonly used in the treatment of insomnia and forgetfulness. Previous studies have indicated that the oligosaccharide esters (OE) derived from Yuanzhi exhibit neuroprotective and memory-enhancing activities. However, its underlying mechanisms, particularly those involving the gut-brain axis, remain unclear.<br><br>PURPOSE OF THE RESEARCH: This study aimed to investigate the therapeutic efficacy and underlying mechanisms of Oligosaccharide Esters (OE) from Polygala tenuifolia Willd. against memory dysfunction in mice, with a specific focus on the gut-brain axis.<br><br>METHODS: A mouse model of memory dysfunction was induced using D-galactose combined with AlCl&#x2083;. Behavioral tests, molecular biology techniques (histopathology, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot), and multi-omics approaches (16S rRNA sequencing and lipidomic analysis) were employed to investigate the therapeutic efficacy of OE against memory dysfunction. Meanwhile, with the aid of fecal microbiota transplantation (FMT) assay, we observed the repair of brain and colonic tissues, inflammatory responses and intestinal permeability, further clarified the regulatory effect of OE on gut microbiota, and ultimately revealed the underlying mechanisms of OE mediated by the gut-brain axis.<br><br>RESULTS: OE administration significantly enhanced learning and memory in MD mice, repaired neuronal damage in the hippocampal regions (CA1, CA3, DG) of the MD mouse brain, and increased the number of Nissl bodies. OE elevated the serum levels of BDNF and CREB and reduced the TMAO level; simultaneously, it enhanced the activities of SOD and GSH-Px and decreased the MDA content in the brain tissue. OE treatment modulated the relative abundance of the gut microbiota in MD mice, restored the microbial imbalance induced by memory deficits, and particularly affected the abundances of Firmicutes, Bacteroidetes, their ratio (F/B), and genera such as Ligilactobacillus. Lipidomics analysis indicated that OE exerts its therapeutic effects primarily by regulating the glycerophospholipid metabolism pathway, and a total of 17 key differential lipid metabolites were identified. Correlation analysis further revealed that the levels of key differential lipid metabolites, LysoPC(22:2) and PC(38:4), were significantly positively correlated with the levels of neuroprotective factors (CREB, BDNF) and the activities of antioxidant enzymes (SOD, GSH-Px), but were significantly negatively correlated with the harmful metabolite TMAO and the oxidative damage product MDA. In contrast, the lipid metabolite GPEA exhibited a trend opposite to that of LysoPC(22:2) and PC(38:4). Further investigation results demonstrated that OE could repair pathological damage in colon tissue, regulate the levels of the microbial metabolite TMAO and the neurotransmitter 5-HT, reduce the levels of pro-inflammatory factors (LPS, TNF-&#x3b1;, IL-6) in both the brain and colon, and inhibit the abnormal activation of astrocytes and the abnormal hyperphosphorylation of Tau protein. The results of correlation analysis indicated that beneficial bacteria [e.g., Ligilactobacillus) and beneficial lipids (e.g., LysoPC(22:2) and PC(38:4)] were collectively significantly negatively correlated with key pathological indicators (e.g., TMAO and TNF-&#x3b1;) and were positively correlated with the neurotransmitter (e.g., 5-HT). OE also significantly up-regulated the expression of tight junction proteins (Occludin, Claudin-5) in both brain and colon tissues, thereby structurally repairing the damaged gut-brain barrier. FMT experiments showed that FMT improved the learning and memory abilities of mice, repaired neuronal damage in the hippocampus (CA1, CA3, DG), and increased the number of Nissl bodies. In addition, FMT alleviated colonic tissue injury, attenuated inflammatory responses in the brain and colon, and reduced intestinal permeability in MD mice, exerting a therapeutic effect similar to that of OE.<br><br>CONCLUSION: OE exerted anti-amnestic effects via the gut-brain axis, primarily by alleviating neuroinflammation and oxidative stress, restoring gut microbiota homeostasis, and regulating glycerophospholipid metabolism, ultimately improving learning and memory abilities in MD mice.}, }
@article {pmid42261357, year = {2026}, author = {Zhu, Q and Liu, Y and Hu, W and Liu, Y and Fu, S and Xie, W and Liu, J and Xiong, Y and Sun, T and Gong, B}, title = {Lactobacillus johnsonii-Derived Extracellular Vesicles Ameliorate Alcohol-Exacerbated Experimental Autoimmune Prostatitis by Inhibiting M1 Macrophage Polarization.}, journal = {International journal of nanomedicine}, volume = {21}, number = {}, pages = {596237}, pmid = {42261357}, issn = {1178-2013}, mesh = {Animals ; Male ; *Prostatitis/therapy/chemically induced/microbiology/immunology ; Mice ; *Macrophages/drug effects/immunology ; *Extracellular Vesicles ; *Autoimmune Diseases/therapy/chemically induced ; RAW 264.7 Cells ; Cytokines/metabolism ; Disease Models, Animal ; Ethanol/adverse effects ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Lacticaseibacillus ; }, abstract = {PURPOSE: This study investigated how alcohol exacerbated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and assessed gut microbiota-targeted therapeutic strategies.<br><br>METHODS: An alcohol&#x2011;treated experimental autoimmune prostatitis (EAP) mouse model was established to evaluate the exacerbating effect of alcohol on CP/CPPS. The involvement of gut microbiota was assessed by antibiotic depletion and fecal microbiota transplantation (FMT). 16S rRNA sequencing was applied to profile microbial alterations, particularly the abundance of Lactobacillus johnsonii (L. john). Oral administration of live L. john or intravenous injection of Lactobacillus johnsonii-derived extracellular vesicles (LjEVs) was tested as therapeutic interventions. Mechanistic studies were conducted in lipopolysaccharide (LPS)&#x2011;stimulated RAW 264.7 macrophages using transcriptomics, qRT-PCR, Western blot, and flow cytometry.<br><br>RESULTS: Alcohol consumption aggravated pelvic tactile hypersensitivity and prostatic inflammation, increased pro-inflammatory cytokines (IL-1&#x3b2;, IL-6, TNF-&#x3b1;), and promoted M1 macrophage polarization in EAP mice. Fecal microbiota transplantation from alcohol-fed EAP mice reproduced the aggravated phenotype, confirming that gut microbiota mediates this effect. Alcohol specifically reduced the relative abundance of L. john. Oral L. john or intravenous LjEVs alleviated tactile hypersensitivity and inflammation, and inhibited M1 macrophage polarization in alcohol-fed EAP mice. In vitro, LjEVs were internalized by macrophages, suppressed LPS-induced M1 macrophage polarization and pro-inflammatory gene expression, and inhibited TNF-&#x3b1;/NF-&#x3ba;B signaling. Exogenous TNF-&#x3b1; reversed the inhibitory effects of LjEVs on M1 macrophage polarization.<br><br>CONCLUSION: Alcohol exacerbated EAP by reducing L. john, which in turn promoted prostatic M1 macrophage polarization via the TNF-&#x3b1;/NF-&#x3ba;B pathway. Supplementation with L. john or LjEVs ameliorated the disease by suppressing this pathway, offering a microbiota-targeted therapy for alcohol-aggravated CP/CPPS.}, }
@article {pmid42262096, year = {2026}, author = {Li, G and Li, L and Shen, P and Wang, J and Feng, Y and Yu, Y and Xu, H and Wang, H and Li, J and Zheng, X and Mao, Y}, title = {Harmane induces apoptosis through RRM2B and suppresses colorectal cancer progression.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0170425}, doi = {10.1128/msystems.01704-25}, pmid = {42262096}, issn = {2379-5077}, abstract = {Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and chemotherapy resistance often leads to poor patient prognosis. Harmane, a natural indole alkaloid, is found in Leguminosae plants (particularly those of the Crotalaria genus), as well as in mammalian tissues and certain food products. It exhibits potential anticancer activities through multiple mechanisms in various cancers, including liver, breast, and thyroid cancers. However, the role of harmane in the treatment of CRC remains unclear. In this study, we demonstrate that harmane induces cell cycle arrest and apoptosis in CRC cells via the p53-RRM2B axis. Furthermore, at the level of the gut microbiota, harmane reshapes microbial composition, thereby contributing to its anti-tumor effects.IMPORTANCEThis study is the first to demonstrate a progressive decline of harmane levels in the gut from healthy individuals to advanced adenoma and CRC patients, suggesting its potential protective role in CRC development. We further found that harmane promotes CRC cell apoptosis via RRM2B-mediated regulation, revealing the underlying molecular mechanism. Moreover, in vivo experiments showed that harmane can modulate gut microbial composition and its derived metabolites, and fecal microbiota transplantation experiments indicated that harmane exerts anticancer effects by regulating both the gut microbiota and microbial metabolites. This study proposes a novel therapeutic strategy for CRC, highlighting the importance of incorporating gut microbiota modulation into cancer treatment.}, }
@article {pmid42262109, year = {2026}, author = {Mehta, N and Hvas, CL}, title = {Revisiting Cost-Effectiveness of Commercial or Traditional Fecal Microbiota Transplantation to Prevent C. difficile Recurrence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciag264}, pmid = {42262109}, issn = {1537-6591}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, }
@article {pmid42264080, year = {2026}, author = {Abdullah, M and Jayadevan, K and Therayil, A and Kumaraguruparan, N and Kavyasree, PKV and Dilna, P and Faiza, A}, title = {Pharmaco-microdynamics (PMD): Redefining Dose, Exposure, and Control for Living Drug Carriers.}, journal = {Annales pharmaceutiques francaises}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pharma.2026.06.002}, pmid = {42264080}, issn = {2772-803X}, abstract = {Living drug delivery systems including probiotics, engineered microbial therapeutics, and live biotherapeutic products represent a rapidly emerging therapeutic modality whose behavior fundamentally diverges from the assumptions underlying classical pharmacokinetics and pharmacodynamics (PK/PD). Unlike chemically defined, non-replicating drugs, living therapeutics persist, replicate, adapt, and generate bioactive molecules in situ, such that therapeutic exposure is not externally imposed but biologically generated over time. As a result, administered dose functions only as an initiating condition, while realized exposure emerges from population dynamics, ecological establishment, spatial localization, and regulated functional output. These properties render concentration-based PK/PD frameworks insufficient for predicting efficacy, safety, and controllability of living drug carriers. We introduce pharmaco-microdynamics (PMD) as a quantitative delivery-science framework designed to define, measure, and control exposure for living therapeutics. PMD is operationalized through a set of formal metrics including the functional exposure integral (F-AUC), colonization efficiency (CE), residence-time-weighted activity (RTWA), effective functional concentration (EFC50), and the genetic stability index (GSI)that serve as living-system analogues of AUC, bioavailability, mean residence time, EC50, and product-identity specifications. PMD reconceptualizes exposure as a time-integrated biological process governed by four interdependent axes: population kinetics, functional output kinetics, spatial pharmacology, and evolutionary dynamics. By integrating principles from pharmacology, microbial ecology, synthetic biology, biomaterials science, and systems modeling, PMD provides an operational vocabulary for translating adaptive biological agents into predictable and engineerable delivery systems. We further delineate PMD from adjacent frameworks such as quantitative systems pharmacology (QSP) and ecological microbiome modeling, and critically discuss boundary conditions under which classical PK/PD remains applicable to non-replicating or transient microbial interventions. This review critically examines the limitations of classical PK/PD in modeling living drug carriers, formalizes the core principles of PMD, and illustrates them through three quantitative case studies: SYNB1618 for phenylketonuria, synchronized-lysis bacterial tumor therapies, and fecal microbiota transplantation for recurrent Clostridioides difficile infection. Regulatory and clinical implications are addressed, emphasizing the need to shift from dose- and concentration-centric evaluation toward functional biomarkers, persistence metrics, and model-informed assessment of biological activity. Collectively, pharmaco-microdynamics establishes a unifying conceptual and quantitative foundation for the rational development of living medicines.}, }
@article {pmid42264216, year = {2026}, author = {Guo, L and Li, J and An, J and Miao, J and Yi, Y and Zhu, K and Cai, Q and Wang, S and Su, Z and Ye, X and Wang, Y and Pan, M and Lu, Q and Cui, B and Zhang, F and Mao, J and Liu, X and Lu, Y and Ding, D}, title = {Neuroprotective role of Faecalibacterium prausnitzii-derived butyrate in diabetic gastrointestinal autonomic neuropathy.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2026.06.005}, pmid = {42264216}, issn = {1673-8527}, abstract = {Diabetic gastrointestinal autonomic neuropathy (DGAN) is a common yet poorly understood complication of diabetes that is characterized by gastrointestinal dysmotility and enteric neurodegeneration. Here, we investigate whether gut microbiota dysbiosis contributes to DGAN pathogenesis and explore the potential involvement of microbiota-derived metabolites in enteric nervous system (ENS) injury. Gut microbiota profiling reveals disease-associated compositional alterations in patients with DGAN, including depletion of Faecalibacterium-associated signals, with Faecalibacterium prausnitzii identified as a putative species-level annotation and negatively associated with gastrointestinal symptom severity. Fecal microbiota transplantation from patients with DGAN into db/db mice aggravates gut dysmotility and increases apoptosis of ChAT[+] and nNOS[+] myenteric neurons. Further experiments indicate that butyrate, the predominant metabolite produced by F. prausnitzii, attenuates neuronal apoptosis under high-glucose conditions. This biological process is accompanied by enhanced BCL2 expression, downregulation of cleaved caspase-3, and activation of the PI3K/Akt signaling cascade. Collectively, our findings support the presence of a gut microbiota-ENS axis in DGAN and identify butyrate as an important candidate neuroprotective metabolite associated with F. prausnitzii. These results provide a rationale for microbiota-targeted therapeutic strategies for diabetic enteric neuropathy.}, }
@article {pmid42266133, year = {2026}, author = {Duggar, M and Leardini, D and Muratore, E and Margolis, EB and Masetti, R}, title = {Gut Microbiome-Immune Interactions During Pediatric Hematopoietic Cell Transplantation: From Conditioning to GvHD Prevention.}, journal = {Pediatric transplantation}, volume = {30}, number = {6}, pages = {e70371}, doi = {10.1111/petr.70371}, pmid = {42266133}, issn = {1399-3046}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Child ; *Graft vs Host Disease/prevention &amp; control/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Transplantation Conditioning/methods ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Hematopoietic stem cell transplantation (HCT) offers curative potential for children with high-risk hematologic malignancies. However, this treatment carries significant risks, particularly acute graft-versus-host disease (aGvHD), which affects 30%-60% of pediatric recipients and causes 15%-20% of post-transplant deaths. The gut microbiome has emerged as a critical factor in aGvHD development, yet pediatric microbiome dynamics differ substantially from adult patterns. This review seeks to evaluate the current state of knowledge of how the gut microbiome impacts aGvHD pathogenesis and the methods of microbiome modulation that may lead to aGvHD prevention and treatment. Children's microbiomes undergo more rapid compositional shifts and contain distinct bacterial compositions enriched in taxa like Bifidobacterium and Lactobacillus. During transplant, conditioning regimens and antibiotics cause dramatic microbiome disruption in children. This eliminates beneficial bacteria that normally maintain intestinal barrier integrity and produce immunomodulatory metabolites. Consequently, this disruption triggers inflammatory cascades through bacterial translocation, impaired immune education, and altered metabolite production. Unlike adults, where low diversity consistently predicts poor outcomes, pediatric studies show inconsistent diversity-outcome relationships, with only pre-transplant microbiome patterns reliably predicting aGvHD risk. Several promising interventions have emerged from this research. These include enteral nutrition to preserve beneficial bacteria, targeted antibiotic strategies, and fecal microbiota transplantation. Fecal microbiota transplantation has shown remarkable response rates in pediatric steroid-resistant aGvHD cases. Nevertheless, significant knowledge gaps remain regarding pediatric-specific mechanisms, optimal biomarkers, and age-appropriate therapeutic approaches for microbiome-directed aGvHD prevention.}, }
@article {pmid42266271, year = {2026}, author = {Dulay, MS and Chrysostomou, D and Campos, M and Storch, M and Roberts, LA and Dev, DS and Raza, N and Assaf, R and Tan, T and Marber, M and Sharma, R and Lüscher, T and Marchesi, JR and Dar, O}, title = {Investigating the gut microbiota in advanced heart failure and cardiac cachexia.}, journal = {Gut microbes reports}, volume = {3}, number = {1}, pages = {2670244}, pmid = {42266271}, issn = {2993-3935}, abstract = {Cardiac cachexia (CC) is associated with advanced heart failure (AHF), characterized by unintentional weight loss (UWL) of fat/muscle. It is exacerbated by right ventricular systolic dysfunction (RVSD). The potential pathogenic role of gut microbiota (GM) changes has not been investigated in CC. We aimed to explore this. Patients with AHF with or without CC/UWL, stable chronic heart failure (HF), and healthy controls (HCs) were recruited following national ethical approval. Fecal bacterial DNA was extracted, quantified, and 16S rRNA gene sequencing was performed. GM composition, alpha, and beta diversity were compared between CC/UWL-AHF and the rest of the cohort (ROC). The secondary analyses compared AHF, HF, and HCs, and patients with and without RVSD. Sixty-seven patients returned samples, including 14 with CC/UWL-AHF. No taxonomic differences were observed between CC/UWL-AHF and ROC. A weak trend toward compositional differences was observed (beta diversity R[2] = 0.016, p = 0.071). No differences were observed in RVSD. Numerous significant GM alterations were observed across the HF spectrum, including changes to Streptococcus spp., Alistipes, and Bacteroides. CC/UWL-AHF may be associated with subtle GM compositional changes. Larger studies are required to investigate this further.}, }
@article {pmid42266678, year = {2026}, author = {Rao, X and Zou, L and Cai, X and Yao, Y and Zhong, L}, title = {Microbiome-orchestrated cross-organ immunity in autoimmunity: from metabolites to therapeutic targets.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1761834}, pmid = {42266678}, issn = {1664-3224}, mesh = {Humans ; *Autoimmunity/immunology ; Animals ; *Gastrointestinal Microbiome/immunology ; *Autoimmune Diseases/immunology/therapy/metabolism/microbiology ; }, abstract = {Autoimmune diseases are systemic disorders in which barrier-site immune activation, especially in the gut, can reshape inflammatory programs in distant organs. This review advances a metabolite-centered, cross-organ framework for understanding how gut microbial ecology influences autoimmunity beyond individual gut-organ axes. We synthesize evidence that short-chain fatty acids, bile acid derivatives, tryptophan catabolites, polyamines and related microbial products act as mobile biochemical checkpoints linking intestinal barrier integrity, pattern-recognition signaling, immune-cell metabolism and tissue-specific inflammation in joints, kidneys, skin, lungs and the central nervous system. Across these axes, shared mechanisms include barrier failure, altered microbial metabolite pools, dysregulated MAMP sensing, trafficking or systemic conditioning of lymphoid and myeloid cells, and local stromal imprinting in target organs. We also discuss sex-dependent microbiome-immune interactions, including the microgenderome concept, as a framework for explaining why microbiome composition, hormone metabolism and immune responses may shape autoimmune risk and treatment response differently in females and males. Finally, we evaluate multi-omics, single-cell and spatial profiling, organ-on-chip platforms and causal computational tools, and we outline translational strategies ranging from diet, probiotics, fecal microbiota transplantation and engineered consortia to pharmacologic targeting of metabolite receptors. By treating microbial metabolites as actionable cross-organ immune checkpoints, this review highlights opportunities and limitations for biomarker-guided, metabolite-focused precision therapy in autoimmunity.}, }
@article {pmid42266888, year = {2026}, author = {Mesonero-Cavia, S and Freixas-Bermejo, M and Álvarez-Beltran, M and Redecillas-Ferreiro, S and Cabello-Ruiz, V and Raya-Muñoz, J and Mercadal-Hally, M and Martin-Nalda, A and Segarra-Cantón, O}, title = {De novo Crohn's Disease Treated with Ustekinumab in a Pediatric Liver Transplant Recipient with Tyrosinemia: A Case Report.}, journal = {Case reports in gastroenterology}, volume = {20}, number = {1}, pages = {138-148}, pmid = {42266888}, issn = {1662-0631}, abstract = {INTRODUCTION: De novo inflammatory bowel disease (IBD) is more frequent in transplant recipients than in the general population and should be considered in the differential diagnosis of chronic diarrhea. In pediatric liver transplant recipients, an incidence of 206 vs. 20 cases per 100,000 patient-years has been reported, suggesting an underrecognized complication of immunosuppression.<br><br>CASE PRESENTATION: We report an 11-year-old girl with tyrosinemia type 1 who underwent liver transplantation and later developed de novo Crohn's disease. Despite maintenance therapy with tacrolimus, methylprednisolone, and everolimus, she presented with chronic diarrhea, weight loss, and elevated inflammatory markers after several episodes of Clostridioides difficile infection treated with oral vancomycin and only transient improvement. Initial inflammatory markers were only mildly elevated but showed a progressive rise over 18 months despite antibiotic therapy, alongside positive ASCA IgG and ASCA IgA with negative pANCA at the time of formal evaluation. Colonoscopy showed patchy aphthous and serpiginous ulcers with a cobblestone appearance, and histology revealed cryptitis and a mixed lymphoplasmacytic infiltrate without granulomas. Magnetic resonance enterography demonstrated ileocolic inflammation with wall thickening and mesenteric vessel engorgement. Infectious and drug-induced colitis and Epstein-Barr virus-related disease were excluded, and de novo ileocolic Crohn's disease (Paris A1b L3 B1 G1) was diagnosed. Ustekinumab (260 mg intravenously, then 90 mg subcutaneously every 4 weeks) was added to baseline immunosuppression, inducing clinical remission with normalization of C-reactive protein and a decrease in fecal calprotectin to 10 &#xb5;g/g by week 20, sustained at 18 months with preserved graft function.<br><br>CONCLUSION: This case illustrates the diagnostic challenges of de novo Crohn's disease in pediatric liver transplant recipients with metabolic liver disease and supports ustekinumab as a safe and effective option when other biologics are limited by prior infectious or lymphoproliferative.}, }
@article {pmid42267483, year = {2026}, author = {Sun, Y and Ma, T and Chen, R and Shen, L and Tang, X and Shen, Z and Zhao, H}, title = {Anti-inflammatory and osteogenic effects of transcutaneous electrical nerve stimulation in knee osteoarthritis rats via the regulation of the intestinal microbiota.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70209}, pmid = {42267483}, issn = {2576-2095}, support = {202201AY070001-008/202401AY070001-091/202501AY0001//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; 202302AA310021//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; CYJS-2019-036//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; JG2023001//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; 202501AT070594//Applied Basic Research Foundation of Yunnan Province/ ; }, abstract = {BACKGROUND: This study revealed the function and mechanism of the intestinal microbiota in knee osteoarthritis (KOA) rats treated using transcutaneous electrical nerve stimulation (TENS).<br><br>METHODS: KOA model rats were randomly divided into low-/medium-/high-intensity TENS groups, sodium hyaluronate (SH)-positive control group (SH), and model control group (KOA rat). After 1, 2, and 3&#x2009;weeks of treatment, the improvement in KOA severity was assessed, and the expression of interleukin-1&#x3b2; (IL-1&#x3b2;)/IL-6/IL-8/bone morphogenetic protein 2 (BMP-2)/transforming growth factor &#x3b2; (TGF-&#x3b2;) was analyzed. The diversity of the intestinal microbiota in KOA rats was analyzed via 16S ribosomal DNA (rDNA) sequencing. After fecal microbiota transplantation (FMT), which was induced by TENS, the improvement in the intestinal microbiota in KOA rats was analyzed.<br><br>RESULTS: After 3&#x2009;weeks of treatment using TENS, compared to those in the model control group, the biomechanical parameters increased in the SH and TENS groups (p&#x2009;<&#x2009;0.05); the gait parameters improved in the SH and TENS groups; the bone mineral density (BMD) increased in the TENS group (p&#x2009;<&#x2009;0.05); the Mankin scores of the distal femur and proximal tibiofibular muscles decreased in the SH and TENS groups (p&#x2009;<&#x2009;0.05). IL-1&#x3b2;/6/8 expression levels decreased in the SH and TENS groups (p&#x2009;<&#x2009;0.05). BMP-2/TGF-&#x3b2; expression in the distal femur increased in the TENS group (p&#x2009;<&#x2009;0.05). 16S rDNA sequencing revealed that the intestinal microbiota of KOA rats was changed after TENS treatment, including increases in Escherichia-Shigella, Lachnospira, Eubacterium, Gastranaerophilales, and Rikenellaceae RC9 and decreases in Fusicatenibacter and Mycoplasma. After FMT, which is induced by TENS, similar improvements in KOA rats were obtained.<br><br>CONCLUSIONS: TENS promoted anti-inflammatory and osteogenic effects by downregulating the Il-1&#x3b2;/6/8 expression levels and upregulating the BMP-2/TGF-&#x3b2; signaling pathway. 16S rDNA sequencing revealed that the intestinal microbiota of KOA rats was changed after TENS treatment via the gut-knee joint axis, and that these dominant genera of FMT elicited improvements in KOA rats. TENS caused improvements in KOA rats by regulating the intestinal microbiota; thus, TENS and induced FMT altered intestinal microbiota suggest a potential novel therapeutic avenue for KOA in clinical settings.}, }
@article {pmid42269582, year = {2026}, author = {Bian, L and Cai, Y and Zhang, Y and Shen, L and Wang, H and Gao, F and Cai, N and Chen, W and You, C and Yang, Y and Wang, F and Yuan, Y and Han, B and Yao, H}, title = {Microbiota-driven gut-brain signaling underlies antidepressant effects of a GLP-1 analog.}, journal = {Cell host &amp; microbe}, volume = {34}, number = {6}, pages = {1000-1017.e5}, doi = {10.1016/j.chom.2026.05.003}, pmid = {42269582}, issn = {1934-6069}, mesh = {Animals ; *Antidepressive Agents/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Brain/metabolism/drug effects ; *Glucagon-Like Peptide 1/analogs &amp; derivatives ; Signal Transduction/drug effects ; *Depression/drug therapy ; Glucagon-Like Peptide-1 Receptor/genetics/metabolism ; *Liraglutide/pharmacology ; Mice, Knockout ; Mice, Inbred C57BL ; Arachidonic Acids/metabolism ; Glycerides/metabolism ; Lactobacillus delbrueckii/drug effects ; Fecal Microbiota Transplantation ; Male ; Endocannabinoids ; }, abstract = {Despite widespread clinical use of glucagon-like peptide-1 receptor (GLP-1R) agonists for metabolic disease, their neuropsychiatric effects remain poorly understood and controversial. Here, we demonstrate that liraglutide alleviates depression through a gut-brain pathway that operates independently of GLP-1R. Using both pharmacological and genetic approaches, we demonstrated that liraglutide retained antidepressant efficacy in GLP-1R antagonist-Exn9-treated mice or in Glp1r[-/-] mice, whereas gut microbiota depletion abolished its effects. Multi-omics analyses revealed that liraglutide increased the abundance of Lactobacillus delbrueckii, which in turn restored the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG). The elevation of 2-AG mediated the antidepressant effects by normalizing excessive neuronal activity in emotional processing brain regions. Importantly, fecal microbiota transplantation from liraglutide-treated mice or Lactobacillus delbrueckii colonization replicated the antidepressant effects. These findings uncover a non-canonical mechanism of action for GLP-1 analogs, highlighting a specific microbiota-endocannabinoid metabolic pathway as a potential therapeutic target for depression.}, }
@article {pmid42269666, year = {2026}, author = {Dewey, CW and Rojas, CA and Pomeroy, C and Gerardi, J and Ganz, HH}, title = {Fecal microbiota transplantation shows promise in slowing or reducing cognitive impairment in aging dogs.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-6}, doi = {10.2460/javma.26.03.0231}, pmid = {42269666}, issn = {1943-569X}, abstract = {OBJECTIVE: To investigate potential effects of fecal microbiota transplantation (FMT) on cognitive scores and bacterial microbiota composition in dogs with suspected canine cognitive dysfunction (CCD).<br><br>METHODS: The study was conducted from September 19, 2024, to September 11, 2025. Dogs with presumptive CCD were given oral FMT capsules daily for 90 days. Each dog received 1 FMT capsule every 12 hours. Fecal samples and cognitive (disorientation, impaired social interactions, sleep disturbance, house soiling, learning and memory loss, activity changes, and anxiety and fear [DISHAA]) assessments were completed at baseline and on days 30, 60, and 90. Fecal samples were submitted for 16S rRNA gene sequencing.<br><br>RESULTS: 11 dogs were enrolled; 10 dogs had no adverse events from FMT treatment, and 1 dog developed gastrointestinal signs and was removed from the study. All 10 remaining dogs had complete microbiome data; however, owners of 4 dogs did not report final (90-day) DISHAA scores. Of the 6 dogs with complete data, cognition improved in 4 (mean, -8.25 points) but worsened in 2 (mean, +7 points) according to owner-reported DISHAA scores. Microbiome richness and diversity increased in 4 of the 6 dogs. Several dogs also showed positive modulation of microbiome composition including reductions in Streptococcus spp and increases in Peptacetobacter hiranonis, Prevotella copri, and Bacteroides spp.<br><br>CONCLUSIONS: These findings provided preliminary evidence that FMT may help improve cognitive function in dogs with CCD. However, the study sample size was small and ideal FMT dosing level and treatment duration remain undefined. A larger study with longer follow-up is warranted, based on our results.<br><br>CLINICAL RELEVANCE: FMT showed promise in slowing or reducing cognitive impairment in aging dogs and may be considered as adjunct therapy in these cases.}, }
@article {pmid42270269, year = {2026}, author = {Wang, X and Zhang, J and Wang, Y and Zhou, Y and Xu, H}, title = {Lactobacillus reduction drives oxidative gut-liver adverse effects of heterogeneous aggregates polylactic acid nanoplastics and silica nanoparticles.}, journal = {Food research international (Ottawa, Ont.)}, volume = {239}, number = {}, pages = {119558}, doi = {10.1016/j.foodres.2026.119558}, pmid = {42270269}, issn = {1873-7145}, mesh = {Animals ; *Silicon Dioxide/toxicity/chemistry ; *Nanoparticles/chemistry/toxicity ; *Polyesters/toxicity/chemistry ; Male ; *Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Mice ; *Liver/drug effects/pathology/metabolism ; *Lactobacillus ; *Microplastics/toxicity ; Gastrointestinal Microbiome/drug effects ; Dysbiosis/chemically induced ; Food Packaging ; Fecal Microbiota Transplantation ; Feces/microbiology ; }, abstract = {Polylactic acid (PLA) plastics are increasingly used in food packaging as biodegradable substitute to petroleum-based plastics. However, the high temperatures used to reconstitute powdered foods, which often contain silica nanoparticles (SiNPs), readily induce PLA degradation, generating large amounts of PLA nanoplastics (PLA NPs). Due to the high affinity of PLA NPs to contaminants, this study investigated the interactions between PLA NPs and SiNPs, and their gut-liver adverse effects. Following the oral administration of PLA NPs and SiNPs to C57BL/6J male mice for 90 days, liver, colon, blood, and fecal samples were collected to assess liver damage, gut function and microbiota composition. The results showed that PLA NPs and SiNPs formed heterogeneous aggregates complexes (HAC), resulting in different hydrodynamic size and zeta potential. Compared with PLA NPs or SiNPs, HAC induced more severe hepatic and intestinal injuries and further disrupted gut microbial homeostasis. In the fecal microbiota transplantation and key bacteria supplementation experiments, liver oxidative stress induced by HAC was partly attributed to gut dysbiosis and the reduced abundance of Lactobacillus. In conclusion, HAC exhibited different physicochemical and toxicological properties than single contaminant, and oxidative stress is the key factor in gut-liver adverse effects. These findings uncover the potential interactions among contaminants and their combined adverse effects, and provided a new perspective for risk assessment process related to food contaminant exposure.}, }
@article {pmid42270545, year = {2026}, author = {Louvet, A and Ntandja Wandji, LC and Mathurin, P}, title = {Updates in clinical science: Alcohol-related hepatitis.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2026.04.016}, pmid = {42270545}, issn = {1600-0641}, abstract = {Alcohol-related hepatitis (AH) is a complex disease associated with numerous unmet needs, particularly in diagnosis and treatment. The epidemiology of AH has evolved in recent years, reflecting changes in alcohol consumption during the COVID-19 pandemic and the increasing incidence of AH following bariatric surgery. Advances have also been made in the non-invasive diagnosis of AH, helping to reduce the need for liver biopsy, as well as in the management of infection. Several novel therapeutic strategies have been evaluated, including faecal microbiota transplantation, IL-1 receptor antagonists, oxysterols, and reduced exposure to corticosteroids or antibiotics. Although the results of these trials have been relatively disappointing, they have helped identify promising directions for future research. In patients with the most severe form of AH, particularly those who do not respond to corticosteroids, several studies have suggested that the indications for early liver transplantation could be expanded. Overall, developments over recent years have generated increased optimism regarding the management of patients with severe AH.}, }
@article {pmid42271360, year = {2026}, author = {Chen, Y and Kang, H and Yang, B and Feng, L and Tong, R and Zhao, Z and Liang, L and Li, X and Liu, X and Tong, Z}, title = {Gut mycobiota alteration contributes to the pathogenesis of Pneumocystis pneumonia.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08153-7}, pmid = {42271360}, issn = {1479-5876}, abstract = {BACKGROUND: Pneumocystis is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised hosts, with increasing incidence in HIV-negative individuals. Although the gut mycobiota has emerged as a critical regulator of distal immunity, its role in HIV-negative Pneumocystis pneumonia (PCP) remains entirely unexplored.<br><br>METHODS: We established a murine model of Pneumocystis murina infection and performed full-length internal transcribed spacer (ITS) sequencing to characterize longitudinal changes in gut fungal communities over five weeks. Untargeted metabolomics was conducted on plasma samples to identify systemic metabolic alterations. To investigate causality, gut fungal communities were depleted using fluconazole, and fecal microbiota transplantation (FMT) was performed in germ-free mice to assess the functional role of gut fungi in modulating pulmonary immune responses.<br><br>RESULTS: While &#x3b1; diversity of the gut mycobiota remained unchanged, &#x3b2; diversity analysis revealed significant structural alterations beginning week 3 (w3) post-infection, coinciding with peak pulmonary fungal burden. Linear discriminant analysis effect size identified Purpureocillium lilacinum and Talaromyces verruculosus as enriched opportunistic taxa. Untargeted metabolomics demonstrated marked metabolic reprogramming at w3, with significant perturbations in glycine, serine, and threonine metabolism, as well as the tricarboxylic acid cycle. Fluconazole-mediated depletion of gut fungi significantly increased pulmonary Pneumocystis burden and exacerbated lung inflammation, accompanied by reduced pulmonary Th1 cell responses. Critically, FMT from fluconazole-treated donors into germ-free mice recapitulated the exacerbated phenotype, confirming that gut fungal dysbiosis is sufficient to impair Th1-mediated antifungal immunity and worsen disease severity.<br><br>CONCLUSIONS: This study establishes, for the first time, that gut fungal dysbiosis actively contributes to the pathogenesis of HIV-negative PCP via the gut-lung axis. Our findings reveal that commensal gut fungi support pulmonary Th1 immune responses essential for controlling PCP, and their disruption exacerbates disease. These results provide new insights into the gut mycobiota as a potential therapeutic target in PCP and caution against indiscriminate antifungal use in susceptible populations.}, }
@article {pmid42274997, year = {2026}, author = {Hirsch, W and Enns, EA and Khoruts, A and Rajasingham, R and Vaughn, BP}, title = {Cost-effectiveness of Commercial or Traditional Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciag263}, pmid = {42274997}, issn = {1537-6591}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is the cost-effective strategy for managing recurrent Clostridioides difficile infection (rCDI). Prior costing models assumed FMT administration via colonoscopy. With the commercialization of microbiota therapeutics for rCDI, this study sought to determine the impact of commercial, Food and Drug Administration (FDA) approved microbiota-based therapeutics relative to traditional FMT on the cost-effectiveness for rCDI.<br><br>METHODS: We used a Markov model to simulate a cohort of patients with rCDI to evaluate the cost-effectiveness of varied methods of FMT administration for rCDI. The model includes estimates of cure, recurrence, and mortality. Data sources were taken from national guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).<br><br>RESULTS: FMT by colonoscopy is the cost-effective strategy for preventing second or subsequent rCDI with an incremental cost-effectiveness ratio (ICER) of $44 158. Assuming a willingness-to-pay threshold of $100 000 per quality adjusted life years (QALY) gained, FMT by colonoscopy was optimal in the majority (70%) of simulations. At a willingness-to-pay threshold of $100 000 per quality adjusted life year (QALY), commercial, FDA approved microbiota therapeutics were not cost effective under any circumstance when donor-derived FMT products are available.<br><br>CONCLUSIONS: Traditional FMT administered by colonoscopy is the optimal cost-effective strategy for preventing second or subsequent episodes of rCDI. If FMT is not available, then microbiota therapeutics are not a cost-effective option for rCDI at current pricing.}, }
@article {pmid42275128, year = {2026}, author = {Takahashi, K and Yoshikawa, Y and Chaki, T and Yamakage, M}, title = {Gut Microbiota Modulation Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetic Mice.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002882}, pmid = {42275128}, issn = {1540-0514}, abstract = {BACKGROUND: The gut microbiome is increasingly being recognized as a regulator of cardiometabolic health; however, whether microbiome interventions can attenuate myocardial ischemia-reperfusion injury (IRI) in diabetic hearts remains unclear. Therefore, we tested whether fecal microbiota transplantation (FMT) from lean non-diabetic donors could mitigate myocardial IRI in type 2 diabetes mellitus (T2DM) db/db mice and explored candidate taxa associated with protection.<br><br>METHODS: Male db/db mice (T2DM model) received a 14-day course of FMT from lean db/m donors or a vehicle after antibiotic pretreatment. Myocardial IRI was induced, and infarct size was quantified. The gut microbiota was evaluated by 16S rRNA gene sequencing.<br><br>RESULTS: FMT significantly reduced the infarct size as a percentage of the area at risk compared to the IRI group (38.7 &#xb1; 13.4% vs. 58.7 &#xb1; 4.3%, P = 0.003). Microbiome analysis revealed that among alpha-diversity metrics only the Simpson index differed between the donor and diabetic groups. In beta-diversity analyses, diabetic mice clustered separately from donor mice, and the microbiome intervention induced a modest but significant shift detected by the presence or absence of Unweighted UniFrac. Differential abundance analysis and exploratory LEfSe further suggested Akkermansia, particularly Akkermansia muciniphila, as a candidate taxon reduced in diabetic mice and partially restored after the FMT intervention.<br><br>CONCLUSION: A donor-derived microbiome intervention attenuated myocardial IRI in db/db mice and was accompanied by partial remodeling of the gut microbiota. Akkermansia muciniphila emerged as a candidate taxon associated with a reduced susceptibility to IRI in diabetic hearts.}, }
@article {pmid42276984, year = {2026}, author = {Lange-Andrzejewska, O and Budny, A and Janczy, A and Wilczynski, M and Szymanski, M and Proczko-Stepaniak, M and Sledzinski, T and Mika, A}, title = {Longitudinal analysis of short-chain fatty acid profiles in stool of sleeve gastrectomy patients.}, journal = {Nutrition &amp; diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41387-026-00441-x}, pmid = {42276984}, issn = {2044-4052}, support = {2021/43/B/NZ5/00039//Narodowe Centrum Nauki (National Science Centre)/ ; }, abstract = {Obesity presents significant health risks, including metabolic disorders and depressive symptoms, necessitating effective interventions such as sleeve gastrectomy (SG), which enables substantial weight loss and metabolic improvements. The primary question of this study was whether SG also affects faecal short-chain fatty acid (SCFA) profiles over 12 months, and whether these changes are related to anthropometric, biochemical, and psychological parameters. A total of 37 female patients with obesity were included in this prospective, observational study. Patients underwent SG and were followed for 12 months postoperatively. SCFA profiles were analysed by gas chromatography-mass spectrometry (GC-MS). Faecal samples for SCFA analysis, anthropometric measurements, blood biochemical markers, food intake and psychological assessments were collected at baseline and at regular intervals after surgery. Our results indicate that SG leads to significant reductions in body mass index, lipid profiles, and systemic inflammation markers, with concurrent alterations in SCFA concentrations, particularly a decrease in major SCFAs (acetic, propionic, and butyric acids) over time. An increase in branched SCFAs was observed post-surgery, which may reflect shifts in the gut microbiota composition and fermentation processes. Patients also reported improvements in emotional well-being and dietary habits. These findings support the hypothesis that SG induces changes in gut microbiota metabolism and underscore the complex interplay between bariatric surgery, gut microbiota, SCFA metabolism, and psychological health. They highlight the need for further research to clarify the long-term implications of these changes and the mechanisms involved.}, }
@article {pmid42277050, year = {2026}, author = {Xu, J and Han, Z and Xue, Q and Wang, H and Li, Y and Song, J and Li, L and Hu, M and Wang, D}, title = {Gut commensal Odoribacter splanchnicus attenuates hyperlipidemic periodontitis via gut-oral metabolic transmission of β-GPA.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-01033-4}, pmid = {42277050}, issn = {2055-5008}, support = {82470987//National Natural Science Foundation of China/ ; jcsz2025678-2//Science and Technology Project of Jilin Province Department of Finance/ ; 2024JBGS07//"Medicine+X" Interdisciplinary Innovation Project/ ; }, abstract = {Hyperlipidemic periodontitis (HPD) represents a prevalent comorbidity linking systemic metabolic dysregulation with local inflammation, yet the microbial mechanisms driving this gut-oral crosstalk remain elusive. Here, the comorbid state of HPD is linked to hyperlipidemia-associated gut microbiota changes, which are prominently accompanied by the depletion of Odoribacter splanchnicus in both patients and mice. Fecal microbiota transplantation demonstrates that this gut dysbiosis exacerbates periodontal destruction when local inflammation is present. Mechanistically, intragastric administration of live O. splanchnicus ameliorates HPD by remodeling the gut ecosystem and upregulating the metabolite β-guanidinopropionic acid (β-GPA). Notably, direct supplementation with β-GPA reproduces these protective effects. Furthermore, β-GPA is proposed as a systemic effector linking the gut and periodontal tissues, where its protective effect is associated with the suppression of the pro-inflammatory Toll-like receptor 4 (TLR4) signaling cascade. These findings highlight a link involving O. splanchnicus, β-GPA, and the modulation of TLR4 signaling, offering a potential microbiome-based therapeutic strategy for managing complex metabolic-inflammatory comorbidities.}, }
@article {pmid42278360, year = {2026}, author = {Mardnaybin, H and Demirci, M and Kirkoyun Uysal, H}, title = {The Gut Microbiome in HIV Pathogenesis: Interconnections Between Dysbiosis, Immune Dysfunction, and Viral Persistence.}, journal = {International journal of molecular sciences}, volume = {27}, number = {11}, pages = {}, pmid = {42278360}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *HIV Infections/immunology/microbiology/virology ; Animals ; *Gastrointestinal Microbiome/immunology ; }, abstract = {The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4[+] T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome-HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions-including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics-and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication.}, }
@article {pmid42278620, year = {2026}, author = {Lu, Z and Chen, G and Chang, M and Wang, N and Xia, T and Zhang, Y and Xu, G and Zhao, Q and Shen, P and Zhou, W and Ni, Z and Gao, Y}, title = {Effects of High-Altitude Environments on Gut Microbiota and Their Mechanisms in Immune Regulation and High-Altitude Adaptation.}, journal = {International journal of molecular sciences}, volume = {27}, number = {11}, pages = {}, pmid = {42278620}, issn = {1422-0067}, support = {2025YFC3507500//National Natural Science Foundation of China/ ; 2025YFC3507502//National Natural Science Foundation of China/ ; zyyzdxk-2023311//State Administration of Traditional Chinese Medicine of the People's Republic of China/ ; }, mesh = {Humans ; *Altitude ; Animals ; *Gastrointestinal Microbiome/immunology ; *Acclimatization ; *Adaptation, Physiological ; Intestinal Barrier Function ; Dysbiosis ; Homeostasis ; }, abstract = {High-altitude environments, characterized by hypoxia, low temperature, and intense ultraviolet radiation, profoundly disrupt host intestinal homeostasis and reshape the gut microbiota, thereby influencing immune regulation and acclimatization. This review systematically summarizes the dynamic compositional and functional changes in the gut microbiota in high-altitude natives, immigrant populations, short-term visitors, and relevant animal models. Current evidence indicates that long-term high-altitude adaptation is associated with directional microbial remodeling, including the enrichment of anaerobic and short-chain fatty acid (SCFA)-associated taxa, which may support energy metabolism and immune homeostasis. In contrast, acute high-altitude exposure more readily induces dysbiosis, impairs intestinal barrier integrity, and promotes the translocation of endotoxins and bioactive metabolites. Mechanistically, the gut microbiota and its metabolites participate in high-altitude adaptation and high-altitude-related disease pathogenesis by modulating barrier function, inflammatory responses, oxidative stress, and immune signaling, and by mediating interorgan communication-characterized by metabolite-driven systemic inflammation or tolerance-through the gut-lung, gut-heart, gut-brain, gut-kidney, and gut-testis axes. SCFAs, bile acids, amino acid-derived metabolites, and succinic acid may control immune homeostasis and inflammatory responses through pathways including TLR4/NF-κB and NLRP3. Although the causal relationships, core microbial effectors, and population-specific heterogeneity remain incompletely defined, microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, have shown promise for promoting acclimatization and preventing high-altitude-related disorders. Overall, this review provides an integrated framework linking environmental stress, gut microbial ecology, and host immune-metabolic adaptation at high altitude, and highlights future directions for mechanistic and translational research in high-altitude medicine.}, }
@article {pmid42279278, year = {2026}, author = {Liu, Z and Ang, MY and Kue, CS}, title = {Gut Microbiota in Colorectal Cancer: Mechanistic Insights, Clinical Strategies, and a Regional Perspective with a Focus on Sichuan, China.}, journal = {Cancers}, volume = {18}, number = {11}, pages = {}, pmid = {42279278}, issn = {2072-6694}, abstract = {CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment.}, }
@article {pmid42279294, year = {2026}, author = {Newell, LF and Twohey, E and Sweetnam, J and Skendzel, S and Stingle, J and Vartanian, KA and Davis, BA and Layman, CE and Carbone, L and Ray, K and Fei, SS and Karstens, L and He, FC and El Jurdi, N and Blaes, AH and Meyers, G and Cook, RJ and Baraki, A and Dengel, DR and Holtan, SG}, title = {Attenuation of Immune Senescence Markers After Intensive Cancer Therapy Through Resistance Training: A Pilot Study.}, journal = {Cancers}, volume = {18}, number = {11}, pages = {}, pmid = {42279294}, issn = {2072-6694}, abstract = {Background: Chemotherapy and radiation accelerate aging of multiple systems, including the immune and musculoskeletal systems. Resistance training may mitigate some of the late physiologic effects of cancer therapy. Methods: We developed a community-based pilot study of resistance training for long-term cancer survivors meeting criteria for pre-frailty or frailty (N = 8; 6 allogeneic hematopoietic cell transplant, 1 autologous hematopoietic transplant, 1 breast cancer survivor) and their caregivers (N = 8 healthy controls) consisting of a baseline assessment, 10 weeks of personalized resistance training at least once weekly as a group and as many additional times on an individual basis as their schedule allowed, and an end-of-study assessment to measure change in strength and body composition. Blood samples were collected at the start of the study and after the 10-week training program to assess changes in peripheral blood mononuclear cell DNA methylation patterns, gene expression measured by RNA sequencing, and stool microbiome analysis using metagenomics. The median number of resistance training sessions was 25 sessions. Results: Cancer survivors and controls both more than doubled their squat and press volume after 10 weeks. At baseline, cancer survivors exhibited a pro-inflammatory transcriptomic and epigenetic profile with elevated interferon signaling and reduced naïve T cell signatures compared to healthy controls, consistent with immune senescence. After 10 weeks of resistance training, these differences normalized, suggesting that exercise exerted anti-inflammatory and immune-restorative effects in cancer survivors at both gene expression and methylation levels. Ten fecal microbial pathways that were lower in relative abundance in patients compared with controls at baseline were no longer significantly different post-exercise. Conclusions: Our data suggest that in addition to beneficial changes in body composition, resistance training may exert an immune restorative effect in cancer survivors.}, }
@article {pmid42280407, year = {2026}, author = {Acierno, C and Caturano, A and Barletta, F and Rinaldi, L and Sasso, FC and Adinolfi, LE and Nevola, R}, title = {Nutritional Interventions Targeting the Gut Microbiome in MASLD: From Prebiotics and Probiotics to Postbiotics and Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {18}, number = {11}, pages = {}, pmid = {42280407}, issn = {2072-6643}, mesh = {Humans ; *Prebiotics/administration &amp; dosage ; *Fecal Microbiota Transplantation ; *Probiotics/administration &amp; dosage ; *Gastrointestinal Microbiome ; *Fatty Liver/therapy/microbiology ; Synbiotics/administration &amp; dosage ; Dysbiosis ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut-liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints-including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts-rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers.}, }
@article {pmid42281500, year = {2026}, author = {Rashidi, SK and Dezfouli, MA and Khalili, H and Kiani, AKD}, title = {The role of gut microbiota in the neurobiology and treatment of Alzheimer's disease.}, journal = {General physiology and biophysics}, volume = {45}, number = {2}, pages = {129-151}, doi = {10.4149/gpb_2025042}, pmid = {42281500}, issn = {0231-5882}, mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome ; Animals ; *Brain/physiopathology ; Amyloid beta-Peptides/metabolism ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Alzheimer's disease (AD) is the most common cause of dementia in the elderly population and characterized by progressive cognitive decline. The major pathological features of AD are the accumulation of extracellular amyloid-beta protein as neuritic plaques and intracellular hyperphosphorylated tau protein as neurofibrillary tangles. Studies have shown that gut microbiota are involved in several central nervous system disorders through regulation of neurotransmitter production, blood-brain barrier permeability and immune responses. The gut microbiota establishes a two-way communication between the gut and the brain through neural, endocrine, and immune pathways, which play a role in various neurological diseases, including AD. Alterations in the composition and function of the gut microbiota may influence neuroinflammation, amyloid-beta accumulation, and tau pathology. Targeting the balance of the gut microbiota through probiotics, prebiotics, and fecal microbial transplantation could be promising therapeutic approach against neurodegeneration. Understanding the complex relationship between the gut microbiota and AD pathobiology could pave the way for novel preventive and therapeutic strategies. Here, we summarized advances in the role of gut microbiota in AD pathobiology and updated rising concerns from recent reports. Moreover, the possibility of applying the capability of the gut microbiota as a promising treatment against AD has been discussed in this review.}, }
@article {pmid42281763, year = {2024}, author = {Winston, JA and Suchodolski, JS and Gaschen, F and Busch, K and Marsilio, S and Costa, MC and Chaitman, J and Coffey, EL and Dandrieux, JRS and Gal, A and Hill, T and Pilla, R and Procoli, F and Schmitz, SS and Tolbert, MK and Toresson, L and Unterer, S and Valverde-Altamirano, &#xc9; and Verocai, GG and Werner, M and Ziese, AL}, title = {Clinical Guidelines for Fecal Microbiota Transplantation in Companion Animals.}, journal = {Advances in small animal care}, volume = {5}, number = {1}, pages = {79-107}, pmid = {42281763}, issn = {2666-450X}, }
@article {pmid42283215, year = {2026}, author = {Chernova, VO and van Prehn, J and Groenewegen, B and van Lingen, E and Kuijper, EJ and Lambregts, MMC and van Nood, E and Choi, G and Hazenberg, MD and Keller, JJ and Terveer, EM}, title = {Biovigilance in Faecal Microbiota Transplantation: 7-Year Cohort Study and Framework for Microbiological Assessments of Infectious Adverse Events.}, journal = {United European gastroenterology journal}, volume = {14}, number = {5}, pages = {e70239}, pmid = {42283215}, issn = {2050-6414}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/adverse effects/methods/standards ; Netherlands/epidemiology ; Prospective Studies ; Recurrence ; Treatment Outcome ; Aged, 80 and over ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transplantation (FMT) is increasingly used. However, no systematic approach exists to assess infectious risks after FMT, leading to underreporting. We evaluated infectious complications at the Netherlands Donor Feces Bank (NDFB) and proposed a structured biovigilance approach aligned with the EU Regulation on Substances of Human Origin (SoHO).<br><br>METHODS: We conducted a prospective observational cohort study of all patients receiving frozen donor faecal suspensions from the NDFB (May 2016-December 2023) for recurrent Clostridioides difficile infection (rCDI) or via an extended access programme (EAP) for non-CDI indications. (Serious) adverse events ((S)AEs) were reported by physicians and recorded at 3&#xa0;weeks, 3&#xa0;months, and 6&#xa0;months. Serious adverse reactions (SARs) were defined as SAEs probably or definitely related to FMT.<br><br>RESULTS: We included 290 rCDI patients (322 FMTs) and 35 EAP patients (75 FMTs). FMT efficacy was favourable overall: 92% of rCDI patients remained free of rCDI within 8&#xa0;weeks, and 49% of EAP patients achieved at least a partial response. Sixty-one per cent of rCDI patients and 34% of EAP patients had mild gastrointestinal AEs. AE incidences were comparable across groups (rCDI: 5.1 vs. EAP: 4.4 per 100 patient-weeks). SAEs were more frequent in EAP patients (0.66 vs. 0.28 per patient), reflecting higher immunosuppression and comorbidity. FMT-attributable SARs occurred after 6 of 322 FMTs (1.9%) in the rCDI group and after 3 of 75 FMTs (4.0%) in the EAP group. Two donor-derived Escherichia coli infections in EAP patients with predisposing conditions were confirmed, consistent with early donor-strain colonisation rather than a direct FMT effect. Most SAEs were unrelated.<br><br>CONCLUSIONS: In this 7-year cohort, donor-derived infections were rare but present, particularly in non-CDI patients with substantial comorbidity, whereas overall safety remained favourable. A SoHO-compliant biovigilance protocol incorporating microbiological investigation and donor/sample traceability is essential for the safe clinical use of FMT and faecal microbiota products.}, }
@article {pmid42283380, year = {2026}, author = {Van Hoef, S and Welvaert, C and Allaeys, M and Berrevoet, F}, title = {Incidence of tissue-based inguinal hernia repair in Belgium: a web-based national survey.}, journal = {Acta chirurgica Belgica}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/00015458.2026.2689120}, pmid = {42283380}, issn = {0001-5458}, abstract = {BACKGROUND: Inguinal hernia repair is one of the most commonly performed procedures worldwide. Several different methods for repair exist, where the preferred surgical procedure for a non-complicated unilateral inguinal hernia is still up for debate. Originally described as a tissue repair, the introduction of prostheses have led many surgeons to move away from this type of repairs. However, recently updated guidelines still recommend non-mesh treatment, in a subgroup of patients, with a preference for the Shouldice technique. Therefore, we set out to map the incidence and knowledge about tissue-based repair of a primary inguinal hernia in Belgium.<br><br>METHODS: We designed a voluntary, open web-based survey for both surgeons and trainees asking about their knowledge, experience and indication for tissue-based suture repair, using a Google-forms document. The survey included level of experience and surgical preference, practice of tissue-based inguinal repair, indications for tissue-based repair, and technique and knowledge about tissue-based repair. Data was collected between 1st of December 2023 and 31st of January 2024 and analyzed using Microsoft Excel (version 16.77.01).<br><br>RESULTS: A total of 122 respondents filled out the questionnaire, 47 trainees and 75 surgeons, of which 4 were discarded due to inaccurate data. Only 15 out of 71 surgical respondents still performed a non-mesh based repair in an elective setting, where the Shouldice repair was the preferred technique (n&#x2009;=&#x2009;12, 80%). Knowledge about tissue-based mesh was rated mainly moderate (43.7%) and a non-mesh based repair was still considered an option when faced with fecal contamination (54.9%). Upon patient's request, 67.7% respondents would convince patients of mesh superiority. Among surgical trainees eighteen respondents (38.3%) had never seen a tissue based repair before and 36.1% respondents said tissue-based repair was not taught in their current or previous hospital(s). Most surgical trainees (48.9%) had basic knowledge and know a single technique. Considering indications for primary tissue repair, 57.4% mentioned a contaminated field as a valid indication. Comparable to the surgeon's response, 66% of surgical trainees would convince the patient of mesh superiority when asked for a pure tissue-based repair.<br><br>CONCLUSION: Our survey confirms the declining rate of tissue based repairs, with only 7% of surgical respondents performing sufficient procedures to allow for equivocal result compared to mesh-based repairs. Centralizing these procedures into specific hernia centers might allow for an increased case-load and dedicated training pathways giving trainees and future surgeons proper training.}, }
@article {pmid42284364, year = {2026}, author = {Li, M and Sun, P and Zhou, X and Yang, X and Li, W}, title = {Microbial modulation of CNS remyelination in multiple sclerosis: the missing link in gut-brain axis research.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/1028415X.2026.2686736}, pmid = {42284364}, issn = {1476-8305}, abstract = {Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) marked by demyelination and neurodegeneration. While much attention has focused on immune dysregulation and neuroinflammation, the failure of effective remyelination is a key driver of disease progression, especially in progressive MS. Recently, the gut microbiome has emerged as a potent modulator of systemic immunity and CNS function, influencing processes such as neuroinflammation and neurogenesis. This review examines current evidence on microbiota-derived metabolites, including short-chain fatty acids (SCFAs), indole derivatives, and bile acids, and their potential roles in pathways associated with oligodendrocyte precursor cell (OPC) biology and remyelination. Evidence from preclinical models, including germ-free systems, fecal microbiota transplantation (FMT), and probiotic interventions, suggests that microbial signals can modulate immune responses and CNS environments that may indirectly affect demyelination and repair processes. However, direct causal effects on OPC differentiation and functional remyelination remain incompletely established. We critically evaluate the strengths and limitations of existing studies, highlighting inconsistencies across experimental models and the context-dependent nature of microbiota-host interactions. Clinical evidence remains limited, with current studies primarily assessing inflammatory or metabolic outcomes rather than direct measures of remyelination. Key translational challenges include uncertainties regarding metabolite bioavailability in the CNS, cell-specific mechanisms of action, and reproducibility of microbiome-targeted interventions.}, }
@article {pmid42286318, year = {2026}, author = {La Rosa, F and Guzzardi, MA and Conti, G and Petroni, D and Pardo Tendero, M and Bernardi, S and Barone, M and Panetta, D and Tedeschi, L and Fabbri, C and Casavecchia, F and Riabitch, D and Granziera, F and Ragusa, R and Caselli, C and Giorgetti, A and Campani, D and Baglini, E and Menichetti, L and Elsinga, P and Luurtsema, G and Brigidi, P and Iozzo, P}, title = {Functional PET imaging of gut microbiota with [[18]F]fluorodeoxyglucose, [[18]F]fluorodeoxysorbitol and [[11]C]choline reflects Clostridia and Lactobacillales abundance in caecum and small intestine and host metabolic interactions.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {}, number = {}, pages = {}, pmid = {42286318}, issn = {1619-7089}, abstract = {PURPOSE: Interaction of gut microbiota (GM) with dietary sugars (glucose, sorbitol) and choline has been transversely implicated in the pathogenesis of multiple chronic diseases. Our aim was to develop functional PET imaging of GM, using a multi-tracer approach to capture bacteria classes involved in sugar fermentation and choline catabolism at their gastrointestinal (GI) location.<br><br>METHODS: Adult and young sex-balanced groups of mice underwent oral administration of [[18]F]FDG, [[18]F]FDS or [[11]C]choline ([[11]C]cho) and repeated PET imaging over 4-5 h. Antibiotics, probiotic or faecal microbiota transplantation (FMT) served to quantify the specific role and site of bacteria action. GM was sequenced ex-vivo; gut histology and metabolic profiles were assessed in subsets.<br><br>RESULTS: [[18]F]FDG and [[18]F]FDS reflected caecum abundance of Clostridia and Bacteroidia fermenters, with [[18]F]FDG exhibiting strongest and broadest relations. Clearance of [[11]C]cho from small gut reflected Bacilli and Lactobacilli abundance. In vitro cultures supported these relationships. Urinary [11]C-excretion was nearly abolished by antibiotics. PET imaging was able to differentiate and predict gut bacteria classes in mice receiving FMT from two age-extreme human donors. Urinary [[18]F]FDS excretion reflected small-gut goblet cell activation; high caecum [[18]F]FDG retention and small gut [[11]C]cho clearance predicted body glucose use and low systemic inflammation.<br><br>CONCLUSION: Imaging of ingested probes is simple and effective to map GM characteristics in situ and the functional crosstalk with host processes in mice in real-time. Our data confirm that the GI ecosystem is highly diversified, pointing to small intestine and caecum GM as dominant players in gut-body handling of our target nutrients.}, }
@article {pmid42286837, year = {2026}, author = {Gavanji, S and Suhail, M and Bencurova, E and Dandekar, T and Othman, EM}, title = {Recent advances and clinical relevance of microbiome dynamics in health and disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2679197}, pmid = {42286837}, issn = {1949-0984}, mesh = {Humans ; Probiotics/administration &amp; dosage ; Dysbiosis/microbiology/therapy ; Prebiotics ; *Microbiota ; *Gastrointestinal Microbiome ; Animals ; Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Gastrointestinal Tract/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The human microbiome, comprising trillions of bacteria, viruses, fungi, and archaea, represents an essential partner in human biology rather than a passive collection of microbes. These microbial communities inhabit diverse niches, including the gut, skin, oral cavity, respiratory tract, and urogenital system, where they contribute to digestion, vitamin biosynthesis, immune development, and regulation of host metabolism. Their dynamic interactions form a complex ecosystem that profoundly shapes health across the lifespan. However, with ever increasing reports on the microbiome including perceived health benefits, diagnostic use, detrimental species and immune modulation, we synthesize findings from multiple biomedical fields for this review. It first describes beneficial functions of commensal microbes in maintaining immune tolerance and metabolic balance, then analyzes the effect of diet, geography and medication exposure, the consequences of dysbiosis in gastrointestinal, metabolic, neurological, cardiovascular, autoimmune, and oncological disorders. The article examines the functional potency of the gut microbiome, keystone taxa as well as disease-stage-specific and general dynamics, how microbiomes modulate drug absorption, metabolism, and efficacy, thereby influencing individualized responses to therapy. Furthermore, it evaluates therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial strategies that seek to restore microbial equilibrium. The significance of this review lies in its integrative perspective, as it links microbiome research to precision medicine, emphasizing that safeguarding microbial diversity is crucial for prevention, early diagnosis, and the personalization of future medical interventions.}, }
@article {pmid42286862, year = {2026}, author = {Othman, EM and Bencurova, E and Ferretti, P and Bork, P and Rodriguez Del Rio, A and Huerta-Cepas, J and Caruana, I and Abdel-Latif, R and Akash, A and Albacete, A and Lafi, F and Dandekar, T and Naseem, M}, title = {Diet and microbiome shape small-molecule cytokinin pools in mammals.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2679497}, pmid = {42286862}, issn = {1949-0984}, mesh = {Animals ; *Cytokinins/blood/metabolism ; Humans ; Mice ; *Diet ; *Gastrointestinal Microbiome ; *Mammals/metabolism ; Metabolomics ; Metagenomics ; Feces/chemistry ; Swine ; Bacteria/classification/genetics/metabolism/isolation &amp; purification ; *Microbiota ; }, abstract = {Cytokinins (CKs) are adenine-derived metabolites traditionally characterized as plant hormones, yet their origin, distribution, and functions in mammalian systems remain largely undefined. Using integrated metabolomics, microbiome, and metagenomics approaches, we provide a systematic characterization of CK occurrence and potential sources in mammals. Serum profiling across five animal species revealed consistent detection of multiple CK derivatives, with concentrations markedly lower than in plant tissue. The CK storage form, zeatin-O-glucoside, predominated in mammalian sera, followed by trans-zeatin and kinetin, indicating a CK composition distinct from that in plants. Species-specific differences, such as reduced trans-zeatin in mice and lower kinetin in humans, further suggest divergent regulatory patterns. In mice, CKs were present in vascular tissues of the kidney, heart, and liver, demonstrating systemic distribution. Dietary manipulation showed that starvation significantly reduced CK abundance in serum, colon, feces, and urine, confirming that diet is a major contributor to the mammalian CK pool. Meta-omics analysis of gut microbiomes identified CK-related genes across multiple microbial taxa, with the highest representation in human microbiomes, followed by those of mouse and pig. Germ-free mouse experiments showed substantially lower CK levels than conventionally raised counterparts, establishing a microbiome-dependent contribution. Collectively, our findings identify CKs as diet and microbiome modulated metabolites in mammals, warranting future investigation to elucidate their physiological significance in mammalian biology.}, }
@article {pmid42286999, year = {2026}, author = {Felten, V and West, EA and Martini, F and Favrot, C and Unterer, S and Suchodolski, J and Scharl, M and Renz, H and Fischer, NM and Rostaher, A}, title = {Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.}, journal = {Veterinary dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/vde.70092}, pmid = {42286999}, issn = {1365-3164}, support = {215128/WT_/Wellcome Trust/United Kingdom ; 03162//American Kennel Club Canine Health Foundation/ ; //Westie Foundation of America/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear.<br><br>HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo.<br><br>ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n&#x2009;=&#x2009;20, placebo n&#x2009;=&#x2009;20).<br><br>MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90&#x2009;days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90).<br><br>RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7&#x2009;&#xb1;&#x2009;6 vs. 16&#x2009;&#xb1;&#x2009;12; p&#x2009;=&#x2009;0.006) and month 3 (8&#x2009;&#xb1;&#x2009;6 vs. 15&#x2009;&#xb1;&#x2009;12; p&#x2009;=&#x2009;0.020). Sustained responders (&#x2265;&#x2009;50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p&#x2009;=&#x2009;0.044). In the FMT group, the medication scores were lower at M2 (16&#x2009;&#xb1;&#x2009;10 vs. 23&#x2009;&#xb1;&#x2009;11; p&#x2009;=&#x2009;0.033) and M3 (13&#x2009;&#xb1;&#x2009;10 vs. 24&#x2009;&#xb1;&#x2009;15; p&#x2009;=&#x2009;0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p&#x2009;=&#x2009;0.028). FMT was well tolerated.<br><br>Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.}, }
@article {pmid42287485, year = {2026}, author = {Yang, X and Zhang, J and Jiang, N and Yang, L and Li, H and Dong, Y and Chen, Y and Chang, R and Li, R and Ma, Y and Yang, Y and Liu, P and Song, P}, title = {Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.}, journal = {Journal of bioenergetics and biomembranes}, volume = {58}, number = {1}, pages = {}, pmid = {42287485}, issn = {1573-6881}, mesh = {Animals ; *Reperfusion Injury/metabolism/pathology ; Mice ; *Toll-Like Receptor 4/metabolism ; *Gastrointestinal Microbiome ; *Neutrophil Infiltration ; Male ; *Receptors, Interleukin-8B/metabolism ; *Liver/pathology/metabolism ; Mice, Inbred C57BL ; *MAP Kinase Signaling System ; Signal Transduction ; Disease Models, Animal ; }, abstract = {Liver ischemia/reperfusion injury (IRI) is a major complication of hemorrhagic shock, hepatectomy and liver transplantation. Intestinal microecology has momentous functions in various human diseases. The present study aimed to elucidate the role and underlying mechanism of intestinal microecology in liver IRI. A liver IRI mouse model was constructed and validated using hematoxylin and eosin staining, enzyme-linked immunosorbent assay and Naphthol AS-D chloroacetate esterase staining. The function of intestinal microecology in liver IRI was evaluated using flow cytometry and western blot analysis. Moreover, the mechanisms of intestinal microecology in liver IRI were assessed using a series of molecular experiments. The results revealed that liver IRI associated with intestinal microecology dysbiosis exhibited increased hepatic neutrophil infiltration, MAPK pathway activation and inflammatory cytokine production. The 16 S rRNA gene sequencing of fecal samples from Sham, IRI, IRI+antibiotic pre-treatment and fecal transplantation (FT) groups revealed microbial community alterations, with shifts in Bacteroidota and Firmicutes abundance associated with liver injury and neutrophil recruitment. PCA, PCoA and taxonomic profiling further confirmed group-dependent remodeling of the gut microbial community. FT using fecal microbiota from IRI donor mice exacerbated liver neutrophil infiltration, MAPK/CXCR2 activation and inflammatory responses, whereas TAK-242-mediated TLR4 blockade attenuated these effects. Overall, the present study suggests that gut microbiota dysbiosis may enhance liver IRI by promoting neutrophil recruitment, at least in part through the TLR4/MAPK/CXCR2 axis, revealing a novel microbe-immune-liver interaction that may be targeted therapeutically.}, }
@article {pmid42287567, year = {2026}, author = {Hao, YY and Zhao, ZA and Zhang, LM and Zhao, ZG}, title = {Targeting the gut-brain axis: microbial interventions for neurological disorders.}, journal = {Metabolic brain disease}, volume = {41}, number = {1}, pages = {}, pmid = {42287567}, issn = {1573-7365}, support = {82570586//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Nervous System Diseases/microbiology/therapy/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism ; Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; *Brain-Gut Axis/physiology ; Diet, Ketogenic/methods ; Blood-Brain Barrier/metabolism ; }, abstract = {The pathogenesis of neurological disorders involves complex interactions among genetic, environmental, immunological, and metabolic factors. Characterized by high disability rates and prolonged disease courses, these conditions impose a significant burden on patients and society. As a dynamic and modifiable component of the internal environment, gut microbiota plays a central role in the onset and progression of neurological disorders through the "gut-brain axis." Bidirectional communication occurs between gut microbiota and the central nervous system via neural, immune, and endocrine pathways. This interplay regulates blood-brain barrier integrity, modulates neuroinflammatory responses, and maintains neurotransmitter balance, thereby influencing disease progression. This review systematically summarizes current evidence on the role of gut microbiota in representative neurological disorders, such as traumatic brain injury, stroke, and epilepsy, and critically evaluates the therapeutic potential of microbiota-targeted interventions, including fecal microbiota transplantation, ketogenic diets, and probiotics. Collectively, this review provides novel insights into disease pathogenesis and highlights innovative microbiome-based therapeutic strategies for the prevention and management of neurological diseases.}, }
@article {pmid42287814, year = {2026}, author = {Li, Y and Zhang, B and He, G and Shen, C and Chang, F and Yang, J and Wang, S and Wang, Y and Zong, J and Luo, Y and Wang, N and Sun, Y and Sui, Y and Wu, M and Lu, D and Li, C and Zhou, X}, title = {Saikosaponin A restores the IDO1-driven gut-testis kynurenine axis to alleviate oligozoospermia.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {158}, number = {}, pages = {158414}, doi = {10.1016/j.phymed.2026.158414}, pmid = {42287814}, issn = {1618-095X}, mesh = {Male ; Animals ; *Oleanolic Acid/analogs &amp; derivatives/pharmacology ; *Saponins/pharmacology ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; *Oligospermia/chemically induced/drug therapy/metabolism ; *Testis/drug effects/metabolism ; *Kynurenine/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Mice ; Spermatogenesis/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Busulfan (Bus)-induced oligozoospermia still lacks a disease-modifying therapy, and its pathogenesis has been largely attributed to germ-cell DNA damage. Emerging evidence indicates that microbiota-derived metabolites are key determinants of spermatogenic failure. Saikosaponin A (SSA), a major triterpenoid from Bupleurum, has never been evaluated in male infertility. Consequently, its regulatory role in the gut microbiota-metabolite axis and causal efficacy remain completely undefined.<br><br>PURPOSE: To determine whether SSA rescues Bus-induced oligozoospermia via the gut microbiota-metabolite axis, and to uncover a novel pathogenic mechanism of Bus, beyond the known germ-cell DNA damage pathway, revealing a gut microbiota-metabolite-mediated regulatory axis.<br><br>METHODS: Bus-induced oligozoospermia was established in male C57BL/6 J mice and followed by SSA treatment. Sperm count, testis index, and histology were assessed; spermatogenic proteins were quantified by Western blot. Microbiota and metabolites were profiled via 16S rDNA sequencing; serum metabolomics; and fecal microbiota transplantation (FMT) from SSA donors. Testicular transcriptome sequencing identified differentially expressed pathways. Indole-3-carboxaldehyde (ICA) administration and Kynurenine (Kyn) supplementation were performed in parallel. Indoleamine 2,3-dioxygenase 1 (IDO1) protein level and activity were measured by Western blot and ELISA. ICA-IDO1 interaction was verified by molecular docking and surface plasmon resonance (SPR). The l-tryptophan/L-kynurenine ratio was determined by targeted liquid chromatography-mass spectrometry (LC-MS/MS).<br><br>RESULTS: SSA restored sperm count, testis index, and tubular architecture while increasing DDX4, DAZL, and SYCP1/3. It reversed Bus-induced Lactobacillus expansion, decreased colonic ICA, relieved ICA-mediated IDO1 inhibition, thereby restoring colonic IDO1 activity, and elevated Kyn. FMT from SSA donors reproduced these protective effects. Transcriptomics showed up-regulation of AKT-mediated targets: pro-growth (CCND1), antioxidant (NRF2), and anti-apoptotic (Bcl-2), with down-regulation of pro-apoptotic genes. Mechanistically, SSA reshaped the gut microbiota, lowered colonic ICA, relieved ICA-mediated IDO1 inhibition, and restored Kyn-dependent testicular antioxidant and anti-apoptotic signaling.<br><br>CONCLUSION: By reshaping the gut microbiota, reducing colonic ICA and relieving ICA-mediated IDO1 inhibition, SSA restored Kyn-driven testicular antioxidant and anti-apoptotic signaling. This suggests a microbiota-directed, non-hormonal candidate preclinical approach for Bus-induced oligozoospermia; the gut microbiota-ICA-IDO1-Kyn axis offers a framework awaiting human validation.}, }
@article {pmid42288145, year = {2026}, author = {Zhang, X and Wang, XR and Gai, SL and Han, YQ and Quan, XY and Yin, S and Li, J and Wang, N}, title = {Gut microbiota reshaped by exercise improved glycolipid metabolism in obese mice via increasing the production of medium and long chain fatty acids: a multi-omics study.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110447}, doi = {10.1016/j.jnutbio.2026.110447}, pmid = {42288145}, issn = {1873-4847}, abstract = {Exercise is effective in combating obesity and regulating the composition of the gut microbiota. However, the molecular mechanism by which exercise alters gut microbiota and its metabolites to exert weight loss has not been fully elucidated. In this study, the mechanism of gut microbiota and microbial metabolites reshaped by exercise in weight loss were investigated by macrogenomic sequencing, metabolomics analysis and fecal microbiota transplantation (FMT). The results showed that exercise significantly increased the abundance of beneficial bacteria such as Oscillibacter, Lachnoclostridium, and unclassified_f__Lachnospiraceae, and decreased the abundance of Lactobacillus and Desulfovibrio. Meanwhile, exercise significantly increased medium- and long-chain fatty acid (MCFA and LCFA) content, as well as butyric acid, and decreased fructose levels. These metabolites were associated with fatty acid degradation, and unsaturated fatty acid synthesis pathways. In addition, FMT from exercised mice significantly reduced high-fat diet (HFD)-induced obesity and lipid accumulation, increased insulin sensitivity, and improved glucose homeostasis, with decreased the levels of serum lipids and lipopolysaccharide (LPS). FMT also attenuated hepatic and pancreatic dysfunction, as well as hepatic steatosis. Notably, FMT from exercised mice significantly increased the content of MCFAs and LCFAs in the intestines of HFD-treated mice and upregulated the expression of genes related to glycolipid metabolism and the secretion of Glucagon-like Peptide-1 (GLP-1). Finally, caprylic, lauric, cardamic and stearic acids can significantly increase GLP-1 levels in Caco-2 cells. Taken together, the mechanism by which exercise suppresses obesity may inhibit appetite by optimizing the intestinal microbiota, promoting the synthesis of MCFAs and LCFAs, and up-regulating GLP-1 secretion.}, }
@article {pmid42288685, year = {2026}, author = {Lin, ML and Gao, HN}, title = {Transplantation of encapsulated fecal microbiota: research progress and future trends.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, pmid = {42288685}, issn = {1867-0687}, support = {2022YFC2304500//National Key Research and Development Program/ ; 2021YFA1301104//National Key Research and Development Program/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) demonstrates significant efficacy in treating intestinal disorders, such as recurrent Clostridioides difficile infection (rCDI). However, traditional FMT relies on invasive delivery methods (e.g., colonoscopy or use of a nasoenteric tube) and lacks standardized donor screening, limiting its widespread clinical adoption and scalability. As a key formulation of live biotherapeutic products (LBPs), encapsulated FMT represents a transition from empirical microbial transfer to engineered biotherapeutics, offering a safer and more convenient approach for clinical application.<br><br>DATA SOURCES: This review synthesizes, compares, and integrates data in a narrative fashion from PubMed and the China National Knowledge Infrastructure.<br><br>RESULTS: Research on encapsulated FMT in adults has progressed toward standardization and the exploration of new indications. In contrast, pediatric studies remain primarily focused on rCDI treatment and lack large-scale randomized controlled trials. Evolution toward encapsulated, standardized products is driving a shift from whole-community microbial formulations toward more defined consortia and, ultimately, synthetic biology-based innovations. Concurrent significant regulatory challenges persist, as definitions of LBPs remain inconsistent and clear, harmonized international guidelines are yet to be established.<br><br>CONCLUSIONS: This review summarizes progress and emerging research priorities in encapsulated FMT while also examining current regulatory challenges and innovative directions within the LBP framework. Future developments are poised to advance encapsulated FMT from whole-community transplantation toward the precise modulation of functional microbial consortia. This progression will help drive microbial therapeutics toward greater standardization and personalization, offering improved treatment strategies for intestinal and other microbiome-associated diseases.}, }
@article {pmid42289709, year = {2026}, author = {Lei, L and Wang, A and Dong, L and Wu, T and He, W and Yang, Y and Li, J and Bi, X and Cai, Y and Guan, X and Zhu, X}, title = {Food-grade TiO2 impairs intestinal mucus barrier via disrupting the gut microbiota-ILA-mucin sulfation axis: novel insights and dietary intervention strategies.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04679-6}, pmid = {42289709}, issn = {1477-3155}, support = {82304152//National Natural Science Foundation of China/ ; 2024040801020373//Natural Science Foundation (Exploration Project) of Wuhan City/ ; WX23Q28//the Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; 2023AFB392//Natural Science Foundation of Hubei Province/ ; }, abstract = {The use of titanium dioxide (TiO2) as a food additive has persistently elicited concerns about its potential toxicity, primarily attributed to the significant presence of nanoparticles. Studies have recently demonstrated that nano- or micro-sized food-grade TiO2 (fg-TiO2) particles can disrupt gut microbial balance and weaken the intestinal barrier; however, the underlying mechanisms remain poorly understood. Furthermore, research on dietary interventions for repairing fg-TiO2-induced intestinal injury is limited. This study delved into the role of the interactions among gut microbes, indole-3-lactic acid (ILA) and mucin sulfation in fg-TiO2-induced intestinal mucosal barrier damage through multi-omics analysis, and revealed the protective effects of quercetin. Prolonged oral administration of fg-TiO2 at doses pertinent to human exposure resulted in notable intestinal inflammation and mucosal barrier damage through diminishing mucin sulfation. Further analysis demonstrated that fg-TiO2 caused significant gut microbiota dysbiosis and metabolite changes. It was found that Lactobacillus and its metabolite ILA, an aryl hydrocarbon receptor (AHR) agonist, was significantly downregulated following oral ingestion of fg-TiO2, which decreased the activation of AHR and ultimately led to a loss in mucin sulfation in colon tissues. Notably, experiments involving fecal microbiota transplantation (FMT) and ILA supplementation indicated gut microbial shifts and the consequent decrease in colonic ILA levels were accountable for the detrimental effects of fg-TiO2 on mucin sulfation and intestinal barrier integrity. Moreover, this study found that dietary intervention with quercetin could effectively reverse the damage to the intestinal mucosal barrier induced by fg-TiO2 through targeting gut microbiota-ILA-mucin sulfation axis. This research uncovered the adverse impacts of fg-TiO2 on gut homeostasis and indicates the potential of quercetin to combat the intestinal toxicity of fg-TiO2. These findings enhanced our comprehension of the safety profile of fg-TiO2 and proposed a nutritional approach to mitigate the health risks associated with fg-TiO2 exposure.}, }
@article {pmid42290978, year = {2026}, author = {Jin, Z and Zhang, Y and Zhong, Z and Shen, Z and Huang, L and Hu, H and Chen, X and Liu, W and Li, L and Gao, C}, title = {Dynamic feedback BacGuard anchors microbial metabolism to host symbiosis in real-time ulcerative colitis therapy.}, journal = {Bioactive materials}, volume = {65}, number = {}, pages = {365-379}, pmid = {42290978}, issn = {2452-199X}, abstract = {The escalating global burden of ulcerative colitis (UC) underscores the limitations of conventional anti-inflammatory therapies. Although multi-omics insights have propelled gut microbiota modulation to the forefront of therapeutic innovation, current strategies relying on probiotics or fecal transplants remain constrained by empirical designs due to the lack of spatiotemporal precision and real-time monitoring of microbial metabolic vitality in situ. In this study, BacGuard, a metabolically orthogonal microgel platform, was developed to unify the probiotic surveillance and guided dynamic dose regulation with spatially targeted microbiota-associated metabolic modulation. Our core design featured a β-xylosidase-activated chemiluminescent probe (XOS-CL) that was conjugated with xylooligosaccharide-based hyperbranched polymers (HBXOK) and orally delivered via microgels. Thereby, this system enabled real-time monitoring of probiotic abundance and metabolic activity in the colon through enzyme-responsive signaling, while simultaneously promoting short-chain fatty acid (SCFA) production via redirected bacterial metabolic flux. This dual-action system created a self-reinforcing therapeutic loop and optically quantifying the microbial activity in a dynamic manner. By resolving the causal disconnects between enzymatic activity, microbiota proliferation, and host interactions, the BacGuard bridged the diagnostic metrics to functional therapeutic outcomes. Anchoring both sensing and treatment to microbial metabolic flux, our platform reimagined the precision gut ecosystem engineering, establishing an image-guided dynamic dose regulation framework that actively preserved the microbiota-host symbiosis through in-time and function-adaptive modulation.}, }
@article {pmid42292220, year = {2026}, author = {Ge, J}, title = {Functional redundancy as a stabilizing principle in bacterial communities under antibiotic perturbation: mechanisms, trade-offs, and emerging frameworks.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1834295}, pmid = {42292220}, issn = {2296-858X}, abstract = {The widespread use of antibiotics has severely disrupted the structure of microbial communities, but the responses of these communities vary in different environments. Interestingly, even when the species composition changes, some microbial communities can still maintain crucial functions, a phenomenon known as "decoupling of structure and function." Among them, functional redundancy (FR) - the characteristic that multiple microorganisms perform the same ecological function - is the key mechanism for maintaining this stability. This review focuses on how functional redundancy may enhance microbial community resilience under antibiotic perturbation. We first start from the insurance hypothesis and the YAS (yield - acquisition - stress) framework to explain the ecological principles behind functional redundancy, and explain how microorganisms allocate resources and make trade-offs in different environments. We systematically analyze the multi-level defense strategies of microorganisms at five levels, including: ecological niche differentiation at the species level, horizontal transfer of resistance genes at the genetic level, cross-feeding reconstruction of metabolic networks, dormancy strategies at the temporal dimension (seed bank), and population regulation mediated by bacteriophages. Methodologically, we review metatranscriptomic approaches for distinguishing active signals from residual DNA, structural entropy algorithms for inferring FR, and AI-based tools for identifying latent resistance genes. Evidence from ecosystems such as the gut, respiratory tract, soil, and wastewater suggests the broad relevance of functional redundancy, although its stabilizing effect depends on antibiotic type, exposure duration, initial community composition, and ecological context. Finally, we explore the application prospects of this principle in the construction of synthetic communities and the optimization of fecal microbiota transplantation, and point out the evolutionary costs that may accompany maintaining functional redundancy, which is an important challenge that future research needs to address.}, }
@article {pmid42292438, year = {2026}, author = {Wang, K and Zhu, X and Ju, X and Zhou, M and Shen, G}, title = {From nutritional intervention to immune modulation: a multi-database bibliometric and topic modeling study of vitamin D in inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1845767}, pmid = {42292438}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/immunology/diet therapy ; *Vitamin D/therapeutic use ; Bibliometrics ; Animals ; *Immunomodulation ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent inflammatory episodes in the gastrointestinal tract. Conventional therapies, including biologics, corticosteroids, and immunosuppressive drugs, can effectively alleviate disease activity. However, their utility is often limited by adverse effects. Vitamin D plays a role in modulating immune function, intestinal barrier integrity, and the gut microbiota. It has emerged as a promising adjunctive therapy for IBD.<br><br>OBJECTIVE: To map the research landscape of vitamin D in IBD using bibliometric analysis, focusing on knowledge evolution, core themes, and emerging trends.<br><br>METHODS: Publications from 2006 to 2025 were collected by searching the Web of Science Core Collection (WoSCC) and Scopus databases. After removing duplicates, 2,659 articles and reviews were obtained for analysis. Networks were constructed using CiteSpace, VOSviewer, R, and Python. PubMed clinical trials were included for complementary analysis, and BERTopic was applied to identify latent topics and their temporal dynamics.<br><br>RESULTS: A total of 2,659 publications spanning 970 journals were identified, with a steady increase in output. The USA was the leading contributor and also demonstrated strong international collaboration. Ananthakrishnan Ashwin N. was the most influential author, and Inflammatory Bowel Diseases was the journal with the leading journal. Core themes included vitamin D deficiency, gut microbiota, inflammatory response, diet and nutrition. The focus has shifted toward gut microbiota, immune regulation, micronutrients, and evidence-based approaches. Furthermore, BERTopic modeling identified 12 latent topics, with increasing emphasis on gut microbiota, fecal microbiota transplant, and nutritional deficiencies.<br><br>CONCLUSION: This bibliometric analysis provides a concise, data-driven overview of research on vitamin D in IBD. The results highlighting its structure, evolution, and emerging trends, and informing future mechanistic and translational research.}, }
@article {pmid42292442, year = {2026}, author = {Leng, F and Xia, R and Pei, J and Shi, Y and Gao, C and Wang, F and Li, Y}, title = {The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1840903}, pmid = {42292442}, issn = {1664-3224}, mesh = {Humans ; *Breast Neoplasms/immunology/pathology/therapy/microbiology ; Female ; *Tumor Microenvironment/immunology ; *Microbiota/immunology ; Animals ; Neoplasm Metastasis ; Epithelial-Mesenchymal Transition/immunology ; Immunomodulation ; Neoplastic Cells, Circulating/immunology ; }, abstract = {Breast cancer metastasis remains the leading cause of cancer-related mortality and is closely linked to immune evasion and tumor microenvironment (TME) remodeling. Emerging evidence suggests that intratumoral microbiota (ITM), typically low in biomass and predominantly intracellular, may be associated with tumor progression. This review summarizes the compositional features of ITM and their potential roles in metastasis, including epithelial-mesenchymal transition (EMT), circulating tumor cell (CTC) survival, pre-metastatic niche formation, and distant colonization. Mechanistically, ITM may influence these processes through immune-related signaling pathways (e.g., PRR-mediated cascades) and modulation of immune cell function. However, current evidence is largely derived from preclinical or correlative studies, and causal roles in human breast cancer remain unproven. Methodological challenges associated with low biomass further complicate interpretation. We also discuss microbiota-targeted strategies, including probiotics, antibiotics, and fecal microbiota transplantation, which remain experimental. Future studies using rigorous methodologies and longitudinal human data are required to clarify the role of ITM and its clinical potential.}, }
@article {pmid42292452, year = {2026}, author = {Li, Y and Zhang, J and Wu, S and Liu, Z and Qin, S}, title = {The impact of gut microbiota on cervical cancer and precancerous lesions: neglected status, mechanisms, challenges, and a call to action.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1826283}, pmid = {42292452}, issn = {1664-3224}, mesh = {Female ; Humans ; *Uterine Cervical Neoplasms/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Papillomavirus Infections/immunology/microbiology/virology ; Human Papillomavirus Viruses/immunology ; *Precancerous Conditions/immunology/microbiology ; Animals ; Vagina/microbiology/immunology ; *Uterine Cervical Dysplasia/immunology/microbiology ; Dendritic Cells/immunology ; }, abstract = {Cervical cancer (CC) remains a major global health threat closely associated with persistent high-risk human papillomavirus (HPV) infection. Although immune checkpoint inhibitors (ICIs) have emerged as a therapeutic option, their objective response rates remain unsatisfactory. Variations in the local vaginal microbiota alone cannot fully explain inter-individual differences in HPV clearance, suggesting that additional systemic immune determinants are involved. The gut microbiota, a central regulator of host systemic immunity, can profoundly influence HPV clearance and antitumor immune responses by shaping dendritic cell (DC) function, modulating the Th1/Th2 balance, regulating regulatory T cell (Treg) expansion, and affecting natural killer (NK) cell activity. Emerging evidence indicates that specific gut microbial taxa are causally associated with HPV infection, cervical intraepithelial neoplasia (CIN), and cervical cancer, and may reshape the vaginal microecological environment and enhance immunotherapy responses. However, this dimension has long received insufficient attention. This Perspective systematically addresses four core issues: the neglected status of gut microbiota research and the functional boundaries of vaginal microecology; key mechanisms through which gut microbiota regulate HPV clearance and cervical lesion progression; major challenges restricting progress; and potential strategies for promoting clinical translation. This work aims to establish a theoretical framework for gut microbiota-based interventions in cervical cancer prevention and treatment, providing directional guidance for this emerging interdisciplinary field.}, }
@article {pmid42293159, year = {2026}, author = {Ike, I and Teymouri, F and Crook, C and Guzman, S and Hazeltine, M and Castillo, D and Li, D and Brar, G}, title = {The interplay between bile acid metabolism and gut microbiome in biliary tract cancers.}, journal = {Frontiers in microbiomes}, volume = {5}, number = {}, pages = {1774429}, pmid = {42293159}, issn = {2813-4338}, abstract = {The gut microbiota and bile acids (BAs) exist in a tightly regulated, bidirectional relationship that influences host metabolism, immune function, and disease. Primary BAs synthesized in the liver are chemically transformed by intestinal microbes into a diverse pool of secondary BAs, which exert antimicrobial effects and activate host signaling pathways including Farnesoid X Receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and sphingosine-1-phosphate receptor 2 (S1PR2). These pathways regulate BA homeostasis, epithelial barrier integrity, inflammation, and carcinogenesis. Disruption of this BA-microbiome axis has been implicated in biliary tract cancers (BTCs), a group of aggressive malignancies with rising global incidence and limited therapeutic options. Secondary BAs and BA receptor signaling contribute to tumor initiation and progression through NF-κB activation, oxidative stress, and altered cell survival, whereas reduced FXR signaling and obstructed enterohepatic circulation further promote inflammatory dysregulation. Emerging evidence demonstrates that microbial dysbiosis and altered BA metabolism are associated with distinct BTC microbial profiles, enriched in taxa such as Fusobacterium, Salmonella, Prevotella, and Actinomyces, alongside depletion of commensals including Lactobacillus. These taxa influence inflammatory signaling, BA transformation, and epithelial injury, contributing to carcinogenesis. Microbiome-BA interactions also shape anti-tumor immunity and responses to immune checkpoint inhibitors (ICIs). Specific microbial signatures-particularly enrichment of Lachnospiraceae, Erysipelotrichaceae, Bacteroidetes, and Alistipes-correlate with enhanced immune activation and improved clinical outcomes in hepatobiliary cancers. Modulation of gut microbiota through antibiotics, probiotics, or fecal microbiota transplantation can influence BA composition, immune surveillance, and therapeutic efficacy. Collectively, these data highlight the central role of the BA-microbiome axis in BTC pathogenesis and treatment response. Microbial and BA metabolite profiling represent promising avenues for biomarker development, while targeted manipulation of BA signaling and microbial ecology offers potential therapeutic strategies to improve BTC outcomes.}, }
@article {pmid42293221, year = {2026}, author = {Gong, L and Kong, J and Shao, X and Meng, W and Zhang, R and Zhang, Y and Feng, Y}, title = {Dietary L-arginine supplementation exerts preventive effects on colitis through modulation of the gut microbiota.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1848380}, pmid = {42293221}, issn = {2296-861X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing gastrointestinal disease that imposes an increasing global health burden. Our previous study showed that L-arginine (Arg) could markedly alleviate experimental colitis; however, the relative efficacy of its prophylactic versus therapeutic intervention remains unclear, and the underlying mechanisms require further elucidation.<br><br>METHODS: Mice received Arg supplementation either prior to DSS exposure (BeArg) or during DSS treatment (DuArg). Intestinal barrier function, inflammatory cytokines and gut microbiota alterations were evaluated, followed by fecal microbiota transplantation (FMT) validation.<br><br>RESULTS: BeArg markedly alleviated DSS-induced mice body weight loss, disease activity index (DAI) elevation, and colon shortening, exhibiting a protective efficacy comparable to full-course Arg administration. BeArg also lowered serum lipopolysaccharide, consistent with improved intestinal barrier integrity. In addition, BeArg reduced the expression of tumor necrosis factor-alpha (TNF-&#x3b1;) and interferon-gamma (IFN-&#x3b3;) while augmenting interleukin-10 (IL-10) at both the transcriptional and protein levels. By comparison, DuArg produced only modest clinical improvement and showed limited efficacy in modulating barrier dysfunction and inflammatory responses. 16S rRNA sequencing revealed that BeArg and Arg interventions induced similar alterations in the gut microbial community structure, while FMT further confirmed that Arg-mediated remodeling of the gut microbiota effectively protected against DSS-induced colitis.<br><br>CONCLUSION: These data indicate that Arg exerts a prophylactic effect against colitis by modulating the gut microbiota, underscoring the pivotal role of intervention timing in optimizing its protective effects.}, }
@article {pmid42293516, year = {2026}, author = {Zou, Y and Liu, L and Chen, H and Luo, Z and Zhu, Z and Li, Z and Lin, B and Zhuang, Z and Li, W and Yang, Q and Yang, X and Zhou, H and Luo, M and Dai, D}, title = {Study protocol for a randomized controlled trial of fecal microbiota transplantation via different routes in children with moderate-to-severe autism spectrum disorder.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1829532}, pmid = {42293516}, issn = {1664-302X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) shows promise for autism spectrum disorder (ASD) by modulating the gut-brain axis, but the optimal delivery route remains unknown. Our previous single-arm study suggested efficacy of nasojejunal FMT in children with moderate-to-severe ASD, yet could not exclude placebo effects or compare routes. This randomized controlled trial aims to determine the most effective and tolerable FMT administration route.<br><br>METHODS: This single-center, randomized, triple-blind, double-dummy, placebo-controlled, three-arm parallel-group trial will enroll 75 children (aged 3-16 years) with moderate-to-severe ASD [Childhood Autism Rating Scale, Second Edition (CARS-2) &#x2265;36]. Participants are randomized 1:1:1 to: (1) FMT via nasojejunal tube + sham colonoscopy (FMT-NJT); (2) active FMT via colonoscopy with transendoscopic enteral tube placement (first session) + two subsequent infusions via the indwelling tube + sham nasojejunal intubation (FMT-C); (3) placebo via both routes (sham procedures). Three FMT/placebo sessions (5 mL/kg, max 100 mL) are administered over 5 days. Primary outcome is change in CARS-2 score from baseline to Week 24. Secondary outcomes include changes in Social Responsiveness Scale, Autism Behavior Checklist, Gastrointestinal Symptom Rating Scale, Short Sensory Profile, Children's Sleep Habits Questionnaire, gut metagenomic profiles (baseline, Weeks 2,6,12,24,48), and adverse events.<br><br>RESULTS: This is a study protocol; no results are available.<br><br>CONCLUSIONS: This first head-to-head comparison of FMT routes in pediatric ASD will provide high-level evidence to guide treatment standardization, directly addressing the translational gap identified in our preliminary work.}, }
@article {pmid42294809, year = {2026}, author = {Wu, Z and Yang, J and Zhang, M and Li, Y and Tu, Z and Wang, J and Yu, JT and Guo, K and Luo, R}, title = {Microplastics-Induced Gut Microbiota Dysbiosis Accelerates Alzheimer's-Like Pathology and Cognitive Decline via the Gut-Brain Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e76072}, doi = {10.1002/advs.76072}, pmid = {42294809}, issn = {2198-3844}, support = {82471445//National Natural Science Foundation of China/ ; 32170988//National Natural Science Foundation of China/ ; 561120215//Talent Scientific Fund of Lanzhou University/ ; 842024017//Gansu Longyuan Youth Talents Program/ ; 26JRRA026//Basic Research Program of Gansu Province/ ; 2026QNTD004//Gansu Province Youth Talent Project (Team)/ ; }, abstract = {Alzheimer's disease (AD) is incurable and increasingly attributed to gene-environment interactions. Microplastics (MPs) are omnipresent in the human food chain, yet their impact on neurodegeneration is largely unknown. Here we show that chronic oral exposure to 2-µm amine-modified polystyrene microparticles accelerates cognitive decline, amplifies Aβ deposition, gliosis, and synaptic loss, and cripples autophagic flux in 5XFAD mice through the gut-brain axis. MPs accumulate in the gut, breach the epithelial barrier, and selectively expand the taurine-depleting pathobiont Bilophila, while suppressing taurine-synthesizing commensals. Untargeted metabolomics reveal a systemic taurine deficit that precedes and predicts exacerbated Aβ deposition, gliosis, synaptic loss, and autophagic blockade in 5XFAD mice. Antibiotic-mediated microbiota ablation and fecal microbiota transplantation (FMT) demonstrate that the neurotoxic phenotype is fully microbiota-dependent. Restoring taurine level rebalances microglial homeostasis, reinstates autophagic flux, and rescues memory deficits in MPs-treated 5XFAD mice. Translational validation using Alzheimer's Disease Neuroimaging Initiative (ADNI) plasma shows taurine is significantly lower in AD patients versus cognitively normal controls and inversely correlates with cognitive decline. Our findings identify MPs-induced gut-microbiota dysbiosis as a modifiable environmental driver of AD pathogenesis and establish taurine supplementation as a readily translatable intervention that simultaneously fortifies the intestinal barrier and neutralizes microbiota-mediated neurodegeneration.}, }
@article {pmid42294884, year = {2026}, author = {Tao, E and Wang, L and Yuan, T}, title = {The gut microbiome in preterm infants: development, dysbiosis, and disease implications.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0008826}, doi = {10.1128/cmr.00088-26}, pmid = {42294884}, issn = {1098-6618}, abstract = {SUMMARYPreterm infants face a unique trajectory of gut microbiome assembly, shaped by the convergence of physiological immaturity, necessary clinical interventions, and the neonatal intensive care unit environment. This dysbiotic ecosystem-characterized by low diversity, depletion of beneficial commensals such as Bifidobacterium, and expansion of pathobionts, including Enterobacteriaceae-is increasingly recognized as a central mediator of neonatal morbidity. This review synthesizes current evidence on preterm microbiome development, its role in necrotizing enterocolitis through mechanisms involving Toll-like receptor 4 signaling, bile acid dysmetabolism, and immune dysregulation, and its systemic impact via gut-organ axes linking the intestine to the brain, lung, eye, and systemic circulation. We critically evaluate microbiome-targeted interventions across the translational spectrum, from foundational practices such as human milk feeding and antibiotic stewardship to active modulation with probiotics and prebiotics, and emerging precision strategies, including postbiotics, phage therapy, and fecal microbiota transplantation. Methodological advances in multi-omics, machine learning, and digital twin modeling are paving the way for personalized, predictive microbiome-mediated care. We also address the hidden burden of antimicrobial resistance in the preterm gut and the challenges of translating mechanistic insights into clinical practice. Looking forward, embracing the complexity of the preterm microbiome as a dynamic, multi-kingdom ecosystem is essential for developing holistic interventions that improve both short-term survival and long-term neurodevelopmental, respiratory, and metabolic outcomes.}, }
@article {pmid42294946, year = {2026}, author = {Thonghem, A and Chattipakorn, N and Chattipakorn, SC}, title = {Potential Roles of Gut Microbiome and Metabolomes in Interstitial Lung Disease: Evidence across Preclinical and Clinical Research.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxag138}, pmid = {42294946}, issn = {1365-2672}, abstract = {Interstitial lung disease (ILD) is a heterogeneous condition that affects the lung parenchyma with varying degrees of inflammation and/or fibrosis. Several studies have suggested a potential link between the gut microbiome and the pathophysiology of lung diseases, including ILD. Accumulating evidence supports bidirectional gut-lung axis interactions potentially mediated by the microbiota. Alterations in the gut microbiome have been associated with the onset and severity of interstitial lung disease. This review aims to summarize findings from in vivo and clinical studies that have investigated the associations between the gut microbiome and ILD. Changes in the gut microbiome have been consistently found in various ILD subtypes, including idiopathic pulmonary fibrosis, radiation pneumonitis, silicosis, coal worker's pneumoconiosis, and connective tissue disease-related ILD. Preclinical studies demonstrate that gut dysbiosis is associated with altered immune responses, increased pro-inflammatory cytokines, and enhanced fibrotic pathways, with mechanistic evidence suggesting the involvement of specific microbial metabolites (short-chain fatty acids, bile acids, and immune mediators. Interventional studies in animal models suggest that fecal microbiota transplantation may attenuate pulmonary inflammation and fibrosis; however, clinical evidence remains limited. This review synthesizes findings across study types, highlights proposed mechanistic pathways, discusses contradictory results, and identifies critical knowledge gaps requiring future investigation to establish causality and inform potential therapeutic development.}, }
@article {pmid42295788, year = {2026}, author = {Pan, G and Pang, K and Duan, S and Liu, L and Ma, X and Qi, H and Zhao, T}, title = {Study on the Effects and Mechanisms of an Ulvan Derivative in NAFLD through Gut Microbiota Fermentation.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.6c01387}, pmid = {42295788}, issn = {1520-5118}, abstract = {Nonalcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota dysbiosis and lacks effective therapies. This study evaluated the effects of HU, a high-sulfated derivative of Ulva pertusa polysaccharide, using an HFD-induced NAFLD mouse model. Structural characterization showed that HU possessed a porous and aggregated surface morphology with heterogeneous nanoscale features. In HFD-fed mice, HU significantly reduced body weight gain, hepatic lipid accumulation, and inflammation, while improving serum biochemical parameters, including 44.0% lower triglycerides and 30.7% lower aspartate aminotransferase levels.16S rRNA sequencing revealed that HU markedly modulated gut microbial composition. In vitro fermentation showed enrichment of beneficial genera, while in vivo experiments demonstrated increased Faecalibaculum and reduced Acinetobacter. Fecal microbiota transplantation further supported the involvement of HU-modulated gut microbiota in the protective effects against HFD-induced NAFLD. These findings suggest that HU ameliorates NAFLD by reshaping gut microbiota, suppressing inflammation, and alleviating hepatic lipid accumulation.}, }
@article {pmid42296911, year = {2026}, author = {Kim, OY and Song, J}, title = {Tryptophan metabolism as a key integrator within the gut-lung-brain axis: Mechanistic insights and nutritional therapeutic strategies for inflammatory and neuropsychiatric disorders.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {201}, number = {}, pages = {119527}, doi = {10.1016/j.biopha.2026.119527}, pmid = {42296911}, issn = {1950-6007}, abstract = {The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways. Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis. Trp catabolism follows three divergent pathways: the kynurenine (Kyn) pathway, which is involved in immune tolerance but can generate neuroactive and potentially neurotoxic metabolites; the serotonin pathway, essential for mood and gastrointestinal motility; and the microbial indole pathway, which supports epithelial barrier function through aryl hydrocarbon receptor activation. Gut dysbiosis and chronic inflammation may disrupt these pathways and contribute to the "metabolic hijacking" of Trp, shifting its metabolism away from serotonin and indole synthesis toward increased production of Kyn pathway metabolites. This shift has been implicated in the pathogenesis of respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis, as well as neuropsychiatric conditions, including depression and Alzheimer's disease. These alterations contribute to systemic low-grade inflammation and immune dysregulation, which further propagate cross-organ pathology within the GLB axis. This review synthesizes current evidence on how Trp metabolites may function as cross-organ mediators, contributing to the "leaky gut" and "leaky brain" phenotypes. Furthermore, we evaluate the potential of precision nutrition and therapeutic interventions, including psychobiotics, dietary phytochemicals, cofactor supplementation, and fecal microbiota transplantation, to restore metabolic equilibrium. Targeting the Trp-GLB metabolic axis may therefore offer an integrative therapeutic framework for managing interconnected inflammatory and neuropsychiatric comorbidities.}, }
@article {pmid42298631, year = {2026}, author = {Yan, Q and Li, M and Wang, G and Zhang, A and Li, Y and Guo, R and Zhang, Y and Yang, W and Zhang, Y and Liu, X and Li, X and Zheng, N and Wang, L and Fan, S and Ma, R and Lu, T and Zhou, S and Guan, T and Xing, G and Li, S and Wang, L and Li, Y}, title = {Cross-kingdom microbial associations characterize responsiveness to fecal microbiota transplantation in patients with irritable bowel syndrome.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08269-w}, pmid = {42298631}, issn = {1479-5876}, abstract = {BACKGROUND: Precise outcome prediction for fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) remains a clinical challenge. The roles of the gut virome and its interplay with bacteria in FMT efficacy are particularly underexplored. This secondary analysis aimed to conduct an exploratory, hypothesis-generating investigation into these cross-kingdom dynamics.<br><br>METHODS: We conducted a secondary, integrative analysis of a published cohort, performing longitudinal, cross-kingdom metagenomic profiling on 83 samples from 22 IBS patients and healthy donors. We integrative approach combined microbial diversity, species-specific biomarker identification, bacterial-viral associated networks, and exploratory random forest modeling to identify microbial features associated with FMT outcomes.<br><br>RESULTS: IBS patients showed higher bacterial and viral alpha diversity than donors. Cross-kingdom profiling identified 223 bacterial and 724 viral biomarkers. Donor-enriched biomarkers were predominantly health-associated Bacteroidetes (e.g., B. ovatus, B. faecis), whereas pre-FMT-enriched biomarkers were largely Firmicutes (e.g., B. obeum) with potential pathobiont roles. The Effect and No effect groups displayed different microbial trajectories. Although both groups shifted toward a donor-like composition initially, only responders maintained a stable donor-like ecology throughout the 12-month follow-up, supported by more resilient bacterial-viral association networks. Exploratory random forest modeling highlighted microbial features, such as R. pickettii, with high relative importance for outcome discrimination. However, permutation testing (p&#x2009;=&#x2009;0.548-0.616) confirmed that model performance on this small cohort did not exceed chance level, underscoring the risk of overfitting and the exploratory nature of these computational findings.<br><br>CONCLUSIONS: This integrative re-analysis provides preliminary evidence that cross-kingdom gut microbiome profiles are strongly associated with FMT outcomes in IBS. Successful outcomes appear linked to sustained donor-like remodeling and stable bacterial-viral networks. Our findings are primarily hypothesis-generating and offer a framework of candidate biomarkers for future validation in larger cohorts. This work underscores the necessity of external validation to develop robust, microbiome-based tools for personalized FMT therapy.}, }
@article {pmid42301720, year = {2026}, author = {Zuo, G and Yao, Y and Shen, Y and Liu, F and Chang, F and Tang, B and Huang, H and Huang, JA and Liu, Z and Lin, Y}, title = {Optimized Extraction Process of Fu Brick Tea Polysaccharides Using Ultrasound-Assisted Enzymatic Strategy and Their Enhanced Antioxidant and Immunoprotective Activities.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.6c01025}, pmid = {42301720}, issn = {1520-5118}, abstract = {The immunomodulatory mechanisms of Fu brick tea polysaccharides (FBTPs) remain poorly defined, particularly regarding their structure-bioactivity relationship and the causal involvement of the gut microbiota. To address this, we investigated structurally distinct FBTPs prepared via an optimized ultrasound-assisted enzymatic extraction protocol (designated UAEPS). Characterization revealed that UAEPS possesses unique structural features, such as a lower molecular weight and higher carbohydrate content, distinguishing it from polysaccharides obtained via traditional method (HWEPS). Functionally, UAEPS exhibited potent in vitro bioactivities, including significant antioxidant, anti-inflammatory, and cytoprotective effects. In immunosuppressed mouse model, UAEPS restored immune homeostasis, attenuated multiorgan damage, and reshaped the gut microbiota, with marked enrichment of Lactobacillus. The causal role of the gut microbiota was further confirmed by a fecal microbiota transplantation experiment, where recipients mirrored the protective immunomodulatory effects. Collectively, UAEPS represents structurally distinct FBTPs whose immunomodulatory activity is mediated through gut microbiota remodeling.}, }
@article {pmid42301903, year = {2026}, author = {Yuan, S and Liu, Y and Gao, P and Sun, J and Wang, Y and Du, Z and Lei, J and Hong, J and Fang, X and Tu, P and Lu, Y and Jiang, Y}, title = {Lactobacillus reuteri targets FXR-dependent bile acid homeostasis to ameliorate alcoholic liver disease.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrag153}, pmid = {42301903}, issn = {1751-7370}, abstract = {Alcoholic liver disease (ALD) is characterized by gut dysbiosis, yet the functional contribution of specific commensals remains largely unexplored. Here, we identify a significant reduction of Lactobacillus reuteri in both ALD patients and mouse models compared with their respective healthy controls. Using fecal microbiota transplantation (FMT), we first establish a causative role of the dysbiotic gut microbiota in driving ALD pathophysiology. In line with this finding, oral supplementation with L. reuteri ameliorates ALD phenotypes. Mechanistically, L. reuteri activates the farnesoid X receptor (FXR) signaling pathway, thereby restoring bile acid homeostasis, as evidenced by reduced levels of cholic acid (CA) and deoxycholic acid (DCA). The functional importance of FXR is further validated in Fxr-/- mice, where the protective effects of L. reuteri on both ALD and bile acid metabolism are largely abrogated. Moreover, both in vitro and in vivo experiments confirm that CA and DCA directly compromise hepatocyte viability and exacerbate liver injury, reinforcing their roles as pathogenic effectors downstream of FXR dysregulation. Expanding upon these mechanistic insights, we identify the natural compound echinacoside as a gut microbiota-targeting intervention that not only enriches L. reuteri but also potentiates FXR signaling, leading to significant improvement of ALD. Collectively, our findings define a microbiota-host metabolic axis centered on L. reuteri and FXR-dependent bile acid homeostasis, offering a conceptual framework for targeting host-microbe interactions in alcoholic liver disease.}, }
@article {pmid42302008, year = {2026}, author = {Fei, Y and Gao, MY and Qiao, N and Hu, J and He, L and Zhou, JL and Zheng, NN and Liu, TT}, title = {Bioinformatic identification of CD8+ T cell activation mediated by key genes in fecal microbiota transplantation for irritable bowel syndrome.}, journal = {PloS one}, volume = {21}, number = {6}, pages = {e0351574}, pmid = {42302008}, issn = {1932-6203}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/genetics/immunology/microbiology ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; *Fecal Microbiota Transplantation/methods ; *Lymphocyte Activation/genetics ; *Computational Biology/methods ; Gene Expression Profiling ; Transcriptome ; }, abstract = {BACKGROUND: The effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.<br><br>METHODS: Transcriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023-December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug-gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.<br><br>RESULTS: Ten key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8&#x2009;+&#x2009;T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8&#x2009;+&#x2009;T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8&#x2009;+&#x2009;T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.<br><br>CONCLUSION: An association between key gene regulation and CD8&#x2009;+&#x2009;T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.}, }
@article {pmid42302222, year = {2026}, author = {Pereira, MAOM and Tudella, GCN and Klostermann, AU and Ohannesian, VA and Gonçalves, OR and da Silva, RO and Andrade Fernandes, JV and Ahmed, A and Alencar, ABB and de Morais, STA and Almeida, KJ}, title = {Fecal Microbiota Transplantation in Parkinson Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.}, journal = {Neurology}, volume = {107}, number = {1}, pages = {e218175}, doi = {10.1212/WNL.0000000000218175}, pmid = {42302222}, issn = {1526-632X}, mesh = {Humans ; *Parkinson Disease/therapy ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVES: Parkinson disease (PD) is a progressive neurodegenerative disorder increasingly linked to gut microbiota dysbiosis, which may influence disease mechanisms and symptom expression. Fecal microbiota transplantation (FMT) targets the gut-brain axis, but clinical evidence remains inconsistent. This study aimed to evaluate the efficacy and safety of FMT in PD.<br><br>METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with protocol registration in International Prospective Register of Systematic Reviews (CRD420251142846). MEDLINE, Embase, and the Cochrane Library were searched from inception through September 2025. Randomized controlled trials (RCTs) and observational studies enrolling adults with mild-to-moderate PD who received FMT through any administration route were eligible. The primary outcome was motor function assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) part III. Secondary outcomes included UPDRS part II, quality of life (Parkinson's Disease Questionnaire-39 [PDQ-39]), constipation severity (Wexner score), and adverse events. Random-effects models pooled effect estimates with 95% CIs, and exploratory meta-regression assessed follow-up duration, publication year, and sample size.<br><br>RESULTS: Eight studies (5 RCTs and 3 observational studies) including 220 participants were analyzed. The mean age ranged from approximately 60 to 70 years, and women comprised about 40% of participants. FMT was associated with significant improvement in motor function (UPDRS part III: mean difference [MD] -9.67, 95% CI -16.81 to -2.53) and constipation severity (Wexner score: MD -3.91, 95% CI -7.68 to -0.13). Improvements in UPDRS part II and PDQ-39 were observed at 12 weeks but not sustained at 24 weeks. In RCT-only analyses, UPDRS part III improvement remained significant (MD -6.82, 95% CI -11.23 to -2.40), whereas other outcomes were not consistently significant. Meta-regression indicated that longer follow-up was associated with greater improvement in UPDRS part II (p = 0.043). FMT was generally well tolerated; however, gastrointestinal adverse events were more frequent in the FMT group (risk ratio 3.12, 95% CI 1.14-8.53), predominantly mild to moderate.<br><br>DISCUSSION: FMT may provide short-term improvements in motor and gastrointestinal symptoms in PD, but effects appear transient. Small sample sizes, heterogeneity, and limited follow-up restrict conclusions, underscoring the need for larger randomized trials. Pooled estimates reflected evidence from observational studies and should be interpreted cautiously.}, }
@article {pmid42304226, year = {2026}, author = {Yan, Y and Liang, S and Li, S and Xie, S and Wang, X and Zhang, H}, title = {Gut dysbiosis modulates hyperoxia-induced bronchopulmonary dysplasia by promoting EMT through activating TLR4/NF-κB pathway.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {}, number = {}, pages = {}, doi = {10.1186/s10020-026-01529-x}, pmid = {42304226}, issn = {1528-3658}, support = {2024BS022//Research foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor/ ; 011302064//Guangzhou Postdoctoral Science Foundation/ ; 20261A031030//Guangzhou Health and Wellness Science and Technology Youth Talent Cultivation Project/ ; }, abstract = {BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of morbidity and mortality in premature infants. Although gut microbial dysbiosis is implicated in BPD pathogenesis, the underlying mechanisms are poorly defined. This study aims to elucidate the specific pathway through which gut dysbiosis drives BPD pathology and to identify potential therapeutic targets.<br><br>METHODS: The experimental BPD model was established by hyperoxia (FiO2 85%) in neonatal mice from postnatal days 1 to 14. Pulmonary alveolarization and inflammation were analyzed at postnatal day 15. The modulatory role of gut microbiota was assessed using antibiotic-induced dysbiosis and fecal microbiota transplantation (FMT) from normoxic mice. Gut microbiome analysis was performed using 16S rRNA gene sequencing. The specific signaling pathway was investigated using a pharmacological inhibitor of TLR4. Furthermore, the molecular mechanisms were investigated through western blotting, real-time quantitative PCR, ELISA, and immunofluorescence.<br><br>RESULTS: Hyperoxia exposure induced impaired alveolarization, disrupted gut barrier integrity, and gut dysbiosis. These pathological changes were accompanied by elevated pulmonary inflammation, potent activation of the TLR4/NF-&#x3ba;B pathway, and upregulation of epithelial-mesenchymal transition (EMT) associated markers. These changes were exacerbated by early postnatal antibiotic administration, whereas FMT from normoxic mice rescued these phenotypes, restored gut barrier function, suppressed TLR4/NF-&#x3ba;B signaling, and reversed EMT progression. Notably, pharmacological inhibition of TLR4 mirrored the protective effects of FMT, effectively attenuating hyperoxia-induced lung injury and EMT.<br><br>CONCLUSIONS: Our findings establish a mechanistic link for the gut-lung axis in BPD, demonstrating that gut dysbiosis is a critical modulator of lung development impairment and pathological EMT via activation of the TLR4/NF-&#x3ba;B pathway.}, }
@article {pmid42304699, year = {2026}, author = {Feng, YC and Liu, XX and Yu, H and Liu, R and Pang, TS and Wang, HN and Peng, ZW}, title = {Fecal Microbiota Transplantation From Patients With Social Anxiety Disorder Is Associated With General Anxiety-Like Behavior and Gut Microbiota Alterations in Mice.}, journal = {Brain and behavior}, volume = {16}, number = {6}, pages = {e71561}, pmid = {42304699}, issn = {2162-3279}, support = {82171512//National Natural Science Foundation of China/ ; XJZT25QN50//Xijing Hospital/ ; LHJJ24YF06//Xijing Hospital/ ; //Boost plan of Xijing Hospital/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice ; Male ; Humans ; *Anxiety/microbiology ; *Phobia, Social/microbiology/therapy ; *Behavior, Animal/physiology ; Female ; Mice, Inbred C57BL ; Adult ; *Dysbiosis/microbiology ; Tryptophan/blood ; }, abstract = {PURPOSE: Growing evidence implicates gut microbiota dysbiosis in social anxiety disorder (SAD), yet direct causal evidence remains limited. This study investigated whether fecal microbiota transplantation (FMT) from individuals with SAD was associated with general anxiety-like behaviors and accompanying gut microbial and predicted metabolic alterations in mice.<br><br>METHODS: Fecal samples were collected from five patients diagnosed with SAD and five matched healthy controls and transplanted into antibiotic-treated mice. Anxiety-like behaviors were evaluated using the open-field test (OFT) and elevated-plus maze test (EPMT). Gut microbiota composition was assessed by 16S rRNA gene sequencing, microbial functional potential was inferred using PICRUSt2, and plasma tryptophan-pathway metabolites were quantified.<br><br>RESULTS: Mice receiving SAD microbiota (SAD group) showed general anxiety-like behaviors, characterized by more time spent in the periphery of the OFT and fewer entries and less time in the open arms of the EPMT compared to mice receiving healthy control microbiota (control group). Although &#x3b1;-diversity did not differ significantly, &#x3b2;-diversity was distinct between groups. The SAD group showed enrichment of Bacteroidota/Bacteroidales-related bacteria (e.g., Muribaculum), whereas the control group had higher abundance of butyrate producers (e.g., Butyricimonas). Functional prediction indicated lower predicted abundance of selected DNA-repair and biosynthetic pathways in the SAD group. Plasma tryptophan levels were nominally lower in the SAD group.<br><br>CONCLUSIONS: These findings suggest that specific gut microbiota alterations and predicted functional pathway changes in individuals with SAD may be associated with anxiety-related behavioral phenotypes, supporting the gut microbiome as a potential contributing factor to the pathophysiology of SAD.}, }
@article {pmid42304879, year = {2026}, author = {Mirjalili, S and Hosseini Hooshiar, M and Abbasabadarabi, S and Aliramezani, A}, title = {Host immunity and recurrent Clostridioides difficile infection: a comprehensive review.}, journal = {Pathogens and global health}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/20477724.2026.2686115}, pmid = {42304879}, issn = {2047-7732}, abstract = {Clostridioides difficile is a leading cause of healthcare-associated gastrointestinal infection, with outcomes that range widely in severity. The pathogenesis of C. difficile is driven by virulence factors that induce colonic inflammation and epithelial damage. This illness is categorized as an urgent threat, and in recent years, its prevalence has increased, with recurrent episodes occurring in approximately 15-35% of cases. The life cycle of C. difficile infection (CDI) is multifactorial and strongly influenced by antibiotic exposure, host immune responses, the gut microbiota, and microbial metabolites. Disruption of intestinal homeostasis gradually alters the ecological niches of C. difficile and the immunological landscape of the disease. In addition to these risk factors, recurrent C. difficile infection (rCDI) can be exacerbated by certain 'hypervirulent' strains that are more difficult to eradicate. As in many infectious diseases, host immunological responses, particularly in rCDI, appear to play a crucial role in determining recovery versus recurrence. Recent strategies to address this problem include fecal microbiota transplantation (FMT) and novel therapeutic approaches such as polyclonal and monoclonal antibodies. Nevertheless, the immunological mechanisms underlying rCDI remain incompletely understood. A deeper insight into how the immune response develops and functions during rCDI may facilitate the identification of new therapeutic targets. In this review, we summarize current knowledge on C. difficile recurrence and highlight the host immune response in the context of rCDI.}, }
@article {pmid42304908, year = {2026}, author = {Patel, AK and Singh, N and Chandra, P and Sachan, N and Goswami, PK and Shivam, }, title = {Microbiome Drug Interactions in Cancer Pharmacology: Mechanisms and Therapeutic Opportunities.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328479943260605055353}, pmid = {42304908}, issn = {2772-4336}, abstract = {INTRODUCTION: Interindividual variability in cancer therapy response cannot be fully explained by host genetics or tumor characteristics alone. Emerging evidence indicates that the gut microbiome is a critical modulator of anticancer drug metabolism, immune responses, and therapeutic outcomes, positioning it as an important determinant in cancer pharmacology.<br><br>METHODS: This narrative review employed a structured literature search of PubMed, Scopus, and Web of Science (2005-2025) to synthesise preclinical and clinical evidence on microbiome-drug interactions, focusing on pharmacokinetics, immune modulation, toxicity, and resistance across chemotherapy, immunotherapy, and targeted therapies.<br><br>RESULTS AND DISCUSSION: The gut microbiome influences anticancer therapy through enzymatic biotransformation, immune regulation, metabolite signalling, and maintenance of intestinal barrier integrity. Clinically, favourable microbiome profiles have been associated with improved immunotherapy outcomes, with reported hazard ratios for survival ranging from ~0.5 to 0.7, while prior antibiotic exposure is linked to a 20-40% reduction in response rates. Microbial enzymes such as &#x3b2;- glucuronidase contribute to irinotecan-induced toxicity, affecting up to 20-40% of patients. Specific taxa, including Akkermansia muciniphila and Bifidobacterium spp., are associated with enhanced therapeutic response. Microbiome-targeted interventions, including faecal microbiota transplantation, have demonstrated response restoration in approximately 30-40% of refractory cases in early clinical studies. However, heterogeneity in microbial composition, lack of standardisation, and safety concerns limit clinical translation.<br><br>CONCLUSION: The gut microbiome represents an adaptable determinant of cancer pharmacology. Integrating microbiome-informed strategies offers a promising pathway toward precision oncology, although robust clinical validation remains essential for routine implementation.}, }
@article {pmid42304911, year = {2026}, author = {Ding, W and Li, R and Gong, L and Yi, J and Wang, Y and Xiao, D and Wu, H and Hu, W and Li, J and Li, H and Lu, X and Liu, Z and Qin, Z and Lu, X and Li, Z}, title = {Efficacy and Safety of Fecal Microbiota Transplantation for Patients with Treatment-resistant Schizophrenia: A Double-blind, Randomized Clinical Trial Protocol.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X431672260406044032}, pmid = {42304911}, issn = {1875-6190}, abstract = {OBJECTIVES: This randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy and safety of Fecal Microbiota Transplantation (FMT) in patients with Treatment-Resistant Schizophrenia (TRS), comparing two delivery methods: intraduodenal administration via gastroscopy and oral capsule ingestion.<br><br>METHODS: This study employed a randomized, double-blind, placebo-controlled design. Eligible subjects will be randomized into three groups: (1) intraduodenal FMT administration via gastroscopy, (2) oral FMT capsule administration, and (3) placebo control. Before and after the intervention, fecal, urine, and venous blood samples will be collected for microbiomics and metabolomic analyses. Clinical symptom severity will be assessed using standardized psychiatric scales to evaluate the efficacy and safety of FMT.<br><br>DISCUSSION: Should Fecal Microbiota Transplantation be found to be as clinically and cost-effective for patients with treatment-resistant schizophrenia, this approach has the potential to be considered as an adjunctive treatment for those with a broader range of psychiatric conditions.<br><br>ChiCTR2400092799.}, }
@article {pmid42305042, year = {2026}, author = {Xie, X and Yan, W and Zhang, X and Gan, C and Lei, X and Huang, Y and Xiong, W and Tang, H and Zhu, H}, title = {FMT from IBS-D Rats Impairs Intestinal Barrier Function and is Associated with Increased Intestinal Benzoic Acid and Ruminococcus Abundance.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2602004}, pmid = {42305042}, issn = {1738-8872}, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology ; Rats ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Disease Models, Animal ; Male ; *Ruminococcus/isolation &amp; purification ; Tumor Necrosis Factor-alpha/blood/genetics ; Rats, Sprague-Dawley ; Dysbiosis ; Intestinal Mucosa/metabolism ; Amine Oxidase (Copper-Containing)/blood ; Intestines/microbiology ; Feces/microbiology ; }, abstract = {While the etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is multifactorial, current studies have converged to identify gut microbiota dysbiosis as a principal contributor. This study aimed to elucidate the role of the gut microbiota in IBS-D progression and to uncover the underlying mechanisms. In this study, a rat model of IBS-D was successfully established, characterized by prominent visceral hypersensitivity and diarrhea. To assess the impact of the gut microbiota, recipient rats pretreated with broad-spectrum antibiotics underwent fecal microbiota transplantation (FMT) from IBS-D model rats. The model-microbiota recipient rats (the MR group) developed IBS-D-like symptoms, such as abdominal pain, diarrhea, and depression-like behaviors. Both the IBS-D and MR groups exhibited elevated serum diamine oxidase (DAO) concentrations, reduced intestinal tight junction protein levels, increased serum TNF-α concentrations, upregulated TNF-α mRNA expression, and downregulated IL-10 mRNA expression in the intestine. These findings indicated that the transplanted microbiota disrupted intestinal barrier integrity and triggered low-grade inflammation. Moreover, an elevated abundance of Ruminococcaceae in the gut microbiota was a common feature of both the IBS-D and MR groups. Metabolomic analysis revealed an enrichment in the phenylalanine, tyrosine, and tryptophan biosynthesis pathway in both IBS-D and recipient groups, with benzoic acid being particularly prominent. Pearson correlation analysis demonstrated a strong positive correlation between the Ruminococcus abundance and benzoic acid levels. Together, these findings indicated that FMT robustly recapitulated core IBS-D pathophysiology in recipient rats, and the identified bacteria and metabolites provided novel insights into the pathogenesis of IBS-D.}, }
@article {pmid42305614, year = {2026}, author = {Jiang, C and Nageeb, WM and Batool, S and Hashish, A and Alkhawagah, SM and Abdelsattar Ibrahim, HA and Zhu, W and Che, C and Li, X and Jin, M and Zhang, X and Ghonaim, AH and Ren, M and Li, S}, title = {Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities.}, journal = {iScience}, volume = {29}, number = {6}, pages = {116224}, pmid = {42305614}, issn = {2589-0042}, abstract = {The gut microbiota-brain axis constitutes a dynamic, bidirectional communication network that integrates neural, endocrine, immune, and metabolic pathways to regulate host physiology and behavior. Accumulating evidence indicates that disturbances within this axis have been consistently associated with metabolic, autoimmune, and neuropsychiatric disorders; however, much of the current evidence, particularly from human studies, remains largely correlative, and causal relationships are still under active investigation, highlighting its systemic relevance to health and disease. This review synthesizes current understanding of the structural and functional components of the gut microbiota-brain axis, including microbial community dynamics, neural signaling pathways, and key endocrine and immune mediators. We examine mechanistic insights into how microbial-derived metabolites influence brain function, cognition, mood regulation, stress responses, and disease pathogenesis. In addition, we discuss emerging therapeutic strategies targeting the gut microbiota-brain axis, including psychobiotics and fecal microbiota transplantation, while acknowledging dietary approaches, such as prebiotic supplementation, fiber-rich diets, and fermented food consumption, as complementary strategies that modulate microbiota composition that may indirectly support gut-brain axis function. By integrating mechanistic, clinical, and translational perspectives, this review aims to clarify current knowledge gaps and highlight future directions for leveraging the gut microbiota-brain axis in personalized approaches to neuropsychiatric disease management.}, }
@article {pmid42307051, year = {2026}, author = {Lang, T and Farowski, F and Al-Gousous, J and Langguth, P and Vehreschild, MJGT}, title = {Validation of an Automated Fluorescence- and Image-Based Viable Cell Counting Method for Fecal Microbiota Transplantation Drug Products.}, journal = {Biotechnology journal}, volume = {21}, number = {6}, pages = {e70269}, pmid = {42307051}, issn = {1860-7314}, support = {//German Centre for Infection Research/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Escherichia coli/cytology ; Humans ; Bacillus subtilis ; Reproducibility of Results ; Cell Count/methods ; Fluorescence ; }, abstract = {Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection. As a drug product, FMT is subject to pharmaceutical quality standards, including accurate quantification of viable bacteria to ensure product consistency. We developed and validated an automated fluorescence- and image-based viable-cell counting method for FMT products; total-cell enumeration was examined secondarily. The QUANTOM Tx system (Logos Biosystems) was validated according to ICH Q2(R2) using Escherichia coli and Bacillus subtilis as reference strains. The Viable Cell Staining Kit was validated with Escherichia coli, whereas the Total Cell Staining Kit was examined in selected experiments using both strains. Applicability to complex FMT matrices was confirmed using authentic fecal samples. Viable-cell counting showed strong linearity across a range of 9.4 × 10[6]-1.2 × 10[8] cells/mL, with adequate accuracy and precision. Specificity was ensured by particle-size gating, unaffected by nonviable cells or diluent. Robustness was confirmed across operators and time points. Fecal samples showed linear quantifiability and acceptable precision; total-cell enumeration fulfilled linearity and precision requirements. The validated method enables rapid, reproducible viable-cell quantification suitable for Quality Control of FMT drug products, supporting formulation development, and dosing verification. Viable-cell quantification remains the analytical focus, despite limitations in spore detection. Total-cell enumeration provides complementary process information.}, }
@article {pmid42309058, year = {2026}, author = {Li, J and Wang, Y and Li, R and Huang, H and Zhu, X and Li, X and Sun, Z and Zhang, L and Zheng, P and He, Y and Liu, J and Zhang, X and Ren, S and Liu, M and Wang, H and Luo, Y and Wang, F and Zhou, J and Yang, J and Wang, G}, title = {Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.05.017}, pmid = {42309058}, issn = {1934-6069}, abstract = {Gut microbiota may influence antidepressant treatment outcomes, yet whether targeted modulation can enhance efficacy remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in patients with major depressive disorder, administering a 2-week course of fecal microbiota transplantation (FMT) capsules or placebo as an adjunct to escitalopram (ChiCTR2300071421). Remission rates at week 8 did not differ significantly between groups, but FMT produced greater reductions in Hamilton Depression Rating Scale, 17-item version (HAMD-17) scores at weeks 2 and 8. FMT was well-tolerated with a safety profile comparable to placebo. Multi-omics analyses show durable donor microbial engraftment and enrichment of beneficial Lachnospiraceae and Oscillospiraceae taxa. Microbial remodeling is accompanied by an increase in serum bile acids that correlate with the alleviation of depressive symptoms. Mediation analysis supports a bile-acid-mediated suppression of inflammatory pathways linking microbial changes to antidepressant effects. Overall, FMT may provide a safe avenue to enhance escitalopram efficacy through microbiota-directed regulation of bile-acid metabolism and inflammation.}, }
@article {pmid42311013, year = {2026}, author = {Pouliou, C and Poulios, P and Piperi, C}, title = {Unravelling the Critical Interplay of Oral and Gut Microbiota in Disease Development.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673440488260516210738}, pmid = {42311013}, issn = {1875-533X}, abstract = {The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, the gut microbiota, consisting of trillions of microorganisms, functions as a barrier protection, modulating the immune system and facilitating the absorption of nutrients. Although they have distinct anatomical locations, these ecosystems are highly interconnected and play a pivotal role in human health and disease. The most common routes of interaction between the oral and gut microbiota are the enteral, the hematogenous, and the immune cell migration routes. Many oral pathogens interact with intestinal microbes, activating the host's mechanisms that establish dysbiosis and pave the way for the development of various diseases, ranging from inflammatory bowel disease and colorectal cancer to metabolic and neurodegenerative disorders. In this review, we delineate the mechanisms underlying these ecosystems to offer novel insights into disease pathogenesis while also unveiling new avenues for preventive and therapeutic interventions. Although current therapeutic approaches include the administration of antibiotics, prebiotics, and probiotics, novel personalized therapeutic approaches have also emerged. Fecal microbiota transplantation (FMT), gut bacteria engineering, nanomedicine-based techniques, and the use of miRNA to foster microbiota balance in both compartments hold great promise and may prove critical for the prevention and management of systemic diseases.}, }
@article {pmid42311388, year = {2026}, author = {Zhang, T and Wang, L and Ren, Z and Man, R and Cheng, X and Wang, L and Wang, J and Bu, X and Yu, Y}, title = {Gut microbiota alterations associated with anxiety and depression in inflammatory bowel disease: a systematic review of prospective cohorts and randomized trials.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1853009}, pmid = {42311388}, issn = {1664-302X}, abstract = {BACKGROUND: Anxiety and depression are highly prevalent among patients with inflammatory bowel disease (IBD) and are closely associated with reduced quality of life and poor treatment adherence. The gut-brain axis has been proposed as a key mechanistic framework, with the gut microbiota playing a central role. However, findings from clinical studies remain inconsistent, and a comprehensive synthesis of the evidence is lacking.<br><br>OBJECTIVE: This systematic review aimed to integrate evidence from randomized controlled trials (RCTs) and prospective cohort studies to evaluate the associations between gut microbiota characteristics, microbiota-targeted interventions, and symptoms of anxiety and depression in patients with IBD.<br><br>METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, EBSCOhost, and Scopus. The search covered records from database inception to October 17, 2025. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A descriptive synthesis approach was used to summarize the findings. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist.<br><br>RESULTS: Ten studies were included, comprising six prospective cohort studies and four RCTs. These studies included a total of 1,040 patients with IBD. Cohort studies consistently showed that anxiety and depressive symptoms were associated with reduced microbial &#x3b1;-diversity, enrichment of pro-inflammatory taxa, and depletion of short-chain fatty acid (SCFA)-producing bacteria. These associations persisted after adjustment for inflammatory markers. They were also observed when analyses were restricted to patients in remission. This suggests that the associations may not be fully explained by disease activity. Evidence from RCTs showed that microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, modulated microbial composition and reduced anxiety and depression scores. Studies combining psychological interventions with microbiota profiling also suggested potential effects on gut microbial composition. However, the findings remain heterogeneous.<br><br>CONCLUSION: Current evidence supports a close and potentially bidirectional association between gut microbiota dysbiosis and anxiety and depression in patients with IBD. Both microbiota-targeted interventions and psychological therapies may represent promising strategies for managing psychological comorbidities in IBD. Future large-scale, standardized longitudinal studies and randomized controlled trials are warranted to clarify directionality, test causal hypotheses, and develop personalized intervention approaches.<br><br>https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251166542.}, }
@article {pmid42311414, year = {2026}, author = {Liu, W and Chen, J and Gu, W and Shen, Y and Liu, M and Wang, S and Lu, Z and Mao, W and Liu, X and Wang, R and Zhang, L}, title = {Qitu qushi formula ameliorates diabetic kidney disease potentially through gut microbiota-derived indole-3-propionic Acid-Mediated regulation of the Sirt1/FoxO1 pathway.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1802567}, pmid = {42311414}, issn = {1663-9812}, abstract = {BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, and current pharmacotherapies provide limited renal protection. Qitu Qushi Formula (QTQSF), a traditional Chinese medicine prescription, has shown therapeutic potential in DKD, but its underlying mechanisms remain unclear. This study aimed to elucidate whether QTQSF alleviates DKD via gut microbiota-mediated pathways.<br><br>METHODS: Clinical, animal, and cellular studies were integrated to investigate the therapeutic effects of QTQSF. Clinical samples from 30 patients with type 2 DKD received QTQSF treatment for 6 months was used to assess renal function and gut microbiota. To explore microbiota-mediated mechanisms, db/db mice, pseudo-germ-free models, and fecal microbiota transplantation (FMT) were utilized. Multi-omics analyses, including 16S rRNA sequencing, untargeted and targeted metabolomics, and transcriptomics, were conducted to uncover key pathways underlying QTQSF's efficacy.<br><br>RESULTS: QTQSF significantly improved renal function and remodeled gut microbial composition in DKD patients. In db/db mice, QTQSF reduced albuminuria, fibrosis, and apoptosis, whereas these protective effects were attenuated after gut microbiota depletion. FMT supported that gut microbiota mediated the renoprotective effects of QTQSF. Integrated multi-omics analyses revealed that QTQSF enhanced microbial tryptophan metabolism and increased the gut microbiota-derived metabolite indole-3-propionic acid (IPA). Elevated IPA levels were associated with regulation of the renal Sirt1/FoxO1 pathway, which was further validated in podocytes as a key mechanism underlying the anti-apoptotic effects.<br><br>CONCLUSION: QTQSF may ameliorate DKD by enhancing gut microbiota-derived IPA production and regulating the Sirt1/FoxO1 signaling pathway, thereby attenuating renal injury. These findings provide mechanistic insight into the renoprotective effects of QTQSF and highlight a gut microbiota-metabolite-host signaling axis in DKD.}, }
@article {pmid42311675, year = {2026}, author = {Zhang, H and Fan, B and Ma, R and Jiang, R and Qin, Z and Qu, X and Wang, J and Xue, J and Wang, C and Liu, X and Guo, L}, title = {Gut microbiota and sepsis-associated acute kidney injury: a narrative review.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1724266}, pmid = {42311675}, issn = {1664-3224}, mesh = {Humans ; *Acute Kidney Injury/microbiology/etiology/therapy/immunology ; *Sepsis/complications/microbiology/immunology ; Animals ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Intestinal Barrier Function ; Signal Transduction ; }, abstract = {BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) carries high morbidity and mortality, yet its pathogenesis remains incompletely understood. Emerging evidence underscores the gut-kidney axis as a critical pathway in SA-AKI development.<br><br>OBJECTIVE: This review aims to synthesize current knowledge on how sepsis-driven gut dysbiosis compromises intestinal barrier integrity and contributes to SA-AKI, and to explore potential therapeutic strategies targeting the gut microbiota.<br><br>METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases for publications between 2005 and 2026. Studies focusing on gut-kidney crosstalk mechanisms in sepsis/AKI were included. Key findings from human and animal studies were summarized.<br><br>RESULTS: Sepsis induces marked gut dysbiosis characterized by loss of microbial diversity and expansion of pathobionts. This dysbiosis compromises intestinal barrier integrity, facilitating translocation of bacterial products such as lipopolysaccharide (LPS). Upon entering circulation, these mediators activate systemic inflammation and renal signaling cascades, including the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-&#x3ba;B) pathway, leading to tubular injury and impaired renal function. Recent human metagenomic studies have identified specific microbial signatures associated with AKI, such as increased Clostridium asparagiforme and decreased Roseburia spp., alongside elevated uremic toxin-producing bacteria like Gordonibacter pamelaeae. Additionally, gut-derived metabolites including indoxyl sulfate, p-cresol sulfate, and trimethylamine N-oxide (TMAO) have been implicated in promoting renal inflammation and fibrosis. Importantly, renal dysfunction further disrupts gut homeostasis, establishing a pathological gut-kidney feedback loop. Targeting the gut-kidney axis via fecal microbiota transplantation, probiotic supplementation, or short-chain fatty acid administration may offer novel therapeutic avenues.<br><br>CONCLUSIONS: Sepsis induces gut microbiota dysregulation play an important role in the development of SA-AKI. The intestine-kidney crosstalk may provide a basis for the treatment of sepsis-induced organ injury and also provide new ideas for the treatment of SA-AKI.}, }
@article {pmid42312308, year = {2026}, author = {Morrison, S and Talley, N}, title = {Diagnosis and management of irritable bowel syndrome.}, journal = {Australian prescriber}, volume = {49}, number = {3}, pages = {93-98}, pmid = {42312308}, issn = {0312-8008}, abstract = {Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterised by recurrent abdominal pain or discomfort that is often related to defaecation or associated with a change in stool frequency or form. IBS is common in Australia and affects women more than men. The exact pathophysiology remains unclear, though it can be multifactorial and relate to gastrointestinal dysmotility, post-infection and microbial changes, and a patient's psychosocial background. A positive clinical diagnosis can be made when the Rome V criteria are met, alarm features are absent and simple screening tests (full blood count, C-reactive protein, coeliac serology) are negative. If alarm features are present, further examination, laboratory testing or imaging may be helpful in assessing for organic pathology. Management involves lifestyle and dietary modifications, and psychological and pharmacological therapies. Pharmacological therapy should be individualised to the patient's IBS subtype and symptoms. Examples of drug classes that are used include antispasmodics, osmotic laxatives, antidiarrhoeal drugs and neuromodulators (tricyclic antidepressants). There is insufficient evidence to support the use of therapies such as probiotics, faecal microbiota transplantation, and mesalamine.}, }
@article {pmid42315021, year = {2026}, author = {Melhorn, P and Dominik, N and Rüsing, LZ and Cserna, J and Knaus, HA and Schulenburg, A and Mitterbauer, M and Greinix, HT and Rabitsch, W}, title = {Clinical trials in graft-versus-host disease: changes in study characteristics, investigated drugs, and endpoints over time.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2026.06.023}, pmid = {42315021}, issn = {2666-6367}, abstract = {BACKGROUND: Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). Mapping the trial landscape is essential to identify innovation barriers and optimize future study designs and trial conduct.<br><br>OBJECTIVES: This analysis characterized GvHD treatment trials registered on ClinicalTrials.gov to evaluate design features and results reporting trends.<br><br>RESULTS: Following screening of 1,713 identified records, 384 trials met the specified inclusion criteria. Phase distribution was 15.9% phase 1, 38.8% phase 2, and 11.2% phase 3 studies. Single-group (61.1%) and parallel (31.3%) designs predominated, with sponsors being primarily academic (60.4%) or industry (30.7%). Regarding study status, 37.0% were completed, 22.9% prematurely halted, and 24.7% ongoing (15.4% unknown). For completed studies, the median number of participants was 30 and the median duration to reach the primary outcome was 3.13 years. Chronic GvHD was studied slightly more often (47.9%) than acute GvHD (43.5%), with significant differences in terms of study phases, recruitment status, duration, sponsor, and organ involvement. The most frequently studied treatments were corticosteroids (n=64), mesenchymal stromal cells (n=52), ruxolitinib (n=31), extracorporeal photopheresis (n=26), fecal microbiota transplantation (n=17), rituximab (n=15), and belumosudil (n=13). The majority of trials (55.2%) investigated steroid-refractory GvHD or later-line treatment. Over the last decade, a significant shift toward industry sponsorship (13.4% to 38.9%, p<0.001), multicenter designs, and targeted therapies was observed. Response was the predominant (60.1%) co-/primary endpoint of GvHD studies, followed by safety (28.2%), whereas patient-reported outcomes played a minor role (6.4%). Time to result reporting differed significantly based on trial phase and design.<br><br>CONCLUSIONS: While the trial landscape is evolving toward multinational collaborations and biology-based agents, the high rate of premature termination remains a substantial barrier to progress. Optimizing the study design, including regulatory advice, recruitment, and logistics, is critical to improve long-term outcomes in transplant recipients.}, }
@article {pmid42316154, year = {2026}, author = {Seo, E and Kim, SH and Kwak, MJ and Hwang, JK and Mustafa, G and Chang, YS and Hoh, JK and Jeon, BH and Park, HK and Kim, Y}, title = {Gut dysbiosis associated with neonatal respiratory distress syndrome and biological plausibility of disease-specific probiotic intervention: a translational study.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08462-x}, pmid = {42316154}, issn = {1479-5876}, support = {202400000002957//College of Medicine, Hanyang University/ ; RS-2023-00255939//Korea Institute of Energy Technology Evaluation and Planning/ ; NSIT; RS-2025-16068814//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Neonatal respiratory distress syndrome (RDS) is among the most prevalent morbidities in late preterm and term infants. Although the gut-lung axis has been implicated in neonatal respiratory disease, the relationship between RDS and early gut microbiome composition remains poorly characterized. This study aimed to characterize gut microbiome alterations associated with RDS and surfactant replacement therapy (SRT), and to evaluate the biological plausibility of a disease-specific probiotic intervention.<br><br>METHODS: Two complementary cohorts were prospectively enrolled. In the clinical observational cohort (n&#x2009;=&#x2009;45), fecal samples collected within 48&#xa0;h of birth were analyzed by Nanopore 16S rRNA sequencing across three groups: infants without RDS (control group, n&#x2009;=&#x2009;25), infants with RDS who did not receive SRT (RDS(S-) group, n&#x2009;=&#x2009;7), and infants with RDS who received SRT (RDS(S+) group, n&#x2009;=&#x2009;13). In the probiotic discovery cohort (n&#x2009;=&#x2009;40), gut microbiota of infants without RDS (CON group, n&#x2009;=&#x2009;17) and infants with RDS (RDS group, n&#x2009;=&#x2009;23) were characterized by metagenomic sequencing and culturomics. Candidate probiotic strains were evaluated in a fermenter for intestinal microbiota model (FIMM) and a fecal microbiota transplantation (FMT) mouse model.<br><br>RESULTS: The RDS(S-) group exhibited depletion of beneficial taxa including Bifidobacterium and Lacticaseibacillus and enrichment of opportunistic pathogens including Enterococcus and Staphylococcus. Following SRT, gut microbial profiles partially shifted toward those of the control group. Limosilactobacillus fermentum SLAM_LAF05 and Bifidobacterium longum SLAM_BIL02 were identified as CON-enriched candidate probiotic strains through direct microbiome comparison and selected based on superior acid and bile tolerance and adhesion capacity. In the FIMM model, probiotic supplementation increased microbial diversity and suppressed opportunistic pathogens. In the FMT mouse model, probiotic supplementation was associated with upregulation of ZO-1, MUC2, and Reg3g, reduction of fecal calprotectin, and restoration of serum IgG levels.<br><br>CONCLUSIONS: This study provides an early translational characterization of RDS-associated gut dysbiosis and its partial resolution following SRT, and establishes proof-of-concept for a disease-specific probiotic approach. These findings offer a new perspective on the interplay between gut microbial dynamics and the early postnatal respiratory course, and provide a basis for future investigations into microbiota-targeted strategies in neonates with RDS.}, }
@article {pmid42316284, year = {2026}, author = {Wang, X and Cheng, L and Yin, K and Wang, B and Yan, X and Chen, S}, title = {Chronic proton pump inhibitor exposure aggravates intestinal injury by impairing intestinal stem cell self-renewal through the microbiota-7-ketolithocholic acid Axis.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08448-9}, pmid = {42316284}, issn = {1479-5876}, abstract = {BACKGROUND: Long-term proton pump inhibitor (PPI) use is associated with increased intestinal disease risk, but its damaging mechanisms remain unclear.<br><br>METHODS: Mice were administered rabeprazole (Rab) for 4&#x2009;weeks before dextran sulfate sodium (DSS) or ionizing radiation (IR) injury. We employed RNA sequencing, metabolomics, and metagenomics, evaluated intestinal stem cell (ISC) function, and used organoids for validation.<br><br>RESULTS: Long-term Rab induced small intestinal mucosal injury and exacerbated DSS/IR-induced damage, manifesting as crypt/villus atrophy and reduced ISC numbers. Mechanistically, Rab downregulated the Wnt pathway and impaired mucosal defense and regeneration. Microbiota involvement was indicated by fecal transplantation. Integrated metagenomic and metabolomic analyses revealed that Rab induced intestinal dysbiosis and reduced ileal bile acids, particularly 7-ketolithocholic acid (7KLCA) and chenodeoxycholic acid (CDCA). Faecalibaculum rodentium supplementation restored ISC self-renewal by converting CDCA to 7KLCA. In vitro, 7KLCA activated Wnt signaling to rescue Rab-induced stem cell impairment. In vivo, both 7KLCA and Gly-&#x3b2;-MCA (intestinal FXR antagonists) suppressed the FXR-FGF15 axis, restored the expression of hepatic bile acid synthesis enzymes, and promoted epithelial repair, thereby mitigating DSS-induced injury.<br><br>CONCLUSIONS: Chronic PPI use impairs ISC self-renewal by disrupting the microbiota-7KLCA-Wnt axis. F. rodentium or 7KLCA supplementation ameliorates PPI-induced effects, highlighting a microbe-metabolite axis as a pivotal mechanism and potential therapies for PPI-associated intestinal damage.}, }
@article {pmid42316904, year = {2026}, author = {Saheb Sharif-Askari, N and Eladham, MW and Mdkhana, B and Sekar, P and Hafezi, S and Shakartalla, SB and Hachim, I and Saheb Sharif-Askari, F and Halwani, R}, title = {The Role of Fecal Microbiome Transplantation in Steroid Hyporesponsive Asthma.}, journal = {Comprehensive Physiology}, volume = {16}, number = {3}, pages = {e70196}, doi = {10.1002/cph4.70196}, pmid = {42316904}, issn = {2040-4603}, support = {24010902170//University of Sharjah/ ; 25011103119//University of Sharjah/ ; 2401110399//University of Sharjah/ ; 24010903159//University of Sharjah/ ; ORF-RC-2026-0509//King Saud University/ ; }, mesh = {*Asthma/therapy/microbiology ; *Fecal Microbiota Transplantation ; Animals ; *Gastrointestinal Microbiome ; Humans ; Dysbiosis/therapy ; *Adrenal Cortex Hormones/therapeutic use ; }, abstract = {Asthma is a chronic inflammatory airway disease characterized by airflow obstruction, airway hyperresponsiveness, and structural remodeling. Corticosteroids remain the mainstay of asthma therapy; however, a substantial proportion of patients with severe disease develop steroid hyporesponsiveness, limiting therapeutic efficacy and increasing disease burden. Emerging evidence implicates the gut microbiome as a key regulator of systemic immune responses, with growing relevance to asthma pathogenesis and treatment responsiveness. In this study, we investigated whether gut microbiota dysbiosis contributes to steroid hyporesponsive lung inflammation and whether fecal microbiota transplantation (FMT) can restore steroid responsiveness. Using a steroid-hyporesponsive asthma model, we demonstrate that the disease is associated with significant gut microbial dysregulation, characterized by reduced microbial diversity and depletion of immunoregulatory taxa. FMT partially restored gut microbial diversity, normalized community structure, and selectively replenished beneficial commensal bacteria, including Akkermansia muciniphila and Faecalibacterium prausnitzii, while suppressing pathogenic taxa. Importantly, restoration of gut microbial balance was associated with attenuation of lung inflammation and improved steroid responsiveness. These findings support a functional gut-lung axis in steroid hyporesponsive asthma and identify modulation of gut microbiota as a potential therapeutic strategy. Incorporating microbiota-directed interventions such as FMT may represent a novel adjunct approach for the management of refractory steroid-hyporesponsive asthma.}, }
@article {pmid42316995, year = {2026}, author = {Gu, Y and Li, L and Zhang, H and Ye, T and Zhu, Q and Zhao, X and Xie, K and Ge, R and Han, J and Qin, Y}, title = {Dietary purple sweet potato anthocyanin extracts attenuate intestinal barrier decline in naturally aged mice via the microbiota-autophagy-stem cell axis.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d6fo00039h}, pmid = {42316995}, issn = {2042-650X}, abstract = {Age-related deterioration of the intestinal epithelial barrier exacerbates systemic metabolic and functional decline, highlighting the gut as a key target for dietary interventions in healthy aging. Here, using naturally aged mice and intestinal organoids, we demonstrate that supplementation with purple sweet potato anthocyanins (PSPAs) alleviates systemic aging phenotypes, including impaired motor coordination, hepatic lipid dysregulation, insulin resistance, and cellular senescence, while concurrently restoring intestinal barrier integrity. PSPAs enhanced tight junction protein expression and epithelial architecture, independently of inflammation resolution, and promoted the proliferative and differentiation capacity of intestinal stem cells (ISCs). Metagenomic profiling revealed that PSPAs remodeled aging-associated gut microbiota composition and functions. Fecal microbiota transplantation established the causal contribution of microbiota remodeling to ISC rejuvenation, while luminal content-organoid assays confirmed the role of microbial metabolites. Integrative metabolomics identified metabolic changes linked to autophagy-related processes, including altered SCFA profiles, while transcriptomic analysis highlighted PI3K-AKT signaling as a major pathway associated with microbial and metabolic remodeling. Collectively, this multi-omics study establishes a mechanistic framework in which PSPAs alleviate aging-associated barrier decline through a "microbiota-autophagy-stem cell" axis, providing important insights into polyphenol-based strategies for gut-centered healthy aging.}, }
@article {pmid42317335, year = {2026}, author = {Yang, A and Zhang, B and Ju, J and Tian, J and Zhang, D and Li, J and Yang, L and Zhang, X}, title = {Mechanism of blueberry anthocyanins in ameliorating radiation-induced intestinal injury through gut microbiota modulation.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1771482}, pmid = {42317335}, issn = {1664-3224}, mesh = {Animals ; *Anthocyanins/pharmacology ; *Blueberry Plants/chemistry ; *Gastrointestinal Microbiome/drug effects/radiation effects ; Male ; Mice ; *Radiation Injuries, Experimental/microbiology/drug therapy/pathology ; Mice, Inbred C57BL ; *Intestines/radiation effects/drug effects/pathology ; *Radiation Injuries ; *Radiation-Protective Agents/pharmacology ; Intestinal Mucosa/drug effects/metabolism/radiation effects/pathology ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Radiation-induced intestinal injury denotes structural and functional impairment of the intestines resulting directly or indirectly from ionizing radiation, such as that employed in radiation therapy for malignant tumors in the abdominal or pelvic regions, within the treatment area. It is a prevalent and severe consequence of radiation therapy for abdominal and pelvic tumors, greatly affecting treatment outcomes and patients' quality of life. Western medicine primarily employs symptomatic management, including medical drug therapy, hyperbaric oxygen therapy, nutritional support therapy, endoscopic and surgical interventions, as well as stem cell transplantation. However, current therapeutic agents for RIII fall far short of achieving ideal outcomes. Previous studies indicate that blueberry anthocyanins (BA) possess not only anticancer properties but also potent anti-inflammatory, antioxidant, and anti-radiation activities.<br><br>METHODS: Seventy male C57BL/6J mice (6-8 weeks old) were categorized into five groups: a normal control group (Con), an irradiation-only group (IR), groups administered low-dose BA prior to and following irradiation (IR+BA-L, 100 mg/kg bw), a high-dose BA group (IR+BA-H, 200 mg/kg bw), and a group receiving the clinical radiation protection agent amphotericin (IR+WR-2721, 30 mg/kg bw). Furthermore, a group for antibiotic-induced gut microbiota depletion and a validation group for fecal microbiota transplantation (FMT) were established. A model of radiation-induced intestinal damage was created utilizing a single 14 Gy dose of abdominal X-ray irradiation. The irradiation field encompassed a 2.5&#xa0;cm by 20&#xa0;cm region extending from the pubic symphysis to the xiphoid process. BA was supplied through oral gavage from 14 days prior to irradiation until 3.5 days post-irradiation at a dose of 0.2 mL/day per mouse, whereas the normal control group received saline via gavage for 14 consecutive days. Tissue samples were obtained 3.5 days post-irradiation. Through the assessment of survival rates, body mass, intestinal histopathology, inflammatory cytokine concentrations (IL-1&#x3b2;, IL-6, TNF-&#x3b1;), oxidative stress indicators (SOD, MDA), and intestinal barrier proteins (occludin, claudin-1), alongside immunohistochemical analysis of the proliferative cell marker Ki67 and the Paneth cell marker lysozyme, the proliferation and differentiation of intestinal stem cells will be evaluated. Furthermore, 16S rDNA sequencing was executed on colonic contents, and non-targeted metabolomics analysis was undertaken on colonic tissue to assess alterations in gut microbiota and host metabolism.<br><br>RESULTS: Mice treated with BA intervention exhibited significant alleviation of intestinal injury, manifested as reduced weight loss, increased survival rate, markedly elongated colon length, substantially mitigated intestinal damage, and elevated histological scores. Concurrently, BA therapy downregulated levels of pro-inflammatory cytokines IL-1&#x3b2;, TNF-&#x3b1;, and IL-6, while decreasing elevated SOD content and MDA levels. Immunohistochemical analysis revealed that BA intervention significantly increased Ki67[+]proliferating cells and Lysozyme[+] Paneth cells in the crypt region of the colon. Western blot analysis demonstrated that BA upregulated the levels of intestinal tight junction proteins Occludin and Claudin-1. 16S rDNA sequencing revealed that BA improved gut microbiota composition by increasing the abundance of beneficial bacteria and reducing pathogenic bacteria. Metabolomic analysis revealed altered metabolic patterns in mouse colon tissue following both radiation exposure and BA intervention. BA restored levels of 53 potential biomarkers. Finally, fecal microbiota transplantation (FMT) validated BA's protective effect against RIII via the gut microbiota.<br><br>CONCLUSIONS: The results of this study show that blueberry anthocyanin (BA) exerts significant protective effects against radiation-induced intestinal injury (RIII). It ameliorates RIII by modulating gut microbiota composition and associated metabolites. FMT experiments further validate that BA's protective action depends on gut microbiota regulation. The findings suggest that BA, as a gut microbiota-modulating agent, holds promise for preventing and treating RIII.}, }
@article {pmid42317353, year = {2026}, author = {Lohani, SC and Zhang, C and Mandal, S and Zhao, M and Cheng, Y and Ramer-Tait, AE and Li, Q}, title = {Fecal microbiota transplantation reduces inflammation and modulates gene expression in HIV-infected double humanized-BLT (dHu-BLT) mice on antiretroviral therapy.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1773716}, pmid = {42317353}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *HIV Infections/therapy/immunology/microbiology/genetics/drug therapy ; Mice ; Humans ; *Inflammation/therapy/immunology ; Gastrointestinal Microbiome ; Disease Models, Animal ; *Anti-Retroviral Agents/therapeutic use ; Gene Expression Regulation ; }, abstract = {INTRODUCTION: Persistent immune activation and inflammation remain significant barriers to managing comorbidities in people living with HIV (PLWH) on suppressive antiretroviral therapy (ART). While ART substantially reduces plasma viral loads to an undetectable level, it fails to fully restore gut microbial homeostasis and prevent microbial translocation, a critical pathogenic contributor to systemic persistent immune activation and inflammation. To evaluate the potential of human fecal microbiota transplantation (FMT) as an adjunctive therapy to restore gut health and attenuate inflammation and immune activation in PLWH on ART, we utilized a double humanized-BLT (dHu-BLT) mouse model, featuring a functional human immune system and a human-like microbiome.<br><br>METHODS: Two groups of HIV-infected dHu-BLT mice were used in the study. One group received FMT in addition to ART, while the control group received ART alone. Using both a multi-omics approach (16S rRNA sequencing and RNA-seq) and an immune-based assay, we compared alterations in gut microbial composition, profiled transcriptomic changes in the intestinal tissue, and quantified markers of systemic immune activation and inflammation between the groups.<br><br>RESULT: FMT supplementation in ART-treated mice increased the relative abundance of beneficial bacteria and modulated the transcriptomic profile of both human- and murine-related genes. Notably, genes associated with cellular structure and tissue maintenance, including Mcpt4, were upregulated, along with the extracellular matrix organization pathway predicted as the most strongly activated pathway in the FMT-supplemented group compared to ART alone. In contrast, genes and signaling pathways associated with inflammation were downregulated. Importantly, the FMT-supplemented group exhibited a significant reduction of plasma inflammatory markers, including CD62E, sCD14, sCD163, and FABP2, relative to the ART alone group.<br><br>CONCLUSION: These results suggest that FMT may serve as a promising adjunctive strategy for mitigating systemic inflammation by improving gut health, thereby contributing to the reduction of comorbidities in PLWH on ART.}, }
@article {pmid42317360, year = {2026}, author = {Jia, Y and Liu, Y and Liu, J}, title = {The relationship between gut microbiota and cancer immune response and immunotherapy.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1833138}, pmid = {42317360}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods/adverse effects ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; }, abstract = {The gut microbiota critically regulates cancer immunity and immunotherapy outcomes. It does so through complex, bidirectional interactions with the host immune system. Key microbial metabolites drive this process. These include short-chain fatty acids (SCFAs), tryptophan derivatives, inosine, trimethylamine N-oxide (TMAO), and bile acids. These molecules direct immune cell differentiation and activity via pattern recognition receptor signaling and epigenetic regulation. Clinical studies have linked specific microbial compositions to responses to immune checkpoint inhibitors (ICIs) across multiple cancer types. These studies also highlight a dual role of the microbiota. It can both increase therapeutic efficacy and mitigate immune-related adverse events (irAEs). Several therapeutic strategies are under active investigation. These include fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary interventions. However, challenges remain regarding engraftment, standardization, and formulation consistency. Large-scale, well-designed studies are still needed. Such studies will help establish the gut microbiota as a reliable prognostic biomarker and a viable therapeutic adjunct in cancer immunotherapy.}, }
@article {pmid42317568, year = {2026}, author = {McMahan, ZH and Santis, MC and Cricchio, AL and Alcala-Gonzalez, LG and Clarke, J and O'Connor, A and Bellando-Randone, S and Denton, CP and Galetti, I and Lescoat, A and Matucci-Cerinic, M and Matucci-Cerinic, P and McLaughlin, J and Murray, C and Volkmann, ER and Alunno, A and Bandini, G and Hughes, M}, title = {Expert recommendations for the management of fecal incontinence in systemic sclerosis: A report from the World Scleroderma Foundation (WSF) Gastrointestinal "Ad hoc committee".}, journal = {Journal of scleroderma and related disorders}, volume = {11}, number = {1}, pages = {}, pmid = {42317568}, issn = {2397-1991}, abstract = {BACKGROUND: Fecal incontinence (FI) affects up to 50% of patients with systemic sclerosis (SSc), significantly impairing quality of life and daily functioning. Despite its prevalence, patients may not disclose their symptoms and there is limited guidance on evaluation and management. Given the complexity of SSc and delays in gastroenterology referrals, rheumatologists often initiate care. To address this gap, an expert panel was convened to develop practical, consensus-based recommendations for assessing and managing SSc-FI.<br><br>METHODS: An international Steering Board (n=19) was assembled under the auspices of the World Scleroderma Foundation GI ad hoc committee, including clinicians from rheumatology, gastroenterology, and GI surgery, as well as a methodology expert and a patient representative. A working definition of SSc-FI was established. Draft recommendations were developed through a literature review and expert consensus. Two rounds of online voting were conducted, requiring &#x2265;75% agreement in round one and &#x2265;60% in round two for inclusion.<br><br>RESULTS: In the first and second voting rounds, participation rates were 63.2% and 84.2%, respectively. All 22 draft recommendations were approved, with most (21) reaching consensus in the first round. Recommendations span five domains: general management approach (n=3); clinical assessment and non-pharmacological interventions (n=7 and n=3, respectively); management of FI in the context of diarrhea (n=5); and alternative interventions and strategies (n=4).<br><br>CONCLUSION: These are the first practical recommendations for managing SSc-related FI. They emphasize a structured, multidisciplinary approach to care, highlight unmet clinical needs, and lay the foundation for a research agenda to advance the understanding and treatment of this underrecognized complication in patients with SSc.}, }
@article {pmid42317757, year = {2026}, author = {Chen, J and Xiong, Z and Yu, C and Wang, J and Yu, C and Zhu, S and Peng, H and Yang, L and Hu, C and Xiong, X and Qiu, M and Zhang, Z and Xia, B and Song, X and Du, L and Yang, C}, title = {Age influences serum immune indices and gut microbiota composition in adult broilers.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1802596}, pmid = {42317757}, issn = {1664-302X}, abstract = {While the gut microbiota is recognized as a key modulator of host immunity, its age-related dynamics in adult-to-senescent broilers remain poorly characterized. This study aimed to comprehensively analyze age- and sex-related variations in serum immune indices and gut microbiota composition in yellow-feathered broilers aged 1 to 4 years (n = 40). Peripheral blood and fecal samples were gathered for immune profiling using ELISA (STP, IgA, IgG, IL-4, IFN-γ) and 16S rDNA sequencing. The results indicated that serum STP levels peaked at 1 year (p < 0.01), whereas IgG levels exhibited an age-related increase (p < 0.05). Although no significant compositional separation was detected among age groups by PERMANOVA (Adonis p = 0.14), within-group beta dispersion differed significantly across ages (p < 0.05). Firmicutes and Proteobacteria dominated the fecal microbiota at the phylum level. Exploratory Spearman correlation analysis (based on nominal p-values) identified potential associations, such as a positive nominal correlation between Limosilactobacillus abundance and IgG levels (p < 0.01), and a negative nominal correlation between Achromobacter and IL-4 (p < 0.01); however, these findings require further validation due to the lack of correction for multiple testing. Notably, one-year-old hens exhibited the highest abundance of beneficial taxa, such as Lactobacillus, which corresponded with their elevated STP levels. These findings highlight age- and sex-specific interactions between the gut microbiota and immune responses. From a theoretical perspective, one-year-old hens display a gut microbiota and immune profile that could be favorable for microbiota transplantation; however, direct functional validation (e.g., FMT experiments in recipient models) is required to support this hypothesis. This study offers novel insights into avian aging models and microbiota-mediated immune regulation, presenting potential strategies to enhance poultry health in intensive farming systems.}, }
@article {pmid42317762, year = {2026}, author = {Joshi, G and Rani, S and Bharti, D and Panda, N and Chavan, P and Mathpal, S and Ramaiah, S and Anbarasu, A}, title = {The role of the gut microbiome in antibiotic-driven antimicrobial resistance.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1856738}, pmid = {42317762}, issn = {1664-302X}, abstract = {Antimicrobial resistance (AMR) is one of the most pressing threats to global health system. The human gut harbors a complex microbial ecosystem coordinated through mechanisms of metabolic interdependence. The gut microbiota plays a vital role in normal growth and physiological processes of the human body. It serves both as a target of antibiotic-mediated disruption and as a reservoir for the propagation of antimicrobial resistance genes. Although antibiotics remain indispensable for the treatment of bacterial infections, their broad ecological impact on the gut microbiota can undermine the microbial balance that protects the host against pathogen invasion and metabolic dysfunction. The gut microbiome also functions as a reservoir of antimicrobial resistance genes collectively termed the "resistome," which can be mobilised and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms such as conjugation, transformation, and transduction. This review examines the composition and functions of the human gut microbiota, the mechanism of antibiotic-induced gut dysbiosis, and the role of host factors like age, genetics, diet and immune status, on microbiome dynamics and AMR development. We further evaluate emerging methods for resistome characterisation, which include PCR, next-generation sequencing, functional metagenomics and artificial intelligence-driven tools. Finally, we discuss microbiome-targeted therapeutic strategies such as faecal microbiota transplantation (FMT), phage therapy, CRISPR-based therapies, and antimicrobial peptides for combating AMR and restoring gut microbial homeostasis. Overall, this review highlights that maintaining and re-establishing the integrity of the gut microbiome should be considered a fundamental component of antimicrobial stewardship strategies aimed at controlling AMR worldwide.}, }
@article {pmid42318200, year = {2026}, author = {Gou, Y and Liu, X and Zhu, W and Yuan, Y and Wang, Y and Xie, Q}, title = {Beyond the 'second brain': the gut microbiota as a constitutive co-constructor of embodied cognitive network.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1808839}, pmid = {42318200}, issn = {1662-4548}, abstract = {Traditional cognitive science has historically confined the mind within the cranium. While the "second brain" metaphor underscores the autonomy of the enteric nervous system, it remains entrenched in a neurocentric paradigm. Here, we propose a transformative framework: the gut microbiota may function as a constitutively relevant contributor to specific embodied cognitive architectures. We contend that cognition, emotion, and behavior are not fully understandable in brain-isolated terms. Instead, these processes emerge from a sustained, bidirectional dialogue between the host and its symbiotic microbial ecosystem. Integrating 4E cognition theory, we systematically delineate how gut microbiota functions as an embedded signaling system-producing cognitively active metabolites, such as short-chain fatty acids and neuroactive substances-to shape interoceptive states and neural function via neural, immune, and metabolic/endocrine interfaces. We establish a rigorous evidential chain, categorized as "deprivation, replacement, observation, and intervention," synthesizing germ-free animal models, fecal microbiota transplantation, human multi-omics, and clinical interventions. These data-drawn from animal models that establish causal necessity and sufficiency, human cohort studies that reveal systematic ecological associations, and proof-of-concept intervention trials that demonstrate clinical plasticity-converge to support the view that microbiota-derived processes may be constitutively relevant to the realization of specific embodied cognitive architectures, especially those organized through interoceptive prediction, affective appraisal, and vagal-metabolic signaling, rather than functioning as merely transient or incidental regulators. The multi-level nature of this evidence base, spanning causal mechanisms in controlled settings to ecological validity in human populations, provides a robust foundation for reframing the gut microbiota as a symbiotic co-constructor of the embodied mind. Ultimately, we move beyond the linear "gut-brain axis" model to outline a multispecies framework for understanding the embodied architectures within which interoceptive, affective, and related cognitive processes unfold. This paradigm shift offers a novel biological foundation for the mind and enables precision interventions for mental health, such as psychobiotics and targeted ecological remodeling. Looking forward, we envision a unified "microbiota-mind" model that integrates computational modeling and ethical frameworks. This endeavor challenges the traditional concept of a "self" bounded by the skin, providing a roadmap for the future of precision psychiatry and cognitive science.}, }
@article {pmid42319691, year = {2026}, author = {Amruthavarshini, SN and Kumari, N and Anand, S}, title = {A Comprehensive Review on the Microbial Signatures and Metabolic Mechanisms Underlying the Gut-Alzheimer's Disease Axis.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {}, pmid = {42319691}, issn = {1559-1182}, mesh = {Humans ; *Alzheimer Disease/metabolism/microbiology ; Animals ; *Gastrointestinal Microbiome/physiology ; Brain/metabolism ; Probiotics ; }, abstract = {Alzheimer's disease (AD) is the most common form of dementia, driven by complex interactions among aging-related biological changes, neuronal degeneration, mitochondrial dysfunction, and environmental factors. Despite extensive research, effective disease-modifying therapies remain unavailable. Increasing evidence highlights the gut-brain axis as an important contributor to AD pathogenesis, particularly through amyloid-producing gut microbes that promote immune activation, neuroinflammation, and cerebral amyloid accumulation. This review summarizes current evidence linking gut microbiota (GM) dysbiosis to AD, focusing on microbial metabolites, neuroinflammatory pathways, and microbiota-targeted therapeutic strategies. A systematic analysis of experimental and clinical studies reveals that altered gut microbial composition is associated with systemic and neuroinflammation, blood-brain barrier dysfunction, oxidative stress, and neuronal damage. Key microbial metabolites, including short-chain fatty acids and indole derivatives, exhibit neuroprotective effects by regulating immune responses, maintaining barrier integrity, and supporting neuronal energy metabolism; disruption of these metabolites may accelerate neurodegeneration. Microbiota-based interventions such as probiotics, prebiotics, dietary modification, and fecal microbiota transplantation show beneficial effects in preclinical models by restoring microbial balance and reducing neuropathological features, although clinical evidence in humans remains limited. Overall, current findings support a contributory role of gut dysbiosis in AD and suggest that targeting the GM may offer a promising complementary strategy for disease modification and future therapeutic development.}, }
@article {pmid42320473, year = {2026}, author = {Xu, S and Lyu, J and Bao, G and Zheng, P and Li, Y and Ning, Z and Li, B and Zhuang, M and Wong, HK and Wang, M and Zeng, Y and Zheng, Y and Luo, J and Liu, Q and Zhang, L and Lin, C and Xiao, H and Yuan, CS and Wong, HLX and Bian, Z and Zhai, L}, title = {Gut bacteria that produce fatty acid ethanolamides alleviate diarrhea-predominant IBS with insulin resistance.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.05.020}, pmid = {42320473}, issn = {1934-6069}, abstract = {Individuals with diarrhea-predominant irritable bowel syndrome (IBS-D) are at an increased risk of insulin resistance. Here, we identify a critical role for gut-microbe-derived fatty acid ethanolamides (FAEs) in the treatment of IBS-D with insulin resistance. In IBS-D patients with insulin resistance, serum levels of FAE are significantly reduced compared with healthy controls, and lower FAE levels negatively correlate with the severity of GI symptoms. Oral administration of FAE, specifically oleoylethanolamide (OEA), alleviates diarrhea and visceral hypersensitivity in murine IBS-D-like models. Mechanistically, OEA acts as a PPARα agonist to upregulate the serotonin transporter (SERT), limiting peripheral serotonin availability. Furthermore, fecal microbiota transplantation from high-FAE donors or treatment with FAE-producing bacteria (Escherichia coli[ereT+] or Eubacterium rectale) elevates fecal FAE and alleviates symptoms via the PPARα-SERT axis. Our findings reveal a microbial FAE-driven pathway linking IBS-D and insulin resistance, presenting a therapeutic target for this comorbidity. This study was registered at ClinicalTrials.gov (NCT02822677 and NCT03457324) and Chinese Clinical Trial Registry (ChiCTR2300069830 and ChiCTR2300067254).}, }
@article {pmid42320811, year = {2026}, author = {Wang, Y and Wu, X and Deng, H and Yan, G and Xu, Z and Zhu, L}, title = {A high-molecular-weight polysaccharide from Polygonatum sibiricum inhibits distant tumor growth associated with gut microbiota remodeling and synergizes with αPD-1 therapy.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {153116}, doi = {10.1016/j.ijbiomac.2026.153116}, pmid = {42320811}, issn = {1879-0003}, abstract = {BACKGROUND: Defined polysaccharide fractions can reshape the gut microbiome and influence systemic antitumor immunity. We investigated whether an operationally defined high-molecular-weight Polygonatum sibiricum polysaccharide fraction (PSP-H) enriched by 100 kDa ultrafiltration suppresses growth of subcutaneous MC38 tumors via microbiota-dependent mechanisms and potentiates anti-PD-1 therapy.<br><br>MATERIALS AND METHODS: PSP-H was isolated by cascade ultrafiltration and compared with a total polysaccharide extract (PSP-T) and lower-MW fractions. We profiled fecal metagenomes, serum metabolites, tumor molecular readouts (immunoblotting; HDAC activity), and immunity. Fecal microbiota transplantation (FMT) tested the microbiota dependence and sufficiency of PSP-H-remodeled communities to transfer the immunometabolic phenotype. Combination with anti-PD-1 (RMP1-14) was evaluated.<br><br>RESULTS: PSP-H showed minimal direct cytotoxicity while suppressing tumor growth, selectively enriching butyrate-producing taxa (e.g., Lachnospiraceae) and elevating serum butyrate and inosine, with TNF-&#x3b1; reduced. In vitro, butyrate enhanced T-cell IFN-&#x3b3;/IL-2/granzyme-B, inhibited tumor HDAC activity, and counteracted IFN-&#x3b3;-induced PD-L1; in vivo, PSP-H created a T-cell-activating milieu with adaptive STAT1/PD-L1 up-regulation. FMT recapitulated the key metabolite/cytokine signature. PSP-H&#x202f;+&#x202f;anti-PD-1 synergistically increased intratumoral CD8[+] T cells and yielded superior tumor control versus monotherapy.<br><br>CONCLUSION: PSP-H is a defined microbiota-modulating adjuvant that engages a microbiome-butyrate-immune axis to restrain subcutaneous tumors and sensitizes them to PD-1 blockade by converting systemic immunity while inducing targetable adaptive resistance.}, }
@article {pmid42321866, year = {2026}, author = {Yan, S and Fang, N and Zhang, Y and Zhang, N and Liang, Q and Duan, Y and Li, L and Li, Y and Gong, Y}, title = {Gut microbiota-associated leucine elevation promotes cold-induced atherosclerotic plaque formation and instability.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08492-5}, pmid = {42321866}, issn = {1479-5876}, support = {2024YFA1307001//the National Key R&amp;D Program of China/ ; JD2023SJ44//the Key Research and Development Plan of Heilongjiang Province/ ; HMUMIF-22001//the HMU Marshal Initiative Funding/ ; 82370314//the National Natural Science Foundation of China/ ; 2022YFC2503500//the National Key Research and Development Project of China/ ; }, abstract = {BACKGROUND: Environmental factors such as cold exposure have been increasingly recognized as contributors to atherosclerosis progression, yet the underlying mechanisms linking environmental stress to vascular pathology remain incompletely understood. In particular, the role of the gut microbiota and microbiota-associated metabolites in cold-induced atherosclerosis has not been fully elucidated.<br><br>METHODS: A cold exposure model was established in ApoE&#x207b;/&#x207b; mice fed a Western diet. Integrated multi-omics analyses were combined with fecal microbiota transplantation (FMT) and mechanistic cellular assays to investigate gut microbiota remodeling, metabolic alterations, and immune regulation during cold-induced atherosclerosis.<br><br>RESULTS: In this study, we demonstrate that cold exposure accelerates atherosclerotic plaque growth and instability in parallel with pronounced gut microbiota dysbiosis and alterations in host metabolic profiles. FMT combined with metabolomic analyses showed that cold-associated gut microbiota is closely associated with elevated circulating leucine levels, suggesting that cold-induced microbial remodeling may participate in this process by modulating host systemic leucine availability. Mechanistically, increased leucine suppressed the Zic family member 2 (Zic2) in macrophages, leading to reduced expression of growth arrest-specific 6 (Gas6), a key mediator of efferocytosis. Impaired Gas6-dependent efferocytosis resulted in defective clearance of apoptotic cells, heightened vascular inflammation, and increased plaque instability. Importantly, supplementation with Lactobacillus johnsonii, a commensal bacterium depleted under cold exposure, normalized circulating leucine levels, restored Zic2-Gas6 signaling, enhanced macrophage efferocytosis, and attenuated atherosclerotic plaque progression. Conversely, leucine supplementation recapitulated the effects of cold exposure on plaque development and instability.<br><br>CONCLUSIONS: Collectively, these findings identify a previously unrecognized cold-microbiota-leucine-Zic2-Gas6-efferocytosis axis that links environmental stress to atherosclerosis progression. Targeting gut microbial regulation of host systemic leucine levels, including L. johnsonii-based interventions, may represent a promising therapeutic strategy for preventing cold-induced atherosclerotic cardiovascular disease.}, }
@article {pmid42322483, year = {2026}, author = {Sangiovanni, C and Orazi, V and Belardi, I and Gallotta, L and Ferretti, F and Calderola, S and Malaspina, P and Guadano-Procesi, I and Fiorilla, C and Di Cave, D and Berrilli, F}, title = {Environmental effects on the lung and gastrointestinal parasite fauna of wild boar: a comparative study between alpine and Mediterranean ecosystems.}, journal = {Acta parasitologica}, volume = {71}, number = {4}, pages = {}, pmid = {42322483}, issn = {1896-1851}, mesh = {Animals ; *Ecosystem ; *Sus scrofa/parasitology ; Feces/parasitology ; Swine ; Italy/epidemiology ; Prevalence ; *Swine Diseases/parasitology/epidemiology ; Seasons ; Environment ; *Intestinal Diseases, Parasitic/veterinary/parasitology/epidemiology ; Mediterranean Region/epidemiology ; *Parasites/isolation &amp; purification/classification ; *Gastrointestinal Tract/parasitology ; *Lung Diseases, Parasitic/veterinary/epidemiology/parasitology ; }, abstract = {PURPOSE: This study aims to explore environmental factors associated with parasite infections in faecal samples collected from wild boar populations, by analysing the prevalence, intensity, and abundance of parasite communities across two Italian ecosystems: the alpine environment in the Orco Valley (Gran Paradiso National Park) and the Mediterranean lowland in the Maremma Regional Park.<br><br>METHODS: Seasonal faecal samples were collected from November 2023 to July 2025 along systematic transects in both study areas. Samples were analysed using the Mini-FLOTAC technique to quantify parasite eggs and (oo)cysts, and prevalence, intensity, and abundance were calculated. Environmental variables, including elevation, land use, temperature, precipitation, and season, were linked to each sample. Generalized linear models (GLMs) were fitted to evaluate the effects of environmental factors on parasite presence and abundance.<br><br>RESULTS: Parasite communities were dominated by Eimeria spp., gastrointestinal strongyles, and Metastrongylus spp., whereas other taxa (e.g., Balantioides coli, Capillaria spp., Cystoisospora sp.) were sporadic. Significant differences in intensity and/or abundance of dominant taxa were observed between the two areas. Models based on infection abundance, rather than presence, revealed environmental associations: Metastrongylus spp. abundance decreased with increasing elevation, possibly reflecting constraints on intermediate host availability; while gastrointestinal strongyles abundance was lower in open natural habitats, reflecting microclimatic influences on larval survival.<br><br>CONCLUSIONS: This study highlights associations between habitat characteristics and parasite community structure in wild boar populations, providing insights into the environmental factors potentially influencing parasite transmission across heterogeneous landscapes.}, }
@article {pmid42322762, year = {2026}, author = {Xie, Y and Lin, J and Huang, Z and Jiang, D and Peng, L and Luo, Y and Liang, J and Han, Y and Guo, S and Jiang, X}, title = {Lichang decoction suppresses AOM+DSS-induced colitis-associated cancer via regulating intestinal flora and suppressing the Wnt/β-catenin signaling pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {159}, number = {}, pages = {158385}, doi = {10.1016/j.phymed.2026.158385}, pmid = {42322762}, issn = {1618-095X}, abstract = {BACKGROUND: Lichang Decoction (LCD), a traditional Chinese medicine formula clinically used for intestinal disorders, has shown anti-inflammatory potential; however, its therapeutic efficacy and underlying mechanism in colitis-associated colorectal cancer (CAC) remain unclear.<br><br>PURPOSE: The objective of this study is to investigate the effects and mechanisms of LCD in an AOM+DSS-induced CAC mouse model.<br><br>METHODS: The primary constituents of LCD were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). An azoxymethane/dextran sulfate sodium (AOM+DSS)-induced CAC mouse model was established and treated with low- or high-dose LCD, or 5-fluorouracil (5-Fu). Clinical symptoms, tumor burden, histopathological changes and inflammatory responses were evaluated. Intestinal barrier integrity was assessed by tight junction and mucus-related markers. Transcriptomic analysis, quantitative PCR and Western blotting were performed to investigate the Wnt/&#x3b2;-catenin signaling pathway. Gut microbiota alterations were analyzed by 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted to determine the causal role of microbiota in LCD-mediated protection.<br><br>RESULTS: LCD treatment significantly alleviated weight loss, diarrhea and hematochezia, reduced disease activity index scores, and markedly suppressed tumor number and size in CAC mice. LCD attenuated colonic inflammation by decreasing serum and tissue levels of IL-1&#x3b2;, TNF-&#x3b1;, IL-6 and IFN-&#x3b3;, while reducing CD11b&#x207a; and MPO&#x207a; inflammatory cell infiltration. Moreover, LCD restored intestinal barrier function and increased goblet cell abundance. Mechanistically, transcriptomic, molecular analyses and molecular docking revealed that LCD significantly inhibited aberrant activation of the Wnt/&#x3b2;-catenin pathway, evidenced by reduced expression of Wnt4, &#x3b2;-catenin, c-Myc and cyclin D1. However, LCD treatment in HCT116 cells did not affect the Wnt/&#x3b2;-catenin pathway. Additionally, LCD reshaped gut microbiota composition by suppressing tumor-associated bacterial taxa (Bacillota and Bacteroidota) and enriching beneficial Verrucomicrobiota. Correlation and functional prediction analyses linked microbial modulation to Wnt/&#x3b2;-catenin signaling and tumor progression. Importantly, FMT derived from LCD exerted an inhibitory effect on tumor progression in pseudo-germ-free CAC mice, but direct administration of LCD in pseudo-germ-free CAC mouse model did not demonstrate a significant tumor-suppressive effect.<br><br>CONCLUSION: LCD effectively suppresses CAC by remodeling gut microbiota to inhibit Wnt/&#x3b2;-catenin signaling, thereby alleviating inflammation, restoring intestinal barrier function and restraining tumor progression. These findings indicate that LCD represents a viable therapeutic intervention for CAC treatment.}, }
@article {pmid40865967, year = {2025}, author = {Jee, JJ and Park, S and Kim, J and Lee, H and Koh, H and Koo, BN}, title = {Bacterial extracellular vesicle as a predictive biomarker for postoperative delirium status after spinal surgery: a prospective cohort study.}, journal = {International journal of surgery (London, England)}, volume = {111}, number = {12}, pages = {9239-9249}, pmid = {40865967}, issn = {1743-9159}, mesh = {Humans ; Prospective Studies ; Male ; Female ; Aged ; *Extracellular Vesicles/metabolism ; Middle Aged ; Biomarkers/blood ; *Delirium/diagnosis/etiology/microbiology ; *Postoperative Complications/diagnosis/microbiology ; Gastrointestinal Microbiome ; Prognosis ; *Spine/surgery ; *Bacteria ; }, abstract = {BACKGROUND: Prognostic factors significantly associated with postoperative delirium (POD) have been reported discordantly, possibly due to heterogeneous cohorts. Here, bacteria extracellular vesicles (BEVs) were introduced to predict the POD status of a unique patient cohort.<br><br>METHODS: One hundred twenty-eight patients who underwent spinal surgery participated in this prospective cohort study. Significant preoperative factors (i.e., baseline characteristics, and sequences of 16s rRNA genes from bloods and stools) between patients with and without delirium were subjected to random forest classifiers for prediction model, and potential metabolites that regulate the POD were inferred in silico .<br><br>RESULTS: No significant differences were found between patients with and without delirium in terms of demographics, anthropometrics, intervention history or preoperative cognitive function scores, except for circulating BEVs; delirium group had less diverse BEVs dominated with EVs from Gammaproteobacteria, whereas more diverse BEVs enriched with EVs from Bacilli and Alphaproteobacteria were significantly associated with non-delirium. Compared to that with baseline characteristics or gut microbiome, prediction model using random forest classifier with the significant BEVs yielded the lowest error rate of 21.59%, and was validated with an independent data set, resulting in 80% accuracy. Moreover, EVs from Moraxellaceae and Acinetobacter showed the highest probabilities of prediction of the POD despite their low relative abundance, indicating the most significant prognostic markers for the POD. As the inference of a potential metabolites that regulate the POD, succinate and enterobacterial common antigens delivered from BEV cargo were expected to participate in pathogenic events, whereas S-methyl-5'-thioadenosine, 2-oxoglutarate, pyruvate, acetate and butyrate may play a neuroprotective role in the POD.<br><br>CONCLUSIONS: The profile of circulating preoperative BEVs is the key prognostic factor for distinguishing POD in elderly surgical patients with controlled baseline conditions. Metabolites of defensive and offensive mechanisms inferred from BEVs will be essential for developing next-generation POD prevention strategies.}, }
@article {pmid40866789, year = {2025}, author = {Kusakabe, S and Kurashige, R and Fukushima, K and Shimizu, K and Yoshihara, T and Motooka, D and Nakamura, S and Kurashige, M and Nakata, K and Hino, A and Kasahara, H and Ueda, T and Fujita, J and Hosen, N and Takehara, T and Oda, J}, title = {Fecal microbiota transplantation for Crohn's disease-like intestinal lesions arising after allogeneic stem cell transplantation.}, journal = {International journal of hematology}, volume = {122}, number = {5}, pages = {771-777}, pmid = {40866789}, issn = {1865-3774}, mesh = {Humans ; Female ; Middle Aged ; *Crohn Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Transplantation, Homologous ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/therapy ; }, abstract = {Several cases of inflammatory bowel disease (or similar gastrointestinal lesions) arising after allogeneic hematopoietic stem cell transplantation have been reported, but the effect of intestinal dysbiosis on development of these lesions remains unclear. We performed fecal microbiota transplantation (FMT) and 16S rRNA microbiome analysis in a patient who developed Crohn's disease-like lesions after allogeneic transplantation. A 62-year-old woman underwent haploidentical stem cell transplantation from her daughter to treat double-hit lymphoma relapsed after chimeric antigen receptor T-cell therapy, and achieved remission without developing acute graft-versus-host disease. Eight months later, she developed Crohn's disease-like intestinal lesions after cytomegalovirus enteritis. Her condition did not improve with the conventional treatment, so she underwent FMT from her daughter as part of a clinical trial. Diarrhea gradually improved, and follow-up endoscopy 4 months after the FMT showed ulcer healing and scarring. The 16S rRNA analysis revealed a reduction in the relative abundance of the Enterococcus genus after FMT, suggesting that dysbiosis may have contributed to lesion development. The patient is currently on a regular diet, with no symptom recurrence, and the primary disease remains in remission. Although this outcome suggests that FMT is effective, careful patient selection is required to reduce the risk of FMT-associated sepsis.}, }
@article {pmid40867077, year = {2025}, author = {Ebadi, M and Reddi, S and Senyshyn, L and Minot, SS and Gooley, T and Kabage, AJ and Lee, SJ and Hill, GR and Khoruts, A and Rashidi, A}, title = {Effect of fecal microbiota transplantation on gut microbiota functional profile in recipients of allogeneic hematopoietic cell transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2551882}, pmid = {40867077}, issn = {1949-0984}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Middle Aged ; Female ; Adult ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; *Dysbiosis/therapy/microbiology ; Transplantation, Homologous ; Feces/microbiology ; Aged ; }, abstract = {Intestinal dysbiosis has been associated with both the effectiveness and toxicity of immunotherapy in cancer patients, inspiring multiple trials investigating fecal microbiota transplantation (FMT) in these patients. FMT restores microbial community structures damaged by antibiotics and enriches the microbiota with beneficial bacteria. However, the precise mechanism through which FMT exerts its effects and provides clinical benefits remains incompletely understood. Efforts to date have primarily focused on characterizing taxonomic changes following FMT. We hypothesized that FMT may also modify the functional pathways and metabolic capabilities of the gut microbiota, with possible clinical impact. To investigate this, we conducted a study involving 17 patients with blood disorders who received prophylactic FMT from one of the three healthy donors shortly after hematopoietic cell transplantation (HCT). By analyzing shotgun metagenomic profiles of the baseline, pre-FMT, and post-FMT gut microbiota, we demonstrate that FMT effectively restored pathways that had been depleted following HCT. However, it did not significantly reduce pathways that had expanded, indicating that FMT operates primarily through a restorative mechanism, reestablishing lost functional capabilities in the microbiota rather than suppressing overactive pathways. These findings highlight the potential for optimizing FMT protocols and identifying patient populations where FMT may be particularly beneficial.}, }
@article {pmid40868023, year = {2025}, author = {Kullar, R and Johnson, S and Goldstein, EJC}, title = {Clostridioides difficile in Peripartum Women: Review of Outcomes and Treatment.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {40868023}, issn = {2079-6382}, abstract = {Background:Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the United States with increasing rates in younger patients and those in the community. CDI incidence may also be on the rise in peripartum women. Methods: We conducted a literature review to assess the incidence and outcomes of CDI in the peripartum population and review treatment options. Results: Peripartum patients have a high risk of complications and adverse events associated with CDI. Most patients have been treated with vancomycin or metronidazole; however, cases of patients recurring on standard treatment have been described, with patients having successful outcomes with fidaxomicin or fecal microbiota transplantation (FMT). Probiotics have been shown to be safe in peripartum women; however, the role in preventing primary and secondary CDI has not been studied. Conclusions: Peripartum women that develop CDI are at increased risk for complications. Treatment includes vancomycin, metronidazole, or fidaxomicin or FMT for recurrent cases.}, }
@article {pmid40868053, year = {2025}, author = {Maruyama, T and Ishikawa, D and Kurokawa, R and Masuoka, H and Nomura, K and Haraikawa, M and Orikasa, M and Odakura, R and Koma, M and Omori, M and Ishino, H and Ito, K and Shibuya, T and Suda, W and Nagahara, A}, title = {Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868053}, issn = {2227-9059}, support = {None//MiZ Co., Ltd/ ; }, abstract = {Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger's clinical activity index, 3-10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events.}, }
@article {pmid40868265, year = {2025}, author = {Haidar, L and Bănărescu, CF and Uța, C and Zimbru, EL and Zimbru, RI and Tîrziu, A and Pătrașcu, R and Șerb, AF and Georgescu, M and Nistor, D and Panaitescu, C}, title = {Beyond the Skin: Exploring the Gut-Skin Axis in Chronic Spontaneous Urticaria and Other Inflammatory Skin Diseases.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868265}, issn = {2227-9059}, abstract = {Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions between innate and adaptive immunity, mast cell dysregulation, and non-IgE-mediated pathways. This review explores the gut-skin axis as a unifying concept linking intestinal dysbiosis to inflammatory skin diseases, including atopic dermatitis, psoriasis, rosacea, and acne. Special emphasis is placed on CSU, where altered gut microbial composition, characterized by reduced diversity, depletion of short-chain fatty acid-producing bacteria, and expansion of Proteobacteria, may contribute to increased intestinal permeability, systemic immune activation via toll-like receptors, and heightened mast cell sensitivity. We discuss findings from animal models demonstrating that gut microbiota modulation can attenuate mast cell hyperreactivity and reduce urticarial symptoms. In parallel, we examine clinical evidence supporting the potential role of probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation as adjunctive strategies in CSU management. Despite promising findings, challenges remain in translating microbiome research into effective therapies due to interindividual variability, the complexity of host-microbiome interactions, and a lack of standardized protocols. Future research should focus on identifying predictive microbial patterns and developing personalized microbiome-targeted interventions. Understanding the bidirectional gut-skin relationship may open new therapeutic avenues beyond symptomatic treatment, positioning the microbiome as a novel target in CSU and related inflammatory dermatoses.}, }
@article {pmid40869967, year = {2025}, author = {Fu, Y and Bonifacio-Mundaca, J and Desterke, C and Casafont, &#xcd; and Mata-Garrido, J}, title = {Genomic Alterations and Microbiota Crosstalk in Hepatic Cancers: The Gut-Liver Axis in Tumorigenesis and Therapy.}, journal = {Genes}, volume = {16}, number = {8}, pages = {}, pmid = {40869967}, issn = {2073-4425}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Liver Neoplasms/genetics/microbiology/therapy/pathology ; *Carcinoma, Hepatocellular/genetics/microbiology/therapy/pathology ; *Carcinogenesis/genetics ; Liver/pathology/metabolism/microbiology ; *Cholangiocarcinoma/genetics/microbiology/therapy ; Mutation ; Epigenesis, Genetic ; Animals ; }, abstract = {Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut-liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host-microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut-liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA.}, }
@article {pmid40870405, year = {2025}, author = {Bibolar, AC and Nechita, VI and Lung, FC and Crecan-Suciu, BD and Păunescu, RL}, title = {Gut Feelings: Linking Dysbiosis to Depression-A Narrative Literature Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {8}, pages = {}, pmid = {40870405}, issn = {1648-9144}, mesh = {Humans ; *Dysbiosis/complications/psychology/physiopathology/microbiology ; *Depression/microbiology/etiology/psychology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches.}, }
@article {pmid40871301, year = {2025}, author = {Chen, S and Liu, T and Chen, J and Shen, H and Wang, J}, title = {Fecal Virome Transplantation Confirms Non-Bacterial Components (Virome and Metabolites) Participate in Fecal Microbiota Transplantation-Mediated Growth Performance Enhancement and Intestinal Development in Broilers with Spatial Heterogeneity.}, journal = {Microorganisms}, volume = {13}, number = {8}, pages = {}, pmid = {40871301}, issn = {2076-2607}, support = {Project No. CZ004306//"Tianshan Talent" Program/ ; Project No. XJLG-CYJSTX-10//Xinjiang Modern Agriculture Industry Technology System/ ; }, abstract = {Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution.}, }
@article {pmid40871460, year = {2025}, author = {Ren, J and Wang, Q and Hong, H and Tang, C}, title = {Fecal Microbiota Transplantation in Alzheimer's Disease: Mechanistic Insights Through the Microbiota-Gut-Brain Axis and Therapeutic Prospects.}, journal = {Microorganisms}, volume = {13}, number = {8}, pages = {}, pmid = {40871460}, issn = {2076-2607}, support = {HY202411//One health Interdisciplinary Research Project, Ningbo University/ ; D16013//National 111 Project of China/ ; the Health Fund of Translational Biomedicine//the Health Fund of Translational Biomedicine/ ; }, abstract = {Alzheimer's disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota-gut-brain axis (MGBA) have unveiled potential correlative mechanisms that may contribute to AD pathogenesis, though causal evidence remains limited. Dysregulation of GM composition (dysbiosis) exacerbates AD progression via neuroinflammation, amyloid-β (Aβ) deposition, and tau hyperphosphorylation (p-tau), while restoring microbial homeostasis presents a promising therapeutic strategy. Fecal microbiota transplantation (FMT), a technique to reconstitute gut ecology by transferring processed fecal matter from healthy donors, has demonstrated efficacy in ameliorating cognitive deficits and neuropathology in AD animal models. Preclinical studies reveal that FMT reduces Aβ plaques, normalizes tau phosphorylation, suppresses inflammasome activation, and restores microglial homeostasis through modulation of microbial metabolites and immune pathways. Although clinical evidence remains limited to case reports and small-scale trials showing potential therapeutic effect, safety concerns regarding long-term effects and protocol standardization necessitate further investigation. This review synthesizes current knowledge on GM-AD interactions, evaluates FMT's mechanistic potential, and discusses challenges in translating this ancient practice into a cutting-edge AD therapy. Rigorous randomized controlled trials and personalized microbiota-based interventions are imperative to advance FMT from bench to bedside.}, }
@article {pmid40872257, year = {2025}, author = {Cianci, G and Maini, G and Ferraresi, M and Pezzi, G and Bortolotti, D and Rizzo, S and Beltrami, S and Schiuma, G}, title = {Immune Modulation by Microbiota and Its Possible Impact on Polyomavirus Infection.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {40872257}, issn = {2076-0817}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Polyomavirus Infections/immunology/microbiology/virology/therapy ; *Polyomavirus/immunology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Animals ; Immunocompromised Host ; }, abstract = {Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation.}, }
@article {pmid40873073, year = {2025}, author = {, }, title = {[Expert consensus on the clinical application of gut microbiota transplant therapy in chronic liver disease (version 2025)].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {33}, number = {8}, pages = {738-746}, pmid = {40873073}, issn = {1007-3418}, support = {82470598//National Natural Science Foundation of China/ ; 2023A0505010007//Science and Technology Planning Project of Guangdong Province/ ; K-202401210//Guangdong Weiji Medical Development Foundation Specialized Research Fund for Gastroenterology/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Liver Diseases/therapy ; Chronic Disease ; Liver Cirrhosis/therapy ; Liver Neoplasms/therapy ; }, abstract = {The gut microbiota plays an important role in maintaining host health and liver function, and gut microbiota transplant (also known as fecal microbiota transplantation) has shown potential clinical benefits in the treatment of chronic liver disease. To help clinical professionals to quickly master and standardize the clinical application of gut microbiota transplant in chronic liver disease, the Group of the Liver Disease-related Gastroenterology Branch of the Chinese Medical Association organized experts in related fields to formulate the "Expert Consensus on the Clinical Application of Gut Microbiota Transplant in the Treatment of Chronic Liver Disease" such as chronic hepatitis, cirrhosis and liver cancer, including indications, contraindications, effectiveness, safety, donor selection, transplant routes, transplant precautions, prevention and treatment of adverse reactions, and other aspects to provide reference and guidance for clinicians to implement gut microbiota transplant.}, }
@article {pmid40873417, year = {2025}, author = {You, Y and Xiang, T and Yang, C and Xiao, S and Tang, Y and Luo, G and Ling, Z and Luo, F and Chen, Y}, title = {Interactions between the gut microbiota and immune cell dynamics: novel insights into the gut-bone axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2545417}, pmid = {40873417}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Bone and Bones/immunology ; Dysbiosis/immunology/microbiology ; Animals ; Osteoarthritis/immunology/microbiology ; Arthritis, Rheumatoid/immunology/microbiology ; Probiotics ; Osteoporosis/immunology/microbiology ; *Bone Diseases/immunology/microbiology ; Immune System ; Gastrointestinal Tract/immunology/microbiology ; Prebiotics ; }, abstract = {Over the past few decades, accumulating evidence has demonstrated that gut microbiota engages in a sustained dialog with the immune system, leading to microbiota-driven immune responses that mediate the regulation of bone-related diseases. Despite the complexity of the dynamic interactions within the gut-immune-bone axis, advancements in high-throughput multi-omics sequencing have significantly facilitated the detailed exploration of this intricate network, thereby providing the potential to develop novel therapeutic strategies for bone-related diseases. In this review, we first summarize the variations in gut microbiota composition observed in patients with bone-related diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and osteoporosis (OP), in comparison to healthy controls, along with the factors influencing these changes. The review that follows synthesize evidences highlighting the profound effects of gut microbial dysbiosis on immune homeostasis and bone microenvironment, respectively. We further elaborate that the gut-immune axis and gut-bone axis are not independent but three-dimensional networks, emphasizing gut microbial dysbiosis as a pivotal driver of immune dysregulation and subsequent bone homeostasis imbalance. Therapeutic strategies to manipulate the gut-immune-bone axis based on the use of probiotics as well as prebiotics, fecal microbiota transplantation, dietary modifications, and pharmacological interventions are also discussed. Finally, we discuss the challenges of current research on the gut-immune-bone axis and propose future directions for identifying novel therapeutic targets based on this axis to treat these diseases.}, }
@article {pmid40873657, year = {2025}, author = {Chapon, J and Scanzi, J and Sokol, H and Pereira, B and Buisson, A}, title = {Efficacy of different modalities of faecal microbiota transplantation in ulcerative colitis: systematic review and network meta-analysis.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251369624}, pmid = {40873657}, issn = {1756-283X}, abstract = {BACKGROUND: While several small sample size randomized controlled trials suggested the superiority of faecal microbiota transplantation (FMT) over placebo in ulcerative colitis (UC), the most effective modality to perform FMT remains unknown.<br><br>OBJECTIVES: To compare the efficacy of different modalities of FMT to induce clinical remission in patients with UC.<br><br>DATA SOURCES AND METHODS: We performed a systematic review and network analysis (sources: MEDLINE, Embase, Cochrane CENTRAL; random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. The primary endpoint, that is, clinical remission (total Mayo score &#x2a7d;2 with Mayo endoscopic score &#x2a7d;1), was assessed between weeks 6 and 12. Results are expressed as relative risks with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics. Ranking of FMT modalities was calculated as their surface under the cumulative ranking (SUCRA).<br><br>RESULTS: Among the 12 selected studies, patients were exclusively bio-na&#xef;ve in 4 studies (4/12), while between 9% and 32% had prior biologics exposure in the other trials. The risk of bias was low across all domains in seven studies. Contrary to upper gastrointestinal tract (GI) FMT (Relative risk (RR)&#x2009;=&#x2009;1.1 (0.2-7.7)), oral capsule (RR&#x2009;=&#x2009;7.1 (1.8-33.3)), lower GI FMT (RR&#x2009;=&#x2009;4.5 (1.7-12.5) and combination of both (RR&#x2009;=&#x2009;12.5 (2.1-100)) are more effective than placebo to induce clinical remission. The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR&#x2009;=&#x2009;10.7 (1.1-104.2)). Combination of lower GI FMT and oral capsule ranked the highest for the induction of clinical remission (SUCRA&#x2009;=&#x2009;0.93). Multidonor FMT did not perform better than single donor FMT. Autologous FMT ranked lower than placebo (SUCRA&#x2009;=&#x2009;0.12 vs 0.22).<br><br>CONCLUSION: The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.<br><br>TRIAL REGISTRATION: PROSPERO registration number: CRD42023385511.}, }
@article {pmid40873717, year = {2025}, author = {Li, D and Tao, H and Tan, X and Ling, H and Lu, Y and Zhang, H and Theany, S and Xu, H}, title = {Gut microbiota and their metabolites ameliorate acute and chronic colitis in mice via modulating Th17/Treg balance.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643209}, pmid = {40873717}, issn = {1664-302X}, abstract = {INTRODUCTION: Ulcerative colitis (UC) is a recurrent inflammatory bowel disease affecting the colorectum, which remains a prominent research focus due to significant individual variations in clinical therapeutic outcomes. Fecal microbiota transplantation (FMT), as a therapeutic approach to restore intestinal homeostasis, has demonstrated favorable efficacy in UC management. However, given the characteristic alternating cycles of active and remission phases in UC, there remains a paucity of in-depth research regarding the optimal timing for FMT intervention. Concurrently, butyrate - a crucial microbial metabolite - ameliorates murine colitis through both direct and indirect mechanisms, while the therapeutic effectiveness of FMT in UC correlates closely with intestinal butyrate concentration.<br><br>METHODS: This study established acute and chronic UC murine models and employed FMT and butyrate interventions to monitor dynamic alterations in gut microbiota and lymphocyte subsets. Through comprehensive analyses, we aimed to elucidate the interplay between gut microbiota and host immune mechanisms, identify the optimal therapeutic timing for UC interventions, and evaluate the mechanistic role of butyrate. These findings provide theoretical foundations for personalized microbiota-targeted therapies in UC.<br><br>RESULTS: Our findings demonstrate that gut microbiota and their metabolites exert therapeutic effects on murine acute/chronic colitis through modulation of the T helper cell 17 (Th17)/T regulatory cell (Treg) ratio. Specifically, the remission phase represents a more favorable window for intestinal homeostasis modulation, with combination therapy involving microbial metabolites exhibiting superior anti-inflammatory efficacy.<br><br>DISCUSSION: The maintenance of an appropriate Th17/Treg equilibrium during microbiota restoration demonstrates therapeutic advantages. Notably, butyrate synergistically enhances microbial therapeutic effects, providing experimental evidence for personalized modulation of gut ecosystems in inflammatory bowel disease management.}, }
@article {pmid40873786, year = {2025}, author = {Pinto, S and Benincà, E and Nooij, S and Terveer, EM and Keller, JJ and van der Meulen-de Jong, AE and Steyerberg, EW and Bogaards, JA}, title = {Ecological resilience in ulcerative colitis: microbial dynamics of donor and resident species in a longitudinal fecal microbiota transplantation study.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf119}, pmid = {40873786}, issn = {2730-6151}, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for the chronic immune-mediated disease ulcerative colitis (UC). However, the microbial dynamics underlying clinical remission remain poorly understood. To investigate these dynamics, we analysed data from 22 UC patients treated with four rounds of FMT donated by two healthy donors. Microbiota samples from patients were collected at nine timepoints before, during, and after treatment, covering a period of 14 weeks. Additionally, 27 donor samples were analysed. Species in the recipients' gut microbiota were categorised into ecological categories based on their origin and temporal dynamics: species already present in the recipient pre-FMT, species derived from the donor, or novel species, i.e. absent before FMT in both recipient and donor but detected during or after treatment. Overdispersed Poisson regression models were employed to model the number of species within each category over time. Furthermore, we investigated the change in relative abundance for recipient, colonising, and novel species. The results revealed that recipient species with higher relative abundances prior to FMT were more likely to persist following FMT. Notably, patients who achieved combined clinical and endoscopic remission at week 14 retained a higher number of recipient species compared to non-responders. In contrast, non-responders initially exhibited colonisation of more donor species than responders, but colonisation rate decreased over time in non-responders whereas colonisation rate remained stable in responders. These findings suggest that clinical remission following FMT is associated with controlled incorporation of donor species without replacement of resident species, which may reflect a resilient recipient gut community.}, }
@article {pmid40875477, year = {2025}, author = {Guo, YF and Wang, Y and Wu, H and Wang, L and Miao, X}, title = {Rauvolfia Verticillata Pectic Polysaccharides Alleviate Inflammation-Associated Colorectal Cancer and Correlate with Modulation of Gut Microbiota, Short-Chain Fatty Acid Metabolism, and NF-κB/IL-6/STAT3 Signaling Pathways.}, journal = {Nutrition and cancer}, volume = {77}, number = {10}, pages = {1183-1199}, doi = {10.1080/01635581.2025.2551294}, pmid = {40875477}, issn = {1532-7914}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; STAT3 Transcription Factor/metabolism ; NF-kappa B/metabolism ; Interleukin-6/metabolism ; *Colorectal Neoplasms/drug therapy/metabolism/etiology ; Signal Transduction/drug effects ; Mice ; Mice, Inbred C57BL ; *Polysaccharides/pharmacology ; *Fatty Acids, Volatile/metabolism ; Male ; Dextran Sulfate ; Inflammation/complications/drug therapy ; Fecal Microbiota Transplantation ; Azoxymethane ; *Phaeophyceae/chemistry ; }, abstract = {Background: Colorectal cancer (CRC) is increasingly common in younger individuals and strongly linked to chronic inflammation. Gut microbiota and pathways like NF-κB/STAT3 play key roles, which highlights the therapeutic potential of natural compounds that target intestinal immunity and microbial balance. Objective: To investigate the therapeutic effects of pectic polysaccharides (PPs) from Rauvolfia verticillata in inflammation-associated CRC via the modulation of of gut microbiota and NF-κB/IL-6/STAT3 signaling pathways. Methods: C57BL/6 mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC and treated with PP (100 mg/kg/day), the STAT3 inhibitor W2014-S (10 mg/kg), or fecal microbiota transplantation (FMT) from PP-treated donors. Histopathology, immunohistochemistry (IHC), Western blot, immunofluorescence (IF), 16S rRNA sequencing, and SCFA analysis were performed to assess inflammation, signaling pathways, gut microbiota composition, and metabolic changes. Results: PP intervention significantly mitigated AOM/DSS-induced weight loss, intestinal lesions, and disease activity index (DAI) scores while suppressing NF-κB and STAT3 activation. PP restored gut microbiota diversity, reduced pro-inflammatory genera, and regulated SCFA levels, particularly hexanoic those of and isohexanoic acids. FMT from PP-treated donors similarly attenuated colitis and inhibited NF-κB/STAT3 pathways. Conclusions: PP alleviates CRC and is associated with modulation of gut microbiota, SCFA metabolism, and NF-κB/IL-6/STAT3 signaling, offering a potential therapeutic strategy for inflammation-driven CRC.}, }
@article {pmid40876127, year = {2025}, author = {Cao, S and Guo, X and Xin, M and Wang, X and Huo, J and Yue, Y and Li, X and Xu, D and Liu, L}, title = {Sesamin ameliorates ulcerative colitis by modulating the DUSP1/ERK feedback loop and restoring gut microbiota homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {147}, number = {}, pages = {157188}, doi = {10.1016/j.phymed.2025.157188}, pmid = {40876127}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/microbiology/chemically induced ; *Lignans/pharmacology ; Mice ; *Dioxoles/pharmacology ; Male ; *Dual Specificity Phosphatase 1/metabolism ; Homeostasis/drug effects ; Disease Models, Animal ; Intestinal Mucosa/drug effects ; Dextran Sulfate ; Mice, Inbred C57BL ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Anti-Inflammatory Agents/pharmacology ; Molecular Docking Simulation ; Feedback, Physiological/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Sesamin (SSM), a plant-derived lignan, possesses anti-inflammatory and immunomodulatory effects. The pathogenesis of ulcerative colitis (UC) is complex and involves intestinal mucosal damage, inflammation, and dysbiosis of the gut microbiota. However, to date, the protective effects and therapeutic mechanisms of SSM in UC have hardly been investigated.<br><br>PURPOSE: The purpose of the study was to investigate the protective effects and therapeutic mechanisms of SSM in UC.<br><br>METHODS: This study utilized a dextran sulfate sodium-induced mouse model of UC to investigate the therapeutic effects of SSM and its impact on gut microbiota using molecular biology techniques, including histological staining, western blotting, proteomics, molecular docking, 16S rRNA sequencing, and fecal microbiota transplantation.<br><br>RESULTS: SM significantly alleviated inflammation, repaired intestinal mucosal barrier, and improved gut microbiota structure in mice with UC (p < 0.05). Further studies revealed that SSM upregulated dual-specificity phosphatase 1 (DUSP1) by suppressing extracellular signal-regulated protein kinase (ERK) phosphorylation, whereas DUSP1 knockdown increased p-ERK levels (p < 0.05). Additionally, SSM regulated the distribution of gut microbiota by increasing the abundance of beneficial bacteria (such as Lactobacillus), reducing the abundance of opportunistic pathogens (such as Staphylococcus), and restoring gut microbiota homeostasis (p < 0.05).<br><br>CONCLUSION: In summary, this is the first study to demonstrate that SSM exerts anti-inflammatory and intestinal barrier-restoring effects through modulating the DUSP1/ERK feedback loop and restoring gut microbiota homeostasis, thereby offering a novel therapeutic strategy for UC.}, }
@article {pmid40876561, year = {2025}, author = {Guimarães de Oliveira, D and Machado, A and Lacerda, PC and Karakikla-Mitsakou, Z and Vasconcelos, C}, title = {Systemic lupus erythematosus and the gut microbiome: To look forward is to look within - A systematic review and narrative synthesis.}, journal = {Autoimmunity reviews}, volume = {24}, number = {12}, pages = {103921}, doi = {10.1016/j.autrev.2025.103921}, pmid = {40876561}, issn = {1873-0183}, mesh = {Humans ; *Lupus Erythematosus, Systemic/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; }, abstract = {BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease shaped by complex interactions involving genetic and environmental factors. Among these, the gut microbiome is emerging as potentially modulating immune responses and influencing disease susceptibility, progression, and activity.<br><br>OBJECTIVES: To synthesize current evidence on gut microbiome changes in adult SLE patients, framed along the clinical pathway - from diagnosis to treatment - to help bridge bench and bedside for microbiome-informed SLE care and research.<br><br>METHODS: A systematic search identified primary research studies examining gut microbiota in adult SLE patients. Studies were reviewed in a stepwise manner by independent investigators. Findings were synthesized narratively, emphasizing human data.<br><br>RESULTS: SLE patients exhibit gut microbiome dysbiosis, with reduced microbial richness and altered bacterial taxa. A lower Firmicutes/Bacteroidetes ratio is frequently observed. Enrichment of specific taxa, such as Enterococcus, Lactobacillus, and Ruminococcus gnavus, is reported. Dysbiosis correlates with increased gut permeability, immune activation, and autoreactivity. Clinical associations include disease activity, flares, nephritis, and other manifestations. SLE treatments, such as hydroxychloroquine and corticosteroids, influence the microbiome. Emerging interventions such as dietary modulation and fecal microbiota transplantation show promise in early studies. However, considerable heterogeneity exists across studies in terms of patient characteristics, methodology, and taxa-level findings.<br><br>CONCLUSIONS: The gut microbiome has multifaceted associations with SLE pathogenesis, disease activity, and therapeutic response. Translation will require standardized methods, functional validation, longitudinal follow-up, and clinical integration. While uncertainties remain, the gut microbiome is increasingly relevant, and clinicians caring for patients with SLE should be aware of its emerging implications.}, }
@article {pmid40876612, year = {2025}, author = {Xie, X and Ge, W and Luo, Y and Xing, X and Sun, X}, title = {Ginsenoside Rb3 modulates gut microbiota to alleviate cerebral inflammation and ferroptosis via the NLRP3/NF-κB/GPX4 pathway in rats with cerebral ischemia/reperfusion injury.}, journal = {European journal of pharmacology}, volume = {1005}, number = {}, pages = {178091}, doi = {10.1016/j.ejphar.2025.178091}, pmid = {40876612}, issn = {1879-0712}, mesh = {Animals ; *Ginsenosides/pharmacology/therapeutic use ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; NF-kappa B/metabolism ; Male ; *Reperfusion Injury/drug therapy/metabolism/pathology/microbiology ; Rats ; *Ferroptosis/drug effects ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Neuroinflammatory Diseases/drug therapy/metabolism ; Blood-Brain Barrier/drug effects/metabolism ; *Brain Ischemia/drug therapy/metabolism ; Disease Models, Animal ; }, abstract = {Cerebral ischemia/reperfusion injury (CIRI) poses a significant threat to human life and health. Ginsenoside Rb3 (Rb3) is known to exhibit protective effects against myocardial ischemia, its impact on CIRI remains unclear. Therefore, we investigated the protective effects of Rb3 on CIRI and its underlying mechanisms. Our results showed that Rb3 reduced cerebral infarct volume, decreased blood-brain barrier (BBB) permeability, and improved neurological deficits in CIRI rats. Rb3 also mitigated cerebral ferroptosis and alleviated neuroinflammation, as evidenced by decreased iron levels, reduced MDA content, an improved GSH/GSSG ratio, and lower levels of TNF-α, IL-1β, and IL-6, through modulation of the NLRP3/NF-κB/GPX4 pathway. Additionally, Rb3 alleviated intestinal inflammation, improved the intestinal barrier, and corrected gut microbiota dysbiosis and reduced the microbial metabolites TMAO and LPS in CIRI rats. It is noteworthy that in pseudo germ-free rats with CIRI, fecal microbiota transplants (FMT) from Rb3-treated rats conferred similar protective effects as Rb3. Summarily, this study reveals that Rb3 reduces neuroinflammation and ferroptosis in the brains of middle cerebral artery occlusion/reperfusion (MCAO/R) rats via the NLRP3/NF-κB/GPX4 pathway in a gut microbiota-dependent manner.}, }
@article {pmid40877311, year = {2025}, author = {Wilson, BC and Zuppi, M and Derraik, JGB and Albert, BB and Tweedie-Cullen, RY and Leong, KSW and Beck, KL and Vatanen, T and O'Sullivan, JM and Cutfield, WS and , }, title = {Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7786}, pmid = {40877311}, issn = {2041-1723}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adolescent ; Male ; Female ; Follow-Up Studies ; Double-Blind Method ; *Pediatric Obesity/therapy ; Treatment Outcome ; Body Composition ; Body Mass Index ; Gastrointestinal Microbiome ; *Obesity/therapy ; Metabolic Syndrome/therapy ; Feces/microbiology ; }, abstract = {Faecal microbiota transplantation (FMT) has been explored as a potential treatment for obesity, but its long-term effects on metabolic health remain unclear. Here, we report 4-year follow-up findings from a double-blind, randomised, placebo-controlled trial assessing FMT in adolescents with obesity (ACTRN12615001351505, Australian New Zealand Clinical Trials Registry). This unblinded follow-up study evaluated 63% (55/87) of the original participants (27 FMT, 28 placebo). There was no difference in BMI between the two groups, after adjusting for sex, age, diet, and physical activity (-3.6 kg/m[2], p = 0.095). However, FMT recipients showed clinical improvements in body composition and metabolic health compared to the placebo group. Specifically, FMT recipients had smaller waist circumference (-10.0 cm, p = 0.026), total body fat (-4.8%, p = 0.024), metabolic syndrome severity score (-0.58, p = 0.003), and systemic inflammation (-68% hs-CRP, p = 0.002) and higher levels of HDL cholesterol (0.16 mmol/L, p = 0.037). No group differences were observed in glucose markers, or other lipid parameters. Shotgun metagenomic sequencing revealed sustained long-term alterations in gut microbiome richness, composition and functional capacity, with persistence of donor-derived bacterial and bacteriophage strains. These findings highlight the potential relevance of FMT as a microbiome-augmenting intervention for obesity management and metabolic health, warranting further investigation.}, }
@article {pmid40878918, year = {2025}, author = {Liu, X and Xie, Y and Yang, S and Jiang, C and Shang, K and Luo, J and Zhang, L and Hu, G and Liu, Q and Yue, B and Fan, Z and He, Z and Li, J}, title = {Multi-omics investigation of spontaneous T2DM macaque emphasizes gut microbiota could up-regulate the absorption of excess palmitic acid in the T2DM progression.}, journal = {eLife}, volume = {14}, number = {}, pages = {}, pmid = {40878918}, issn = {2050-084X}, support = {2021YJ0136//Science and Technology Foundation of Sichuan Province/ ; 32171607//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/microbiology/pathology/metabolism ; *Palmitic Acid/metabolism ; Macaca mulatta ; Mice ; Disease Models, Animal ; Male ; Gene Expression Profiling ; Metabolome ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; Multiomics ; }, abstract = {Although gut microbiota and lipid metabolites have been suggested to be closely associated with type 2 diabetes mellitus (T2DM), the interactions between gut microbiota, lipid metabolites, and the host in T2DM development remains unclear. Rhesus macaques may be the best animal model to investigate these relationships given their spontaneous development of T2DM. We identified eight spontaneous T2DM macaques and conducted a comprehensive study investigating the relationships using multi-omics sequencing technology. Our results from 16 S rRNA, metagenome, metabolome, and transcriptome analyses identified that gut microbiota imbalance, tryptophan metabolism and fatty acid β oxidation disorders, long-chain fatty acid (LCFA) accumulation, and inflammation occurred in T2DM macaques. We verified the accumulation of palmitic acid (PA) and activation of inflammation in T2DM macaques. Importantly, mice transplanted with spontaneous T2DM macaque fecal microbiota and fed a high PA diet developed prediabetes within 120 days. We determined that gut microbiota mediated the absorption of excess PA in the ileum, resulting in the accumulation of PA in the serum, consequently leading to T2DM in mice. In particular, we demonstrated that the specific microbiota composition was probably involved in the process. This study provides new insight into interactions between microbiota and metabolites and confirms causative effect of gut microbiota on T2DM development.}, }
@article {pmid40880458, year = {2025}, author = {Dinis, L and Pinheiro, H and Póvoa, P and Calhau, C and Pestana, D and Marques, C}, title = {Advancing Access to Intestinal Microbiota Transplant: Bridging the Gap Between National Practices and the European Strategy.}, journal = {Acta medica portuguesa}, volume = {38}, number = {10}, pages = {639-647}, doi = {10.20344/amp.22750}, pmid = {40880458}, issn = {1646-0758}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Europe ; *Gastrointestinal Microbiome ; Portugal ; *Health Services Accessibility ; Biological Specimen Banks ; }, abstract = {Clostridioides difficile is an opportunistic pathogen that can cause a range of conditions, from asymptomatic carriage to severe illness, posing a significant public health threat due to its high mortality rates and substantial healthcare costs. Traditional treatment options, including antibiotics, often fail to eradicate the infection, leading to recurrent cases that severely impact patients' lives. Intestinal microbiota transplant (IMT) has emerged as an effective strategy for decolonizing pathogenic agents, demonstrating safety and efficacy, particularly in treating recurrent Clostridioides difficile infection (rCDI). Despite its potential, access to IMT is limited due to safety concerns, logistical challenges, and a lack of proper guidance, underscoring the urgent need for structured intestinal microbiota banks (IMBs). These organized facilities are crucial for the collection, screening, processing, and distribution of intestinal microbiota preparations, thereby facilitating the clinical application of IMT. In this narrative review, we discuss the relevance of applying IMT for the treatment of rCDI in Europe, with a focus on Portugal. We highlight the existence and distribution of IMBs across Europe and their importance in improving access to IMT. This review also addresses the challenges in creating an IMB and the development of such a structure in Portugal as a centralized repository for high-quality, standardized microbiota preparations, making IMT accessible for national hospitals. Additionally, it emphasizes the need to raise awareness among healthcare providers and the public to support the broader adoption of IMT.}, }
@article {pmid40881288, year = {2025}, author = {Pourrat, A and Baillieu, V and Ansel, S and Leonardi, M and Poiron, P and Bellais, S and Paul, M and Nebbad, B}, title = {Standardized freeze-dried FMT: is the ideal protectant out there?.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1618067}, pmid = {40881288}, issn = {1664-302X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infections. Freeze-drying offers a next-generation, more practical, and aesthetically acceptable FMT formulation that could facilitate standardized preparation methods. Viable preservation is a critical step in freeze-drying, yet no universal medium effectively protects both anaerobes and aerobes.<br><br>OBJECTIVE: This study aimed to evaluate different protectants compared to trehalose 5% (T5) after confirming its efficacy.<br><br>METHODS: A mix of inulin and glucosamine (IG5) and a High-antioxidant Matrix with trehalose (HM) were tested. Viability was assessed using colony-forming unit (CFU) enumeration and flow cytometry with a LIVE/DEAD&#x2122; staining method.<br><br>RESULTS: T5 demonstrated satisfactory bacterial recovery after freeze-drying, with viability of 84&#x202f;&#xb1;&#x202f;28% for anaerobes and 59&#x202f;&#xb1;&#x202f;39% for Bifidobacterium (BIF), confirming its efficiency in our preparation facilities. While HM showed highest results (91&#x202f;&#xb1;&#x202f;7% for anaerobes, 121&#x202f;&#xb1;&#x202f;33% for BIF), it did not significantly outperform T5. IG5, however, resulted in a significant loss of bacteria, with only 16&#x202f;&#xb1;&#x202f;12% viability for anaerobes (p&#x202f;=&#x202f;0.016) and 19&#x202f;&#xb1;&#x202f;9% for BIF (p&#x202f;=&#x202f;0.031).<br><br>CONCLUSION: HM and T5 both proved effective for freeze-dried FMT, with HM yielding the highest recovery but not significantly outperforming T5. Given its simplicity and consistent results, T5 may serve as a reliable standalone protectant or as a base for improved formulations. IG5 showed significant bacterial loss and is unsuitable. Further biological validation and stability data will guide the development of optimized freeze-dried oral FMT capsules.}, }
@article {pmid40882395, year = {2025}, author = {Chen, X and Zou, J and Hong, T and Zhang, H and Yang, J and Mai, H and Shi, H and Li, X and Feng, D}, title = {Bisphenol A increases fat mass in adipose tissue by disturbing gut microbiota-dependent bile acid metabolism and TGR5/UCP1 signaling pathways in CD-1 mice.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118922}, doi = {10.1016/j.ecoenv.2025.118922}, pmid = {40882395}, issn = {1090-2414}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Benzhydryl Compounds/toxicity ; Mice ; Male ; *Phenols/toxicity ; *Bile Acids and Salts/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/drug effects ; *Adipose Tissue/drug effects/metabolism ; Uncoupling Protein 1/metabolism ; Obesity/chemically induced ; Bisphenol A Compounds ; }, abstract = {Disorder of gut microbiota-mediated bile acid (BA) metabolism plays a pivotal role in the pathogenesis of obesity. Our previous research showed that bisphenol A (BPA) exposure induced hepatic fat accumulation and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alteration is involved in BPA-induced fat accumulation and obesity remains elusive. This study aimed to investigate the gut microbiota-dependent metabolic mechanism of obesity induced by BPA. Male CD-1 mice were exposed to a low dose of BPA (50 μg/kg/day) for six months. Our findings demonstrated that BPA exposure significantly augmented the fat mass of both brown and white adipose tissue, along with the proportion of adipose tissue weight relative to body weight. Furthermore, BPA reduced the relative abundance of Bacteroides, Parabacteroides, and Akkermansia, which are associated with BA metabolism. Additionally, serum levels of lithocholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), and TGR5 expression in adipose tissue were substantially diminished following BPA exposure. Inhibition of TGR5 reduced cyclic adenosine monophosphate levels, subsequently decreasing the expression of iodothyronine deiodinase 2 and fibroblast growth factor 21. These changes down-regulated the expression of uncoupling protein 1 (UCP1), ultimately leading to reduced energy expenditure and increased fat mass. Moreover, further fecal microbiota transplantation and microbiota elimination confirmed the role of gut microbiota in BPA-induced adverse effects. Collectively, our study demonstrated that the suppression of gut microbiota-BA-TGR5/UCP1 signaling pathways may constitute a potential mechanism underlying BPA-induced fat mass gain, providing a novel target for the prevention of BPA-induced obesity.}, }
@article {pmid40884832, year = {2025}, author = {Chen, S and Liu, F and Han, X and Jia, D and Chen, J and Wei, Y and Yu, Z and He, L and Liao, C and Ding, K}, title = {Exposure to Bovine Viral Diarrhea Virus Disrupts Intestinal Barrier Function via NLRP3/Caspase-1-Mediated Pyroptosis and Gut Microbiota Dysbiosis.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {36}, pages = {22384-22396}, doi = {10.1021/acs.jafc.5c04854}, pmid = {40884832}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome ; Cattle ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; *Pyroptosis ; *Dysbiosis/virology/microbiology/genetics/veterinary ; *Caspase 1/genetics/metabolism ; *Intestinal Mucosa/virology/metabolism/microbiology ; *Diarrhea Viruses, Bovine Viral/physiology ; *Intestines/virology/microbiology ; Inflammasomes/metabolism/genetics ; *Bovine Virus Diarrhea-Mucosal Disease/virology/microbiology/genetics/metabolism ; Mice ; Humans ; Intestinal Barrier Function ; }, abstract = {Bovine viral diarrhea virus (BVDV) is a major global pathogen that causes severe economic losses in dairy herds due to diarrhea, reproductive disorders, and reduced milk yield. Despite its well-documented systemic effects, the mechanism of BVDV-induced intestinal damage remains unclear. In our study, BVDV triggered cytopathic effects in intestinal epithelial cells, including cell death, goblet cell depletion, and disruption of barrier proteins. Although BVDV alters gut microbiota by activating the NLRP3/caspase-1 inflammasome pathway and thereby causing pyroptosis and intestinal injury, fecal microbiota transplantation mitigated those effects by suppressing NLRP3/caspase-1's activation. Those findings reveal key pathways in BVDV's pathogenesis and suggest novel therapeutic strategies to combat livestock infections.}, }
@article {pmid40885910, year = {2025}, author = {Huang, W and Chai, Y and Li, X and Zhang, Q and Yan, Z and Wang, Y and Tao, X and Zhang, J and Qiu, F}, title = {Metagenomics and metabolomics to evaluate the potential role of gut microbiota and blood metabolites in patients with cerebral infarction.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {567}, pmid = {40885910}, issn = {1471-2180}, support = {2018YFA0108601//Clinical research on intracerebral precision transplantation of neural stem cells for stroke treatment/ ; L255012//The Huairou Innovation Joint Fund Project of Beijing Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cerebral Infarction/microbiology/blood/metabolism ; *Metabolomics/methods ; *Metagenomics/methods ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Middle Aged ; Female ; Aged ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Tandem Mass Spectrometry ; Adult ; Chromatography, High Pressure Liquid ; }, abstract = {Cerebral infarction, a cerebrovascular disorder, is characterized by the sudden onset of neurological deficits and clinical symptoms. It ranks among the leading causes of death and severe disability worldwide. The etiology of cerebral infarction is multifaceted, with common risk factors including dietary patterns, smoking, hypertension, and diabetes mellitus. In recent years, the role of the gut microbiota in systemic immunity and tumorigenesis has been intensively explored, thrusting the research on the gut-brain axis into the spotlight. However, there is a lack of literature investigating the relationship between the gut microbiota and blood metabolites in cerebral infarction. In this study, we employed 16S rRNA analysis and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for a comprehensive metagenomic and metabolomic analysis of fecal samples from cerebral infarction patients and the general population. Our results revealed a significant correlation between the gut microbiome and serum metabolites, highlighting the impact of the microbiome on metabolic pathways. Specifically, we found that 35 gut microbiome taxa, such as Actinobacteriota and Peptostreptococcales-Tissierellales, were significantly enriched in the control group (N group). Through Linear Discriminant Analysis Effect Size (LEfSe) analysis, 72 taxa showed significant differences between cerebral infarction patients and healthy individuals. Among them, 22 key taxa were identified as microbial biomarkers for differentiating patients from healthy controls. These findings suggest that variations in the microbiome and metabolites could potentially serve as biomarkers for future diagnostic and therapeutic strategies in cerebral infarction.}, }
@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}, mesh = {Animals ; *Zebrafish ; *Tylosin/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/chemically induced ; *Anti-Bacterial Agents/toxicity ; *Water Pollutants, Chemical/toxicity ; Behavior, Animal/drug effects ; *Neurotoxicity Syndromes/etiology ; }, 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.}, }
@article {pmid40886868, year = {2026}, 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 = {354}, number = {}, pages = {120513}, doi = {10.1016/j.jep.2025.120513}, pmid = {40886868}, issn = {1872-7573}, mesh = {Animals ; *Thermogenesis/drug effects ; *Nelumbo/chemistry ; *Adipose Tissue, Brown/drug effects/metabolism ; *Obesity/drug therapy/microbiology/metabolism ; Plant Leaves/chemistry ; Diet, High-Fat/adverse effects ; *Plant Extracts/pharmacology/therapeutic use ; Male ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Anti-Obesity Agents/pharmacology/isolation &amp; purification ; *Flavonoids/pharmacology/isolation &amp; purification/therapeutic use ; Mice, Inbred C57BL ; Energy Metabolism/drug effects ; }, 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.<br><br>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.<br><br>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 16&#xa0;S 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.<br><br>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-1&#x3b1;, UCP1) and repressing inflammatory responses, potentially through activation of &#x3b2;3-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.<br><br>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 {pmid40889045, year = {2026}, 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 = {69}, number = {3}, pages = {832-845}, pmid = {40889045}, issn = {1869-1889}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Diet, High-Fat/adverse effects ; *Hypertension/etiology/metabolism/microbiology ; *Obesity/complications/metabolism/microbiology ; *Histones/metabolism ; Male ; Rats ; Butyrates/metabolism ; Rats, Sprague-Dawley ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/metabolism/genetics ; Butyric Acid/metabolism ; Kidney/metabolism ; }, 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 {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/ ; }, mesh = {Adult ; Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; Young Adult ; *Bile Acids and Salts/metabolism ; Biomarkers/blood ; Cholestenones/blood ; Cohort Studies ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/metabolism ; *Malabsorption Syndromes/therapy ; Prospective Studies ; *Steatorrhea/therapy ; Diarrhea ; }, 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).<br><br>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.<br><br>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&#xa0;months after FMT, along with a significantly decrease of C4 (P&#x2009;<&#x2009;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.<br><br>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.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT01790061 and NCT01793831.}, }
@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 = {71}, number = {3}, pages = {239-267}, doi = {10.23736/S2724-5985.25.03866-5}, pmid = {40891897}, issn = {2724-5365}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fatty Acids, Volatile/metabolism ; *Nervous System Diseases/microbiology/physiopathology/therapy ; *Brain/metabolism ; Parkinson Disease/microbiology ; }, 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 {pmid40893829, year = {2025}, author = {Allegretti, JR}, title = {Current Status of Fecal Microbiota Transplantation for Inflammatory Bowel Disease Management.}, journal = {Gastroenterology &amp; hepatology}, volume = {21}, number = {7}, pages = {451-453}, pmid = {40893829}, issn = {1554-7914}, }
@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}, 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 {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 = {}, pmid = {40894608}, issn = {2692-8205}, support = {R01 AA029124/AA/NIAAA NIH HHS/United States ; R21 AA030358/AA/NIAAA NIH HHS/United States ; }, abstract = {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.}, }
@article {pmid40894980, year = {2025}, author = {Wang, YM}, title = {How to Approach Immune Checkpoint Inhibitor Enterocolitis.}, journal = {Gastroenterology &amp; hepatology}, volume = {21}, number = {8}, pages = {501-503}, pmid = {40894980}, issn = {1554-7914}, }
@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}, 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 {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}, 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.<br><br>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.<br><br>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."<br><br>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 {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}, 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 {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/ ; }, mesh = {Animals ; *Hippocampus/pathology/drug effects ; *Depression/drug therapy/pathology/complications ; *Ferroptosis/drug effects ; Gastrointestinal Microbiome/drug effects ; *Butyric Acid/pharmacology/therapeutic use ; Male ; *Neuroinflammatory Diseases/drug therapy/pathology/complications ; *Pentanoic Acids/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Behavior, Animal/drug effects ; Mice ; *Stress, Psychological/complications ; Fecal Microbiota Transplantation ; Neurons/drug effects/pathology/metabolism ; Signal Transduction/drug effects ; Inflammation/pathology ; rho-Associated Kinases/metabolism ; }, 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.<br><br>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&#xa0;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.<br><br>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.<br><br>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 {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 = {19}, number = {1}, pages = {}, pmid = {40899693}, issn = {1751-7370}, support = {5242016//Beijing Natural Science Foundation/ ; 32470487//National Natural Scientific Foundation of China/ ; 32200381//National Natural Scientific Foundation of China/ ; }, mesh = {Animals ; *Ursidae/microbiology/metabolism/physiology ; *Gastrointestinal Microbiome/physiology ; *Energy Metabolism ; Seasons ; Fecal Microbiota Transplantation ; Mice ; *Adaptation, Physiological ; Bacteria/classification/genetics/isolation &amp; purification ; Feces/microbiology ; }, 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 {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 = {73}, number = {37}, pages = {23633-23643}, doi = {10.1021/acs.jafc.5c06410}, pmid = {40899722}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Glutathione/metabolism ; Mice, Inbred C57BL ; Male ; Dextran Sulfate/adverse effects ; *Colitis, Ulcerative/microbiology/metabolism/chemically induced ; Humans ; *Colitis/microbiology/metabolism ; Disease Models, Animal ; Akkermansia/growth &amp; development ; }, 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 {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&amp;D Program of China/ ; 2022YFC3601305//the National Key R&amp;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.}, }
@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 = {73}, number = {37}, pages = {23449-23468}, doi = {10.1021/acs.jafc.5c08350}, pmid = {40900041}, issn = {1520-5118}, mesh = {Animals ; *Galactose/adverse effects ; Mice ; *Oligosaccharides/chemistry/administration &amp; dosage ; Gastrointestinal Microbiome/drug effects ; *Brain/drug effects/immunology/metabolism ; Male ; *Aging/drug effects/immunology ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; NF-kappa B/genetics/immunology ; *Neuroprotective Agents/administration &amp; dosage/chemistry ; p38 Mitogen-Activated Protein Kinases/genetics/immunology ; *Neuroinflammatory Diseases/drug therapy/genetics/immunology ; Cyclooxygenase 2/genetics/immunology ; Toll-Like Receptor 4/genetics/immunology ; Cyclic AMP Response Element-Binding Protein/genetics/immunology ; Bacteria/classification/isolation &amp; purification/genetics ; }, 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 {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}, 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 {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}, 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 {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}, 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 {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}, 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 {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}, 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 {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 = {112}, number = {}, pages = {102888}, doi = {10.1016/j.arr.2025.102888}, pmid = {40902672}, issn = {1872-9649}, mesh = {Humans ; *Alzheimer Disease/therapy/metabolism/microbiology/diagnosis ; *Gastrointestinal Microbiome/physiology ; Biomarkers/metabolism ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation/methods ; Dysbiosis ; }, 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 {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 = {518}, number = {}, pages = {154274}, doi = {10.1016/j.tox.2025.154274}, pmid = {40902967}, issn = {1879-3185}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Podophyllotoxin/toxicity ; *Fatty Acids, Volatile/metabolism ; Male ; *Inflammation Mediators/metabolism ; Rats ; Rats, Sprague-Dawley ; Cytokines/metabolism ; Colon/drug effects/pathology/microbiology/metabolism ; Multiomics ; }, 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 {pmid40903035, year = {2026}, 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 = {75}, number = {7}, pages = {1322-1337}, doi = {10.1136/gutjnl-2024-334699}, pmid = {40903035}, issn = {1468-3288}, mesh = {Animals ; *Irinotecan/adverse effects/toxicity ; Humans ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/microbiology ; *Tryptophan/metabolism ; *Diarrhea/chemically induced/microbiology ; Female ; Indoleacetic Acids/metabolism ; *Bacteroides/metabolism ; Male ; Intestinal Mucosa/drug effects/microbiology ; Mice, Inbred C57BL ; }, 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.<br><br>OBJECTIVE: This study aimed to explore the role and mechanism of endogenous bacterial metabolites in susceptibility to irinotecan toxicity.<br><br>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.<br><br>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.<br><br>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 {pmid40903950, year = {2026}, 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 = {21}, number = {8}, pages = {3411-3425}, 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 microbiota-based 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 {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}, 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.<br><br>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.<br><br>METHODS: We administered [89]Zr-labeled Lactobacillus crispatus ATCC33820 (Gram-positive) to six female Duroc pigs (weight&#xa0;=&#xa0;33.3&#xa0;&#xb1;&#xa0;4.6&#xa0;kg) and E. coli Nissle 1917 (Gram-negative). Scans were performed between 6&#xa0;h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7&#xa0;&#xb1;&#xa0;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.<br><br>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&#xa0;&#xb1;&#xa0;4.9 &#xb5;Sv/MBq and 28.4&#xa0;&#xb1;&#xa0;7.9 &#xb5;Sv/MBq, respectively) and proximal colon (17.9&#xa0;&#xb1;&#xa0;3.7 &#xb5;Sv/MBq and 18.4&#xa0;&#xb1;&#xa0;5.1 &#xb5;Sv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5&#xa0;&#xb1;&#xa0;9.5 &#xb5;Sv/MBq (L. crispatus) and 66.7&#xa0;&#xb1;&#xa0;14.9 &#xb5;Sv/MBq (E. coli).<br><br>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.}, }
@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 &amp; 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 {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 &amp; 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.}, }
@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.}, }
@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 = {21}, number = {8}, pages = {2529-2547}, pmid = {40906312}, issn = {2629-3277}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Graft vs Host Disease/microbiology ; Treatment Outcome ; Fecal Microbiota Transplantation ; Animals ; Dysbiosis ; }, 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 {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 &amp; control : CCC}, volume = {36}, number = {12}, pages = {1795-1812}, pmid = {40906320}, issn = {1573-7225}, support = {01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; R01 AG083580/AG/NIA NIH HHS/United States ; R01 CA189184/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; R01 CA254108/CA/NCI NIH HHS/United States ; R01 CA211705/CA/NCI NIH HHS/United States ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; }, mesh = {Humans ; Male ; *Cachexia/etiology/microbiology ; Female ; *Colorectal Neoplasms/surgery/microbiology/complications/pathology ; *Gastrointestinal Microbiome/genetics ; Middle Aged ; Aged ; Feces/microbiology ; *Postoperative Complications/etiology ; RNA, Ribosomal, 16S/genetics ; }, 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.<br><br>METHODS: Pre-surgical stool samples from n&#x2009;=&#x2009;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&#xa0;months post-surgery was defined as >&#x2009;5% weight loss over the past 6&#xa0;months and/or body mass index (BMI) of <&#x2009;20&#xa0;kg/m[2] and weight loss of >&#x2009;2%. Associations of microbial metrics with cachexia onset were estimated using multivariable logistic regression models.<br><br>RESULTS: Higher alpha-diversity was positively associated with cachexia onset, with stronger associations in females, patients&#x2009;<&#x2009;65&#xa0;years, those receiving adjuvant treatment, consuming high fiber, or with energy intake outside USDA recommendations (p&#x2009;<&#x2009;0.05). Porphyromonas (OR&#x2009;=&#x2009;0.51, 95% CI 0.26-0.89, p&#x2009;=&#x2009;0.03) and Actinomyces (OR&#x2009;=&#x2009;0.72, 95% CI 0.48-1.03, p&#x2009;=&#x2009;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&#x2009;&#x2264;&#x2009;p&#x2009;<&#x2009;0.10).<br><br>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 {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}, mesh = {*Colitis, Ulcerative/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Benzyl Alcohols/pharmacology ; Animals ; *Receptors, Aryl Hydrocarbon/metabolism ; *Glucosides/pharmacology ; *Tryptophan/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Mice ; Male ; Fecal Microbiota Transplantation ; *Basic Helix-Loop-Helix Proteins/metabolism ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Gastrodia/chemistry ; }, 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 {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 &amp; therapeutics}, volume = {31}, number = {9}, pages = {e70593}, 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.<br><br>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.<br><br>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.<br><br>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.}, }
@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 {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.<br><br>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.<br><br>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.<br><br>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 {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.}, }
@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 {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 {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 to Hepatocellular Carcinoma.}, journal = {Clinical and translational gastroenterology}, volume = {16}, number = {12}, pages = {e00914}, pmid = {40911047}, issn = {2155-384X}, support = {202104041101024//Shanxi Provincial Special Project for Science and Technology Cooperation and Exchange/ ; YDZJSX2025D075//Central Government-Guided Local Science and Technology Development Fund Project/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Carcinoma, Hepatocellular/pathology/etiology/metabolism/microbiology ; Disease Progression ; *Liver Neoplasms/pathology/etiology/metabolism/microbiology/immunology ; *Non-alcoholic Fatty Liver Disease/microbiology/pathology/metabolism/complications/immunology ; *Dysbiosis/microbiology/immunology/metabolism/complications ; Bile Acids and Salts/metabolism ; Methylamines/metabolism ; Liver/pathology/immunology ; Tumor Microenvironment/immunology ; Biomarkers/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; }, abstract = {Nonalcoholic fatty liver disease 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 (GM) and its metabolites playing a pivotal role in this transformation through the "gut-liver axis." This review systematically summarizes the characteristics of GM dysbiosis in patients with MASLD and the regulatory mechanisms of its metabolites (e.g., short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and lipopolysaccharides) in the progression from MASLD to HCC. Short-chain fatty acids 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 (nuclear factor-κB and mitogen-activated protein kinase), inducing oxidative stress, and inhibiting foresaid X receptor signaling. Trimethylamine N-oxide directly drives HCC progression by activating the mitogen-activated protein kinase/nuclear factor-κB pathway, promoting epithelial-mesenchymal transition, and creating an immunosuppressive microenvironment. Lipopolysaccharide accelerates fibrosis and metabolic reprogramming through toll-like receptor 4-mediated chronic inflammation and hepatic stellate cell activation. This review highlights that the dynamic changes in GM 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 {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.}, }
@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}, pmid = {40912148}, issn = {1525-3171}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Diet/veterinary ; Animal Feed/analysis ; *Abdominal Fat/physiology ; *Chickens/physiology/microbiology ; Animal Nutritional Physiological Phenomena ; Probiotics/administration &amp; dosage ; }, 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 {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 = {220}, number = {}, pages = {107941}, doi = {10.1016/j.phrs.2025.107941}, pmid = {40912415}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Iridoids/pharmacology/therapeutic use ; Humans ; Disease Models, Animal ; Male ; *Limosilactobacillus reuteri/metabolism ; *Fecal Microbiota Transplantation ; *Depression/therapy/microbiology/metabolism ; *Butyrates/metabolism ; Rats ; Rats, Sprague-Dawley ; Behavior, Animal/drug effects ; Antidepressive Agents/pharmacology/therapeutic use ; *Major Depressive Disorder/therapy/microbiology/metabolism ; Mice ; }, 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 {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 &amp; 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.}, }
@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.}, }
@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.}, }
@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}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Tacrolimus/pharmacokinetics/adverse effects/administration &amp; dosage ; *Kidney Transplantation/adverse effects ; Male ; Female ; Middle Aged ; *Immunosuppressive Agents/pharmacokinetics/adverse effects ; Adult ; Feces/microbiology ; *Graft Rejection/prevention &amp; control ; Aged ; Metabolomics ; RNA, Ribosomal, 16S/genetics ; }, 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 {pmid40914633, year = {2026}, 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 = {113}, number = {6S}, pages = {S99-S110}, doi = {10.1016/j.bulcan.2025.05.014}, pmid = {40914633}, issn = {1769-6917}, mesh = {*Graft vs Host Disease/therapy/etiology ; Humans ; Nitriles ; Pyrimidines ; *Pyrazoles/therapeutic use ; Acute Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Photopheresis ; Mesenchymal Stem Cell Transplantation ; Adrenal Cortex Hormones/therapeutic use ; }, 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 {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 &amp; metabolic syndrome}, volume = {34}, number = {4}, pages = {434-445}, 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.<br><br>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.<br><br>RESULTS: The study included patients with a mean age of 50.4&#xb1;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.<br><br>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 {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 = {31}, number = {10}, pages = {323-337}, doi = {10.1177/10766294251375937}, pmid = {40916806}, issn = {1931-8448}, mesh = {*Drug Resistance, Multiple, Bacterial/genetics ; *Klebsiella pneumoniae/genetics ; *Klebsiella Infections ; Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Delivery Systems ; Bacteriocins/pharmacology/therapeutic use ; }, 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 {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 {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.<br><br>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.<br><br>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.<br><br>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 {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}, 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.<br><br>METHODS: We collected plasma, serum, and stool samples from 123 adult patients with stable chronic HF and left ventricular ejection fraction (LVEF) &#x2264;40%, and healthy controls (plasma: n&#x2009;=&#x2009;51, stool samples: n&#x2009;=&#x2009;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.<br><br>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.<br><br>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.}, }
@article {pmid40923448, year = {2026}, 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 = {34}, number = {1}, pages = {14-16}, doi = {10.1002/ksa.70056}, pmid = {40923448}, issn = {1433-7347}, mesh = {*Prosthesis-Related Infections/epidemiology/immunology/microbiology/therapy ; *Surgical Wound Infection/epidemiology/immunology/microbiology/therapy ; Humans ; *Microbiota/drug effects/immunology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Outer Membrane/drug effects ; Phage Therapy/methods ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; }, 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 {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}, pmid = {40925130}, issn = {1521-0103}, mesh = {*Lupus Erythematosus, Systemic/microbiology/immunology/therapy/drug therapy ; Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Dysbiosis/immunology ; }, 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 {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}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Arthritis, Rheumatoid/microbiology/therapy/immunology ; *Dysbiosis/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Joints/immunology/microbiology ; Prebiotics/administration &amp; dosage ; }, 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 {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 = {10}, number = {10}, pages = {2550-2564}, pmid = {40926100}, issn = {2058-5276}, support = {BRICS HR0011-15-C-0094//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; R35GM141861//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01 GM130777/GM/NIGMS NIH HHS/United States ; MTM2 2025512//National Science Foundation (NSF)/ ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 AI154075/AI/NIAID NIH HHS/United States ; R35GM143056//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01GM130777//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35 GM141861/GM/NIGMS NIH HHS/United States ; R21AI154075//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35 GM143056/GM/NIGMS NIH HHS/United States ; R35GM149270//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35 GM149270/GM/NIGMS NIH HHS/United States ; P30DK056338//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; *Software ; *Ecosystem ; Bayes Theorem ; *Microbiota ; Feces/microbiology ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Bacteria/classification/genetics ; Models, Biological ; }, 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 {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 {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.}, }
@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 = {73}, number = {38}, pages = {24200-24210}, doi = {10.1021/acs.jafc.5c09135}, pmid = {40928298}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate/adverse effects ; Mice ; *Colitis/microbiology/drug therapy/chemically induced/genetics ; Male ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; Humans ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics/immunology ; }, 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 {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}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Diterpenes/pharmacology ; Mice ; Male ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Dysbiosis/drug therapy ; Molecular Docking Simulation ; Fecal Microbiota Transplantation ; *Non-alcoholic Fatty Liver Disease/drug therapy ; Lipid Metabolism/drug effects ; Liver/metabolism/drug effects ; }, 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.<br><br>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.<br><br>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.<br><br>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 {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 = {112}, number = {}, pages = {102894}, doi = {10.1016/j.arr.2025.102894}, pmid = {40930236}, issn = {1872-9649}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders/therapy/microbiology ; Animals ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Brain ; Brain-Gut Axis/physiology ; Prebiotics ; }, 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), and dietary interventions. Collectively, targeted GM therapy has the potential to be an effective treatment for neuropsychiatric disorders.}, }
@article {pmid40930289, year = {2026}, 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(m[6]A) mediated NLRP3 inflammasome activation.}, journal = {Journal of ethnopharmacology}, volume = {355}, number = {Pt A}, pages = {120577}, doi = {10.1016/j.jep.2025.120577}, pmid = {40930289}, issn = {1872-7573}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Methyltransferases/metabolism/antagonists &amp; inhibitors/genetics ; *Inflammasomes/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; *Orthomyxoviridae Infections/drug therapy/virology ; Gastrointestinal Microbiome/drug effects ; Influenza A virus ; *Lung Injury/drug therapy/virology ; Male ; Lung/drug effects/pathology/virology ; Adenosine/metabolism/analogs &amp; derivatives ; Fecal Microbiota Transplantation ; Interleukin-1beta/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; }, 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.<br><br>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.<br><br>MATERIALS AND METHODS: An intranasal FM1 influenza virus infection model was established in mice. Lung histopathology was assessed by HE staining, and interleukin-1&#x3b2; (IL-1&#x3b2;) levels were measured using ELISA. Global N6-methyladenosine (m[6]A) methylation in lung tissues was detected by dot blot. RNA sequencing and SELECT&#x2122;-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.<br><br>RESULTS: HXD treatment significantly alleviated influenza-induced lung injury, suppressed IL-1&#x3b2; 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-1&#x3b2;. 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.<br><br>CONCLUSION: HXD attenuates influenza-induced pulmonary inflammation by modulating the gut-lung axis and inhibiting METTL3-mediated m[6]A 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 {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 = {}, pmid = {40930304}, issn = {1542-7714}, support = {K23 DK124570/DK/NIDDK NIH HHS/United States ; }, }
@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}, 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.<br><br>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&#x2009;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).<br><br>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.<br><br>TRIAL REGISTRATION NUMBER: NCT05690048.}, }
@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}, 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.<br><br>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.<br><br>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.<br><br>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 {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}, 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.<br><br>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&#x202f;<&#x202f;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.<br><br>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.<br><br>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 {pmid40935212, year = {2026}, 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 = {355}, number = {Pt A}, pages = {120587}, doi = {10.1016/j.jep.2025.120587}, pmid = {40935212}, issn = {1872-7573}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Eucommiaceae/chemistry ; Male ; Glucagon-Like Peptide 1/metabolism ; Mice, Inbred C57BL ; Mice ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/drug effects ; *Plant Extracts/pharmacology/therapeutic use/isolation &amp; purification ; Gastrointestinal Microbiome/drug effects ; Butyrates/metabolism ; Humans ; Liver/drug effects/pathology/metabolism ; Disease Models, Animal ; Plant Bark ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; }, 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.<br><br>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.<br><br>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.<br><br>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&#xa0;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.<br><br>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 {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}, mesh = {Animals ; *Humidity/adverse effects ; *Gastrointestinal Microbiome ; Male ; Mice ; *Blood Glucose/metabolism ; Humans ; *Intestinal Mucosa/metabolism/microbiology ; gamma-Aminobutyric Acid/blood ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Glucagon/blood ; }, 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.<br><br>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.<br><br>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 &#x3b2;-cells. HH exposure also downregulated GAD67 expression, reducing GABA synthesis and leading to enhanced GC secretion from islet &#x3b1;-cells. FMT suggested that gut microbiota alterations mediated HH-induced FBG elevation. ABX treatment effectively reversed these metabolic and microbial changes.<br><br>DISCUSSION: Our findings demonstrate that a high humidity environment disrupts gut microbiota homeostasis, impairs the intestinal barrier, and reduces GABA synthesis in pancreatic &#x3b2;-cells, thereby promoting the development of type 2 diabetes mellitus (T2DM).}, }
@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.<br><br>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.<br><br>RESULTS: A total of 177 patients with cancer who received bezlotoxumab were included. Most (76.8%) experienced <2 CDI episodes, whereas 23.2% experienced &#x2265;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).<br><br>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 {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 {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}, mesh = {Humans ; Animals ; *Fecal Microbiota Transplantation/methods/standards ; *Disease Models, Animal ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Models, Animal ; Probiotics ; *Microbiota ; }, 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 {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 = {}, 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 {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 = {}, pmid = {40941154}, issn = {2304-8158}, support = {2022YFF1100306//National Key Research &amp; 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 {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 = {}, pmid = {40943409}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Atherosclerosis/metabolism/microbiology ; *Biomarkers/metabolism ; Methylamines/metabolism ; Animals ; Dysbiosis/metabolism/microbiology ; Bile Acids and Salts/metabolism ; }, 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 {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 = {}, pmid = {40943575}, issn = {1422-0067}, support = {R01 MD016593/MD/NIMHD NIH HHS/United States ; R56 MD014630/MD/NIMHD NIH HHS/United States ; R56MD014630//National Institute on Minority Health and 510 Health Disparities/ ; R01MD016593//National Institute on Minority Health and 510 Health Disparities/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/physiology ; *Epigenesis, Genetic ; Epigenomics ; Epigenome ; Animals ; DNA Methylation ; }, 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 {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 = {}, 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 {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 = {}, pmid = {40944286}, issn = {2072-6643}, support = {2020NCKXBR_004; P2022Z4EB5; 2022ALX9ZM//Ministero dell'Universit&#xe0; e della Ricerca/ ; Micromeso project//LILT/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/immunology/therapy/microbiology/prevention &amp; control ; *Diet ; Probiotics ; Diet, Mediterranean ; Prebiotics/administration &amp; dosage ; Survivorship ; }, 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 {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}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Leucine/metabolism ; *Depression/drug therapy/microbiology ; Male ; *Antidepressive Agents/pharmacology ; *Drugs, Chinese Herbal/pharmacology ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Behavior, Animal/drug effects ; Social Defeat ; Stress, Psychological/drug therapy ; }, 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.<br><br>PURPOSE: This study aimed to investigate the mechanisms by which MXYS alleviates social avoidance, with particular emphasis on gut microbiota composition and leucine metabolism.<br><br>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.<br><br>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.<br><br>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 {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}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; *Dietary Fiber/therapeutic use/administration &amp; dosage ; *Fecal Microbiota Transplantation/methods ; *Psyllium/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Adult ; Female ; Male ; Combined Modality Therapy ; }, 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 {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}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/etiology/metabolism ; *Gastrointestinal Microbiome ; Animals ; Probiotics/therapeutic use ; Fatty Acids, Volatile/metabolism ; Prebiotics ; Adipose Tissue/metabolism ; Fecal Microbiota Transplantation ; Insulin Resistance ; Obesity/microbiology ; }, 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 {pmid40946868, year = {2026}, author = {Deutschbein, F and Ianiro, G}, title = {Fecal Microbiota Transplantation for Primary Clostridioides difficile Infection. Ready for Prime Time?.}, journal = {Gastroenterology}, volume = {170}, number = {5}, pages = {1067-1068}, doi = {10.1053/j.gastro.2025.09.017}, pmid = {40946868}, issn = {1528-0012}, }
@article {pmid40947025, year = {2026}, 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 = {393}, number = {Pt A}, pages = {120318}, doi = {10.1016/j.jad.2025.120318}, pmid = {40947025}, issn = {1573-2517}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; *Hot Temperature/adverse effects ; *Dysbiosis/microbiology ; *Behavior, Animal/physiology ; Anxiety/microbiology ; Inflammation/microbiology ; Memory, Short-Term/physiology ; Exploratory Behavior/physiology ; Hippocampus/pathology ; }, abstract = {Rising global temperatures pose significant health risks. However, the neurobehavioral consequences of high-temperature exposure remain undefined. In this study, the C57BL/6J mice were exposed to different 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 Mendelian randomization (MR) analysis was employed to estimate the causal impact of gut microbiota composition on inflammation and neurobehavioral abnormalities. Herein, we found that mice exposed to 40 °C for 14 days exhibited impaired motor coordination and working memory, reduced exploratory behavior, and increased anxiety. Neuronal injuries were also 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 the level of lipopolysaccharide, a concomitant dysregulation of inflammatory cytokine, and the pronounced activation of NF-κB signaling pathway. FMT from healthy mice ameliorated these adverse effects caused by high-temperature exposure. Although high-temperature reshaped both fungal and bacterial communities, only bacterial dysbiosis correlated with neurobehavioral abnormalities. MR analysis further indicated that gut microbiota perturbations might be linked with the inflammatory responses and neurobehavioral abnormalities. Taken together, these findings suggest high-temperature exposure evokes inflammatory responses and neurobehavioral abnormalities via dysbiosis.}, }
@article {pmid40947138, year = {2026}, 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 = {75}, number = {2}, pages = {289-301}, pmid = {40947138}, issn = {1468-3288}, mesh = {*Fecal Microbiota Transplantation/methods ; *Enteritis/therapy/etiology/microbiology ; Animals ; Mice ; Humans ; *Radiation Injuries/therapy/microbiology ; Prospective Studies ; Female ; Male ; Gastrointestinal Microbiome ; Middle Aged ; Probiotics/therapeutic use ; Disease Models, Animal ; }, 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.<br><br>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).<br><br>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.<br><br>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-&#x3b3; is an essential pathway for the therapeutic efficacy of Hb-auWMT.<br><br>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 {pmid40948097, year = {2026}, author = {Gao, BY and Chen, SC}, title = {Gut microbiota typing and donor factors relationship with fecal microbiota transplantation response in psoriatic arthritis: comment on the article by Qin et al.}, journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)}, volume = {78}, number = {4}, pages = {997}, doi = {10.1002/art.43392}, pmid = {40948097}, issn = {2326-5205}, }
@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}, pmid = {40948444}, issn = {1949-0984}, support = {R44 AI172703/AI/NIAID NIH HHS/United States ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome/genetics ; *Metagenomics/methods ; *Bacteriophages/genetics/isolation &amp; purification/classification ; *Plasmids/genetics ; Feces/microbiology/virology ; *Clostridium Infections/therapy/microbiology ; *Bacteria/genetics/classification/virology/isolation &amp; purification ; Clostridioides difficile/genetics ; Male ; Female ; Middle Aged ; }, 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 {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 {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 {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 {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}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/therapy/microbiology ; Mice ; *Endothelial Progenitor Cells/physiology ; *Physical Conditioning, Animal ; Glucagon-Like Peptide 1/blood ; Fecal Microbiota Transplantation ; Male ; Cell Proliferation ; Cell Movement ; Mice, Inbred C57BL ; Diabetes Mellitus, Experimental/therapy ; Feces/microbiology ; Disease Models, Animal ; Blood Glucose ; }, 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.<br><br>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.<br><br>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).<br><br>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 {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 {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 = {10}, number = {10}, pages = {e0099125}, pmid = {40952001}, issn = {2379-5077}, support = {988415//Crohn's and Colitis Foundation/ ; APP2011047//National Health and Medical Research Council/ ; Investigator grant//National Health and Medical Research Council/ ; Scientia fellowship//University of New South Wales/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Freeze Drying ; Female ; Male ; Administration, Oral ; Double-Blind Method ; Feces/microbiology ; Adult ; *Bacteria/classification/genetics/isolation &amp; purification ; Middle Aged ; }, 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.<br><br>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 {pmid40952509, year = {2025}, author = {Bretthauer, M}, title = {[What is confirmed in colorectal cancer screening?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {66}, number = {12}, pages = {1251-1257}, pmid = {40952509}, issn = {2731-7099}, mesh = {Humans ; *Colorectal Neoplasms/diagnosis/mortality/prevention &amp; control/epidemiology ; Colonoscopy ; *Early Detection of Cancer/methods ; Female ; Male ; Germany ; Occult Blood ; *Mass Screening ; Randomized Controlled Trials as Topic ; Incidence ; }, 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).<br><br>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.<br><br>MATERIAL AND METHODS: Confirmed high-quality evidence from randomized trials on the benefits of screening for colorectal cancer with respect to incidence and mortality.<br><br>RESULTS: The lifetime risk to develop colorectal cancer in Germany is 5% for women and 6.5% for men. According to a&#xa0;large randomized trial, a screening colonoscopy reduces the risk of colorectal cancer from 1.2% to 0.8-0.9% after 10&#xa0;years. New high-quality evidence from a&#xa0;recent Spanish randomized trial also showed that the benefits of FIT screening every other year are comparable to those of 1 colonoscopy over 10&#xa0;years. The risks of perforation and bleeding during colonoscopy are 0.01% and 0.1%, respectively.<br><br>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 {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/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy/microbiology/metabolism/etiology ; *Gastrointestinal Microbiome ; *Brain/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, 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 {pmid40957477, year = {2026}, author = {La 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 Martin Delgado, J and Vianello, E and Dozio, E and Corsi Romanelli, M 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 = {84}, number = {}, pages = {749-764}, pmid = {40957477}, issn = {2090-1224}, mesh = {*Diabetes Mellitus, Type 2/therapy/microbiology/physiopathology ; *Fecal Microbiota Transplantation/methods ; *Metformin/therapeutic use ; Humans ; Dysbiosis/therapy ; *Gastrointestinal Motility/drug effects ; Gastrointestinal Microbiome/drug effects ; *Hypoglycemic Agents/therapeutic use ; Animals ; Insulin Resistance ; }, 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.<br><br>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.<br><br>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 {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 = {90}, number = {3}, pages = {507-508}, doi = {10.1016/j.rgmxen.2025.09.023}, pmid = {40957789}, issn = {2255-534X}, }
@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 = {90}, number = {3}, pages = {506-507}, doi = {10.1016/j.rgmxen.2025.09.022}, pmid = {40957793}, issn = {2255-534X}, }
@article {pmid40959063, year = {2025}, author = {Xie, X and Liu, H and Wan, K and Li, J and Qi, P}, title = {The gut microbiota in osteoporosis: dual roles and therapeutic prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1617459}, pmid = {40959063}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Osteoporosis/therapy/microbiology/metabolism/etiology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Bone Remodeling ; Prebiotics/administration &amp; dosage ; Bone and Bones/metabolism ; }, abstract = {Recent advances in bone biology have underscored the essential role of the gut microbiota in maintaining skeletal homeostasis. Gut-derived metabolites, particularly short chain fatty acids and tryptophan derivatives, influence bone metabolism through modulation of immune signaling, inflammation, and endocrine networks. Emerging evidence indicates that these effects are context dependent and dose dependent, rather than uniformly beneficial or detrimental. For instance, butyrate and lipopolysaccharide exhibit biphasic effects on both osteogenesis and osteoclastogenesis, contingent on concentration, immune status, and the local microenvironment. Microbiota-targeted strategies such as probiotics, prebiotics, and fecal microbiota transplantation are under active investigation as innovative interventions for osteoporosis in both preclinical and clinical contexts. However, substantial knowledge gaps persist, including inconsistent therapeutic outcomes, limited mechanistic insight into host-microbiota interactions, and the absence of standardized microbial intervention protocols. In addition, safety concerns related to FMT, particularly in immunocompromised elderly populations, emphasize the need for rigorous donor screening, extended follow-up periods, and personalized risk and benefit assessment models. To advance the field, future studies should incorporate multi-omics platforms and precision medicine tools to identify key microbial targets and enhance therapeutic efficacy. This review consolidates current evidence and proposes a conceptual framework to clarify the context-specific roles of the gut microbiota in bone remodeling. A deeper mechanistic understanding will be crucial for translating microbiota-based strategies into safe and effective treatments for metabolic bone disorders.}, }
@article {pmid40960868, year = {2025}, author = {Su, Z and Lin, J and Zeng, X and Li, X and Hou, Q and Wang, Q and Liu, C and Qin, J and Li, Y and Zhang, J and Wang, X and Qian, S and Liao, L}, title = {Ozone water enema activates SIRT1-Nrf2/HO-1 pathway to ameliorate gut dysbiosis in mice receiving COVID-19 patient-derived faecal microbiota.}, journal = {Journal of medical microbiology}, volume = {74}, number = {9}, pages = {}, pmid = {40960868}, issn = {1473-5644}, mesh = {Animals ; *Ozone/administration &amp; dosage/pharmacology ; Mice ; *Dysbiosis/therapy/microbiology ; *COVID-19/microbiology ; *Gastrointestinal Microbiome/drug effects ; *NF-E2-Related Factor 2/metabolism/genetics ; *Heme Oxygenase-1/metabolism/genetics ; *Sirtuin 1/metabolism/genetics ; Humans ; Fecal Microbiota Transplantation ; *Enema/methods ; Male ; SARS-CoV-2 ; Mice, Inbred C57BL ; Disease Models, Animal ; Signal Transduction ; Feces/microbiology ; Water ; Female ; Membrane Proteins ; }, abstract = {Introduction. This study centres on how coronavirus disease 2019 (COVID-19) disrupts the intestinal microbiota and amplifies systemic inflammation and evaluates ozone water enemas as a strategy to restore gut microbial balance and activate the SIRT1 (silent information regulator of transcription 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)/HO-1 (heme oxygenase-1) pathway for alleviating post-viral sequelae. Our findings demonstrate that ozone water intervention markedly improves the intestinal microenvironment in mice receiving COVID-19 patient-derived microbiota and attenuates systemic inflammation, offering a viable adjunctive approach for COVID-19 management.Hypothesis. Despite significant progress in reducing the incidence of COVID-19, its long-term consequences, including hepatic dysfunction, pulmonary injury and gut microbiota dysbiosis, remain challenging. While ozonated water enema therapy has shown efficacy in alleviating inflammation and neutralizing oxidative stress, the precise mechanisms by which ozonated water attenuates COVID-19 progression are not fully understood. We hypothesized that ozonated water enemas could enrich gut microbiota composition in COVID-19 patients, thereby optimizing the gut environment following faecal transplantation in a murine model.Aim. The overarching aim of this investigation was to ascertain whether ozonated water enemas could exert a salutogenic effect on the gut microbiota in a mouse model, as well as on the holistic gut and systemic health of critically ill COVID-19 patients subsequent to faecal transplantation.Methodology. The entire experiment was conducted over a 14-day period. WT mice were randomly allocated into three groups: Sham, FMT (faecal microbiota transplantation) and FMT+O3 (FMT with ozonewater enema treatment). Mid-stage faecal specimens were collected from 21 severe COVID-19 patients and randomly divided into seven subgroups (three specimens per subgroup). These specimens were transplanted into the WT mice of the FMT and FMT+O3 groups via faecal gavage on days 1 through 7. The healthy control group (Sham) received oral administration of ddH2O instead. Starting on day 8 post-transplantation, the FMT+O3 group underwent ozone water enema treatment for seven consecutive days. During this treatment period, assessments were performed to evaluate intestinal barrier function, inflammatory changes and alterations in gut microbiota. Additionally, improvements in intestinal, hepatic, pulmonary and systemic lesions were examined.Results. Our findings indicate that ozonated water enemas modulate the SIRT1-Nrf2/HO-1 pathway, significantly enhancing the intestinal environment in mice that received FMT from COVID-19 patients. This intervention increased microbiota populations, strengthened intestinal barrier integrity and reduced intestinal and systemic inflammatory responses.Conclusion. The results highlight the potential of ozonated water enemas as a therapeutic option for COVID-19 patients, particularly in optimizing intestinal microbiota and mitigating inflammatory responses through SIRT1-Nrf2/HO-1 pathway modulation. This approach offers a novel strategy for addressing residual effects of COVID-19.}, }
@article {pmid40960982, year = {2026}, author = {Weninger, SN and Manley, A and Duca, FA}, title = {Managing Glucose Homeostasis Through the Gut Microbiome.}, journal = {Annual review of physiology}, volume = {88}, number = {1}, pages = {459-486}, doi = {10.1146/annurev-physiol-051524-094728}, pmid = {40960982}, issn = {1545-1585}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Homeostasis/physiology ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; Animals ; Probiotics/therapeutic use ; *Glucose/metabolism ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota is a salient contributor to the development of type 2 diabetes mellitus (T2D) as a vast and complex metabolic cross talk that exists between the bacteria residing in the gastrointestinal tract and the host. This cross talk is largely influenced by external factors including diet, highlighting a potential avenue to effectively manipulate the gut microbiota to treat metabolic diseases such as diabetes. In this review, we discuss the influence of the gut microbiota on T2D development and targeting gut microbiota in both current and novel treatments for T2D, highlighting potential alternative therapies including fecal microbiota transplant, prebiotics, probiotics, synbiotics, or xenobiotics. A better understanding of both the impact of the gut microbiota in the etiology of diabetes and the therapeutic potential for manipulating the gut microbiota in metabolic disease could usher in a new approach to targeted treatment options to ameliorate T2D.}, }
@article {pmid40961234, year = {2025}, author = {Xie, X and Zou, A and Zhang, L and Ma, X and He, Y and Liu, H and Lu, Y and Yang, Y and Ouyang, J and Liu, K and Zhong, P and Li, J and Xu, S and Zhou, L and Han, B and Chen, M and Lv, K and Zhang, D and Liu, L and Mei, Y}, title = {Rbm38 deficiency impairs erythroid heme biosynthesis and induces porphyria via reduced ferrochelatase expression.}, journal = {Blood}, volume = {146}, number = {25}, pages = {3106-3123}, doi = {10.1182/blood.2025028783}, pmid = {40961234}, issn = {1528-0020}, mesh = {Animals ; *Ferrochelatase/genetics/metabolism/biosynthesis ; *RNA-Binding Proteins/genetics/metabolism ; *Heme/biosynthesis ; Mice ; Mice, Knockout ; Erythropoiesis ; Humans ; *Porphyrias/genetics/metabolism/pathology/etiology ; Erythrocytes/metabolism ; Erythroid Cells/metabolism ; Iron/metabolism ; Protoporphyrins ; }, abstract = {RNA splicing and processing are critical for erythropoiesis, because dysregulation of RNA splicing ultimately disrupts protein synthesis. The RNA-binding protein Rbm38 is highly expressed during terminal erythropoiesis. Although in vitro studies have implicated Rbm38 as a key regulator of erythroid differentiation, the landscape of RNA splicing regulated by Rbm38 and its role in terminal erythropoiesis in vivo have not been fully elucidated. Here, we generated whole-body and conditional knockout mouse models for Rbm38 and found that mature red blood cell (RBC) production was impaired in the bone marrow of Rbm38-deficient mice. Rbm38-/- RBCs exhibited reduced hemoglobin content and increased susceptibility to oxidative stress-induced hemolysis. These mutant mice also developed microcytic hypochromic anemia, along with dysregulated iron homeostasis. Additionally, they exhibited decreased mitochondrial heme biosynthesis and accumulation of free protoporphyrin IX (PPIX) in erythrocytes and feces, resembling human erythropoietic protoporphyria (EPP). Mechanistically, Rbm38 regulates the incorporation of ferrous iron (Fe2+) into PPIX to form heme by modulating alternative splicing, messenger RNA decay, and translation of the porphyrin metabolic enzyme gene Ferrochelatase (Fech). Importantly, enforced expression of Fech largely restored erythroid differentiation defects and ameliorated anemia in Rbm38-/- transplants. We further demonstrated that genetic variants in the human RBM38 gene locus influence PPIX levels in erythrocytes from healthy cohorts. Our findings demonstrate that Rbm38 governs terminal erythropoiesis by orchestrating RNA splicing, stability, and translation during heme biosynthesis.}, }
@article {pmid40961414, year = {2026}, author = {Davis, BT and Han, H and Islam, MBAR and Ford, K and Chen, Z and Abdala-Valencia, H and Green, S and Weiss, C and Procissi, D and Schwulst, SJ}, title = {Short-Chain Fatty Acid Supplementation After Traumatic Brain Injury Attenuates Neurologic Injury Via the Gut-Brain-Microglia Axis.}, journal = {Shock (Augusta, Ga.)}, volume = {65}, number = {2}, pages = {329-341}, pmid = {40961414}, issn = {1540-0514}, support = {K99 NS130277/NS/NINDS NIH HHS/United States ; R00 NS130277/NS/NINDS NIH HHS/United States ; R01 GM130662/GM/NIGMS NIH HHS/United States ; R01 NS127865/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Brain Injuries, Traumatic/drug therapy/metabolism ; *Fatty Acids, Volatile/therapeutic use/pharmacology ; Mice ; Male ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; *Microglia/metabolism/drug effects ; *Brain/metabolism ; Dietary Supplements ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) is an underrecognized public health threat. There are limited therapeutic options for TBI, and supportive care remains the mainstay of treatment. Our previously published data demonstrate that post-TBI fecal microbiome transplantation (FMT) can reverse TBI-induced depletion of commensal bacteria, preserve white matter connectivity and neurocognition, and decrease cortical volume loss in mice after TBI.<br><br>HYPOTHESIS: We hypothesized that post-TBI supplementation with short-chain fatty acids (SCFAs), metabolites of commensal gut bacteria, would attenuate neurologic injury after TBI in mice.<br><br>METHODS: 14-week-old male C57BL/6 mice (n = 52) underwent TBI via a controlled cortical impact versus sham injury. Post-TBI, each group was treated with the SCFAs acetate, butyrate, and propionate versus a molar-equivalent sodium chloride vehicle via free access to drinking water for 4 weeks post-TBI. The stool was collected 3 days pre- and 60 days post-TBI to assess the gut microbial community structure via 16s ribosomal RNA gene amplicon sequencing. Neurocognitive testing was performed with open-field and zero-maze testing. Ventricular volume and white matter connectivity were measured with 3D, contrast-enhanced magnetic resonance imaging. Lastly, the transcriptional response of microglia was assessed with single-cell RNA sequencing (scRNAseq).<br><br>RESULTS: SCFA supplementation decreased TBI-induced microbial loss, attenuated ventricular volume loss, preserved white matter connectivity, and altered the transcriptional profile of microglia after TBI. Post-TBI SCFA supplementation preserved the abundance of the butyrate-producing taxa Firmicutes, Clostridia, Ruminoccacaceae , and Peptoccacaceae (P&#x2009;=&#x2009; 0.01). SCFA also reduced the TBI-induced increase in Clostridiales and Bacteroidales compared with the salt vehicle group (P&#x2009;=&#x2009; 0.05). We also observed the preservation of non-TBI murine anxiety-like behavior in SCFA-treated TBI mice compared with vehicle-treated TBI mice in the zero-maze (152.3 &#x2009; &#xb1; &#x2009; 101.8&#x2009;cm vs. 147.5 &#x2009; &#xb1; &#x2009; 60.0&#x2009;cm, P&#x2009;=&#x2009; 0.006). These results were recapitulated with open-field testing (11.7 &#x2009; &#xb1; &#x2009; 3%-time in the center in SCFA-treated TBI mice vs. 15.0 &#x2009; &#xb1; &#x2009; 6%-time in the center of the field in vehicle-treated mice; P&#x2009;=&#x2009; 0.002). Lastly, we observed upregulation of transcripts for the neuroprotective heat-shock family of proteins and downregulation of neurodegeneration-associated transcripts, indicating an overall neuroprotective phenotype in microglia after SCFA supplementation post-TBI.<br><br>CONCLUSIONS: We hypothesized that SCFA supplementation would attenuate neurologic injury after TBI in mice. SCFA supplementation attenuated neurocognitive deficits, reduced cortical volume loss, preserved white matter connectivity, and decreased neuroinflammation. These benefits may result from the direct replacement of SCFAs. However, there may also be secondary mechanisms related to commensal refeeding of butyrate-producing bacteria within the gut microbial community, a neuroprotective heat-shock response, and a decrease in the expression of genes associated with neurodegeneration. The current study highlights the role of SCFAs in microbiome homeostasis and the potential of dietary intervention as a novel therapy in TBI.}, }
@article {pmid40961935, year = {2025}, author = {Brandow, AM and Atkinson, SN and Manjarres, Z and Ehlers, VL and Pratt, ML and Mehta, I and Mudunuri, S and Kappagantu, A and Shiers, SI and Mazhar, K and Simms, MA and Alhendi, S and Sheshadri, A and Cervantes, AM and Reese, JC and Tavares-Ferreira, D and Sankaranarayanan, I and Schaub, MK and Waltz, TB and Hayward, M and Rodríguez García, DM and Dussor, G and Salzman, NH and Palmer, KL and Stucky, CL and Price, TJ and Sadler, KE}, title = {Gut microbiota and metabolites drive chronic sickle cell disease pain in mice.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {10}, pages = {1703-1714.e8}, pmid = {40961935}, issn = {1934-6069}, support = {R37 NS108278/NS/NINDS NIH HHS/United States ; R33 NS114954/NS/NINDS NIH HHS/United States ; K23 HL114636/HL/NHLBI NIH HHS/United States ; K99 HL155791/HL/NHLBI NIH HHS/United States ; U19 NS130608/NS/NINDS NIH HHS/United States ; R61 NS114954/NS/NINDS NIH HHS/United States ; R00 HL155791/HL/NHLBI NIH HHS/United States ; R35 GM122503/GM/NIGMS NIH HHS/United States ; R01 NS070711/NS/NINDS NIH HHS/United States ; R01 HL142657/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Anemia, Sickle Cell/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Mice ; Humans ; Mice, Transgenic ; Fecal Microbiota Transplantation ; TRPM Cation Channels/metabolism ; *Chronic Pain/microbiology/therapy ; Dysbiosis/microbiology ; Disease Models, Animal ; Male ; Probiotics/administration &amp; dosage ; Verrucomicrobia ; Akkermansia ; Female ; }, abstract = {Individuals with sickle cell disease (SCD) suffer from debilitating chronic pain that does not have a clear etiology. Recent 16S ribosomal RNA gene sequencing studies revealed gut dysbiosis in individuals with SCD. It is unclear, however, whether these intestinal microbial changes contribute to chronic SCD pain. Using transgenic SCD mice, we determined that chronic SCD pain is alleviated following fecal microbiota transplantation from healthy controls, specifically by increasing the relative abundance of probiotic Akkermansia muciniphila. Reciprocally, transplantation of the SCD gut microbiome induced persistent pain in wild-type recipients via bilirubin-vagus nerve TRPM2 signaling. Biospecimens from individuals with SCD and spatial transcriptomic analysis of human nodose ganglia tissue identified additional bacterial species and neuronally expressed transcripts that should be explored as novel SCD analgesic targets.}, }
@article {pmid40962064, year = {2026}, author = {Wu, ZN and Zhao, HL and Wang, Q and Chen, JL and Ren, Y and Qin, XM and Tian, JS}, title = {Analysis of a new anti-depression mechanism of Chaigui granules based on multi-omics integration: In-depth mining of intestinal microbiota-metabolite interaction network.}, journal = {Journal of affective disorders}, volume = {393}, number = {Pt A}, pages = {120319}, doi = {10.1016/j.jad.2025.120319}, pmid = {40962064}, issn = {1573-2517}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Mice ; Fecal Microbiota Transplantation ; Humans ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Metabolomics ; Disease Models, Animal ; Female ; *Depression/microbiology/drug therapy ; Adult ; *Antidepressive Agents/pharmacology ; Mice, Inbred C57BL ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Multiomics ; }, abstract = {BACKGROUND: Depression is a common mental disorder that severely affects physical and psychological health of patients. Despite the proven clinical and experimental efficacy of Chaigui granules (CGG), a novel traditional Chinese medicine formulation for depression, its mechanism remains unclear owing to its multi-component nature.<br><br>METHODS: To establish an optimal depression model, the gut microbiota of humanized and murine donors under healthy and depressed conditions was compared, and subsequent behavioral effects via fecal microbiota transplantation (FMT) in mice was assessed. Based on this, the mechanism of CCG in treating depression was characterized through combining 16S rRNA sequencing, LC-MS metabolomics and integration analysis.<br><br>RESULTS: The gut microbiota was markedly disrupted in depressed patients and mice. Through FMT, microbiota from depressed donors successfully colonized recipient mice and induced depression-like behaviors. Comparative results demonstrated the superiority of the murine FMT-induced depression model in terms of stability and translational relevance. CGG produced significant improvements in behavioral phenotypes, metabolic profiles, and microbial composition in depressed mice. Specifically, the treatment regulated 17 key metabolites and 7 bacterial strains, primarily involved in 2 major metabolic pathways. Integrated correlation analysis revealed five bacterial strains and seven metabolites that were strongly associated with depression-like behaviors.<br><br>CONCLUSION: Through integrated approaches, we hypothesize that Chaigui granules alleviate depressive-like behavior in murine FMT-induced depressed mice by modulating Aminoacyl-tRNA biosynthesis and Lysine degradation, inhibiting Bacteroides caccae, Clostridium cocleatum, and Muribaculum intestinale, while promoting Akkermansia muciniphila and Mucispirillum schaedleri, and regulating key metabolites including Glutaric acid, Threonine, Leucine, and Glutamic acid.}, }
@article {pmid40963960, year = {2025}, author = {Wu, R and Teng, X and Guo, Y and Cai, Y and Lv, Y and Gao, H and Zhang, W and Shen, H and Fan, J}, title = {Gut microbiota characteristics and therapeutic effects of fecal microbiota transplantation in children with autism spectrum disorder in central China: a combined cross-sectional and prospective study.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1648471}, pmid = {40963960}, issn = {2296-2360}, abstract = {INTRODUCTION: Gut microbiota dysbiosis is implicated in autism spectrum disorder (ASD), yet scalable therapeutic interventions remain limited. This study investigated gut dysbiosis profiles in children with ASD and evaluated the clinical efficacy of a simplified fecal microbiota transplantation (FMT) protocol using pediatric donors.<br><br>METHODS: In a cross-sectional phase, 48 children with ASD and 51 age-/sex-matched healthy controls underwent gut microbiota analysis. Subsequently, 25 ASD participants received FMT via a streamlined protocol: 3-day bowel preparation followed by 6-day transcolonoscopic microbiota infusion from pediatric donors. Clinical outcomes and microbiota shifts were assessed at 3-month follow-up.<br><br>RESULTS: (1) Baseline Dysbiosis: ASD subjects exhibited reduced microbial diversity, with decreased Faecalibacterium and Bifidobacterium but elevated Megamonas and Akkermansia vs. controls. (2) Clinical Efficacy: Post-FMT, significant improvements occurred in core ASD symptoms and gastrointestinal comorbidities. (3) Microbiota Shifts: FMT recipients showed increased beneficial genera (Prevotella, Faecalibacterium, Agathobacter, Dorea) and reduced Escherichia-Shigella.<br><br>DISCUSSION: A simplified pediatric donor FMT protocol effectively modulates gut microbiota composition and alleviates both behavioral and gastrointestinal symptoms in children with ASD. This strategy demonstrates feasibility for clinical translation, highlighting microbiota-targeted therapy as a promising intervention for ASD.}, }
@article {pmid40964192, year = {2025}, author = {Dong, J and Xie, T and Shi, C and Feng, G and Zhang, H and Xu, Z and Dong, L}, title = {Gut-Spinal Cord Axis in Spinal Cord Injury: Bidirectional Inflammatory Mechanisms and Microbiota-Targeted Therapeutic Strategies.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {12549-12573}, pmid = {40964192}, issn = {1178-7031}, abstract = {Spinal cord injury (SCI) is a complex neurological disorder characterized not only by localized neuroinflammation but also by systemic immune dysregulation and multiorgan dysfunction. Emerging evidence has identified the gut microbiota as a critical extrinsic regulator of neural homeostasis, giving rise to the concept of the "gut-spinal cord axis". This review systematically examines the dynamic and bidirectional alterations in the gut microbial composition following SCI, with a particular emphasis on the role of microbiota-derived metabolites in the gut-spinal cord axis. These metabolites are recognized as key mediators that shape the spinal inflammatory milieu by modulating specific signaling pathways. In addition, the mechanistic basis of the gut-spinal cord axis is further dissected through neural, immune, and metabolic regulatory frameworks, highlighting how gut dysbiosis following SCI contributes to spinal inflammation via the modulation of vagal nerve signaling, immune cell polarization, and metabolic homeostasis. Moreover, the translational potential of microbiota-targeted interventions-such as probiotics and fecal microbiota transplantation (FMT)-is evaluated in terms of their ability to suppress inflammatory amplification and restore the disrupted bidirectional gut-spinal cord feedback loop. By integrating multiomics approaches and adopting a spatiotemporal perspective, this review underscores the importance of cross-system therapeutic strategies in SCI, aiming to provide a theoretical foundation and practical guidance for future precision interventions and translational research.}, }
@article {pmid40965029, year = {2025}, author = {Radhakrishnan, P and Viswanathan, K and Lini, S and Chinta, S and Muthusamy, S}, title = {Unveiling Role of Gut Microbiota in Alzheimer's Disease: Mechanisms, Challenges and Future Perspectives.}, journal = {Current Alzheimer research}, volume = {22}, number = {10}, pages = {711-725}, pmid = {40965029}, issn = {1875-5828}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/metabolism/microbiology ; Animals ; *Dysbiosis/metabolism ; Probiotics/therapeutic use ; Brain/metabolism ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative condition characterized by neuroinflammation, tau hyperphosphorylation, Aβ (Amyloid beta) accumulation, and synaptic dysfunction. New research indicates that the gut-brain axis, a network of two-way communication that involves immunological signals, neural pathways, and microbial metabolites, makes dysbiosis of the gut microbiota essential to the pathogenesis of AD. Alterations in the gut microbiota's composition hinder the production of crucial metabolites, such as short-chain fatty acids, trimethylamine- N-oxide, and secondary bile acids, which affect neuroinflammatory cascades, mitochondrial bioenergetics, and synaptic plasticity. Furthermore, Toll-like receptor 4 -4-mediated microglial responses are triggered by Gram-negative bacterial lipopolysaccharides. This cascade promotes oxidative stress, chronic neuroinflammation, and disruption of the (BBB) blood-brain barrier, all of which encourage the accumulation of neurotoxic proteins. Microbiome-modulating therapies, such as probiotics, prebiotics, and synbiotics, have been shown to have neuroprotective properties. They work by restoring microbial diversity, increasing (Short-chain fatty acids) SCFA-mediated anti-inflammatory pathways, and reducing glial activation. In addition to promoting gut microbiota equilibrium, dietary approaches like the Mediterranean and ketogenic diets, which are enhanced with polyphenols and omega-3 fatty acids, also lower systemic inflammation and increase neural resilience. Furthermore, the potential of postbiotics and fecal microbiota transplantation to attenuate AD-related neurodegeneration and restore gut-derived metabolic balance is being investigated. Translating these methods into standardized clinical applications is difficult, though, because individual microbiome composition varies. It will be essential to address these complications through mechanistic research and extensive clinical trials to establish gut microbiota as a promising therapeutic target in AD.}, }
@article {pmid40965701, year = {2025}, author = {Høyer, KL and Kornum, DS and Baunwall, SMD and Klinge, MW and Drewes, AM and Yderstræde, KB and Mikkelsen, S and Erikstrup, C and Krogh, K and Hvas, CL}, title = {Repeated faecal microbiota transplantation for individuals with type 1 diabetes and gastroenteropathy.}, journal = {Diabetologia}, volume = {68}, number = {12}, pages = {2795-2806}, pmid = {40965701}, issn = {1432-0428}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Diabetes Mellitus, Type 1/complications/therapy ; Feasibility Studies ; *Fecal Microbiota Transplantation/methods/adverse effects ; Follow-Up Studies ; *Gastrointestinal Diseases/etiology/therapy ; Treatment Outcome ; }, abstract = {AIMS/HYPOTHESIS: Faecal microbiota transplantation (FMT) may alleviate gastrointestinal symptoms in individuals with diabetic gastroenteropathy, as demonstrated in a recent placebo-controlled trial. In most participants, symptom relief was transient, raising the need for repeated treatments. This study assessed the long-term efficacy, safety and feasibility of repeated, on-demand FMT as a maintenance treatment in this patient population.<br><br>METHODS: All 20 participants from the randomised clinical trial were offered extended open-label treatment with FMT. Symptom assessments were conducted by telephone every 2-3 months using the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Secondary measures included bowel movement frequency, stool consistency assessed using the Bristol Stool Scale, perceived treatment benefit on a seven-point Likert scale, and adverse events (AEs). FMT was primarily given as oral capsules, and colonoscopy was used for participants who could not swallow capsules.<br><br>RESULTS: Of the original 20 participants, 17 were included in the present study and followed from September 2021 to December 2024, with a median Duration of follow-up of 33.2 months (range 14.7-39.1 months). Participants received a total of 95 FMT treatments, with a median of five per participant and a median interval of 5.3 months between treatments. FMT induced consistent symptom relief, with reduced GSRS-IBS scores across multiple treatments. At the last FMT treatment provided, the mean GSRS-IBS score had decreased from 60 (95% CI 54, 66) at baseline to 35 (95% CI 29, 40), with a mean difference of -25 (95% CI -18, -33). The occurrence of frequent bowel movements 2 weeks after treatment (>&#xa0;7 per day) decreased from 19% (95% CI 10%, 28%) to 3% (95% CI 0%, 7%). Stool consistency improved after treatment, and the frequency of normal stool types (Bristol Stool Scale score 3-5) increased from 28% (95% CI 18%, 39%) to 76% (95% CI 66%, 86%). Participant satisfaction was high, with 86% reporting considerable benefits (Likert scores 5-7). Repeated FMT was generally well tolerated, with most AEs being mild and self-limiting. Fifteen serious AEs were documented, of which only one was deemed to be possibly related to FMT.<br><br>CONCLUSIONS/INTERPRETATION: Repeated, on-demand FMT is effective and safe for long-term treatment of individuals with type 1 diabetes and severe diabetic gastroenteropathy.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04749030 FUNDING: The study was funded by a Steno Collaborative Grant (no. 0058906).}, }
@article {pmid40967079, year = {2025}, author = {Jayaprakash, M and Vijaya Kumar, D and Chakraborty, G and Chakraborty, A and Kumar, V}, title = {Bacteria-mediated cancer therapy (BMCT): Therapeutic applications, clinical insights, and the microbiome as an emerging hallmark of cancer.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {192}, number = {}, pages = {118559}, doi = {10.1016/j.biopha.2025.118559}, pmid = {40967079}, issn = {1950-6007}, mesh = {Humans ; *Neoplasms/therapy/microbiology/immunology ; Animals ; Tumor Microenvironment ; *Bacteria/metabolism/immunology ; Fecal Microbiota Transplantation/methods ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {The host microbiota has emerged as a critical modulator of immunity and cancer pathogenesis, influencing not only tumor initiation and progression but also therapeutic responses. This review explores the multifaceted roles of commensal and engineered bacteria in cancer therapy, highlighting the underlying mechanisms of bacterial tumor targeting, immunomodulation, and synergy with immune checkpoint inhibitors. We summarize the contributions of key bacterial genera-such as Clostridium, Bifidobacterium, Listeria, Salmonella, and Escherichia-focusing on their direct oncolytic properties, delivery systems, and interactions with the tumor microenvironment. Clinical trials employing live bacteria, bacterial metabolites, and fecal microbiota transplantation are also discussed, emphasizing their translational potential and current limitations. Additionally, we explore how the microbiome has been recognized as an enabling hallmark of cancer, capable of influencing inflammation, immune evasion, and therapeutic resistance. Despite significant progress, challenges such as safety, delivery specificity, and regulatory concerns remain. Advances in synthetic biology, precision microbiome engineering, and personalized medicine offer promising strategies to overcome these barriers. By integrating microbial biology with immuno-oncology, bacteria-mediated cancer therapy (BMCT) represents a novel frontier with transformative potential in cancer treatment.}, }
@article {pmid40967279, year = {2025}, author = {Liao, XN and Huang, LL and Yang, J and Hou, YY and Quan, YX and Bai, YH}, title = {Analysis of the potential mechanism of stem cells in the treatment of diabetic nephropathy based on 16S, metabolome and transcriptome.}, journal = {Genomics}, volume = {117}, number = {6}, pages = {111113}, doi = {10.1016/j.ygeno.2025.111113}, pmid = {40967279}, issn = {1089-8646}, mesh = {*Diabetic Nephropathies/therapy/metabolism/genetics ; Animals ; *Metabolome ; Mice ; *Transcriptome ; RNA, Ribosomal, 16S/genetics ; Male ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells/metabolism ; Gene Regulatory Networks ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Diabetic nephropathy (DN) has become a major cause of end-stage renal failure. The therapeutic mechanism of mesenchymal stem cells (MSCs) in DN is not fully understood. In this study, we used transcriptome sequencing, 16S rRNA sequencing, and metabolomics sequencing to perform a combined multi-omics analysis to investigate the potential mechanisms of MSCs for DN.<br><br>METHODS: First, DN mouse model was established. Kidneys, feces, and blood were collected from 6 control, 6 model, and 6 intervention (MSCs) groups for transcriptome sequencing, 16S RNA sequencing, and metabolome sequencing, respectively. Then, candidate genes between the 3 groups were identified and enriched using transcriptomic analysis. Next, with the help of metabolomics analysis, differential metabolites were screened by OPLS-DA analysis for control and model groups, as well as model and MSCs groups, respectively. Similarly, differential microorganisms and candidate microorganisms were selected by 16S rRNA gene sequencing data. Subsequently, the correlations between candidate genes and candidate metabolites, candidate genes and candidate microorganisms, as well as candidate metabolites and candidate microorganisms were explored by Spearman correlation analysis, respectively. Finally, a microbe-metabolite-gene network was constructed to identify key genes, key metabolites and key microbes, and their expression levels were analyzed.<br><br>RESULTS: There were differences in genes, microorganisms, and metabolites among the samples in the control, model, and MSCs groups. Candidate genes enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included adhesion molecules and 2-oxocarboxylic acid metabolism. GDP-mannose biosynthesis and purine ribonucleoside degradation were significantly enriched by different microorganisms. The KEGG pathways mainly enriched for differential metabolites were PPAR signaling pathway, arachidonic acid metabolism, and Rap1 signaling pathway. A microorganisms-metabolite-gene network containing 25 nodes and 53 edges was constructed with interactions including Sorangium-neg-M501T271 and Tmem238l-pos-M373T270, among others. In addition, 10 key genes, 5 key microorganisms and 10 key metabolites were significantly expressed in both the MSCs group and the control group.<br><br>CONCLUSION: This study identified 10 key genes, 10 key metabolites and 5 key microorganisms and a correlation network diagram was constructed. It provided a theoretical reference for exploring the molecular mechanisms of MSCs for DN treatment.}, }
@article {pmid40969441, year = {2025}, author = {Gong, J and Liu, Y and Huang, L}, title = {Laboratory preparation methods for human-derived fecal microbial suspensions for fecal microbiota transplantation: a review and standardization perspectives.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1637673}, pmid = {40969441}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) has advanced significantly as a therapeutic approach over the past few decades. Preparing fecal suspensions for FMT is one of the key steps. However, there is no unified standard or recognized procedure for preparing fecal suspensions in laboratories. This review evaluated the steps currently employed in laboratories to prepare fecal suspensions for FMT, including sample collection, suspension buffers, homogenization, purification, filtration, centrifugation, cryopreservation, dosage, the operating environment, and the transplantation form. This review focuses on the different operations of each preparation step, aiming to provide a reference for the laboratory preparation of fecal suspensions.}, }
@article {pmid40969847, year = {2025}, author = {Wu, H and Pang, MM and Li, YL and Hong, JH and Liu, PM and Bian, M and Yang, JJ}, title = {Allicin Aplealleviates Gouty Arthritis by Regulating the Gut-Joint Axis, Reducing XOD Activity, Inhibiting Oxidative Stress, and Suppressing NLRP3 Inflammasome Activation.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {7887-7907}, pmid = {40969847}, issn = {1177-8881}, mesh = {Animals ; *Sulfinic Acids/pharmacology/administration &amp; dosage ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; *Oxidative Stress/drug effects ; *Inflammasomes/metabolism/antagonists &amp; inhibitors ; Rats ; Gastrointestinal Microbiome/drug effects ; Disulfides/pharmacology ; *Arthritis, Gouty/drug therapy/metabolism/pathology ; Male ; Rats, Sprague-Dawley ; *Superoxide Dismutase/metabolism/antagonists &amp; inhibitors ; Disease Models, Animal ; Dose-Response Relationship, Drug ; }, abstract = {BACKGROUND: Gouty arthritis (GA) is a common joint inflammation closely related to hyperuricemia and urate crystal deposition, and its incidence is on the rise worldwide. Allicin, the primary biologically active component found in freshly crushed garlic extracts, has been reported to possess many beneficial biological functions.<br><br>METHODS: An animal model was used to evaluate the efficacy of allicin on GA rats, and 16S rRNA sequencing and metabolomics were used to explore changes in the gut microbiota and metabolites. Fecal microbiota transplantation (FMT) and fibroblast-like synoviocytes (FLS) used to explore the mechanism of allicin treating GA.<br><br>RESULTS: The results showed that allicin effectively improved the general state of GA rats, inhibited XOD activity, and significantly reduced ROS production and activation of the NLRP3 inflammasome, thereby exerting therapeutic efficacy to protect the kidneys and joints. Examination of the gut microbiota showed that the composition of the gut microbiota of GA rats improved after allicin treatment (increase in Lactobacillus). Metabolomic analysis revealed a significant increase in gut microbial short-chain fatty acid metabolites (butyric acid) following allicin treatment. Furthermore, FMT confirmed that allicin significantly alleviated GA and increased butyric acid content in a gut microbe-dependent manner. Finally, the role of butyric acid in inhibiting ROS generation and NLRP3 inflammasome activation in FLS was elucidated.<br><br>CONCLUSION: This study highlights allicin as a promising therapeutic candidate for GA, emphasizing its potential to inhibit oxidative stress and inflammatory responses by regulating the gut-joint axis.}, }
@article {pmid40972191, year = {2025}, author = {Lévay, K and Kovács, S and Budai, A and Horváth, I and Kovács, N and Máthé, D and Szigeti, K and Dunai, Z and Makra, N and Juhász, J and Ostorházi, E and Bánky, B and Szijártó, A and Fülöp, A}, title = {Physical prehabilitation improves colonic anastomosis healing in a malnourished rat model only if attached to effective nutritional prehabilitation - Experimental study.}, journal = {Surgery}, volume = {188}, number = {}, pages = {109677}, doi = {10.1016/j.surg.2025.109677}, pmid = {40972191}, issn = {1532-7361}, mesh = {Animals ; Anastomosis, Surgical ; *Wound Healing/physiology ; Rats ; *Colon/surgery ; *Malnutrition/complications/therapy ; Gastrointestinal Microbiome ; Male ; Disease Models, Animal ; *Preoperative Exercise ; *Physical Conditioning, Animal ; Rats, Wistar ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: The importance of prehabilitation prior to colorectal surgery has recently gained attention. However, existing literature on its effectiveness is contradictory. Therefore, we investigated the impact of different prehabilitation protocols on intestinal anastomotic healing and the gut microbiome in a malnourished rat model.<br><br>METHODS: Rats were divided into 6 groups: ad libitum fed, ad libitum fed with exercise prehabilitation, malnourished, malnourished with exercise prehabilitation, malnourished with nutritional prehabilitation, and malnourished with combined nutritional and exercise prehabilitation. After 4 weeks of prehabilitation, body weight, body composition (measured by magnetic resonance imaging), gut circulation (assessed by short-wave infrared imaging), and microbiome diversity (evaluated by 16S rRNA sequencing) were determined. Colon resection and anastomosis were then performed. Anastomotic healing was assessed using the rat grimace scale, bursting pressure, adhesion score, bowel motility tests, and histopathologic examination. Correlations between microbiome composition and anastomotic healing parameters were also analyzed.<br><br>RESULTS: Malnutrition negatively affected all measured parameters related to body composition and postoperative outcomes. Physical prehabilitation alone did not improve these parameters in malnourished rats, whereas nutritional and bimodal prehabilitation successfully restored them. Specifically, these interventions led to improved body composition (P < .001), enhanced bowel perfusion (P < .05), and improved anastomotic healing (bursting pressure: P < .001; rat grimace scale: P < .0001; adhesion score: P < .0001) compared with untreated malnourished controls. Furthermore, nutritional and bimodal prehabilitation favorably modulated the fecal microbiome.<br><br>CONCLUSION: Our study demonstrates that nutritional and bimodal prehabilitation plays a primary role in improving colonic anastomotic healing under malnourished conditions. Moreover, we show for the first time that different prehabilitation protocols significantly influence the fecal microbiome, which may be fundamental to postoperative recovery.}, }
@article {pmid40972730, year = {2026}, author = {Wang, X and Chen, M and Su, Y and Zhang, X and Chen, J and Huang, Z and Xie, J and Xie, Q and He, L and Su, L and Su, Z and Wang, H and Li, Y}, title = {A novel cholesterol-reducing mechanism of polygonati rhizoma: Dual action via Bacteroides-mediated cholesterol sulfonation and feedback inhibition of ACAT2 by sulfated metabolite.}, journal = {Journal of ethnopharmacology}, volume = {355}, number = {Pt A}, pages = {120619}, doi = {10.1016/j.jep.2025.120619}, pmid = {40972730}, issn = {1872-7573}, mesh = {Animals ; Mice ; Male ; *Cholesterol/metabolism/blood ; *Polygonatum/chemistry ; *Hypercholesterolemia/drug therapy ; Gastrointestinal Microbiome/drug effects ; Molecular Docking Simulation ; *Bacteroides/metabolism/drug effects ; *Anticholesteremic Agents/pharmacology/isolation &amp; purification ; *Phosphatidylcholine-Sterol O-Acyltransferase/antagonists &amp; inhibitors/metabolism ; Rhizome ; Disease Models, Animal ; *Plant Extracts/pharmacology ; Animals, Outbred Strains ; }, abstract = {Polygonati Rhizoma (PR) has the function of "invigorating spleen and tonifying kidney", and is historically applied as a homology of medicine and food to prevent and treat dyslipidemia in China. However, there is limited experimental evidence to support this application, and the underlying mechanism has not been fully deciphered.<br><br>AIM OF THE STUDY: To analyze the composition and illuminate the cholesterol-lowering potential and molecular mechanism of PR's aqueous extract (PRE) in high-fat emulsion (HFE)-induced hypercholesterolemia mouse model.<br><br>MATERIALS AND METHODS: Ion chromatograph was employed to determine the monosaccharide composition of PRE. HFE-induced Kunming mouse model was constructed to evaluate the anti-hypercholesterolemia effect of PRE. Metagenomic sequences and liquid chromatography-mass spectrometry (LC-MS) analysis were performed to elucidate the mechanism through which PR regulated cholesterol metabolism. Antibiotic cocktail (ABX) intervention and fecal microbiota transplantation (FMT) were used to validate whether PRE regulated cholesterol metabolism through the intestinal microbiota. The cholesterol-reducing effect of cholesterol sulfate (CS) was explored in poloxamer 407 (P407)-induced mouse model of dyslipidemia. Molecular docking and molecular dynamics (MD) simulation were also employed to elucidate the underlying mechanisms. Furthermore, a combination of qRT-PCR, Western blot, and surface plasmon resonance (SPR) were employed to delineate its mechanism.<br><br>RESULTS: Our study indicated that the polysaccharides of PRE were mainly composed of fructose (92.33&#xa0;%) and glucose (5.25&#xa0;%). PRE treatment effectively blocked body weight gain, significantly decreased serum and hepatic levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Additionally, PRE ameliorated hepatic lipid accumulation in mice with HFE-elicited hypercholesterolemia. Notably, metagenomic sequencing and LC-MS analysis indicated that PRE markedly increased the abundance of intestinal genera Bacteroides and significantly elevated the fecal CS concentration in HFE mice. Genome-based functional analysis further indicated that cofactors of sulfonation (ATP sulfurylase CysD and CysN, BT0414-BT0415) were significantly upregulated after treatment with PRE. The cholesterol-lowering effect of PRE was largely contingent upon microbial conversion of cholesterol-to-CS mediated by Bacteroides, as validated by antibiotics-induced intestinal microbiota depletion in pseudo-germ-free model and restoration of gut microbiota through FMT. In vitro study also showed that PRE promoted the growth of Bacteroides thetaiotaomicron. Furthermore, CS markedly alleviated serum, hepatic, bile, and fecal levels of TG, TC, LDL-C, HDL-C, and TBA, indicative of appreciable lipid-lowering effect. MD simulation and SPR results indicated that CS directly bound to ACAT2. Consistent with this interaction, CS greatly downregulated the mRNA and protein expression of ACAT2 in small intestinal tissue.<br><br>CONCLUSION: These findings for the first time suggested that PR acted as a prebiotic agent to ameliorate hypercholesterolemia, at least in part, via dual mechanism involving modulation of Bacteroides-mediated sulfonation metabolic pathway and feedback inhibition of ACAT2 by CS, highlighting its therapeutic potential for cholesterol-related disorders. This work might also offer novel mechanistic insight and further buttressed the ethnopharmacological application of PR in the therapy of hypercholesterolemia.}, }
@article {pmid40972731, year = {2026}, author = {Wang, T and Yang, D and Gao, R and Wen, Y and Liu, Z and Zhai, J and Li, S and Han, N and Yin, J}, title = {The discovery of the material basis and mechanism of gypsum as an antipyretic based on the theory of the diverse applications of raw and processed products.}, journal = {Journal of ethnopharmacology}, volume = {355}, number = {Pt A}, pages = {120623}, doi = {10.1016/j.jep.2025.120623}, pmid = {40972731}, issn = {1872-7573}, mesh = {Animals ; *Calcium Sulfate/pharmacology/chemistry/therapeutic use ; *Antipyretics/pharmacology/chemistry/therapeutic use ; *Fever/drug therapy/chemically induced ; Gastrointestinal Microbiome/drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Medicine, Chinese Traditional ; Lipopolysaccharides ; Cytokines/metabolism ; Metabolomics ; Disease Models, Animal ; }, abstract = {Gypsum (CaSO4·2H2O), recognized as a classical mineral medicine in traditional Chinese medicine (TCM), has been traditionally used to treat fever. However, the specific bioactive constituents and the underlying molecular mechanisms of its action have yet to be fully elucidated.<br><br>AIM OF THE STUDY: To address this knowledge gap, we systematically elucidated the antipyretic material basis and underlying mechanisms of gypsum through integrating the analysis of metal profile, gut microbiota profiling, and serum metabolomics.<br><br>MATERIALS AND METHODS: Metal chemical profiling was firstly used to elucidate the antipyretic composition by comparing the serum composition of gypsum and calcined gypsum. Subsequently, this research investigated the differential antipyretic effects of gypsum, calcined gypsum and key elements in a lipopolysaccharide (LPS)-induced fever model in rats by monitoring changes in body temperature and inflammatory cytokines. Furthermore, the underlying mechanism was explored through western blotting (WB), quantitative real-time PCR (qPCR), and gut microbiota in conjunction with metabolomics.<br><br>RESULTS: The results reveal that Mg, Ca, Zn, and Mo were the strong candidates for active substances of gypsum. Furthermore, the research proved that gypsum and key elements (Mg, Ca, Zn, Mo) exhibits a notable antipyretic effect, while calcined gypsum does not. WB and qPCR analyses revealed a reduction in the expression of cyclooxygenase-2 (COX-2) in hypothalamic tissue in the gypsum-exposed group. Metabolomics profiling of serum suggests that the antipyretic effect of gypsum may involve primary bile acid biosynthesis. Association analysis involving gut microbiota indicated that gypsum may lead to the downregulation of five significant metabolites, including 15-Hydroxy-5,8,11,13-Eicosatetraenoic Acid, PC(16:1 (9Z)/0:0), PC(22:6 (4Z,7Z,10Z,13Z,16Z,19Z)/0:0) and PC(P-18:0/PGJ2), by downregulating Bacteroides, Ruminococcaceae and Roseburia to inhibit fever. Experiments involving fecal microbiota transplantation provide additional evidence for the involvement of gut bacteria in facilitating the antipyretic effects associated with gypsum.<br><br>CONCLUSIONS: This study pioneers in identifying the key elements (Mg, Ca, Zn, Mo) as the core antipyretic component of gypsum while establishing a multidimensional "mineral composition-gut microbiota-host metabolism" interaction network. Our findings provide mechanistic insights for optimizing quality standards of mineral-based TCM formulations.}, }
@article {pmid40973482, year = {2025}, author = {Raja, SS and Costello, SP and Rayner, CK and Day, A and Portmann, L and Uylaki, W and Wheeler, R and Saxon, S and Tucker, EC and Fon, J and Edwards, S and Young, RB and Forster, SC and Goodsall, T and Bryant, RV}, title = {Examining the role of fecal microbiota transplantation for inducing remission in resistant ulcerative proctitis and distal ulcerative colitis (ulcerative proctitis-fecal microbiota transplantation).}, journal = {Journal of Crohn's &amp; colitis}, volume = {19}, number = {10}, pages = {}, doi = {10.1093/ecco-jcc/jjaf169}, pmid = {40973482}, issn = {1876-4479}, support = {//The Hospital Research Foundation was provided through the Michell McGrath Fellowship awarded to R.V.B/ ; }, mesh = {Humans ; Female ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Adult ; Remission Induction/methods ; Pilot Projects ; *Proctitis/therapy/microbiology ; Middle Aged ; Enema ; Treatment Outcome ; Vancomycin/therapeutic use ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {IMPORTANCE: Resistant ulcerative proctitis (UP) represents a clinical conundrum, often necessitating the use of systemic therapy despite the disease being localized. Fecal microbiota transplantation (FMT) has proven efficacy for inducing remission in ulcerative colitis (UC) but has not been evaluated in UP.<br><br>OBJECTIVES: To assess the safety and efficacy of FMT enema therapy for resistant UP.<br><br>DESIGN: Single-arm open-label pilot study.<br><br>SETTING: The Queen Elizabeth Hospital, Adelaide, Australia.<br><br>PARTICIPANTS: Thirty patients with active UP or distal UC (total Mayo 3-10 with endoscopic Mayo subscore &#x2265;1), with maximal disease extent up to &#x2264;3030 cm from anal verge).<br><br>INTERVENTIONS: Vancomycin conditioning and dietary education, followed by six anaerobically prepared single-donor FMT retention enemas administered over 8 weeks.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was safety and tolerability of FMT therapy. Secondary endpoints included combined clinical and endoscopic remission (Mayo Clinic score &#x2264;2 with endoscopic subscore &#x2264;1), histological remission, patient-reported outcomes, and exploratory microbial analysis.<br><br>RESULTS: Thirty participants were enrolled (median age 41 years; 17 [57%] female). Serious adverse events occurred in 3 patients, including flare of UC (n&#x2009;=&#x2009;2) and Clostridioides difficile colitis (n&#x2009;=&#x2009;1). Eighteen patients (60%) reported mild-moderate adverse events, most commonly gastrointestinal symptoms. Combined clinical and endoscopic remission was achieved in 10 patients (33.3%). Higher baseline Mayo score (odds ratio [OR]: 0.28, P&#x2009;=&#x2009;.008) and fecal calprotectin (OR: 0.66, P&#x2009;=&#x2009;.049) predicted failure to achieve remission. Participants demonstrated a decrease in Shannon diversity (P&#x2009;=&#x2009;.02) following the dual intervention of vancomycin conditioning and FMT.<br><br>CONCLUSIONS AND RELEVANCE: Antibiotic conditioning followed by FMT enema therapy was well tolerated and demonstrated efficacy in inducing clinical remission in UP. Further controlled studies of FMT in UP are warranted alongside a mechanistic assessment of both fecal and mucosa-associated microbiome.}, }
@article {pmid40974374, year = {2025}, author = {Hemnani, M and Karatas, M and Cruz, AVS and da Silva, PG and Thompson, G and Poeta, P and Rebelo, H and Matthijnssens, J and Mesquita, JR}, title = {Metagenomic analysis of viral diversity in Portuguese bats.}, journal = {Veterinary research communications}, volume = {49}, number = {6}, pages = {319}, pmid = {40974374}, issn = {1573-7446}, mesh = {Animals ; *Chiroptera/virology ; Metagenomics ; Portugal/epidemiology ; Feces/virology ; *Coronavirus/genetics/isolation &amp; purification/classification ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; *Coronavirus Infections/veterinary/virology/epidemiology ; Phylogeny ; }, abstract = {Bats are highly diverse mammals and known reservoirs of numerous zoonotic viruses. Their role in the ecology of emerging infectious diseases continues to be of significant interest. This study aimed to evaluate the occurrence of coronaviruses (CoVs) in Portuguese bats and predict the affinity of their spike proteins with the aminopeptidase N (APN) receptor of several host species. The study also explored the viral diversity in bat samples using metagenomic sequencing. Ten bats (five Myotis myotis and five Miniopterus schreibersii) were captured at an underground roost in 2022 (Central Portugal), and fecal samples, oral, and anal swabs were collected (n = 27). A Pan-CoV nested RT-PCR was used for initial screening, followed by viral metagenomic sequencing of all fecal samples and one CoV-positive buccal swab. In silico protein docking studies were performed between a Portuguese bat CoV spike protein and APNs of bats, pigs, and humans. Pan-CoV nested RT-PCR identified three positive samples: two fecal samples and one buccal sample. Metagenomic sequencing allowed us to determine two near complete CoV genomes. Protein docking predicted strong binding of this spike protein to bat, porcine, and human APN receptors. Metagenomics also identified picornaviruses, adenovirus, and dependoparvovirus in fecal samples. This study reports the first near complete genome sequences of two members of the Alphacoronavirus genus from a Portuguese bat The identification of other viral families highlights the diverse virome of these cave-dwelling bat species. Protein docking studies suggest a potential for cross-species transmission of this bat CoV between bats, porcines and humans, though further research is needed to confirm these interactions.}, }
@article {pmid40974996, year = {2025}, author = {Liu, J and Sun, G and Zhang, H and Liu, H and Wang, X and Miao, Z}, title = {Glyphosate below no-observed-adverse-effect level exacerbates fatty liver hemorrhagic syndrome in laying hens.}, journal = {Poultry science}, volume = {104}, number = {11}, pages = {105847}, pmid = {40974996}, issn = {1525-3171}, mesh = {Animals ; Female ; *Chickens ; *Glycine/analogs &amp; derivatives/adverse effects ; *Poultry Diseases/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Glyphosate ; Random Allocation ; Animal Feed/analysis ; Diet/veterinary ; *Fatty Liver/veterinary/chemically induced ; Diet, Protein-Restricted/veterinary/adverse effects ; *Hemorrhage/veterinary/chemically induced ; *Herbicides/adverse effects ; Fecal Microbiota Transplantation/veterinary ; }, abstract = {Glyphosate (GLY) can disturb gut microbiota homeostasis through inhibiting bacterial shikimate pathway to pose a health challenge to animals and humans. But little information was reported about the influence of GLY on fatty liver hemorrhagic syndrome (FLHS) in laying hens, especially the exposure below no-observed-adverse-effect level. This study aimed to investigate the effects of GLY exposure on the progression of FLHS using a laying hen FLHS model induced by high-energy low-protein diet (HELPD). Ninety healthy Hyline brown laying hens were randomly allocated into 3 groups and subjected to the following feed for 6 weeks: Control group (fed with a basal diet), FLHS group (fed with HELPD), and FLHS + GLY group [fed with HELPD containing GLY (equal to 47 mg/kg body weight/d)]. Fresh feces were collected for microbiome and metabolome analysis, as well as fecal microbiota transplantation (FMT) experiments. The liver was collected for differentially expressed gene analysis and the colon for gut permeability determination. The results revealed that GLY exposure aggravated liver damage and lipid deposition by reshaping gut microbiota and increasing gut permeability in FLHS hens. Specifically, GLY exposure significantly elevated the relative abundance of Escherichia-Shigella, Bacteroides, Erysipelothrix, Desulfobvibrio, and Eggerthellain, while markedly decreased the relative abundance of Lactobacillus and Bifidobacterium, thus instigating the decline of certain tryptophan metabolites, including 3-hydroxyanthranilic acid, 5-hydroxyindoleacetic acid, kynurenic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, tryptamine, and indole-3-carboxylic acid in the gut, which inhibited aryl hydrocarbon receptor pathway to impair gut integrity. The impaired gut barrier led to the increase of serum LPS level, triggering inflammation and oxidative stress in the liver via activating TLR4/MyD88/NF-κB pathway and inhibiting Nrf2/Keap1 pathway. Furthermore, FMT experiments substantiated that GLY exposure aggravated FLHS in a gut microbiota-dependent manner. Collectively, these findings demonstrate that GLY exposure aggravates the progression of FLHS in laying hens through modulating the gut-liver axis. This study provides theoretical basis for assessing adverse effects of GLY exposure below no-observed-adverse-effect level on animal welfare.}, }
@article {pmid40975229, year = {2025}, author = {Zhao, Y and Wang, B and Wei, X and Liu, D and Wang, R and Xie, S and Qiao, Z and Cui, D and Hou, S and Zhang, H}, title = {Impact of gut microbiota dysbiosis on intestinal barrier integrity and systemic inflammation in a pre-eclampsia mouse model.}, journal = {Microbial pathogenesis}, volume = {209}, number = {}, pages = {108053}, doi = {10.1016/j.micpath.2025.108053}, pmid = {40975229}, issn = {1096-1208}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Pregnancy ; *Pre-Eclampsia/microbiology/pathology ; Disease Models, Animal ; Mice ; Occludin/metabolism/genetics ; Zonula Occludens-1 Protein/metabolism/genetics ; *Inflammation/microbiology/pathology ; Lipopolysaccharides/blood ; Humans ; Interleukin-6/blood ; Tumor Necrosis Factor-alpha/blood ; *Intestinal Mucosa/metabolism/microbiology/pathology ; Fecal Microbiota Transplantation ; Intestines/microbiology ; Feces/microbiology ; }, abstract = {Pre-eclampsia is characterized by systemic inflammation and endothelial dysfunction, with growing evidence suggesting a significant role for gut microbiota in its pathogenesis. This study investigated the effects of fecal microbiota transplantation from pre-eclamptic and healthy donors on intestinal barrier integrity and systemic inflammation in a mouse model. Fecal bacteria solutions from pre-eclamptic and healthy pregnant women were transplanted into pseudo-sterile mice. The expression of ZO-1 and Occludin in colon tissue was assessed using PCR, Western Blot, and immunohistochemistry. Urinary protein content, serum lipopolysaccharide (LPS), TNF-α, and IL-6 levels were measured by ELISA. Fecal microbiota transplantation from pre-eclamptic and healthy donors did not affect tissue morphology in mice but significantly compromised intestinal barrier integrity in the pre-eclampsia model group (PET). This was indicated by reduced levels of the tight junction proteins TJP1 and Occludin. The PET group also exhibited elevated urinary protein levels (4456.24 ± 1509.05 μg/ml) and increased serum levels of LPS (10.26 ± 3.91 μg/ml), TNF-α (13.34 ± 1.07 pg/ml), and IL-6 (16.48 ± 5.33 pg/ml), underscoring systemic inflammation associated with gut microbiota dysbiosis in pre-eclampsia. This study indicates that the dysregulation of the intestinal microbiota in patients with preeclampsia may disrupt the intestinal barrier function and exacerbate systemic inflammation. However, due to the limited number of donors and experimental conditions, the specific mechanism still requires further investigation.}, }
@article {pmid40976345, year = {2026}, author = {Su, SH and Chen, M and Lu, DD and Wu, YF and Huang, XS and Zhang, L}, title = {Fecal microbiota transplantation alleviates chronic cerebral hypoperfusion-induced axonal hypomyelination by regulating gut microbiota-derived metabolism and oligodendrogenesis.}, journal = {The Journal of nutritional biochemistry}, volume = {147}, number = {}, pages = {110122}, doi = {10.1016/j.jnutbio.2025.110122}, pmid = {40976345}, issn = {1873-4847}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Fecal Microbiota Transplantation ; *Oligodendroglia/metabolism ; Male ; *Axons/metabolism/pathology ; *Demyelinating Diseases/therapy/etiology ; }, abstract = {Fecal microbiota transplantation (FMT), aimed at rebuilding gut microbiota, has been proposed as a potential therapeutic approach to central nervous system (CNS) diseases. However, the therapeutic effects of FMT against demyelination-related white matter injury (WMI) have not yet been clarified under chronic cerebral hypoperfusion (CCH) condition. We therefore explored the potential roles and mechanisms of FMT on CCH-induced WMI, focusing on myelin integrity, axonal survival, and oligodendrogenesis. FMT restored mitochondrial electron transport chain (ETC) complex I-V activities and promoted the changes of pyruvate metabolism from lactate-generated to acetyl-CoA-generated mode, strengthening mitochondrial ATP production. Furthermore, FMT mitigated CCH-induced demyelination and axonal degeneration, effects mediated in part by oligodendrogenesis-dependent remyelination. Moreover, FMT altered CCH-induced gut microbiota composition by increasing the proportions of some bacterial groups including Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, Verrucomicrobiota, Akkermansia, and Akkermansia_muciniphila. These gut microbiota were strongly associated with elevated fecal levels of L-tryptophan, 5-hydroxyindoleacetic acid, and N-a-acetylcitrulline, as well as with increased hippocampal concentrations of L-arginine, L-glutamine, N2-succinyl-L-ornithine, N-acetylornithine, indolepyruvate, indoleacetaldehyde, kynurenic acid, 11, 12-EET, 11, 12-DiHETrE and prostaglandin A2, which were almost involved in tryptophan and arginine related metabolism pathways. This study highlights the beneficial effects of FMT strategy in response to demyelination-mediated WMI under chronic cerebral ischemia condition.}, }
@article {pmid40977983, year = {2025}, author = {Liu, H and Li, X and Shi, Y and Hong, K and Wang, X and Huang, C}, title = {Gut-brain axis in adolescent depression: a systematic review of psychological implications and behavioral interventions.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1644245}, pmid = {40977983}, issn = {2296-861X}, abstract = {BACKGROUND: Adolescent depression affects 13% of youths globally, with 30-40% exhibiting treatment resistance. Emerging evidence implicates gut microbiome dysbiosis in core behavioral symptoms (e.g., anhedonia, social withdrawal) via gut-brain axis (GBA) pathways. This systematic review synthesizes clinical and preclinical evidence (2014-2025) to delineate the microbiota-behavior interactions and evaluate microbiome-targeted interventions.<br><br>METHODS: Following PRISMA 2020 guidelines, 45 studies (29 clinical trials, 11 animal models, 5 meta-analyses) were analyzed from PubMed, Web of Science, and Embase. Data extraction focused on microbiome composition, neurobehavioral outcomes, and intervention efficacy. Random-effects meta-analyses pooled effect sizes (95% CIs).<br><br>RESULTS: Depressed adolescents showed reduced gut microbiota &#x3b1;-diversity (Shannon index SMD&#x202f;=&#x202f;-0.92; 95% CI: -1.24, -0.60) and altered taxa abundance (e.g., Bacteroidetes depletion: &#x394;&#x202f;=&#x202f;-32%). Dysbiosis correlated with anhedonia severity (r&#x202f;=&#x202f;0.42; 95% CI: 0.28, 0.55) and impaired social functioning. Psychobiotics (e.g., Lactobacillus plantarum PS128) significantly reduced depressive symptoms (HAM-D &#x394;&#x202f;=&#x202f;-4.2; 95% CI: -5.1, -3.3) vs. placebo and improved emotion recognition (+18%; 95% CI: 2.1, 33.9). Sex-specific effects were prominent: Bifidobacterium breve enhanced reward responsiveness in females (SMD&#x202f;=&#x202f;0.61; 95% CI: 0.22, 1.00). Current data lack large-scale RCTs for fecal microbiota transplantation (FMT) in adolescents.<br><br>CONCLUSION: Gut microbiome modulation shows promise as an adjunct to behavioral therapies (e.g., CBT). Bifidobacterium breve's female-predominant effects suggest hormonal modulation. Future research must address gaps in FMT safety, developmental mechanisms, personalized nutritional interventions.}, }
@article {pmid40978956, year = {2025}, author = {Ray, R and Hack, SA and Vij, AK and Gbenla, KI and Khatri, S and Aravind Rongali, D and Khalid, A and Anjum, A and Fancy, RS and Mirza, MSS}, title = {Efficacy of Fecal Microbiota Transplantation (FMT) Versus Standard Antibiotic Therapy in Recurrent Clostridioides difficile (CDI/rCDI) Infection: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90614}, pmid = {40978956}, issn = {2168-8184}, abstract = {Repeated Clostridioides difficile infection (rCDI) is a hard clinical problem because normal antibiotic treatment usually doesn't stop relapses. Fecal microbiota transplantation (FMT) has come up as another way to try to fix the gut's microbial balance. This review and study looked at how well FMT works and how safe it is compared to normal antibiotic treatment for rCDI. We searched PubMed, Embase, and the Cochrane Library up to December 2023 to find trials and studies. We used a model to calculate risk ratios, and we also looked at subgroups based on how FMT was given and the patient's age. After checking fifteen studies with 1,452 patients, we found that FMT worked better than antibiotics [relative risk (RR) = 1.85, 95% confidence interval (CI): 1.62-2.11, p < 0.001], with recurrence rates of 16% versus 42%. Subgroup checks showed that FMT worked well no matter how it was given, whether by colonoscopy, tube, or capsules. Side effects were usually small and about the same for both FMT and antibiotics. In conclusion, FMT is safer and does a better job than normal antibiotics for rCDI and should be thought of as the main treatment after the first time the infection comes back.}, }
@article {pmid40983096, year = {2026}, author = {Yang, W and Zhang, Y and Xu, Y and Diao, J and Zheng, S and Yuan, C}, title = {Gut Microbial Metabolite Butyrate Regulates Treg/Th17 Cell Balance to Alleviate Diabetic Periodontitis.}, journal = {Journal of clinical periodontology}, volume = {53}, number = {2}, pages = {321-333}, doi = {10.1111/jcpe.70041}, pmid = {40983096}, issn = {1600-051X}, support = {2022YFE0118300//National Key Research and Development Program of China/ ; 2022YFA1206101//National Key Research and Development Program of China/ ; PKUSS-2024CRFG04//The Peking University School and Hospital of Stomatology Series of Clinical Research Projects/ ; }, mesh = {Animals ; *T-Lymphocytes, Regulatory/immunology/drug effects ; *Gastrointestinal Microbiome/physiology ; *Periodontitis/immunology/microbiology/therapy ; Mice ; *Th17 Cells/immunology ; *Butyrates/metabolism/pharmacology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; *Diabetes Mellitus, Experimental/complications ; Dysbiosis ; Disease Models, Animal ; Male ; Feces/microbiology/chemistry ; Alveolar Bone Loss ; }, abstract = {AIM: To investigate whether the gut microbiota-derived metabolite butyrate alleviates the progression of diabetic periodontitis by modulating the Treg/Th17 cell balance.<br><br>MATERIALS AND METHODS: A diabetic periodontitis mouse model was established to assess alveolar bone loss, Treg/Th17 cell subsets, colonic histopathology, faecal microbiota composition and short-chain fatty acid (SCFA) levels. To investigate microbial causality and therapeutic potential, faecal microbiota transplantation (FMT) and butyrate supplementation were conducted.<br><br>RESULTS: Mice with diabetic periodontitis exhibited a disrupted Treg/Th17 balance accompanied by colonic epithelial damage and a decreased abundance of SCFA-producing gut microbiota. Faecal SCFA levels showed a downward trend, although the reduction in butyrate was not significant. FMT from diabetic periodontitis mice aggravated periodontal destruction, impaired the colonic mucus barrier and further disturbed Treg/Th17 homeostasis in the recipient mice. These effects were associated with a decrease in SCFA-producing bacteria and faecal butyrate levels. Moreover, butyrate supplementation significantly alleviated periodontal destruction and restored the Treg/Th17 balance.<br><br>CONCLUSION: Gut microbiota dysbiosis contributes to diabetic periodontitis progression through disruption of the Treg/Th17 balance, whereas butyrate, as an immunomodulatory SCFA, may alleviate periodontal tissue destruction by restoring this balance.}, }
@article {pmid40983156, year = {2025}, author = {Goldsmith, J and Nguyen, D and Delgado-Aros, S}, title = {Response to "Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores Compared to Fecal Microbiota Transplant".}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.09.017}, pmid = {40983156}, issn = {1542-7714}, }
@article {pmid40984900, year = {2025}, author = {Weerakoon, S and Avula, S and Mandefro, BT and Sundara, SV and Lu, X and Busmail, H and Malasevskaia, IA}, title = {Microbiota-Based Therapies for Recurrent Clostridium difficile Infection: A Systematic Review of Their Efficacy and Safety.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90737}, pmid = {40984900}, issn = {2168-8184}, abstract = {Recurrent Clostridium difficile infection (RCDI) remains a significant clinical challenge, with high recurrence rates following standard antibiotic therapy. Emerging evidence supports the role of fecal microbiota transplant (FMT) and standardized microbiome therapeutics (e.g., SER-109, RBX2660) in gut microbiota restoration and recurrence prevention. This systematic review evaluates the effectiveness and safety of these approaches in comparison to traditional therapies. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched the databases PubMed/MEDLINE, ScienceDirect, Cochrane Library, Europe PubMed Central (Europe PMC), ClinicalTrials.gov, Google Scholar, and Elicit AI for studies published between January 2015 and May 2025. Eligible studies included randomized controlled trials (RCTs), observational studies, and case series assessing FMT in adults with rCDI. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (RoB 2) for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies. Seven studies (six RCTs, one cohort; N=1,030 patients) were included. FMT demonstrated superior efficacy compared to antibiotics/placebo, with clinical cure rates ranging from 70% to 91% (versus 23% to 62%). Donor FMT outperformed autologous FMT (90.9% vs. 62.5%, p = 0.042) and standard therapies (71% resolution vs. 33% fidaxomicin/19% vancomycin, p < 0.01). Microbiota-based therapies (SER-109, RBX2660) demonstrated comparable efficacy (RRR up to 68%). Safety profiles were favorable, with predominantly mild gastrointestinal events and no increased risk detected for the specific outcomes measured over a five-year follow-up period. Heterogeneity existed in administration routes (colonoscopy/capsules) and donor material (fresh/frozen). FMT and standardized microbiome therapies are highly effective for treating rCDI, demonstrating robust short-term efficacy and favorable long-term safety. Donor-derived interventions and pharmaceutical-grade products (SER-109, RBX2660) represent promising alternatives to traditional antibiotics, particularly in recurrent or refractory cases. Future research should aim to standardize protocols and include more high-risk populations.}, }
@article {pmid40986483, year = {2026}, author = {Quigley, EMM}, title = {Gut power for better health: microbial therapeutics.}, journal = {Current opinion in gastroenterology}, volume = {42}, number = {1}, pages = {14-18}, doi = {10.1097/MOG.0000000000001136}, pmid = {40986483}, issn = {1531-7056}, mesh = {Humans ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; Prebiotics ; *Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {PURPOSE OF REVIEW: To critically evaluate the literature over the past year on microbial therapeutics in the management of disorders of the large intestine. The primary focus is on disorders where the microbiome has been implicated in pathophysiology, and its modulation has been a therapeutic target.<br><br>RECENT FINDINGS: Though widely consumed, data on the impact of probiotics and prebiotics in gastrointestinal disorders continue to pose challenges in interpretation due to shortcomings in study design; postbiotics, meanwhile, because of some logistical and regulatory advantages, are attracting attention. Though time-honored for its role in infections due to Clostridioides difficile (CDI), FMT has encountered challenges in relation to regulation leading to the appearance of highly standardized, extensively screened and rigorously prepared microbial products [defined as live biotherapeutic products (LBP)], which show great promise; two have been approved by the FDA for prevention of recurrent CDI. Outside of CDI, efforts to define a role for FMT in the management of various diseases have met with mixed results.<br><br>SUMMARY: The translation of findings in studies of microbiome composition to successful therapies has proven disappointing to date, though attempts to develop selective and targeted microbial consortia show promise and may lead the way to personalized bacteriotherapy.}, }
@article {pmid40988801, year = {2025}, author = {Ueno, S and Suzuki, T and Suzuki, M and Marubashi, S and Iseki, K}, title = {Effective Resolution of Postoperative Stoma Edema With Repeated Application of Topical 50% Glucose: A Case Report.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90800}, pmid = {40988801}, issn = {2168-8184}, abstract = {Although glucose-induced osmotic gradients have been used to reduce intestinal edema, no standardized technique has been established. Repeated applications of this method have not been documented, and concerns remain regarding its potential effects on glycemic control. We present a case of a patient in his 20s admitted for treatment of an advanced pressure ulcer over the left greater trochanter. His medical history included spina bifida and type 2 diabetes mellitus. The ulcer was complicated by osteonecrosis of the left femur, and a left hip disarticulation was planned as a life-saving procedure. Before this procedure, a sigmoid colostomy was performed to divert the fecal stream. On postoperative day six following colostomy, the hip disarticulation was performed, and the patient's general condition gradually improved. However, persistent stoma edema was observed 12 days after surgery. Congestive discoloration of the stoma mucosa developed, and complications such as stomal outlet obstruction and abdominal distension were suspected. To address this complication, 20 mL of 50% glucose solution was applied topically to the intestinal mucosa eight times over five days. Following this treatment, a marked reduction in stomatal edema was observed. Notably, the procedure used in our case did not adversely affect perioperative glycemic control, suggesting its feasibility as a minimally invasive approach for managing acute-phase stoma edema.}, }
@article {pmid40990446, year = {2025}, author = {Xu, J and Li, J and Guo, X and Huang, C and Peng, Y and Xu, H and Li, Y and Xu, J and Hu, J and Liao, Y and Nie, Y and Zhou, Y}, title = {Secondary Bile Acids Modified by Odoribacter Splanchnicus Alleviate Colitis by Suppressing Neutrophil Extracellular Trap Formation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {46}, pages = {e09073}, pmid = {40990446}, issn = {2198-3844}, support = {82370552//National Natural Science Foundation of China/ ; 82470579//National Natural Science Foundation of China/ ; 2023A1515030214//Natural Science Foundation of Guangdong Province/ ; 2022-2023//Guangzhou Key Laboratory of Digestive Diseases/ ; KY17010003//Guangzhou Key Laboratory of Digestive Diseases/ ; }, mesh = {Animals ; Mice ; *Extracellular Traps/metabolism ; *Gastrointestinal Microbiome/physiology ; *Colitis/metabolism/microbiology ; *Bile Acids and Salts/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Humans ; Male ; Neutrophils/metabolism ; Fecal Microbiota Transplantation ; Inflammatory Bowel Diseases/metabolism/microbiology ; }, abstract = {The gut microbiota contributes to inflammatory bowel disease (IBD) pathogenesis, yet the functional impact of specific bacterial species remains unclear. Here, Odoribacter splanchnicus (O. splanchnicus) is indentified as a taxon depleted in human IBD cohorts and demonstrated its protective effects in acute and chronic murine colitis models. In mice, O. splanchnicus administration alleviated colonic inflammation and preserved barrier integrity, accompanied by a restructured mucosal immune landscape and reduced neutrophil extracellular traps (NETs) formation. This inhibitory effect on NETs is lost in Pad4[-/-] mice, highlighting its dependence on NETs formation machinery. Metabolomic profiling showed that O. splanchnicus treatment elevated the secondary bile acid lithocholic acid (LCA). This increase is lost following antibiotic cocktail treatment and restored by fecal microbiota transplantation from O. splanchnicus-treated donors, demonstrating a requirement for an intact gut microbiota. Mechanistically, LCA supplementation recapitulated the anti-NETs formation phenotype and suppressed colonic inflamation by inhibiting the NLRP3-GSDMD signaling pathway. Together, these findings define a gut microbiota-metabolite-neutrophil axis in IBD pathogenesis, highlighting the microbiota-dependent regulation of LCA as a key protective mechanism of O. splanchnicus.}, }
@article {pmid40990473, year = {2025}, author = {Liu, X and Liu, C and Qian, X and Zhang, S and Yao, Z and Chai, Y and Shi, Q and Yang, W and Wang, Q and Zhang, L and Zeng, X and Liu, C and Wu, Y and Sun, Q}, title = {Fecal microbiota transplantation alleviated heat-induced colonic tissue damage, epithelial apoptosis, and oxidative stress.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {10}, pages = {e0097625}, pmid = {40990473}, issn = {1098-5336}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Apoptosis ; Mice ; Mice, Inbred C57BL ; *Oxidative Stress ; *Gastrointestinal Microbiome ; *Colon/pathology/injuries ; *Hot Temperature/adverse effects ; Male ; }, abstract = {UNLABELLED: Exposure to high ambient temperatures can cause significant damage to the gastrointestinal tract; however, the therapeutic potential of fecal microbiota transplantation (FMT) in this context remains largely unexplored. We investigated whether FMT could alleviate heat-induced colonic injury in C57BL/6J mice. Mice were randomly divided into four groups: normal control (22°C only), normal-FMT (NF, 22 °C+ FMT), heat exposure (HE, 39°C only), and HE-FMT (HF, 39°C + FMT). The HE and HF groups were exposed to 39°C for 2 hours daily over 15 consecutive days. FMT (100 µL/day) was administered by oral gavage to the NF and HF groups for 15 days, starting after the first HE. Our results showed that FMT significantly modulated gut microbiota composition, increasing the relative abundance of Alistipes, Citrobacter, Parasutterella, Bifidobacterium, Lachnospiraceae_UCG-001, Raoultella, Woeseia, Prevotellaceae_UCG-001, and Christensenellaceae, while decreasing Clostridium_sensu_stricto_1, Eubacterium_xylanophilum_group, Clostridioides, Bilophila, GCA-900066575, and Peptococcus. Notably, FMT markedly restored epithelial integrity and enhanced mucus production, as shown by hematoxylin-eosin and periodic acid-Schiff staining. Moreover, FMT attenuated heat-induced epithelial cell apoptosis, evidenced by reduced apoptotic cells and downregulation of mitochondrial apoptotic markers, including Bax, Bak, cleaved Caspase-3, cleaved Caspase-9, and the phospho-P53/P53 ratio. In addition, FMT mitigated oxidative stress induced by HE, indicated by decreased 3-nitrotyrosine levels and normalization of antioxidant-related proteins, such as Nrf2, Sod1, Cat, and Gpx4. Collectively, these findings demonstrate that FMT alleviates heat-induced colonic injury by restoring mucosal barrier integrity, inhibiting apoptosis, and reducing oxidative stress, highlighting its potential as a promising therapeutic strategy for heat-related gastrointestinal disorders.<br><br>IMPORTANCE: This study is the first to demonstrate the protective role of fecal microbiota transplantation (FMT) against heat-induced colonic injury in a mouse model. We show that FMT mitigates colonic damage by restoring gut microbiota balance, preserving mucosal barrier integrity, inhibiting epithelial cell apoptosis, and reducing oxidative stress. These findings underscore the essential role of the gut microbiota in maintaining intestinal homeostasis under heat stress and highlight the therapeutic potential of microbiota-targeted strategies, such as FMT, in preventing or treating heat-related intestinal injury.}, }
@article {pmid40990659, year = {2026}, author = {Yan, ZB and Han, CL and Jia, JS and Li, H and Lu, DH and Cao, QH and Wang, YX and Jiao, KF and He, Q and Peng, SX and Zhang, DL and Wang, Q and Li, T}, title = {The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.}, journal = {International journal of surgery (London, England)}, volume = {112}, number = {1}, pages = {1673-1695}, pmid = {40990659}, issn = {1743-9159}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Neoplasms/therapy/microbiology/etiology ; *Carcinoma, Hepatocellular/therapy/microbiology/etiology ; *Dysbiosis/complications/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Carcinogenesis ; }, abstract = {Primary liver cancer (PLC) represents a significant global health burden, with hepatocellular carcinoma (HCC) being its predominant subtype. The gut microbiota plays a crucial role in the pathogenesis, treatment, and postoperative recovery of HCC through its regulatory functions along the gut-liver axis. This review systematically elucidates the role of gut microbiota dysbiosis and associated metabolites in the pathogenesis of HCC, specifically addressing the underlying mechanisms whereby gut microbiota and their metabolites mediate hepatic metabolic reprogramming, remodel the immune microenvironment, and promote HCC progression through crosstalk with intratumoral bacteria. It further explores the impact of the gut microbiota on immunotherapy, molecular targeted therapy, conventional chemotherapy, and surgical outcomes. Additionally, the review comprehensively outlines therapeutic strategies targeting the gut microbiota, including oral probiotics, antibiotics, fecal microbiota transplantation (FMT), particular small molecules, and traditional Chinese medicine. In summary, this review provides a comprehensive overview of how the gut microbiota influences the development and treatment of HCC and offers a theoretical foundation for targeting the microbiota to improve surgical prognosis in HCC patients.}, }
@article {pmid40991236, year = {2025}, author = {Dobrila, HA and Hryckowian, AJ}, title = {The emerging view on the roles of butyrate in Clostridioides difficile pathogenesis.}, journal = {Infection and immunity}, volume = {93}, number = {10}, pages = {e0004725}, pmid = {40991236}, issn = {1098-5522}, support = {DGE-2137424//National Science Foundation/ ; N/A//Judy L. and Sal A. Troia Professorship in Gastrointestinal Disease Research/ ; }, mesh = {*Clostridioides difficile/pathogenicity/physiology/metabolism ; Humans ; *Clostridium Infections/microbiology/metabolism ; *Butyrates/metabolism ; Gastrointestinal Microbiome ; Animals ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The Centers for Disease Control and Prevention classifies Clostridioides difficile as an urgent threat to the nation's health, as it causes 450,000 infections, 15,000 deaths, and 1 billion dollars in excess healthcare costs per year in the United States. Current treatments for C. difficile infections (CDIs) are antibiotics and, in recurrent cases, microbiome restoration therapy (MRT). Antibiotics contribute to antibiotic resistance and recurrent CDIs. Although MRTs (e.g., defined consortia of microbes or fecal transplant) are increasingly accessible, the long-term sustainability and accessibility of these treatments remain to be determined. These limitations highlight the need for more precise strategies for coping with CDI. Because a disrupted (dysbiotic) gut microbiome is the primary risk factor for CDI, a better understanding of the interactions between C. difficile, the microbiome, and the host will aid the development of such treatments. Butyrate is a prominent microbiome-host co-metabolite that is influenced by host dietary fiber intake and differentiates healthy from dysbiotic gut ecosystems. Emerging evidence supports that butyrate is a key determinant of C. difficile fitness and pathogenesis. Here, we review the current literature and gaps in knowledge about how butyrate-rich gut environments exclude C. difficile, and how butyrate impacts C. difficile growth, metabolism, toxin production/release, and sporulation. We further discuss the implications of continued study of butyrate's impacts on CDI, including the eventual development of new strategies to mitigate CDI in at-risk human populations.}, }
@article {pmid40992605, year = {2026}, author = {Goetzl, EJ}, title = {Microbiomes in health, diseases and therapeutics.}, journal = {The American journal of medicine}, volume = {139}, number = {2}, pages = {145-149}, doi = {10.1016/j.amjmed.2025.09.002}, pmid = {40992605}, issn = {1555-7162}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; }, abstract = {A microbiome is the aggregate of populations of bacteria, viruses and fungi in an organ system, of which the highly dominant numbers are in the gastrointestinal tract. Some of the bacteria, termed microbiota, support viability and functions of host cells directly by generating beneficial short-chain fatty acid components of dietary fibers and other metabolites of host compounds including secondary bile acids and indole derivatives of tryptophan. Short-chain fatty acids also recruit immune protective elements exemplified by IL-22, which has beneficial effects on intestinal epithelium by their IL-22 receptors. Other bacteria have detrimental effects on host cells through lipopolysaccharides and diverse toxins. An increased ratio of detrimental to beneficial microbiomal bacteria, a state termed dysbiosis, is observed in human diseases of many systems. Therapies for dysbiosis involve largely dietary manipulation and more recently fecal microbiota transplantation. Resistant and recurrent Clostridium difficile diarrhea responds dramatically to fecal microbiota transplantation, but this approach requires additional evaluation in other diseases. The potential prognostic value of microbiome characteristics suggests future uses in precision medicine.}, }
@article {pmid40993162, year = {2025}, author = {Yang, R and Xu, Y and Xu, J and Huang, C and Zhu, F and Wang, T and Kong, R and Xiao, J and He, B and Gu, X and Wang, HL}, title = {Lacticaseibacillus rhamnosus GR-1 prevents autism-like behaviors by reshaping the maternal and offspring microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {187}, pmid = {40993162}, issn = {2055-5008}, support = {JZ2020HGTB0053//Fundamental Research Funds for the Central Universities/ ; 201904e01020001//Anhui Provincial Key Research and Development Plan/ ; 81673624//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Female ; Mice ; Pregnancy ; *Probiotics/administration &amp; dosage ; Male ; *Lacticaseibacillus rhamnosus/physiology ; Gastrointestinal Microbiome ; Disease Models, Animal ; Behavior, Animal ; Fecal Microbiota Transplantation ; Vagina/microbiology ; *Autism Spectrum Disorder/prevention &amp; control/microbiology ; *Autistic Disorder/prevention &amp; control/microbiology ; Mice, Inbred C57BL ; *Microbiota ; Feces/microbiology ; }, abstract = {As a prevalent neurodevelopmental disease, whether ASD (autism spectrum disorder) can be ameliorated by the early use of a single microbe remains unknown. Here we used a lactobacillus strain, Lacticaseibacillus rhamnosus GR-1 (LGR-1), for prenatal intervention in autism-like mice with either environmental or idiopathic origins by exclusively administering to the pregnant dams at a dose of 10[9]/mouse/day, followed by offspring behavioral assessment with 3-chamber trial and marble burying test. The results revealed that LGR-1 prevented the occurrence of autism-like symptoms, as evidenced by the improved behaviors and restored E/I (excitatory-inhibitory) balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, probably mediated by the vertical transmission of maternal microbiome, with its roles further unraveled by fecal microbiota transplant and cross-fostering experiments. In addition to gut commensals, the LGR-1-shaping vaginal microbiota also contributed to the establishment of "beneficial" microbiome. Regarding key taxa in offspring, Akkermansia muciniphila was influenced by LGR-1 and exerted impact on behaviors via pathways related to IL-17-producing lymphocytes. Our findings demonstrate that prenatal microbial administration protects offspring against autism-like behavioral phenotypes through microbiome transmission, highlighting a potential microbe-based therapeutic avenue to mitigate ASD risk.}, }
@article {pmid40993485, year = {2026}, author = {El-Mansoury, B and Esselmani, H and Merzouki, M and Devaraj, E and Hiba, OE and Ortega, A and Najimi, M}, title = {Current advances in the management of hepatic encephalopathy: an updated and critical review.}, journal = {Pharmacological reports : PR}, volume = {78}, number = {1}, pages = {173-193}, pmid = {40993485}, issn = {2299-5684}, mesh = {*Hepatic Encephalopathy/therapy/physiopathology ; Humans ; Animals ; Oxidative Stress/drug effects ; Ammonia/metabolism ; Liver Transplantation/methods ; Probiotics/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is a serious and potentially reversible neuropsychiatric syndrome resulting from severe liver insufficiency. HE is primarily considered a gliopathy in which astrocyte dysfunction is the main neuropathological hallmark, while recently microglia and neuronal alterations have been reported. It is believed that reversible factors trigger more than 80% of the cases. Several causative factors, including ammonia, inflammation, neuroinflammation, and oxidative stress, contribute to its pathogenesis, ultimately leading to abnormalities in neurotransmission and altered neuronal integrity. Current treatment strategies for managing HE include the primary use of rifaximin and lactulose, along with other pharmacological therapies that aim to reduce inflammation, neuroinflammation, and oxidative stress. However, liver transplantation remains the definitive curative treatment for end-stage liver diseases and associated encephalopathy. Recently, probiotics and fecal microbiota transplantation, as well as cell-based therapies, have shown promising results in both experimental studies and clinical trials. This review article highlights advances in understanding the complex pathophysiology of HE and assesses recent treatment strategies that aim to promote liver regeneration, target ammonia toxicity, and modulate immune responses.}, }
@article {pmid40994135, year = {2025}, author = {Li, S and Li, Z and Tuo, Y and Mu, G and Jiang, S}, title = {Mechanisms of Casein-Derived Immunomodulatory Peptides Maintaining Immune Homeostasis via Regulating Gut Microbiota in a Cyclophosphamide-Induced Mouse Model.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {40}, pages = {25394-25412}, doi = {10.1021/acs.jafc.5c07986}, pmid = {40994135}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Cyclophosphamide/adverse effects ; Mice ; *Caseins/chemistry/administration &amp; dosage ; *Peptides/administration &amp; dosage/chemistry/immunology ; Humans ; Male ; Homeostasis/drug effects ; Disease Models, Animal ; *Immunologic Factors/administration &amp; dosage/chemistry ; Intestinal Mucosa/immunology/drug effects/microbiology ; Bacteria/isolation &amp; purification/genetics/classification/drug effects ; }, abstract = {Two immunomodulatory signature peptides (PFPEVFG and SPAQILQW) were obtained from casein hydrolysates produced by Kluyveromyces marxianus JY-1 in our previous studies with the aid of virtual screening. However, their mechanisms for improving the composition of the gut microbiota in immunosuppressed mice remain unknown. The aim of this study was to reveal the mechanisms of immunomodulation and improvement of gut microbiota composition mediated by the casein peptides PFPEVFG and SPAQILQW through a cyclophosphamide (Cy)-induced immunosuppression and intestinal mucosal injury mouse model. The casein peptides PFPEVFG and SPAQILQW reversed Cy-induced intestinal structural damage and could correct for Cy-induced intestinal flora disorders. Importantly, fecal microbiota transplantation (FMT) confirmed that the casein peptides PFPEVFG and SPAQILQW attenuate immunosuppression by targeting participation in the dynamic balance of the gut microbiota. These results indicated that the casein peptides PFPEVFG and SPAQILQW have the potential to be used as natural medicines for the treatment of immunosuppression.}, }
@article {pmid40996271, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {mBio}, volume = {16}, number = {11}, pages = {e0190425}, pmid = {40996271}, issn = {2150-7511}, support = {UM1 CA186644/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Humans ; Feces/microbiology ; *Microbial Consortia ; Metagenomics ; Bacteroides ; Female ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; Bacteria/classification/genetics/isolation &amp; purification ; Akkermansia ; }, abstract = {Composition and function of the gut microbiome are associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models in recapitulating ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure, and their ecological features were compared to human donors by metagenomic sequencing. HMA mice resembled other mice more than their respective human donors in gut microbial composition and function, with taxa including Akkermansia muciniphila and Bacteroides spp. enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse data sets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice was more like other mice than their human donor. Our data suggest that HMA mice are limited models for assessing the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overshadow ecological effects of treatments in humans that HMA models aim to recapitulate.IMPORTANCEHMA mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effects of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, Microbial Ecosystem Therapeutic 4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbor a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.}, }
@article {pmid40996680, year = {2025}, author = {Luo, YM and Dong, L and Li, YL and Lin, M and Xie, DY and Gao, JM and Zhang, YD and Zhu, YZ and Gong, QH}, title = {Icariside II Ameliorates Depression Induced by High-Fat Diet via the Microbiota-Gut-Brain Axis in Mice.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {11}, pages = {5159-5173}, doi = {10.1002/ptr.70103}, pmid = {40996680}, issn = {1099-1573}, support = {ZYSE-2022-02//Future techelite talent development program from Zunyi Medical University/ ; 82160756//Natural Science Foundation of China/ ; GCC[2023]042//hundred level of high-level innovative talents in Guizhou Province/ ; Zunshi Kehe HZ Zi (2023) 170. Qianke Platform Talent [2021] 1350-006//Zunyi Science and Technology and Big Data Bureau, Zunyi Medical University 2023 Science and Technology Joint Fund Project/ ; }, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Depression/drug therapy/etiology ; Male ; *Flavonoids/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Obesity/complications/drug therapy ; Brain/drug effects ; Blood-Brain Barrier/drug effects ; Fatty Acids, Volatile/metabolism/analysis ; Fecal Microbiota Transplantation ; }, abstract = {Obesity can lead to depression via the microbiota-gut-brain axis. Icariside II (ICS II), a flavonoid compound derived from the traditional Chinese medicine Herbal Epimedium, exerts excellent neuroprotective effects. However, the pharmacological effects and underlying mechanisms of ICS II in obesity-induced depression remain unexplored. The present study aims to investigate whether ICS II can mitigate depression induced by a high-fat diet (HFD) in mice through modulating the microbiota-gut-brain axis. Metabolic parameters were reflected through changes in body weight and blood lipids, while depressive phenotypes were evaluated through behavioral tests and neurotransmitter analysis. The microbiota composition was analyzed by 16S ribosomal RNA gene sequencing, and short chain fatty acids (SCFAs) were detected by liquid chromatography-tandem mass spectrometry. The gut barrier and brain blood barrier (BBB) functions were observed by pathological methods. Fecal microbiota transplantation was used to demonstrate the causality of microbiota-mediated effects. The results showed that ICS II alleviated obesity status and depressive-like behaviors. ICS II reshaped gut microbiota and increased SCFAs. Meanwhile, ICS II relieved gut barrier impairment and systemic inflammation. In the brain, ICS II alleviated neuroinflammation and BBB injury. Intriguingly, fecal microbiota from ICS II-treated HFD mice improved depressive-like behaviors, intestinal barrier dysfunction, and BBB damage compared with those receiving microbiota from HFD mice. Our findings reveal for the first time that ICS II improves the obesity-related metabolic dysregulation and alleviates HFD-induced depression via the microbiota-gut-brain axis. Overall, this study indicates that ICS II is a potential candidate compound for treating obesity-related mental diseases.}, }
@article {pmid40997843, year = {2025}, author = {Kao, D and Wong, K and Lee, C and Steiner, T and Franz, R and McDougall, C and Silva, M and Schmidt, TSB and Walter, J and Loebenberg, R and Monaghan, TM and Giebelhaus, RT and Harynuk, JJ and Xu, H and Yaskina, M and MacDonald, KV and Marshall, DA and Louie, T}, title = {Effects of lyophilised faecal filtrate compared with lyophilised donor stool on Clostridioides difficile recurrence: a multicentre, randomised, double-blinded, non-inferiority trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {10}, number = {11}, pages = {986-997}, doi = {10.1016/S2468-1253(25)00190-6}, pmid = {40997843}, issn = {2468-1253}, mesh = {Humans ; Female ; Male ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Middle Aged ; *Clostridium Infections/therapy/prevention &amp; control ; Aged ; Recurrence ; *Clostridioides difficile ; *Feces/microbiology ; Freeze Drying ; Canada ; Treatment Outcome ; Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection. However, it is not known whether live microbes are necessary in mediating FMT efficacy. This study aims to determine whether lyophilised sterile faecal filtrate (LSFF), free of live bacteria, is non-inferior to lyophilised donor stool (LFMT) in efficacy.<br><br>METHODS: This multicentre, randomised, double-blinded, non-inferiority trial was done at four academic centres in Canada. Eligible patients were adults aged 18 years or older with recurrent C difficile infection (at least two recurrences). Eligible patients were randomly assigned (1:1 using a prespecified computer-generated randomisation list with permutation blocks of 2 and 4, stratified by age >65 years or <65 years) to receive oral LSFF or LFMT. Each treatment dose consisted of 15 capsules that appeared identical. Participants and investigators were masked to treatment allocation. The primary outcome was the proportion of participants without recurrent C difficile infection (absence of more than three Bristol type 6 or 7 bowel movements per 24 h persisting more than 2 consecutive days) at 8 weeks. Analysis was done in the per protocol population, in which participants with unknown outcome status at 8 weeks due to death or loss to follow-up were excluded. Non-inferiority was established if the lower bound of the one-sided 95% CI for the difference in proportions of participants without recurrent C difficile between the LSFF and LFMT groups was above the non-inferiority margin of -10%. This trial was registered at ClinicalTrials.gov, NCT03806803, and is complete.<br><br>FINDINGS: Between March 27, 2019, and Nov 6, 2023, we assessed 409 patients for eligibility. 271 were excluded and the remaining 138 were enrolled and randomly assigned to receive LSFF (n=72) or LFMT (n=66). Participants' mean age was 61&#xb7;2 years (SD 18&#xb7;6); 91 (66%) of 138 patients were women and 47 (34%) were male. 127 participants (92%) were White. 130 (94%) of 138 participants completed the trial. At the planned interim analysis, 47 (65%) of 72 participants in the LSFF group and 57 (88%) of 65 participants in the LFMT group did not have C difficile recurrence at 8 weeks (difference -23%, one-sided 95% CI -33&#xb7;8% to infinity; p=0&#xb7;96). Given the pre-specified non-inferiority margin of -10%, non-inferiority of LSFF to LFMT could not be established and the study was terminated at the recommendation of the data safety monitoring board. Serious adverse events included one death (LFMT group) and five hospitalisations (four unrelated, one possibly related to interventions [LSFF group]). One event occurred before treatment and all others 2-20 weeks after study intervention. The most common adverse events were abdominal discomfort (48 [67%] of 72 patients in the LSFF group and 36 (55%) of 66 patients in the LFMT group) and nausea (13 [18%] in the LSFF group and 21 [32%] in LFMT group).<br><br>INTERPRETATION: Among adults with recurrent C difficile infection, non-inferiority of LSFF to LFMT was not established for the prevention of recurrent C difficile infection over 8 weeks, supporting the crucial role of live microbes in mediating clinical efficacy.<br><br>FUNDING: Canadian Institutes of Health Research; University of Alberta Hospital Foundation; Alberta Health Services; Weston Foundation.}, }
@article {pmid40997947, year = {2025}, author = {Bonilla-Moreno, M and Medina-Gómez, C and Guevara-Núñez, D and Saiz-Escobedo, L and Martí, S and Domínguez, M&#xc1; and Carrera-Salinas, A and Rodríguez-Sevilla, G}, title = {Assessing healthcare workers as potential stool donors for faecal microbiota transplantation: a cross-sectional study of antimicrobial-resistant gut bacteria and enteropathogenic micro-organisms.}, journal = {The Journal of hospital infection}, volume = {165}, number = {}, pages = {153-162}, doi = {10.1016/j.jhin.2025.09.004}, pmid = {40997947}, issn = {1532-2939}, mesh = {Humans ; Cross-Sectional Studies ; *Feces/microbiology/parasitology ; *Health Personnel/statistics &amp; numerical data ; Male ; Female ; Adult ; Middle Aged ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Bacteria/drug effects/isolation &amp; purification/classification ; Prevalence ; *Tissue Donors ; Young Adult ; Drug Resistance, Bacterial ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a procedure designed to modulate the gut microbiome, but identifying reliable stool donors remains challenging.<br><br>AIM: This study was conducted at Bellvitge University Hospital to assess the prevalence of enteropathogenic micro-organisms (EPs) and antimicrobial-resistant (AMR) gut bacteria among healthcare workers (HCWs) and evaluate their potential as stool donors.<br><br>METHODS: From November 2022 to April 2023, 106 HCWs were enrolled. Stool samples were tested for a range of EPs using real-time PCR and conventional methods, while AMR gut bacteria were screened using selective culture media. 16SrRNA sequencing was performed, and alpha-diversity was assessed using the Shannon index.<br><br>FINDINGS: EPs were found in 48.1% of samples (51/106), with protozoa being the most prevalent (37.7%, 40/106), followed by bacteria (10.4%, 11/106) and viruses (4.7%, 5/106). Blastocystis hominis (33%, 35/106) and Dientamoeba fragilis (18.8%, 20/106) were the most common protozoa, while enteropathogenic Escherichia coli was the most frequent bacterial pathogen (3.8%, 4/106). Extended-spectrum &#x3b2;-lactamase-producing E. coli was found in 2.8% of samples (3/106). Carbapenemase-producing bacteria, vancomycin-resistant enterococci, meticillin-resistant Staphylococcus aureus or Clostridioides difficile were not present in any sample. HCWs with B. hominis had significantly higher Shannon alpha-diversity than those without (P<0.01).<br><br>CONCLUSION: The prevalence of EPs and AMR gut bacteria among HCWs supports the inclusion of HCWs as potential stool donors for FMT, provided they meet health and screening criteria. This approach could help address the shortage of suitable stool donors for FMT programmes.}, }
@article {pmid40998619, year = {2025}, author = {Metri, AA and Faghih, M and Thompson, E and Noë, M and Mannan, R and Kalyani, R and Gunzelman, E and Afghani, E and Cheesman, L and Akshintala, VS and Gurakar, M and Yousefli, Z and Warren, D and Desai, NM and Sun, Z and Walsh, C and Makary, MA and Hruban, RH and He, J and Zaheer, A and Singh, VK}, title = {Clinical predictors of pancreatic fibrosis in patients with recurrent acute and chronic pancreatitis.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {25}, number = {7}, pages = {1055-1061}, doi = {10.1016/j.pan.2025.09.021}, pmid = {40998619}, issn = {1424-3911}, mesh = {Humans ; Female ; Male ; Adult ; Fibrosis ; Middle Aged ; *Pancreatitis, Chronic/pathology/surgery ; *Pancreas/pathology ; Recurrence ; *Pancreatitis/pathology/surgery ; Acute Disease ; Pancreatectomy ; Retrospective Studies ; Islets of Langerhans Transplantation ; Young Adult ; }, abstract = {OBJECTIVES: Fibrosis is considered the criterion standard for diagnosing chronic pancreatitis (CP) but adequate tissue specimens are difficult to obtain, carry risk and are often obtained at the time of surgery in advanced stages of CP. Noninvasive biomarkers that correlate with fibrosis across the continuum of pancreatitis are needed. Our aim was to determine which clinical variables are associated with fibrosis in patients with recurrent acute pancreatitis (RAP) or CP undergoing total pancreatectomy with islet autotransplantation (TPIAT).<br><br>METHODS: The demographic, clinical and radiologic data for patients undergoing TPIAT for RAP or CP between 2011 and 2023 were reviewed. Excisional biopsies from the proximal and distal pancreas were each scored from 0 to 6 for both perilobular and intralobular fibrosis, and the score of each biopsy was the sum of perilobular and intralobular fibrosis (0-12). The fibrosis score (FS), ranging from 0 to 12, was the mean FS from the proximal and distal pancreas.<br><br>RESULTS: There were 88 patients with a mean age 38 &#xb1; 14 years and 46 (52.3 %) were female. There were 35 (39.8 %) and 53 (60.2 %) with RAP and CP, respectively. Genetic (52.3 %) and idiopathic (37.5 %) were the most common etiologies. The mean FS was 6.52 &#xb1; 3.53. Large duct CP (&#x3b2; = 3, p = 0.001), exocrine pancreatic insufficiency (EPI) (&#x3b2; = 1.5, p = 0.037) and a genetic etiology (&#x3b2; = 1.6, p = 0.03) were significant predictors of fibrosis after adjusting for age, BMI, disease duration and use of oral hypoglycemic drugs and/or insulin.<br><br>CONCLUSION: Large duct CP, genetic etiology and EPI are all independent predictors of pancreatic fibrosis in a cohort of patients undergoing TPIAT. Computed tomography (CT) imaging and fecal elastase-1 (FE-1) concentration may be sufficient to estimate fibrosis without acquisition of a tissue specimen.}, }
@article {pmid40999363, year = {2025}, author = {Pan, Y and Luo, Y and Wu, G and Lu, Y and Yang, P and Kong, P and Zheng, C and Wang, C and Yang, L and Li, X}, title = {Gut microbiota dysbiosis promotes coronary heart disease comorbid with depression through lipopolysaccharides and Toll-like receptor 4.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {588}, pmid = {40999363}, issn = {1471-2180}, support = {2021GXNSFBA196059//the Guangxi Young Scientists Fund/ ; 2022GXNSFDA035086//the Key Project of the Guangxi Natural Science Foundation/ ; 82060835//the National Natural Science Foundation of China/ ; 82360900//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; *Lipopolysaccharides/metabolism ; Rats ; Male ; *Coronary Disease/microbiology/metabolism/etiology ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; Disease Models, Animal ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Myeloid Differentiation Factor 88/metabolism ; Comorbidity ; NF-kappa B/metabolism ; Signal Transduction ; RNA, Ribosomal, 16S/genetics ; Sulfonamides ; }, abstract = {Coronary heart disease (CHD) and depression often coexist and complicate patient care. The gut microbiota plays a crucial role in overall health and is involved in both conditions. Dysbiosis, particularly, increased levels of lipopolysaccharides (LPSs), can activate the Toll-like receptor 4 (TLR4), triggering inflammatory pathways associated with CHD and depression. Although some associations have been observed, the direct mechanistic association among gut dysbiosis, LPSs, TLR4 activation, and comorbidity of CHD and depression remains unclear. Thus, in the present study, we aimed to explore this association and the potential of modulating gut microbiota as a therapeutic strategy. METHODS: A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. RESULTS: We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. CONCLUSION: Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.}, }
@article {pmid41000396, year = {2025}, author = {Liu, C and Wang, J and Lei, L and Li, L and Yuan, X}, title = {Gut microbiota therapy for chronic kidney disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1660226}, pmid = {41000396}, issn = {1664-3224}, mesh = {*Renal Insufficiency, Chronic/microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Probiotics ; Prebiotics ; Medicine, Chinese Traditional ; }, abstract = {Chronic kidney disease (CKD), affecting 13% of the global population, is increasingly linked to gut microbiota dysbiosis, a condition driven by uremic toxins accumulation, metabolic alterations, and dietary factors. This mini review explores gut microbiota modulation as a therapeutic strategy to alleviate CKD symptoms, focusing on interventions that target gut microbiota composition and function. Prebiotics, such as resistant starch, have been shown to lower uremic toxins and reduce inflammation, while dietary adjustments, including low-protein and gluten-free diets, modulate microbial diversity and improve renal biomarkers. Fecal microbiota transplantation (FMT), which stabilizes creatinine levels and shifts gut microbiota toward beneficial taxa, represents another promising approach. However, limitations persist: synbiotics, which often induce gut microbiota shifts, frequently lack clinical impact; probiotics, which enhance glucose control and oxidative stress mitigation, exhibit variable efficacy; and interventions such as propolis or cranberry extract, which have been tested, prove ineffective. The causal relationship between gut microbiota dysbiosis and CKD progression, which remains unclear, is further complicated by methodological heterogeneity across studies. Emerging strategies, including phage therapy and artificial intelligence-driven multi-omics integration, which hold significant promise, require further validation. Future research must prioritize longitudinal studies, maternal gut microbiota optimization, and personalized approaches, which are essential for advancing CKD management. While gut microbiota modulations hold therapeutic potential, translating these findings into clinical practice demands rigorous trials to address inconsistencies and establish mechanistic links, ultimately shifting CKD management from reactive treatment to precision-based prevention.}, }
@article {pmid41000801, year = {2025}, author = {Soriano, S and Marshall, A and Holcomb, M and Flinn, H and Burke, M and Kara, G and Scalzo, P and Villapol, S}, title = {Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's pathology in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41000801}, issn = {2692-8205}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; R56 AG080920/AG/NIA NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.<br><br>OBJECTIVE: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.<br><br>METHODS: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 hours later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1, and 3 days post-injury included Thioflavin-S and 6E10 immunostaining for A&#x3b2;, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.<br><br>RESULTS: TBI increased cortical and dentate gyrus A&#x3b2; burden, with females showing greater vulnerability. FMT reduced A&#x3b2; deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.<br><br>CONCLUSION: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.}, }
@article {pmid41001122, year = {2025}, author = {Bahitham, W and Banoun, Y and Aljahdali, M and Almuaiqly, G and Bahshwan, SM and Aljahdali, L and Sanai, FM and Rosado, AS and Sergi, CM}, title = {"Trust your gut": exploring the connection between gut microbiome dysbiosis and the advancement of Metabolic Associated Steatosis Liver Disease (MASLD)/Metabolic Associated Steatohepatitis (MASH): a systematic review of animal and human studies.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1637071}, pmid = {41001122}, issn = {2296-861X}, abstract = {Metabolic Associated Steatosis Liver Disease (MASLD) and its advanced form, Metabolic Associated Steatohepatitis (MASH), represent growing global health concerns closely linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The gut microbiome has emerged as a key modulator in MASLD pathogenesis through the gut-liver axis, influencing hepatic fat accumulation, inflammation, and fibrosis via microbial metabolites and immune responses. Dysbiosis-characterized by altered microbial diversity and composition-contributes to hepatic lipid dysregulation, systemic inflammation, and impaired bile acid signaling. Metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and ethanol play critical roles in disease progression. Recent innovations in precision medicine, including microbiome profiling, metabolomics, and genomics, offer promising diagnostic and therapeutic strategies. Targeted probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions are under investigation for modulating the gut microbiome. This systematic review, conducted in accordance with PRISMA 2020 guidelines, is the first to comprehensively integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. It uniquely synthesizes microbial taxa, functional metabolites, and region-specific patterns-including data from underrepresented MENA populations. Eligible studies from PubMed, Scopus, and Web of Science evaluated microbial composition, metabolite profiles, and associations with steatosis, inflammation, and fibrosis. The findings underscore the diagnostic and therapeutic potential of microbiome modulation and emphasize the need for longitudinal, mechanistically driven studies. This systematic review is the first to integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. Unlike previous reviews, it uniquely emphasizes microbial taxa, functional metabolites, and region-specific patterns, including underrepresented MENA populations. By synthesizing findings from diverse cohorts, this review highlights diagnostic and therapeutic opportunities while identifying persistent gaps in longitudinal data, regional representation, and multi-omics integration.}, }
@article {pmid41001760, year = {2025}, author = {Jiang, L and Li, M and Zhao, Z}, title = {Intra-tumoral microbial heterogeneity of breast cancer: roles in tumorigenesis, therapeutic responses, and future directions.}, journal = {Journal of applied microbiology}, volume = {136}, number = {9}, pages = {}, doi = {10.1093/jambio/lxaf230}, pmid = {41001760}, issn = {1365-2672}, support = {82274296//National Natural Science Foundation of China/ ; 82473449//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Breast Neoplasms/microbiology/therapy/pathology ; Female ; *Carcinogenesis ; *Microbiota ; Tumor Microenvironment ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Recent advances in microbiome research have revealed that tumor-resident microbiota are not passive bystanders but active contributors to the progression of breast cancer. Similar to the well-characterized gut-breast microbiota axis, emerging evidence points to intricate interactions between intra-tumoral microbiota and breast cancer with implications for carcinogenesis, therapeutic response, and future directions. Intra-tumoral microbes have been shown to initiate inflammation, modulate tumor microenvironment, alter drug metabolism, and produce bioactive metabolites that influence tumor cell proliferation, apoptosis, and epithelial-mesenchymal transition. Distinct microbial signatures have been associated with specific molecular subtypes of breast cancer and may serve as predictive biomarkers for prognosis. Furthermore, dysbiosis within the tumor-resident microbiota has been linked to the development of treatment resistance, including chemotherapy, immunotherapy, and endocrine therapy. Preclinical studies support the feasibility of modulating the microbiota via using antibiotics, probiotics, fecal microbiota transplantation, or bacteriophage-based strategies to enhance antitumor efficacy and overcome resistance. This review summarizes current knowledge on the biological roles of tumor-resident microbiota in breast cancer, highlights subtype-specific microbial patterns and host-microbe interactions, and explores microbiota-targeted interventions as promising adjuncts in overcoming drug resistance.}, }
@article {pmid41002952, year = {2025}, author = {Ji, M and Ji, M and Zhong, Y and Shao, L}, title = {Gut Microbiota in Acute Myeloid Leukemia: From Biomarkers to Interventions.}, journal = {Metabolites}, volume = {15}, number = {9}, pages = {}, pmid = {41002952}, issn = {2218-1989}, abstract = {Acute myeloid leukemia (AML), the most common acute leukemia among adults, poses significant therapeutic challenges due to diagnostic limitations and the frequent development of treatment resistance. While genomics-based approaches have advanced, DNA aberrations do not always reflect the expression levels of genes and proteins, which are more tightly connected to disease phenotypes. Recently, the role of the gut microbiota in AML has gained increasing attention. AML patients often exhibit gut microbiota dysbiosis, which is linked to disease progression and heightened infection risk. Mounting evidence indicates that gut microbiota metabolism influences hematopoiesis and immune function via the "gut-bone marrow axis," with microbiota composition and diversity significantly affecting treatment outcomes and prognosis. High-throughput sequencing and metabolomics have identified correlations between gut microbiota composition and its metabolic products with AML clinical characteristics, paving the way for new biomarkers in diagnosis and prognosis. Additionally, treatments such as fecal microbiota transplantation (FMT) show promise in enhancing chemotherapy efficacy and improving patient outcomes. This review highlights recent advances in understanding the role of the gut microbiota in AML and explores new perspectives for its diagnosis and treatment.}, }
@article {pmid41003873, year = {2025}, author = {Sadeghloo, Z and Sadeghi, A}, title = {Gut microbiota as a hidden modulator of chemotherapy: implications for colorectal cancer treatment.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1717}, pmid = {41003873}, issn = {2730-6011}, abstract = {Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide, with chemotherapy remaining a cornerstone of treatment. Emerging evidence reveals that the gut microbiota significantly influences the metabolism, efficacy, and toxicity of chemotherapeutic agents such as 5-fluorouracil, irinotecan, and oxaliplatin. Microbial enzymes-most notably β-glucuronidases-can reactivate drug metabolites, contributing to adverse effects like mucositis and diarrhea. Additionally, certain bacterial species promote chemoresistance by modulating host immune responses and tumor microenvironments. This review highlights the critical role of the gut microbiota in shaping the efficacy and toxicity of chemotherapy in colorectal cancer, with a focus on microbial metabolism, chemoresistance, and microbiota-targeted therapies. Microbiota-targeted interventions-including probiotics, prebiotics, fecal microbiota transplantation (FMT), and enzyme inhibitors-represent promising strategies to improve treatment outcomes and mitigate toxicity. Enhanced understanding of microbiota-drug interactions is crucial for personalizing chemotherapy regimens, optimizing therapeutic efficacy, and minimizing adverse effects. The gut microbiota thus serves as both a key modulator and a potential therapeutic target in CRC.}, }
@article {pmid41004024, year = {2025}, author = {Longo, M and Rubio, T and Lamelas, A and Jericó, D and Rodenes-Gavidia, A and Cervero, J and Martínez-Blanch, J and Chenoll, E and Martorell, P and Paolini, E and Meroni, M and Riezu-Boj, JI and Solares, I and Sampedro, A and Urigo, F and Collantes, M and Battistin, M and Gatti, S and Quincoces, G and Peñuelas, I and Moreno-Aliaga, MJ and Ávila, MA and Di Pierro, E and Ramón, D and Milagro, FI and Dongiovanni, P and Fontanellas, A}, title = {Oral lipoteichoic and lipoic acids improve insulin resistance and body composition in porphyria mice on a high-carbohydrate diet.}, journal = {Journal of physiology and biochemistry}, volume = {81}, number = {4}, pages = {1077-1092}, pmid = {41004024}, issn = {1877-8755}, mesh = {Animals ; *Insulin Resistance ; *Thioctic Acid/administration &amp; dosage/pharmacology/therapeutic use ; *Lipopolysaccharides/administration &amp; dosage/pharmacology/therapeutic use ; *Body Composition/drug effects ; *Teichoic Acids/administration &amp; dosage/pharmacology/therapeutic use ; Mice ; Male ; *Porphyria, Acute Intermittent/metabolism/diet therapy/drug therapy/microbiology ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Administration, Oral ; Disease Models, Animal ; Hyperinsulinism ; }, abstract = {Acute intermittent porphyria (AIP) is a genetic metabolic disorder characterized by neurovisceral attacks. Although high-carbohydrate diets or intravenous glucose administration can help alleviate incipient attacks in patients, these interventions may also promote insulin resistance and increase metabolic risk. This study explored targeted dietary interventions to manage hyperinsulinemia and to enhance glucose uptake in insulin-sensitive organs under high-carbohydrate diet. Body composition and fecal microbiota profile were also investigated in a murine model of the disease. Wild-type and AIP mice (n = 6/group) were supplemented with tapioca maltodextrin in drinking water for 12 weeks, alongside heat-treated Bifidobacterium animalis subsp. lactis CECT-8145 (BPL1®HT), its by-product lipoteichoic acid (LTA), or the insulin-sensitizing agent α-lipoic acid (α-LA). Liver-targeted therapies, previously assessed in AIP mice, were also included in this study. AIP mice on a high-carbohydrate diet exhibited hyperinsulinemia and tissue-specific differences in glucose uptake compared to wild-type mice. Dysbiosis, marked by reduced fecal Dorea spp. and Adlercreutzia muris, alongside higher abundance of Escherichia coli, was also showed. Supplementation with α-LA and LTA revealed superior ability to improve glucose tolerance test and skeletal muscle glucose uptake, reduce hyperinsulinemia, and enhance body composition by increasing lean mass relative to fat, compared to gene therapy or liver-targeted insulin administration. Notably, LTA restored fecal microbiota profiles resembling those of wild-type mice. In conclusion, supplementation with LTA from BPL1®HT and α-LA may represent promising dietary interventions to manage glucose tolerance, improve insulin sensitivity in muscle and adipose tissues, and potentially ameliorate body composition in AIP patients under a high-carbohydrate diet.}, }
@article {pmid41005008, year = {2026}, author = {Jia, R and Xiao, CX and Zhang, YH and Hu, LY and Jun-Jun, Y and Zuo, R and Hu, YF and Xie, YH and Ma, XL and Li, Q and Hou, KJ}, title = {Microbiota in drug resistance.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {84}, number = {}, pages = {101311}, doi = {10.1016/j.drup.2025.101311}, pmid = {41005008}, issn = {1532-2084}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; Dysbiosis/microbiology/immunology/therapy ; Probiotics/therapeutic use/administration &amp; dosage ; *Antineoplastic Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Drug Resistance, Neoplasm/drug effects ; Prebiotics/administration &amp; dosage ; *Neoplasms/drug therapy/microbiology ; Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Drug resistance, particularly those of anticancer drugs and antibiotics, poses a significant challenge in the treatment of diseases, severely compromising therapeutic efficacy and patient survival rates. In recent years, an increasing number of studies have highlighted the dual role of microbiota in either promoting or mitigating drug resistance. The microbiome exists in symbiosis with the host, playing a crucial role in maintaining physiological functions and regulating immune responses. However, dysbiosis within the microbial community may induce or exacerbate drug resistance. While antibiotic-mediated depletion of gut microbiota has been proposed as a strategy to combat resistance, it may paradoxically lead to increased resistance or even worsen treatment outcomes. In this review, we focus on anticancer and antimicrobial agents as representative examples to elucidate the association of microbiome and drug resistance. We provide a detailed discussion on the mechanisms by which microbial dysbiosis contributes to development of drug resistance. Additionally, we systematically summarize the latest advancements in microbiota-targeted therapeutic strategies aimed at overcoming resistance, including fecal microbiota transplantation, probiotics and prebiotics, and bacterial engineering approaches. Finally, we discuss the potential clinical applications of microbiota-modulating strategies for overcoming drug resistance and examine the current challenges and future research directions in this field.}, }
@article {pmid41005300, year = {2025}, author = {Zhao, CN and Li, SS and Yau, T and Chen, WQ and Ji, R and Guan, XY and Kong, FS}, title = {Phocaeicola vulgatus induces immunotherapy resistance in hepatocellular carcinoma via reducing indoleacetic acid production.}, journal = {Cell reports. Medicine}, volume = {6}, number = {10}, pages = {102370}, pmid = {41005300}, issn = {2666-3791}, mesh = {Metagenomics ; *Gastrointestinal Microbiome/genetics/immunology ; *Carcinoma, Hepatocellular/drug therapy/immunology/microbiology/pathology ; Drug Resistance, Neoplasm/immunology ; *Liver Neoplasms/drug therapy/immunology/microbiology/pathology ; *Indoleacetic Acids/metabolism ; Fecal Microbiota Transplantation ; CD8-Positive T-Lymphocytes/immunology/metabolism ; *Bacteroides/genetics/immunology/isolation &amp; purification/metabolism ; *Dysbiosis/diagnosis/immunology/microbiology ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Metabolomics ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Humans ; Animals ; Mice ; Male ; Female ; Middle Aged ; Aged ; }, abstract = {Immunotherapy has made remarkable achievements in various cancers, but response rates in hepatocellular carcinoma (HCC) remain highly variable. Understanding mechanisms behind this heterogeneity and identifying responsive patients are urgent clinical challenges. In this study, the metagenomic analysis of 65 HCC patients reveals distinct gut microbiota profiles distinguishing responders (Rs) from non-responders (NRs). These findings are further validated through fecal microbiota transplantation (FMT) in mouse models. Notably, Phocaeicola vulgatus (P. vulgatus) is enriched in NRs and diminishes anti-PD-1 efficacy in both syngeneic and orthotopic tumor models. Mechanistically, P. vulgatus suppresses the production of indoleacetic acid (IAA), thereby weakening interferon (IFN)-γ[+] and granzyme B (GzmB)[+]CD8[+] T cells and impairing the antitumor immune response. Furthermore, supplementation with IAA restores CD8[+] T cell cytotoxicity and counteracts the immune-suppressive effects of P. vulgatus. Our findings establish a causal relationship between P. vulgatus and anti-PD-1 resistance in HCC, highlighting IAA as a potential therapeutic target to enhance immunotherapy outcomes.}, }
@article {pmid41006438, year = {2025}, author = {Prylińska-Jaśkowiak, M and Tabisz, H and Kujawski, S and Godlewska, BR and Słomko, J and Januszko-Giergielewicz, B and Murovska, M and Morten, KJ and Sokołowski, &#x141; and Zalewski, P}, title = {The gut microbial composition is different in chronic fatigue syndrome than in healthy controls.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {33075}, pmid = {41006438}, issn = {2045-2322}, mesh = {Humans ; *Fatigue Syndrome, Chronic/microbiology ; *Gastrointestinal Microbiome/genetics ; Male ; Female ; Adult ; Middle Aged ; Feces/microbiology ; Case-Control Studies ; RNA, Ribosomal, 16S/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {The pathogenesis of Chronic Fatigue Syndrome (CFS) is yet unknown. This study aimed to assess the gut microbial composition in CFS patients versus in healthy controls (HCs). The composition of fecal bacteria was examined in twenty-five CFS patients and sixteen HCs using Illumina sequencing of 16 S rRNA gene amplicons targeting the V3-V4 bacterial gene regions. 143 (46%) of the microbial genera were found only in the CFS. In addition, the gut microbial composition in the CFS patients contained a much higher proportion of the 10 most commonly found bacteria compared to the HCs group. A significantly lower observed number of operational taxonomic units (OTUs) was noted in CFS compared to HCs (p = 0.045). Significant between-group differences in the gut microbial composition in CFS compared to HCs were noted. The three most discriminating Amplicon Sequencing Variants (ASVs): ASV 191, ASV 44, and ASV 75, were identified as significantly more abundant in the healthy control group compared to the patient group. In addition, the Neural Network (multilayer perceptron) was able to discriminate gut microbial composition from CFS versus HCs with excellent performance (AUC = 0.935). The gut microbial composition is different in CFS patients compared to HCs. Further studies should assess the pathophysiological consequences of these differences as well as the effectiveness of therapies aimed at modifying the gut microbial composition in CFS patients.}, }
@article {pmid41007667, year = {2025}, author = {Dziedziak, M and Mytych, A and Szyller, HP and Lasocka, M and Augustynowicz, G and Szydziak, J and Hrapkowicz, A and Dyda, M and Braksator, J and Pytrus, T}, title = {Gut Microbiota in Psychiatric and Neurological Disorders: Current Insights and Therapeutic Implications.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, pmid = {41007667}, issn = {2227-9059}, abstract = {Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota-gut-brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota-dysbiosis-are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson's and Alzheimer's. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome-including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)-which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application.}, }
@article {pmid41007706, year = {2025}, author = {Caserta, S and Alvaro, ME and Penna, G and Fazio, M and Stagno, F and Allegra, A}, title = {Gut Microbiota Dysbiosis and Dietary Interventions in Non-Hodgkin B-Cell Lymphomas: Implications for Treatment Response.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, pmid = {41007706}, issn = {2227-9059}, abstract = {Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment.}, }
@article {pmid41007736, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {The Gut Microbiome in Human Obesity: A Comprehensive Review.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, pmid = {41007736}, issn = {2227-9059}, abstract = {An estimated 2.6 billion individuals are currently living with overweight or obesity, and this number is projected to exceed 4 billion by 2035. Consequently, unless this increasing trajectory is effectively addressed, the trend is expected to continue in the coming years. The gut microbiome has emerged as a central regulator of host metabolism and energy homeostasis, making its detailed characterization crucial for the advancement of innovative therapeutic strategies and for elucidating mechanisms underlying metabolic health and disease. This review examines human obesity through the lens of the gut microbiome, providing a comprehensive overview of its role by addressing gut microbiome alterations, microbiome-driven mechanisms, dietary influences, prebiotic effects, microbiome-based therapeutics, and other approaches in the treatment of obesity and related metabolic disorders. The composition of the gut microbiome is altered in obesity and characterized by reduced microbial diversity and inconsistent shifts in dominant bacterial phyla, which collectively contribute to metabolic dysregulation. The gut microbiome influences obesity through multiple mechanisms. These include regulating energy balance and insulin sensitivity via short-chain fatty acids, inducing chronic inflammation, modulating metabolic and appetite genes, altering bile acid signaling, and promoting fat storage by inhibiting fasting-induced adipose factor. Dietary patterns exert a profound influence on gut microbiome composition and function, with plant-based diets conferring protective effects against obesity and its comorbidities. Microbiome-based therapeutics, including probiotics, synbiotics, and fecal microbiota transplantation, have demonstrated potential in modulating key metabolic and inflammatory pathways associated with obesity. As the scientific understanding of the human gut microbiome continues to advance, the integration of microbiome-based therapies into standard clinical practice is poised to become increasingly feasible and therapeutically transformative, particularly for obesity, a complex condition that demands innovative and customized interventions.}, }
@article {pmid41007859, year = {2025}, author = {Wang, J and Chao, J}, title = {Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, pmid = {41007859}, issn = {2227-9059}, support = {82373547//National Natural Science Foundation of China/ ; BF2024054//Jiangsu Province Science and Technology Plan Project/ ; }, abstract = {Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial-immune-endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS.}, }
@article {pmid41008344, year = {2025}, author = {Logan, AC and Cordell, B and Pillai, SD and Robinson, JM and Prescott, SL}, title = {From Bacillus Criminalis to the Legalome: Will Neuromicrobiology Impact 21st Century Criminal Justice?.}, journal = {Brain sciences}, volume = {15}, number = {9}, pages = {}, pmid = {41008344}, issn = {2076-3425}, abstract = {The idea that gut microbes or a "bacillus of crime" might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while intoxicated charges, courts in the United States and Europe have acknowledged that gut microbes can manufacture significant amounts of systemically available ethanol, without a defendant's awareness. Indeed, emergent research is raising difficult questions for criminal justice systems that depend on prescientific notions of free moral agency. Evidence demonstrates that gut microbes play a role in neurophysiology, influencing cognition and behaviors. This may lead to justice involvement via involuntary intoxication, aggression, anger, irritability, and antisocial behavior. Herein, we discuss these 'auto-brewery syndrome' court decisions, arguing that they portend a much larger incorporation of neuromicrobiology and multi-omics science within the criminal justice system. The legalome, which refers to the application of gut microbiome and omics sciences in the context of forensic psychiatry/psychology, will likely play an increasing role in 21st century criminal justice. The legalome concept is bolstered by epidemiology, mechanistic bench science, fecal transplant studies, multi-omics and polygenic research, Mendelian randomization work, microbiome signature research, and human intervention trials. However, a more robust body of microbiota-gut-brain axis research is needed, especially through the lens of prevention, intervention, and rehabilitation. With ethical guardrails in place, greater inclusion of at-risk or justice-involved persons in brain science and microbiome research has the potential to transform justice systems for the better.}, }
@article {pmid41008952, year = {2025}, author = {Huang, W and Lv, Y and Zou, C and Ge, C and Zhan, S and Shen, X and Wu, L and Wang, X and Yuan, H and Lin, G and Yu, D and Liu, B}, title = {Mangosteen Pericarp Extract Mitigates Diquat-Induced Hepatic Oxidative Stress by NRF2/HO-1 Activation, Intestinal Barrier Integrity Restoration, and Gut Microbiota Modulation.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {41008952}, issn = {2076-3921}, support = {32402779//National Natural Science Foundation of China/ ; ZCLMS25C1701//Zhejiang Provincial Natural Science Foundation/ ; 2024GZ39//Public Welfare and Applied Research Project of Huzhou Science and Technology Bureau/ ; }, abstract = {Poultry production exposes birds to diverse environmental and physiological stressors that disrupt redox balance, impair gut-liver axis function, and undermine health and productivity. This study investigated the hepatoprotective and antioxidative effects of mangosteen pericarp extract (MPE) in an experimental model of diquat-induced oxidative stress in laying hens. A total of 270 Hy-Line White laying hens were randomly assigned to three groups: control group (CON), diquat-challenged group (DQ), and MEP intervention with diquat-challenged group (MQ), with six replicates of 15 birds each. The results showed that MPE supplementation effectively mitigated the hepatic oxidative damage caused by diquat, as evidenced by the increased ALT and AST activity, improved lipid metabolism, and reduced hepatic fibrosis. Mechanistically, MPE activated the NRF2/HO-1 antioxidant pathway, thus enhancing the liver's ability to counteract ROS-induced damage and reducing lipid droplet accumulation in liver tissue. MPE supplementation restored intestinal barrier integrity by upregulating tight junction protein expression (Occludin-1 and ZO-1), enhancing MUC-2 expression, and thereby decreasing gut microbiota-derived LPS transferring from the intestine. Additionally, MPE also modulated gut microbiota composition by enriching beneficial bacterial genera such as Lactobacillus and Ruminococcus while suppressing the growth of potentially harmful taxa (e.g., Bacteroidales and UCG-010). Fecal microbiota transplantation (FMT) from MPE-treated donors into diquat-exposed recipients reproduced these beneficial effects, further highlighting the role of gut microbiota modulation in mediating MPE's systemic protective actions. Together, these findings demonstrated that MPE alleviated DQ-induced liver injury and oxidative stress through a combination of antioxidant activity, protection of intestinal barrier function, and modulation of gut microbiota, positioning MPE as a promising natural strategy for mitigating oxidative stress-related liver damage by regulating the gut microbiota and gut-liver axis in poultry.}, }
@article {pmid41009471, year = {2025}, author = {Miftode, IL and Vâţă, A and Miftode, R&#x15e; and Oancea, AF and Pasăre, MA and Parângă, TG and Miftode, EG and Mititiuc, IL and Radu, VD}, title = {The Gut Microbiome and Colistin Resistance: A Hidden Driver of Antimicrobial Failure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, pmid = {41009471}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Colistin/pharmacology/therapeutic use ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; *Drug Resistance, Bacterial/genetics ; Gene Transfer, Horizontal ; }, abstract = {Colistin, a polymyxin antibiotic reintroduced as a last-resort therapy against multidrug-resistant Gram-negative bacteria, is increasingly being compromised by the emergence of plasmid-mediated colistin resistance genes (mcr-1 to mcr-10). The human gut microbiota serves as a major reservoir and transmission hub for these resistance determinants, even among individuals without prior colistin exposure. This review explores the mechanisms, dissemination, and clinical implications of mcr-mediated colistin resistance within the gut microbiota, highlighting its role in horizontal gene transfer, colonization, and environmental persistence. A comprehensive synthesis of the recent literature was conducted, focusing on epidemiological studies, molecular mechanisms, neonatal implications and decolonization strategies. The intestinal tract supports the enrichment and exchange of mcr genes among commensal and pathogenic bacteria, especially under antibiotic pressure. Colistin use in agriculture has amplified gut colonization with resistant strains in both animals and humans. Surveillance gaps remain, particularly in neonatal populations, where colonization may occur early and persist silently. Promising interventions, such as fecal microbiota transplantation and phage therapies, are under investigation but lack large-scale clinical validation. The gut microbiome plays a central role in the global spread of colistin resistance. Mitigating this threat requires integrated One Health responses, improved diagnostics for gut colonization, and investment in microbiome-based therapies. A proactive, multisectoral approach is essential to safeguard colistin efficacy and address the expanding threat of mcr-mediated resistance.}, }
@article {pmid41009869, year = {2025}, author = {Kocsis, B and Szabó, D and Sipos, L}, title = {Gut Microbiome and Intestinal Colonization with Multidrug-Resistant Strains of Enterobacterales: An Interplay Between Microbial Communities.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {41009869}, issn = {2079-6382}, support = {No "0272//HUN-REN-SU, Human Microbiota Study Group/ ; Janos Bolyai Scholarship (BO/00286/22/5)//Hungarian Academy of Sciences./ ; 952491-AmReSu//European Union's Horizon 2020/ ; }, abstract = {Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains.}, }
@article {pmid41010451, year = {2025}, author = {Jiang, Z and Zhu, J and Shen, Z and Gao, L and Chen, Z and Zhang, L and Wang, Q}, title = {The Microecological-Immune Axis in Pediatric Allergic Diseases: Imbalance Mechanisms and Regulatory Interventions.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, pmid = {41010451}, issn = {2072-6643}, support = {(2025KYCX1-A04//Wuhan Yaxin General Hospital Scientific Research and Innovation Fund Key Projects/ ; WCYY2022K02//Wuhan Wuchang Hospital Scientific Research and Innovation Fund Key Projects/ ; }, mesh = {Humans ; *Hypersensitivity/immunology/microbiology/therapy ; Child ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; *Microbiota/immunology ; Lung/immunology/microbiology ; Skin/immunology/microbiology ; Asthma/immunology/microbiology ; }, abstract = {In recent years, the global prevalence of pediatric allergic diseases-including atopic dermatitis, allergic rhinitis, and asthma-has increased significantly. Accumulating evidence underscores the pivotal role of the microbiota-immune axis in the regulation of immune tolerance, wherein microbial dysbiosis is a critical driver in the onset and progression of these conditions. Notably, reduced microbial diversity and imbalanced proportions can also cause immune dysregulation and cross-organ signaling. The skin-lung-gut axis has emerged as a key conduit for multi-organ immune communication. Microbial communities at barrier sites not only mediate local immune homeostasis but also influence distant organs through metabolite production and immune signaling pathways, forming a complex network of organ crosstalk. This mechanism is integral to the maintenance of both innate (e.g., epithelial barrier integrity and phagocytic activity) and adaptive (e.g., the Type 1/Type 2 cytokine balance and regulatory T cell function) immunity, thereby suppressing allergic inflammation. Early microbial colonization is crucial for immune system maturation, and its perturbation is strongly linked to abnormal allergic immune responses. As such, the skin-lung-gut axis functions as a cross-organ microecological-immune regulatory network that is particularly relevant in the context of infantile allergic disorders. Intervention strategies targeting the microbiota-including probiotics, prebiotics, synbiotics, and postbiotics-have demonstrated potential in modulating host immunity. Furthermore, emerging approaches such as engineered probiotics, advanced delivery systems, and fecal microbiota transplantation (FMT) offer promising therapeutic avenues. This review provides a comprehensive overview of microbiota development in early life, its association with allergic disease pathogenesis, and the current progress in microbiota-targeted interventions, offering a theoretical foundation for individualized prevention and treatment strategies.}, }
@article {pmid41010468, year = {2025}, author = {Forcina, G and Di Filippo, P and De Biasio, D and Cesaro, FG and Frattolillo, V and Massa, A and De Cesare, M and Marzuillo, P and Miraglia Del Giudice, E and Di Sessa, A}, title = {Targeting the Gut Microbiota in Pediatric Obesity: A Paradigm Shift in Prevention and Treatment? A Comprehensive Review.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, pmid = {41010468}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Pediatric Obesity/microbiology/therapy/prevention &amp; control ; Probiotics/therapeutic use/administration &amp; dosage ; Child ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Synbiotics/administration &amp; dosage ; }, abstract = {Pediatric obesity represents a growing global health challenge, closely associated with increased cardiometabolic risk and long-term adverse outcomes. Although lifestyle modifications remain the cornerstone of treatment, sustained success is often limited. Emerging evidence suggests that the gut microbiota (GM) plays a pivotal role in the pathogenesis of obesity, influencing host metabolism, energy homeostasis, and systemic inflammation. This narrative review aims to provide a comprehensive and up-to-date overview of the complex interplay between GM and pediatric obesity, with a particular emphasis on microbiota-targeted interventions. These include probiotics, prebiotics, synbiotics, postbiotics, dietary modulation, and fecal microbiota transplantation (FMT). Findings from preclinical studies and early-phase clinical trials indicate that gut dysbiosis may contribute to obesity-related mechanisms, such as altered nutrient absorption, increased adiposity, and dysregulated appetite control. Interventions targeting the microbiota have shown promise in modulating inflammatory pathways and improving metabolic profiles. While preliminary findings underscore the potential of the GM as a novel adjunctive target in managing pediatric obesity, current evidence remains heterogeneous, and robust clinical pediatric data are limited. Further research is needed to clarify the therapeutic efficacy, safety, and long-term outcomes of microbiota-modulating strategies in children with obesity.}, }
@article {pmid41010510, year = {2025}, author = {Petropoulos, A and Stavropoulou, E and Tsigalou, C and Bezirtzoglou, E}, title = {Microbiota Gut-Brain Axis and Autism Spectrum Disorder: Mechanisms and Therapeutic Perspectives.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, pmid = {41010510}, issn = {2072-6643}, support = {//Democritus University of Thrace/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Autism Spectrum Disorder/microbiology/therapy/physiopathology ; Dysbiosis/microbiology/therapy ; *Brain/physiopathology ; Animals ; *Brain-Gut Axis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Gastrointestinal Diseases/microbiology ; }, abstract = {Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota-gut-brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability ("leaky gut") and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut-brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD.}, }
@article {pmid41010985, year = {2025}, author = {Petrelli, F and Ghidini, A and Dottorini, L and Ghidini, M and Zaniboni, A and Tomasello, G}, title = {Clinical Evidence for Microbiome-Based Strategies in Cancer Immunotherapy: A State-of-the-Art Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {9}, pages = {}, pmid = {41010985}, issn = {1648-9144}, mesh = {*Gastrointestinal Microbiome/immunology ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/immunology ; Symbiosis/immunology ; Progression-Free Survival ; *Neoplasms/immunology/mortality/therapy ; Fecal Microbiota Transplantation ; Humans ; Clinical Trials as Topic ; Probiotics/administration &amp; dosage ; }, abstract = {The gut microbiome has emerged as a critical determinant of immune-checkpoint inhibitor (ICI) efficacy. A narrative review of 95 clinical studies (2015-2025) shows that patients with greater gut microbial diversity and relative enrichment of commensals such as Akkermansia, Ruminococcus, and other short-chain fatty acid producers experience longer progression-free and overall survival, particularly in melanoma and non-small-cell lung cancer. Broad-spectrum antibiotics given within 30 days of ICI initiation and over-the-counter mixed probiotics consistently correlate with poorer outcomes. Early phase I/II trials of responder-derived fecal microbiota transplantation in ICI-refractory melanoma achieved objective response rates of 20-40%, while pilot high-fiber or plant-forward dietary interventions improved immunologic surrogates such as CD8[+] tumor infiltration. Machine-learning classifiers that integrate 16S or metagenomic profiles predict ICI response with an area under the ROC curve of 0.83-0.92. Methodological heterogeneity across sampling, sequencing, and clinical endpoints remains a barrier, underscoring the need for standardization and larger, well-powered trials.}, }
@article {pmid41011021, year = {2025}, author = {Savvidis, C and Maggio, V and Rizzo, M and Zabuliene, L and Ilias, I}, title = {The Gut Microbiota Axis in Social Jetlag: A Novel Framework for Metabolic Dysfunction and Chronotherapeutic Innovation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {9}, pages = {}, pmid = {41011021}, issn = {1648-9144}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Circadian Rhythm/physiology ; *Jet Lag Syndrome/complications/physiopathology/microbiology/therapy ; *Metabolic Diseases/etiology ; *Chronotherapy/methods ; Melatonin/therapeutic use ; }, abstract = {Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota-gut-metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian-microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.}, }
@article {pmid41011192, year = {2025}, author = {Cerrito, L and Galasso, L and Iaccarino, J and Pizzi, A and Termite, F and Esposto, G and Borriello, R and Ainora, ME and Gasbarrini, A and Zocco, MA}, title = {Present and Future Perspectives in the Treatment of Liver Fibrosis.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {9}, pages = {}, pmid = {41011192}, issn = {1424-8247}, abstract = {BACKGROUND/OBJECTIVES: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions.<br><br>METHODS: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity.<br><br>RESULTS: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin-angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut-liver axis. Microbiota-directed interventions-probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation-are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations.<br><br>CONCLUSIONS: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis.}, }
@article {pmid41011314, year = {2025}, author = {Meacci, D and Bruni, A and Cocquio, A and Dell'Anna, G and Mandarino, FV and Marasco, G and Cecinato, P and Barbara, G and Zagari, RM}, title = {Microbial Landscapes of the Gut-Biliary Axis: Implications for Benign and Malignant Biliary Tract Diseases.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011314}, issn = {2076-2607}, abstract = {Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut-biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A2, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints-sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines-and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics.}, }
@article {pmid41011331, year = {2025}, author = {Alexandrescu, L and Tofolean, IT and Tofolean, DE and Nicoara, AD and Twakor, AN and Rusu, E and Preotesoiu, I and Dumitru, E and Dumitru, A and Tocia, C and Herlo, A and Alexandrescu, DM and Popescu, I and Cimpineanu, B}, title = {Ethanol-Induced Dysbiosis and Systemic Impact: A Meta-Analytical Synthesis of Human and Animal Research.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011331}, issn = {2076-2607}, abstract = {BACKGROUND: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders.<br><br>METHODS: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined.<br><br>RESULTS: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes.<br><br>CONCLUSIONS: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies.}, }
@article {pmid41011464, year = {2025}, author = {Cano, &#xc1; and Ruiz Arabi, E and Ruiz, L and Nadales, BJ and Baumela, A and Recio, M and Machuca, I and Castón, JJ and Pérez-Nadales, E and Torre Cisneros, J}, title = {Compassionate Use of Encapsulated MKB-01 Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Single-Center Experience.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011464}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridiodes difficile infection (rCDI). However, experience with the oral biologic product MKB-01 remains limited. We describe a series of 13 patients with rCDI treated with FMT using MKB-01 capsules administered orally. Each patient received a single dose of 4 capsules (≥2.1-2.5 × 10[11] microorganisms) with water after a 2 h fasting period. Antibiotic therapy was discontinued pre FMT. Clinical evaluation was performed at weeks 8 and 12. The mean number of prior recurrences was 1.5 (range: 1-3 episodes). In 12 patients (92.3%), FMT was administered after resolution of the current episode; in one patient (7%), it was administered on day 3 of fidaxomicin therapy, prior to symptom resolution. At week 8, clinical cure (Absence of baseline symptoms for at least 72 h) was achieved in 11 patients (84.6%). An additional patient (7%) responded to a second FMT. One recurrence occurred at 8 weeks and was resolved with a second FMT. Therefore, the overall clinical response rate after one or more FMTs was 12 out of 13 patients (92.3%). The procedure was well tolerated; only one patient experienced self-limited diarrhea. These findings support oral FMT with MKB-01 capsules as a safe and effective option for treating rCDI.}, }
@article {pmid41011478, year = {2025}, author = {Cortés, M and Olate, P and Rodriguez, R and Diaz, R and Martínez, A and Hernández, G and Sepulveda, N and Paz, EA and Quiñones, J}, title = {Human Microbiome as an Immunoregulatory Axis: Mechanisms, Dysbiosis, and Therapeutic Modulation.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011478}, issn = {2076-2607}, support = {N&#xb0; 21231033//Agencia Nacional de Investigaci&#xf3;n y Desarrollo/ ; }, abstract = {The human microbiome plays a central role in modulating the immune system and maintaining immunophysiological homeostasis, contributing to the prevention of immune-mediated diseases. In particular, the gut microbiota is a key ecosystem for immune system maturation, especially in early life. This review aimed to analyze the molecular and cellular mechanisms linking the microbiome to immune and neuronal functions, as well as the impact of dysbiosis and emerging therapeutic strategies targeting the microbiome. The analysis was based on scientific databases, prioritizing studies published since 2000, with special emphasis on the past decade. The microbiome influences immune signaling through microorganism-associated molecular patterns (MAMPs) and pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). Additionally, microbial metabolites-such as short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids-exert significant immunomodulatory effects. The intestinal epithelial barrier is also described as an active immunological interface contributing to systemic regulation. The literature highlights innovative therapies, including fecal microbiota transplantation (FMT), probiotics, and microbiome editing with CRISPR-Cas technologies. These strategies aim to restore microbial balance and improve immune outcomes. The growing body of evidence positions the microbiome as a valuable clinical and diagnostic target, with significant potential for application in personalized medicine.}, }
@article {pmid41011482, year = {2025}, author = {Zhu, H and Yan, X and Shi, H and Chen, Y and Huang, C and Zhou, Y and Yan, S and Zhang, N and Wang, J and Zhang, J and Han, C and Chen, Q and Zhao, J and Cao, M}, title = {The Role of Gut Microbiota and Its Metabolites in Mitigating Radiation Damage.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011482}, issn = {2076-2607}, support = {No. 2024ZYD0194//Central Guidance on Local Science and Technology Development Fund of Sichuan Province/ ; No. SZKF202309//Open Project Program of Panxi Crops Research and Utilization Key Laboratory of Sichuan Province/ ; No. 2024LQRD0045//Science and Technology Plan Project of Chengdu Longquanyi District/ ; }, abstract = {With the widespread use of ionizing radiation (IR) in medical and industrial settings, irradiation has become increasingly common, posing significant risks to human health. Among the various organs affected, the gut is particularly sensitive to radiation-induced damage, leading to conditions such as radiation-induced intestinal damage (RIID). Recent studies have emphasized the critical role of gut microbiota and its metabolites in mitigating radiation-induced injury. This review discusses the effects of IR on the mammalian and human gut microbiota. We examine the dynamics of gut microbiota composition during and after irradiation, and emphasize the protective role of the gut flora and the metabolites in the pathophysiological mechanisms exhibited during radiation injury. In addition, this article investigates how specific metabolites, such as short-chain fatty acids and indole derivatives, may contribute to the mitigation of inflammation and promotion of gut barrier integrity. In addition, various therapeutic strategies based on modulating the gut microbiota, such as probiotics, antibiotics, and fecal microbiota transplantation, are discussed to understand their potential to prevent or mitigate RIID. Understanding the interactions between IR, gut microbiota and their metabolites provides new avenues for developing innovative therapeutic approaches to improve patient outcomes during and after radiotherapy. Future research directions could focus on optimizing microbiota-based therapies and exploring the role of diet and lifestyle in enhancing intestinal health during irradiation.}, }
@article {pmid41011526, year = {2025}, author = {Roberts, JL and Park, CC}, title = {Emerging Roles of the Gut Microbiome in Musculoskeletal Injury and Repair.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011526}, issn = {2076-2607}, support = {IK1RX003783//US Department of Veterans Affairs/ ; P30 AR079206/AR/NIAMS NIH HHS/United States ; IK1 RX003783/RX/RRD VA/United States ; RFGA2024-022-010//Arizona Biomedical Research Centre/ ; 5P30AR003783-04/NH/NIH HHS/United States ; }, abstract = {Over the past decade, significant attention has been directed toward understanding the role of the gut microbiome in health and disease. The gut microbiota, comprising a complex and diverse community of microorganisms, has been linked to numerous conditions, including metabolic disorders, gastrointestinal diseases, and inflammatory or autoimmune conditions. Recently, a growing body of evidence has revealed a compelling relationship between gut microbiota composition and musculoskeletal injury recovery, highlighting its potential as a novel therapeutic target. Musculoskeletal injuries, including fractures, post-traumatic osteoarthritis, and tendon or ligament injuries, commonly lead to changes in the community structure of the gut microbiota, intestinal permeability, and systemic inflammation, processes known to negatively influence tissue repair. Preclinical studies demonstrate that microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, effectively restore gut barrier integrity, modulate inflammation, and normalize gut-derived metabolite profiles. Despite these promising findings, critical gaps remain in translating these effects into clinical practice, particularly regarding the mechanisms linking specific microbiota changes to improved musculoskeletal healing outcomes. Future research incorporating rigorous clinical trials, multi-omics analyses, and advanced predictive tools, including artificial intelligence and microbiome-informed digital twins, is urgently needed to fully harness the therapeutic potential of microbiome-based interventions in musculoskeletal injury recovery. This narrative review provides insights into our evolving understanding of the relationship between the gut microbiota and musculoskeletal injury and explores the potential of gut microbiota-targeted therapies for improved healing outcomes.}, }
@article {pmid41011544, year = {2025}, author = {Dai, K and Ding, L and Yang, X and Wang, S and Rong, Z}, title = {Gut Microbiota and Neurodevelopment in Preterm Infants: Mechanistic Insights and Prospects for Clinical Translation.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011544}, issn = {2076-2607}, abstract = {Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut-brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan-serotonin metabolic signalling, hypothalamic-pituitary-adrenal (HPA) axis modulation, and the integrity of intestinal and blood-brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions-including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)-focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial-neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population.}, }
@article {pmid41012834, year = {2025}, author = {Liu, S and Zhou, B and Liu, L and Zhong, J and Zhang, X and Jiang, W and Liu, H and Zhou, Z and Peng, G and Zhong, Y and Zhang, K and Zhong, Z}, title = {Effects and Microbiota Changes Following Oral Lyophilized Fecal Microbiota Transplantation Capsules in Canine with Chronic Enteropathy After Parvovirus Infection: Case Report.}, journal = {Veterinary sciences}, volume = {12}, number = {9}, pages = {}, pmid = {41012834}, issn = {2306-7381}, support = {CGF2024001//the Study on Key Technologies for Conservation of Wild Giant Panda Populations and Its Habitats within Giant Panda National Park System/ ; }, abstract = {(1) Background: Chronic enteropathy (CE) in canines is associated with persistent microbiome dysbiosis, and conventional therapies (e.g., special diets, antimicrobials, and immunosuppressive drugs) are sometimes ineffective. Currently, fecal microbiota transplantation (FMT) has proven successful in treating CE in canines via invasive methods (e.g., enemas or endoscopy) or via oral frozen liquid capsules, which must be stored at -80 °C. However, due to the invasiveness of the administration methods and the storage constraints of the liquid capsules, FMT is not widely used in veterinary clinical practice. (2) Methods: The case of a four-year-old Siberian Husky with a three-year history of CE following canine parvovirus infection received lyophilized FMT capsules for thirty days. Stool samples were collected for metagenomic sequencing and quantification of fecal short-chain fatty acids (SCFAs), both pre- and post-FMT. Blood samples were analyzed using complete blood count (CBC) and biochemical testing. Ultrasound was used to assess the wall thickness of the stomach, duodenum, jejunum, and colon. (3) Results: Post-FMT, improvements in clinical outcomes were observed: fecal scores improved from 6 (unformed stools with mucus) to 2 (formed stool), and body weight increased by 8.3% (from 24.2 kg to 26.2 kg). Abnormal CBC and biochemical parameters were restored to reference ranges, including hematocrit (from 60.6% to 55.7%), hemoglobin (from 208 g/L to 190 g/L), creatinine (from 167 μmol/L to 121 μmol/L), and urea (from 11.9 mmol/L to 7.1 mmol/L). Ultrasound results showed that colonic wall thickness decreased from 0.23 ± 0.03 cm (pathological) to 0.18 ± 0.01 cm (physiological). Metagenomic analysis revealed that microbial richness (operational taxonomic units (OTUs) from 151 to 183) and diversity (Shannon and Simpson indices from 3.16 to 4.8 and from 0.87 to 0.94, respectively) all increased. The microbiota composition of the recipient exhibited a decline in the relative abundance of Firmicutes, falling from 99.84% to 35.62%, concomitant with an increase in Actinobacteria (from 0.08% to 4.78%), indicating a convergence toward a donor-like profile. Fecal SCFAs analysis revealed a 251.4% increase in propionate (from 0.0833 to 0.2929 mg/g) and elevated acetate (from 0.4425 to 0.4676 mg/g). These changes are functionally linked to enriched propanoate metabolism (Z = 0.89) in KEGG pathways. (4) Conclusions: Oral lyophilized FMT capsules resolved clinical signs of CE, enhanced microbial diversity and richness, and restored donor-like abundances of gut microbiota, particularly SCFA-producing taxa. Microbial restructuring increased microbial metabolite output, notably SCFA concentrations, and enriched functional metabolic pathways. Importantly, lyophilized FMT overcomes storage limitations and administration barriers, demonstrating its high clinical viability for treating canine CE.}, }
@article {pmid41013319, year = {2025}, author = {Igbo, CA and Ezeano, C and Adeniran, O and Taha, M and Annan, AA and Nriagu, VC and Boateng, S and Williams, MC and Onyali, C}, title = {The impact of fecal microbiota transplantation on refractory ulcerative colitis: A systematic review and Meta-Analysis of randomised controlled trials.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {654}, pmid = {41013319}, issn = {1471-230X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Refractory ulcerative colitis (UC), characterized by persistent disease activity despite optimized medical therapy, poses a significant therapeutic challenge. Fecal microbiota transplantation (FMT) has shown promise in inducing remission in active ulcerative colitis (UC) by restoring gut microbial balance; however, its efficacy in refractory cases remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of FMT in achieving clinical and endoscopic remission in patients with refractory UC, based on evidence from randomized controlled trials (RCTs).<br><br>METHODS: We searched PubMed, Scopus, Google Scholar Cochrane CENTRAL, and Web of Science up to February 2025 for RCTs comparing FMT to placebo or standard care in adults with refractory UC (Mayo Score&#x2009;&#x2265;&#x2009;3 despite treatment). Primary outcomes were clinical remission (Mayo Score&#x2009;&#x2264;&#x2009;2, no subscore&#x2009;>&#x2009;1) and endoscopic remission (Mayo endoscopic subscore&#x2009;&#x2264;&#x2009;1). Data were pooled using a random-effects model, with heterogeneity assessed via I&#xb2; and Q-tests. Subgroup analyses explored age at diagnosis and disease duration as moderators. The review followed PRISMA guidelines and was registered with PROSPERO (CRD420250651790).<br><br>RESULTS: Six RCTs were included. FMT showed no significant effect on clinical remission (pooled estimate -&#x2009;0.2584; 95% CI -&#x2009;0.9031 to 0.3863; p&#x2009;=&#x2009;0.4321) or endoscopic remission (pooled estimate -&#x2009;0.2229; 95% CI -&#x2009;0.8811 to 0.4353; p&#x2009;=&#x2009;0.5069), with no heterogeneity (I&#xb2; = 0.00%). Subgroup analyses revealed no moderation by age or disease duration (p&#x2009;>&#x2009;0.27). Adverse events were mild and transient.<br><br>CONCLUSION: FMT does not significantly improve clinical or endoscopic remission in refractory UC, suggesting limited efficacy in this population despite a favorable safety profile. Larger, standardized trials are warranted.}, }
@article {pmid41015495, year = {2026}, author = {Castells-Nobau, A and Fumagalli, A and Del Castillo-Izquierdo, &#xc1; and Rosell-Díaz, M and de la Vega-Correa, L and Samulėnaitė, S and Motger-Albertí, A and Arnoriaga-Rodríguez, M and Garre-Olmo, J and Puig, J and Ramos, R and Burokas, A and Coll, C and Zapata-Tona, C and Perez-Brocal, V and Ramio, L and Moya, A and Swann, J and Martín-García, E and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Gut microbial modulation of 3-hydroxyanthranilic acid and dopaminergic signalling influences attention in obesity.}, journal = {Gut}, volume = {75}, number = {4}, pages = {705-724}, pmid = {41015495}, issn = {1468-3288}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Obesity/metabolism/microbiology/psychology ; Mice ; *3-Hydroxyanthranilic Acid/metabolism ; Tryptophan/metabolism/blood ; Humans ; Male ; Fecal Microbiota Transplantation ; Drosophila melanogaster ; Female ; *Dopamine/metabolism ; Metagenomics ; Mice, Inbred C57BL ; Signal Transduction ; ortho-Aminobenzoates/metabolism ; Metabolomics ; }, abstract = {BACKGROUND: Obesity-related alterations in the gut microbiota have been linked to cognitive decline, yet their relationship with attention remains poorly understood.<br><br>OBJECTIVE: To evaluate the possible relationships among gut metagenomics, plasma metabolomics and attention.<br><br>DESIGN: We conducted faecal shotgun metagenomics and targeted plasma tryptophan metabolomics across three independent cohorts (n=156, n=124, n=804) with functional validations in preclinical models, including three faecal microbiota transplantation (FMT) experiments in mice and Drosophila melanogaster.<br><br>RESULTS: Obesity was consistently associated with reduced attention. Metagenomics analyses identified Proteobacteria species and microbial functions related to tryptophan biosynthesis from anthranilic acid (AA) as negatively associated with attention in obesity. Plasma tryptophan metabolic profiling and machine learning revealed that 3-hydroxyanthranilic acid (3-HAA) was positively associated with attention, particularly in obesity, while AA showed a negative association. Bariatric surgery improved attention and enriched microbial species linked to attention. In mice, diet-induced obesity (DIO) and microbiota depletion reduced 3-HAA and 5-hydroxy-indole acetic acid (5-HIAA) concentrations in the prefrontal cortex (PFC), which were restored by FMT. Global metabolic profiling (>600 metabolites) of PFC from the FMT group identified 3-HAA and the tryptophan and tyrosine pathways among the most significant in mice receiving microbiota from high-attention donors. A second FMT experiment also revealed a consistent enrichment of the tryptophan and tyrosine metabolism at the transcriptional level in the PFC, with Haao (3-hydroxyantrhanilic acid dioxygenase) and Aox4 (aldehyde oxidase 4), key in 3-HAA and 5-HIAA degradation, among the significantly regulated genes. In a third FMT study, attentional traits were transmitted from humans to mice alongside modulation of serotonergic and dopaminergic pathways. In Drosophila, mono-colonisation with Enterobacter cloacae and DIO induced attention deficit-like behaviours, which were mitigated by 3-HAA supplementation.<br><br>CONCLUSIONS: We have identified the microbiota and 3-HAA as potential therapeutic targets to improve attention, especially in obesity.}, }
@article {pmid41016739, year = {2026}, author = {Zheng, D and Chen, S and Feng, H and Zhang, S and Zhang, C and Wang, Y and Tan, W and Qing, Q and Liu, L and Liu, X and Wang, Z and Liang, L and Sun, J and Chen, Y}, title = {Oral administration of low-molecular-weight heparin ameliorates colitis by enhancing the gut mucus barrier via microbial tryptophan metabolites.}, journal = {British journal of pharmacology}, volume = {183}, number = {3}, pages = {560-580}, doi = {10.1111/bph.70209}, pmid = {41016739}, issn = {1476-5381}, support = {2021YFA0717000//National Key R&amp;D Program of China/ ; 81800460//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Innovation Program/ ; ZDSYS20220606100800002//Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Heparin, Low-Molecular-Weight/administration &amp; dosage/pharmacology/therapeutic use ; Administration, Oral ; *Tryptophan/metabolism ; Mice ; Male ; Mice, Inbred C57BL ; *Colitis/drug therapy/metabolism/chemically induced/microbiology ; Dextran Sulfate ; *Intestinal Mucosa/drug effects/metabolism ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {BACKGROUND AND PURPOSE: Previous studies have reported that oral low-molecular-weight heparin (LMWH) ameliorated colitis by undefined mechanisms in ulcerative colitis (UC) patients. Our study explored the mechanisms of LMWH on colitis from the perspective of gut microbiota and its metabolites.<br><br>EXPERIMENTAL APPROACH: Dextran sulfate sodium (DSS; 2.5%) was used to induce colitis in mouse model, and LMWH was administered by either oral gavage, intracolonic delivery or subcutaneous injection to compare their therapeutic effects. Pseudo-germ-free mice was established by using antibiotic cocktail, and faecal microbial transplantation (FMT) was performed to verify the role of microbiota in LMWH actions. Alcian blue staining, fluorescence in situ hybridization of EUB338 and immunohistochemical staining were performed to evaluate the integrity of gut mucus barrier. Amplicon sequencing, transcriptome sequencing and untargeted metabolome studies were used to explore LMWH mechanisms. The ameliorating effect of indole-3-propionic acid (IPA) was verified in vitro and in vivo.<br><br>KEY RESULTS: Oral, but not subcutaneous, administration of LMWH alleviated colitis and enhanced the gut mucus barrier. Pseudo-germ-free mice and FMT assays confirmed that therapeutic effects of oral LMWH were dependent on gut microbiota. Oral LMWH increased Firmicutes abundance and decreased Escherichia/Shigella abundance, subsequently increasing microbial tryptophan metabolites, especially IPA. The protective effects of oral LMWH were reproduced by IPA supplementation, with mucus barrier enhancing&#xa0;through regulating the Wnt/&#x3b2;-catenin pathway.<br><br>CONCLUSION AND IMPLICATIONS: The results provide new insights into the signalling mechanisms associated with the therapeutic potential of LMWH in colitis, and highlight the application of IPA for UC treatment.}, }
@article {pmid41016812, year = {2025}, author = {Huang, L and Li, H and Yang, W and Huang, L and Chen, Q and Li, S and Zou, Z and Zhao, L and Zeng, Z}, title = {L-Theanine Ameliorates Metabolic Dysregulation and Adverse Fetal Outcomes in a Mice Model of Gestational Obesity: Association with FXR/FGF15 Signaling.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2504017}, pmid = {41016812}, issn = {1738-8872}, mesh = {Animals ; Female ; Pregnancy ; Mice ; Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; *Glutamates/pharmacology/therapeutic use ; *Fibroblast Growth Factors/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction/drug effects ; Pregnancy Outcome ; Humans ; *Pregnancy in Obesity/metabolism/drug therapy ; Mice, Inbred C57BL ; *Obesity/metabolism ; Mice, Obese ; Placenta ; Receptor, Farnesoid X-Activated ; }, abstract = {In this study, we investigated whether L-theanine (LTA) ameliorates adverse pregnancy outcomes in high-fat diet (HFD)-induced gestational obesity mice. Gestational obese mice models received HFD and fecal microbiota transplantation (FMT) from pregnant obese women, followed by LTA treatment. Gut microbiota DNA from six obese and six normal pregnant women was analyzed. Also assessed were lipid profiles, inflammatory factors, gut permeability, FXR/FGF15 expression, pup weight, and placental function. Alpha- and beta-diversity analyses showed reduced gut microbial diversity in the obese pregnant women. Postpartum hemorrhage, cholesterol, and triglycerides inversely correlated with Weissella, while BMI was positively associated with Escherichia-Shigella. Neonatal weight correlated positively with Subdoligranulum and negatively with Megamonas. Fasting glucose was significantly positively associated with Bacteroides vulgatus, whereas neonatal body weight inversely correlated with Eubacterium ramulus. In gestational obesity mice, LTA administration reduced weight gain, visceral/gonadal adiposity, metabolic markers (fasting glucose/insulin/cholesterol), gut barrier dysfunction (TNF-α, IL-6, IL-8, Claudin-2), and linked to FXR/FGF15 pathway alterations. Furthermore, LTA intervention suppressed MCP-1, IL-1β, F4/80 and hepatic lipid metabolism regulators (CD36, SREBP1c, SCD1, GLUT4, Cyp7a1, IRS-1), while also mitigating placental tissue junction zone abnormalities and pup weight. To sum up, LTA-mediated attenuation of adverse pregnancy outcomes associates with FXR/FGF15 pathway alterations, concomitant with restoration of metabolic homeostasis and inflammation suppression.}, }
@article {pmid41017030, year = {2025}, author = {Jones, JC and García, OG and Villalba, JA and Hinojosa, R and Taylor, ML and Annambhotla, P and Kapturczak, MH and Mayes, B and Karpathy, SE and Gleaton, AN and Moon, L and Singleton, J and Basavaraju, SV and Paddock, CD}, title = {Organ Donor Transmission of Rickettsia typhi to Kidney Transplant Recipients, Texas, USA, 2024.}, journal = {Emerging infectious diseases}, volume = {31}, number = {10}, pages = {1893-1900}, pmid = {41017030}, issn = {1080-6059}, mesh = {Adult ; Animals ; Female ; Humans ; Male ; Middle Aged ; *Kidney Transplantation/adverse effects ; *Rickettsia typhi/isolation &amp; purification ; Texas/epidemiology ; *Tissue Donors ; *Transplant Recipients ; *Typhus, Endemic Flea-Borne/transmission/microbiology/epidemiology/diagnosis ; }, abstract = {Murine typhus, a fleaborne disease caused by the bacterium Rickettsia typhi, is found throughout temperate and tropical regions of the world. Transmission of R. typhi to humans involves several species of fleas, and most infections result from direct inoculation of R. typhi-infected flea feces into abrasions in the skin. We describe the transmission of R. typhi from an organ donor in Texas, USA, to 2 kidney transplant recipients. The donor and 1 recipient died from the infection. The occurrence of R. typhi transmission via transplantation is a harbinger for the reemergence of murine typhus in some of the most densely populated metropolitan areas of the United States. Our findings reinforce the need to improve healthcare provider and public awareness of this life-threatening but treatable infection.}, }
@article {pmid41017540, year = {2026}, author = {Ticinesi, A and Spaggiari, R and Passaro, A and Volpato, S}, title = {Gut microbiota dysbiosis and its relation to osteoporosis and sarcopenia in older people.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {29}, number = {1}, pages = {4-14}, doi = {10.1097/MCO.0000000000001173}, pmid = {41017540}, issn = {1473-6519}, mesh = {Humans ; *Sarcopenia/microbiology ; *Gastrointestinal Microbiome/physiology ; *Osteoporosis/microbiology ; *Dysbiosis/complications/microbiology ; Aged ; Aging/physiology ; Probiotics/therapeutic use ; Bone Density ; }, abstract = {PURPOSE OF REVIEW: Gut microbiome is increasingly recognized as a modulator of the biology of aging. Several preclinical studies suggest that dysbiosis, typically arising in the older age, is associated with osteoporosis and sarcopenia. This review examines the recent findings on the mechanistic aspects of the gut-bone and gut-muscle axes in aging and provides a critical overview on their translation to clinical practice.<br><br>RECENT FINDINGS: Gut microbiome can modulate the pathophysiology of osteoporosis and sarcopenia through multiple mechanisms, particularly involving the production of bioactive mediators such as short-chain fatty acids (SCFAs), bile acids and tryptophan metabolites. Dysbiosis increases the risk of osteoporosis, fragility fractures and muscle wasting, with possible sex-specific differences, but the definition of GM traits associated with each condition is inconsistent across studies. Short-term microbiome-modifying treatments, including probiotics and functional foods, slowed down the age-related decline in bone mineral density and improved muscle function in a handful of small-sized clinical studies.<br><br>SUMMARY: Gut microbiome remains a very promising therapeutic target against osteoporosis and sarcopenia, but no recommendations can be made for clinical practice at the current state-of-art. Microbiome-targeted strategies may soon emerge as valuable adjuvant therapies in the management of age-related musculoskeletal decline.}, }
@article {pmid41018102, year = {2025}, author = {Wang, L and Qiao, W and Zhen, X and Zhang, Y and Dong, Z}, title = {Targeting the gut-liver axis in cholangiocarcinoma: mechanisms, therapeutic advances, and future directions.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1646897}, pmid = {41018102}, issn = {2234-943X}, abstract = {Cholangiocarcinoma (CCA), a highly aggressive biliary tract malignancy, exhibits rising incidence rates and an extremely poor prognosis. Recent studies reveal that gut-liver axis dysregulation drives CCA progression through gut microbiota dysbiosis, bile acid (BA) metabolic disturbances, and immune microenvironment remodeling. Clinical evidence highlights significant alterations in the gut and biliary microbial composition of CCA patients, which correlate with tumor stage, vascular invasion, and survival outcomes. Dysregulated BA metabolism in CCA, characterized by accumulation of primary conjugated BAs, promotes tumor invasiveness via interaction with specific BA receptors and fosters an immunosuppressive microenvironment. Emerging therapeutic strategies include antibiotics for pathogenic microbiota modulation, probiotics for microbial homeostasis restoration, fecal microbiota transplantation, and BA pathway modulators. Future directions necessitate integrating synthetic biology (engineered microbiota), multi-omics, and artificial intelligence to develop precision therapies. Targeting the gut-liver axis offers novel therapeutic perspectives for CCA; however, clinical translation demands deeper mechanistic insights and standardized protocols to address challenges such as microbiota heterogeneity and receptor signaling duality.}, }
@article {pmid41019532, year = {2025}, author = {Li, Z and Zhang, L and Wan, Z and Liu, H and Zhang, T and Li, Y}, title = {Therapeutic potential of the gut commensal bacterium Parabacteroides goldsteinii in human health and disease treatment.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1618892}, pmid = {41019532}, issn = {1664-302X}, abstract = {The gut microbiota, as a critical guardian of human health, maintains physiological homeostasis, modulating immunity, and facilitates nutrient metabolism. Parabacteroides goldsteinii, a probiotic gut commensal, has garnered increasing scientific attention. This review systematically examines its biological characteristics, then analyzes mechanisms promoting health (immunomodulation, metabolic regulation, and intestinal barrier reinforcement), and finally evaluates disease associations (metabolic disorders, neurological diseases, inflammatory conditions, and malignancies). Current evidence shows that therapeutic efficacy against obesity, non-alcoholic fatty liver disease, inflammatory bowel disease, autism spectrum disorder, and colorectal cancer via short-chain fatty acids secretion, bile acid transformation, and host immunity modulation. Dietary factors (e.g., inulin), pharmacological agents (e.g., metformin, aspirin), and lifestyle interventions (e.g., exercise synbiotics) dynamically regulate its abundance, underscoring therapeutic potential. Despite translational challenges-like optimizing cultivation, dose-response characterization, and genetic tool development-emerging applications (engineered probiotics, fecal microbiota transplantation, and synthetic biology) highlight broad prospects. Future research should prioritize context-dependent mechanisms across diseases and refined translation strategies for microbiome-based precision medicine.}, }
@article {pmid41019955, year = {2025}, author = {Hajjar, J and Voigt, AY and Conner, ME and Swennes, AG and Fowler, S and Calarge, C and Mendonca, DD and Armstrong, D and Chang, CY and Walter, JE and Butte, MJ and Savidge, T and Oh, J and Kheradmand, F and Petrosino, JF}, title = {Gut dysbiosis patterns in CVID patients with noninfectious complications observed in a germ-free mouse model through fecal microbiota transplantation.}, journal = {Journal of human immunity}, volume = {1}, number = {1}, pages = {}, pmid = {41019955}, issn = {3065-8993}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; }, abstract = {Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with NIC. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of INF CVID patients. Fecal microbiota transplant from NIC, INF, and their household controls into germ-free mice revealed gut dysbiosis patterns only in recipients from CVID patients with NIC, but not in those from INF CVID or household controls recipients. Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with NIC to germ-free mice recapitulates microbiome alterations observed in the donors.}, }
@article {pmid41020845, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Microbial Metabolomes in Alzheimer's Disease: From Pathogenesis to Therapeutic Potential.}, journal = {Current issues in molecular biology}, volume = {47}, number = {9}, pages = {}, pmid = {41020845}, issn = {1467-3045}, abstract = {BACKGROUND: Accumulating evidence underscores the potential role of the gut microbiome in the pathogenesis of Alzheimer's disease, but much remains to be clarified. This review examines current evidence linking gut microbiome dysbiosis to Alzheimer's disease, focusing on microbial metabolomes and their mechanistic role, as well as on the potential of therapeutic approaches targeting the gut microbiome.<br><br>METHODS: A narrative, non-systematic examination of the literature was conducted to provide a comprehensive overview of the subject under examination. Database searches were performed in PubMed, Scopus, and Web of Science between June and July 2025.<br><br>RESULTS: Alzheimer's disease is linked to reduced gut microbial diversity and altered bacterial taxa. Gut microbiome shifts correlate with inflammation and may drive Alzheimer's disease progression via the microbiota-gut-brain axis. Microbial amyloids and bacterial products can cross both the intestinal and blood-brain barrier, triggering neuroinflammation and promoting amyloid and tau pathologies. Short-chain fatty acids produced by the gut microbiome regulate neuroinflammation, lipid metabolism, and gene expression, impacting Alzheimer's disease pathology. Therapeutics targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating neuroinflammation, reducing amyloid and tau pathology, and improving cognitive function in Alzheimer's disease.<br><br>CONCLUSIONS: The gut microbiome significantly influences Alzheimer's disease pathogenesis, and its modulation offers potential to slow progression. However, further research is required to validate effective clinical interventions.}, }
@article {pmid41022353, year = {2026}, author = {Belvončíková, P and Gardlík, R}, title = {Faecal microbiota transplantation for urinary tract infections.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {32}, number = {2}, pages = {260-263}, doi = {10.1016/j.cmi.2025.09.018}, pmid = {41022353}, issn = {1469-0691}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Urinary Tract Infections/therapy/microbiology ; Gastrointestinal Microbiome ; Dysbiosis/therapy/microbiology ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Recurrent urinary tract infections (rUTIs) are a major clinical burden, increasingly complicated by multidrug-resistant organisms (MDROs) and antibiotic overuse. Growing evidence implicates gut microbiota dysbiosis as a key contributor to urinary tract infections (UTI) susceptibility, with the gastrointestinal tract acting as a reservoir for uropathogens.<br><br>OBJECTIVES: This review examines the emerging role of faecal microbiota transplantation (FMT) as a therapeutic strategy for rUTIs. We synthesize findings from human studies and case reports, evaluate microbiological and clinical outcomes post-FMT, and discuss mechanistic insights, safety concerns, and future research directions.<br><br>SOURCES: We reviewed peer-reviewed publications up to May 2025 using PubMed and Web of Science. Included sources comprised clinical trials, cohort studies, case reports, economic analyses, and expert reviews concerning FMT and UTIs.<br><br>CONTENT: FMT has shown promise in reducing rUTI episodes, particularly in patients with underlying gut dysbiosis or MDRO colonization. Clinical studies and case reports consistently report decreased UTI frequency, lower MDRO burden, and increased gut microbiota diversity post-FMT. Patients previously refractory to antibiotic prophylaxis achieved prolonged infection-free periods. Microbiome analyses often reveal reductions in uropathogen abundance and shifts towards donor-like microbial communities. However, outcomes vary, and some patients experience persistence or transmission of uropathogens from donor stool, underscoring safety and screening concerns.<br><br>IMPLICATIONS: FMT represents a promising microbiome-based intervention for managing rUTIs, particularly in complex or antibiotic-resistant cases. Randomized controlled trials are needed to assess efficacy, define optimal protocols, and address safety concerns. Standardized practices will be essential to integrate FMT into routine UTI care.}, }
@article {pmid41024120, year = {2025}, author = {Huang, J and Tang, J and Wang, Z and Zhang, H and Wang, F and Tang, X and Zhou, X}, title = {Efficacy and safety of fecal microbiota transplantation for ulcerative colitis: protocol for an umbrella review of systematic reviews.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {182}, pmid = {41024120}, issn = {2046-4053}, support = {YN2024GZRPY030//Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Systematic Reviews as Topic ; *Colitis, Ulcerative/therapy ; Research Design ; Meta-Analysis as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: A growing number of systematic reviews and meta-analyses (SRs/MAs) based on randomized clinical trials have been carried out to assess the efficacy of fecal flora transplantation (FMT) in the treatment of ulcerative colitis (UC). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding FMT for UC. This is a protocol for an overview of SRs/MAs. We will search eight public electronic databases for the studies of FMT on UC. SRs/MAs of clinical trials evaluating the effect of FMT on UC will be included. Two independent authors will screen titles and abstracts retrieved in the literature search and select reviews meeting the eligibility criteria for full-text review. The methodological quality, reporting quality, and evidence quality of the included studies will be assessed, using, respectively, the AMSTAR-2 tool, PRISMA checklists, and GRADE system.<br><br>RESULTS: From this study, the methodological quality, reporting quality, and evidence quality of the included SRs/MAs will be evaluated. We will also evaluate the efficacy of FMT in patients with UC.<br><br>IMPLICATIONS: We will ascertain the efficacy of FMT in UC patients to provide evidence to guide the treatment of UC with FMT in the future.<br><br>ETHICS AND DISSEMINATION: As a secondary study based on SRs/MAs, this study does not contain any individual patient information or violate participant rights. It is therefore not necessary to obtain ethics approval. We will report our findings in peer-reviewed journals or disseminate them at relevant conferences.<br><br>TRAIL REGISTRATION: Systematic review registration. PROSPERO CRD42023388682.}, }
@article {pmid41024199, year = {2025}, author = {Yang, G and Gao, L and Liu, Y and Xu, X and Yang, W}, title = {The impact of altered intestinal microbiota on intestinal immune function after acute exhaustive exercise in mice.}, journal = {BMC sports science, medicine &amp; rehabilitation}, volume = {17}, number = {1}, pages = {279}, pmid = {41024199}, issn = {2052-1847}, support = {ZL22018//2022 Campus-Level Talent Special Project/ ; }, abstract = {PURPOSE: Long-term training or intense exercise alters gut microbiota. This study aimed to determine the effects of microbiota on colonic permeability and immune function in mice subjected to acute exhaustive exercise.<br><br>METHODS: C57BL/6 mice were randomly divided into the blank control (C), no exercise experience (NE), under a training protocol (E), phosphate-buffered saline (PBS) transplantation (PT), and fecal microbiota transplantation (FMT) groups. The E group underwent 14 weeks of moderate intensity training. At the end of the 14th week, fecal suspensions were prepared from mice in Group E and transplanted into Group FMT via enema, while Group PT received PBS enemas twice daily for 7 days. Prior to transplantation, both Groups PT and FMT were gavaged with antibiotics for 7 days, followed by 3 days of polyethylene glycol bowel cleansing. The C group was euthanized after a rest period, and the other groups were euthanized after acute exhaustive exercise. Colonic zonulin, occludin, ZO-1, CD14, TLR-4, MD-2, and TNF-&#x3b1; protein levels were detected via western blot, and enzyme-linked immunosorbent assays were used to detect serum LPS, IL-6, and colonic sIgA.<br><br>RESULTS: Colonic zonulin protein expression was significantly higher (P&#x2009;<&#x2009;0.01) and occludin and ZO-1 expression levels were significantly lower in the NE, PT, and FMT groups compared with the C group (P&#x2009;<&#x2009;0.01). ZO-1 was significantly higher in the FMT group compared with the PT group (P&#x2009;<&#x2009;0.05). Colonic MD-2, TLR-4, and CD14 expression levels were significantly lower in the FMT group compared with the PT group (P&#x2009;<&#x2009;0.01, P&#x2009;<&#x2009;0.05, and P&#x2009;<&#x2009;0.05, respectively). Serum LPS and IL-6 expression levels were significantly lower in the FMT group compared with the PT group (P&#x2009;<&#x2009;0.01). Colonic sIgA levels were significantly lower in the NE, E, PT, and FMT groups compared with the C group (P&#x2009;<&#x2009;0.01), and levels in the FMT group were significantly higher than the levels in the PT group (P&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: Fecal microbiota transplantation attenuated the increased intestinal permeability, enhanced intestinal immune function, and reduced systemic inflammation induced by acute exhaustive exercise in mice without prior exercise experience.}, }
@article {pmid41024761, year = {2025}, author = {Quiñones-Calvo, M and Alvarado-Jara, R and García-Renedo, P and Stallings, E and Grifol-Clar, E and Fernández-Rodríguez, CM}, title = {Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival.}, journal = {World journal of gastroenterology}, volume = {31}, number = {35}, pages = {109987}, pmid = {41024761}, issn = {2219-2840}, mesh = {Humans ; *Hepatitis, Alcoholic/mortality/therapy ; Liver Transplantation ; *Adrenal Cortex Hormones/therapeutic use ; Treatment Outcome ; Severity of Illness Index ; Time Factors ; Nutritional Support/methods ; }, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) carries a 90-day mortality rate approaching 50%. Management includes corticosteroids, nutritional support, and early liver transplantation in selected cases. However, the mid-term impact of available therapies remains unclear. This systematic review provides a critical evaluation of treatments for SAH, specifically focusing on survival or mortality at 90 days as an essential window that captures short- and mid-term outcomes. The 90-day window is clinically significant, as it reflects the remission of systemic inflammation, early liver recovery, and minimizes confounding long-term behaviors such as alcohol relapse.<br><br>AIM: To review the effect of different treatments for SAH on survival and mortality at 90 days.<br><br>METHODS: A systematic search of PubMed and EMBASE (last updated March 2025) was performed without language restrictions, focusing on studies published in the last decade. Study selection and data extraction were performed independently by at least two reviewers. Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools. Due to heterogeneity in study designs and interventions, a meta-analysis was not feasible. A qualitative synthesis was conducted using narrative summaries and evidence tables.<br><br>RESULTS: Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE. Of these 2161 studies, 618 were duplicates and therefore removed. A total of eight studies were included in qualitative synthesis. Among the included publications, six were randomized control trials (RCT) and two were retrospective cohort studies. These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids (n = 2), pentoxifylline (n = 1), anakinra plus zinc (n = 2), granulocyte colony-stimulating factor (n = 1), amoxicillin-clavulanate (n = 1), fecal microbiota transplantation (n = 1) or extracorporeal liver assist device (n = 1). While most studies were conducted in Western countries, two had a global scope.<br><br>CONCLUSION: Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit. These results highlight the need for multicenter, biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.}, }
@article {pmid41024767, year = {2025}, author = {Ezzat, WM}, title = {Machine learning as an artificial intelligence application in management of chronic hepatitis B virus infection.}, journal = {World journal of gastroenterology}, volume = {31}, number = {35}, pages = {109776}, pmid = {41024767}, issn = {2219-2840}, mesh = {Humans ; *Hepatitis B, Chronic/therapy/microbiology/diagnosis/virology ; *Machine Learning ; *Gastrointestinal Microbiome ; *Hepatitis B virus/pathogenicity ; Algorithms ; Artificial Intelligence ; Antiviral Agents/therapeutic use ; Supervised Machine Learning ; }, abstract = {Let's review the role of gut microbiota in pathogenesis of chronic hepatitis B infection as addressed in by Zhu et al. Zhu et al used high-throughput technology to characterize the microbial ecosystems, which led to an explosion of various types of molecular profiling data, such as metagenomics, metatranscriptomics, and metabolomics. To analyze such data, machine learning (ML) algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and, particularly, for generating models that can accurately predict phenotypes. Strong evidence suggests that such gut microbiome-based stratification could guide customized interventions to benefit human health. Supervised learning includes designing an algorithm to fix a pre-identified problem. To get an answer, ML software must access data that have been nominated. On the other hand, unsupervised learning does not address any pre-defined problems. Bias should be eliminated as much as possible. In unsupervised learning, an ML algorithm works to identify data patterns without any prior operator input. This can subsequently lead to elements being identified that could not be conceived by the operator. At the intersection between supervised and unsupervised learning is semi-supervised ML. Semi-supervised learning includes using a partially labeled data set. The ML algorithm utilizes unsupervised learning to label data (that has not yet been labelled) by drawing findings from the labeled data. Then, supervised techniques can be used to solve defined problems involving the labeled data. Reinforcement learning, which is similar to supervised learning in the meaning, is goal-oriented. Reinforcement learning does not need labeled data, instead, it is provided with a set of regulations on a problem. An algorithm will carry out operations to try to answer questions involving the problem. Based on obtained data of gut microbiota, various therapeutic modalities can be applied: Prebiotics, probiotics, postbiotics, engineered bacteria, bacteriophage, and novel microbe-materials therapeutic system and fecal transplantation. In conclusion, ML is an artificial intelligence application that helps in providing new perspectives on tailored therapy. Furthermore, assessing the impact of gut microbiota modification is a critical step in advanced liver disease management. These new artificial intelligence techniques although promising, still require further analysis and validation in future studies.}, }
@article {pmid41024876, year = {2025}, author = {Mishra, AK and Goel, A}, title = {Stratification and selection of therapies to improve survival in severe alcoholic hepatitis.}, journal = {World journal of hepatology}, volume = {17}, number = {9}, pages = {109118}, pmid = {41024876}, issn = {1948-5182}, abstract = {Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. The SAH population exhibits extreme heterogeneity in disease severity, clinical presentation, decompensations, and outcomes. Nonetheless, improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis. Currently, steroids are the standard of care for SAH with Maddrey's discriminant function > 32 and model for end stage liver disease > 20; however, they have limited usage due to ineligibility in approximately two-third of such patients. Approximately 25% of patients do not respond to steroids and require alternative therapies. An array of evolving therapies, such as granulocyte colony-stimulating factors, plasma exchange, fecal microbiota transplantation, antibiotics, anti-cytokine therapies, and N-acetylcysteine, showing variable success, are emerging. Hence, it is also crucial to select appropriate therapy. The present review discusses the standard of care, the existing therapies, risk stratification for outcomes, and the selection of appropriate therapy to improve survival in SAH patients.}, }
@article {pmid41024883, year = {2025}, author = {Abdelwahab, MM and Ghattas, AS and Tawheed, A}, title = {Implications of gut microbiota in hepatic and pancreatic diseases: Gut-liver-pancreas axis.}, journal = {World journal of hepatology}, volume = {17}, number = {9}, pages = {109965}, pmid = {41024883}, issn = {1948-5182}, abstract = {The gut-liver-pancreas axis (GLPA) is a critical network shaped by gut microbiota (GM) and their metabolites, essential for maintaining metabolic and immune balance. Disruption of this microbial equilibrium, known as dysbiosis, contributes to the development and progression of various hepatic and pancreatic diseases. Through mechanisms such as increased intestinal permeability and exposure to microbial products-including lipopolysaccharide, trimethylamine-N-oxide, and secondary bile acids-dysbiosis promotes inflammation, oxidative stress, insulin resistance, and carcinogenesis. These changes are linked to conditions including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, hepatocellular carcinoma, pancreatitis, pancreatic ductal adenocarcinoma, and diabetes. Emerging tools like stool metagenomics and serum metabolomics help identify microbial biomarkers for diagnosis and risk stratification. While interventions such as probiotics, dietary changes, and fecal microbiota transplantation aim to restore microbial balance, their success remains inconsistent. This work aims to highlight the pathogenic role of GM across the GLPA, with special emphasis on the underexplored gut-pancreas connection. Advancing our understanding of the GLPA can unlock novel microbiota-targeted approaches for early diagnosis and treatment of hepatopancreatic diseases.}, }
@article {pmid41024984, year = {2025}, author = {Marano, G and Anesini, MB and Milintenda, M and Acanfora, M and d'Abate, C and Lisci, FM and Pirona, I and Traversi, G and Pola, R and Gaetani, E and Mazza, M}, title = {Discovering a new paradigm: Gut microbiota as a central modulator of sexual health.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {3}, pages = {107823}, pmid = {41024984}, issn = {2150-5330}, abstract = {The gut microbiota plays a pivotal role in human health, influencing diverse physiological processes, including those related to sexual health. Emerging evidence suggests a bidirectional relationship between the gut microbiota and sexual health, mediated by its impact on systemic inflammation, hormonal regulation, and immune function. A balanced gut microbiota supports optimal levels of sex hormones, such as estrogen and testosterone, which are critical for sexual function and reproductive health. Additionally, gut-derived metabolites such as short-chain fatty acids contribute to maintaining mucosal barrier integrity and regulating immune responses, which are essential for protecting against infections that may impair sexual health. Conversely, dysbiosis, an imbalance in gut microbial composition, has been linked to conditions such as erectile dysfunction, polycystic ovary syndrome, and reduced libido, emphasizing its role in sexual dysfunction. Lifestyle factors, including diet, stress, and antibiotic use, can modulate the gut microbiota and, consequently, sexual health outcomes. Recent therapeutic approaches, such as probiotics, prebiotics, and fecal microbiota transplantation, offer potential for restoring gut balance and improving sexual health. This review highlights the central role of the gut microbiota in sexual health, emphasizing its importance as a target for therapeutic interventions to enhance overall well-being.}, }
@article {pmid41024986, year = {2025}, author = {Singla, N and Singla, K and Attauabi, M and Aggarwal, D}, title = {Gut-skin axis: Emerging insights for gastroenterologists-a narrative review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {3}, pages = {108952}, pmid = {41024986}, issn = {2150-5330}, abstract = {The gut-skin axis (GSA) embodies a complex, bidirectional interaction between the gastrointestinal (GI) system and skin, driven by immune modulation, systemic inflammation, and gut microbiota dynamics. Disruptions in gut homeostasis, including dysbiosis and increased intestinal permeability, are increasingly recognized as contributing factors to dermatological conditions such as acne, psoriasis, and atopic dermatitis. For gastroenterologists, appreciating this interplay is essential, as diseases and their treatments frequently present with cutaneous manifestations, offering diagnostic and therapeutic insights. This review explores the underlying mechanisms of the GSA, focusing on the microbiome and its metabolites as key regulators of inflammation and immunity. It underscores the clinical importance of microbiome-targeted therapies, such as probiotics, prebiotics, and dietary modifications, in addressing both GI and dermatological disorders. Furthermore, the review examines the influence of GI conditions, including inflammatory bowel disease and celiac disease on skin health. This article seeks to equip gastroenterologists with practical insights for identifying, diagnosing, and managing skin conditions associated with GI health. The article also highlights the current limitations in knowledge regarding the GSA. The GSA represents a promising avenue for therapeutic advancements, encouraging interdisciplinary collaboration between gastroenterology and dermatology to optimize patient care.}, }
@article {pmid41027059, year = {2025}, author = {Shan, R and Wang, K and Chen, Q and Bao, L and Wu, K and Zhao, Y and Han, Y and Gao, Y and Zhang, N and Hu, X and Fu, Y and Zhao, C and Bian, W}, title = {Phytosphingosine alleviates DSS-induced colitis by regulating the gut microbiota and inflammatory responses.}, journal = {International immunopharmacology}, volume = {166}, number = {}, pages = {115610}, doi = {10.1016/j.intimp.2025.115610}, pmid = {41027059}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate ; *Colitis/chemically induced/drug therapy/microbiology/therapy/immunology ; Mice ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; *Sphingosine/analogs &amp; derivatives/therapeutic use/pharmacology ; Male ; Disease Models, Animal ; Colon/drug effects/pathology/microbiology ; NF-kappa B/metabolism ; Cytokines/metabolism ; Humans ; Dysbiosis ; }, abstract = {Inflammatory bowel disease is becoming increasingly prevalent and represents a major concern in global public health. However, conventional therapies often come with various adverse effects. Phytosphingosine (PS), a key metabolite in sphingolipid metabolism, is widely found in plants and fungi and possesses notable anti-inflammatory properties. In this study, we aimed to evaluate the protective effects of PS against dextran sulfate sodium (DSS)-induced experimental colitis in mice and elucidate its underlying mechanisms. Our results showed that oral administration of PS significantly alleviated DSS-induced colonic injury and reduced levels of proinflammatory cytokines such as TNF-α and IL-1β. Additionally, PS improved intestinal barrier function disrupted by DSS, as indicated by increased expression of mucin-2 and tight junction proteins. Furthermore, PS suppressed the activation of the NF-κB signaling pathway, oxidative stress and enhanced PPARγ expression. We also observed that PS mitigated DSS-induced gut dysbiosis in mice, characterized by an increase in Bacteroidota and a decrease in Proteobacteria. To explore the role of the gut microbiota in PS-mediated protection against colitis, fecal microbiota transplantation (FMT) was conducted in DSS-treated mice. Recipients of FMT from PS-treated donors exhibited reduced inflammatory responses and improved intestinal integrity, accompanied by a higher abundance of Bacteroidota in the gut. Additionally, PS treatment modified the profile of short-chain fatty acids in the mice, with a notable increase in the levels of butyrate and propionate. Overall, our findings demonstrate that PS attenuates DSS-induced colitis in mice through modulation of the gut microbiota, providing a potential strategy for IBD intervention via microbiota regulation.}, }
@article {pmid41028744, year = {2025}, author = {Chen, C and Su, Q and Zi, M and Hua, X and Zhang, Z}, title = {Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {190}, pmid = {41028744}, issn = {2055-5008}, mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Fusobacterium nucleatum ; }, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, yet improvements in survival have been modest despite advances in conventional therapies. The gut microbiota has emerged as a critical player in CRC pathogenesis and a promising therapeutic target to enhance clinical outcomes. Mounting evidence implicates specific microorganisms, notably Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis, in tumor initiation and progression through DNA damage, inflammatory modulation, and immunosuppressive mechanisms. Clinical trials investigating microbiome modulators-including faecal microbiota transplantation, probiotics, prebiotics, and engineered biotherapeutics-highlight their potential to augment chemotherapy, radiotherapy, immunotherapy, and surgical recovery, with encouraging preliminary efficacy in treatment-resistant CRC subtypes. Nonetheless, translating microbiome interventions into standardized clinical practice requires rigorous mechanistic validation, robust biomarker development, and careful management of safety concerns. Future research must focus on integrating high-resolution multi-omics, spatial microbiome mapping, artificial intelligence analytics, and innovative microbiome-targeted nanotechnologies to precisely reshape gut microbial communities, thereby ushering in a new era of precision oncology in colorectal cancer management.}, }
@article {pmid41028942, year = {2025}, author = {Ma, S and Li, X and Shang, S and Zhai, Z and Wu, M and Song, Q and Chen, D}, title = {Targeting gut microbiota and metabolites in cancer radiotherapy.}, journal = {Clinical and translational medicine}, volume = {15}, number = {10}, pages = {e70481}, pmid = {41028942}, issn = {2001-1326}, mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects/drug effects/physiology/immunology ; *Neoplasms/radiotherapy ; *Radiotherapy/methods/adverse effects ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation/methods ; }, abstract = {Radiotherapy (RT) is a cornerstone in cancer treatment, but often causes radiation-induced injury. Accumulating evidence points to the gut microbiota in modulating immune functions and maintaining intestinal integrity to impact RT efficacy. This review examines the current understanding of intestinal flora and their metabolites within the context of RT. We outlined the current research applications in how microbiota-targeted strategies such as probiotics, prebiotics, dietary interventions, and faecal microbiota transplantation could restore microbial balance, reduce toxicity, and improve patient prognosis. Microbial byproducts such as short-chain fatty acids, bile acids and tryptophan exhibit protective effects against radiation damage, supporting immune modulation and enhancing tumour radiosensitivity. These microbial products underscore the potential of gut microbiota-targeted therapies as adjunctive treatments in RT, with implications for reducing toxicity and personalizing cancer care. All these strategies targeting gut microbiota and metabolites potentially aim to develop innovative therapies that boost RT effectiveness while minimizing side effects, and finally revolutionizing personalized cancer treatment. KEY POINTS: RT alters gut microbiota composition and contributes to intestinal injury and systemic toxicity. Gut microbiota regulate mucosal integrity, immune responses and therapeutic outcomes of RT. Microbial metabolites, including SCFAs, BAs and tryptophan derivatives, protect against radiation injury and enhance tumour radiosensitivity. Microbiota-targeted interventions (e.g. probiotics, prebiotics, dietary strategies, FMT) show promise for reducing RT-related toxicity and improving patient prognosis.}, }
@article {pmid41030253, year = {2025}, author = {Bautista, J and Villegas-Chávez, JA and Bunces-Larco, D and Martín-Aguilera, R and López-Cortés, A}, title = {The microbiome as a therapeutic co-driver in melanoma immuno-oncology.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1673880}, pmid = {41030253}, issn = {2296-858X}, abstract = {Melanoma, one of the most aggressive skin cancers, remains a major clinical challenge due to its high metastatic potential, therapy resistance, and rising global incidence. Although immune checkpoint inhibitors have transformed management, variable responses and acquired resistance limit durable benefit. Emerging evidence positions the microbiome as a pivotal determinant of melanoma biology and therapeutic outcomes. Dysbiosis in the skin, gut, and oral compartments fosters tumor-promoting inflammation, immune evasion, and oncogenic signaling, whereas enrichment of specific commensals, such as Akkermansia muciniphila and Faecalibacterium prausnitzii, enhances antigen presentation and effector T cell activity, improving ICI efficacy. Mechanistically, microbial metabolites, including short-chain fatty acids, tryptophan derivatives, and bile acids, modulate epigenetic programs, G-protein-coupled receptor signaling, and oncogenic cascades such as PI3K-AKT and RAS-RAF-MEK-ERK. Beyond the gut, cutaneous microbiota such as Staphylococcus epidermidis exert direct antitumor effects, while pathogenic oral taxa propagate systemic inflammation that shapes the melanoma tumor microenvironment. These insights are driving the development of microbiome-targeted interventions, including fecal microbiota transplantation, defined consortia, probiotics, and dietary modulation, with early clinical studies showing the potential to overcome resistance to immunotherapy. Integration of circadian biology further suggests that host-microbiome-immune interactions are temporally regulated, opening new dimensions for therapeutic optimization. By synthesizing mechanistic, clinical, and translational advances, this review highlights the microbiome as both a biomarker and a therapeutic axis in melanoma, underscoring its promise to transform precision immuno-oncology.}, }
@article {pmid41030553, year = {2025}, author = {Xie, H and Zhu, S and Xue, P and Xie, F and Zhao, L and Chu, X}, title = {Yanggan Yizhong decoction prevents liver metastasis from colorectal cancer by targeting myeloid-derived suppressor cells through the regulation of bile acid metabolism in the gut microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1639442}, pmid = {41030553}, issn = {1664-302X}, abstract = {INTRODUCTION: Liver metastasis (LM) exhibits a high incidence in colorectal cancer (CRC), yet effective preventive therapies are still lacking. Based on the prophylactic principle of harmonizing the liver and spleen, Yanggan Yizhong (YGYZ) decoction has shown clinical effectiveness in preventing LM. This study aims to explore the active components and underlying mechanisms of YGYZ in the prevention and treatment of LM.<br><br>METHODS: The components of YGYZ were analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UPLC-HR-MS/MS). The LM mouse model was established through intrasplenic injection of ct26-luc cells to evaluate the effect and safety of YGYZ on LM. Fecal microbiota transplantation (FMT) was performed to create microbiota-altered mice, and liver tissue morphology along with HE staining was utilized to dynamically monitor LM progression. Flow cytometry and inflammatory factor assays were conducted to assess the immune microenvironment (IME) of the liver pre-metastatic niche (PMN). Additionally, 16S rRNA sequencing and bile acid (BA) metabolomics were employed to investigate the role of YGYZ in modulating gut microbiota (GM) and BA. Western blot analysis was performed to identify key targets of YGYZ in the GM-BA-immunity pathway.<br><br>RESULTS: UPLC-HR-MS/MS analysis identified 95 compounds in YGYZ, Glycyrrhizic acid, Bergapten, and Icariin as the main compounds. YGYZ and its FMT inhibited LM of CRC with safety, inhibited CD11b+Ly6G+ and CD11b+Ly6C+ cells in the pre-metastatic stage, decreased CD11b+Ly6G+ cells in the metastatic stage, reduced immunosuppressive factors such as Arg-1, TGF-&#x3b2;, and IL-10, and improved the CD4+/CD8+ T-cell ratio, regulating liver PMN. YGYZ also improved the GM structure, particularly decreasing the abundance of Clostridium in the LM mice. For the hepatic BAs profile, YGYZ increased the content of primary BAs-Nor cholic acid (NorCA), Taurocholic acid, Taurochenodeoxycholic Acid, and Tauro &#x3b2;-Muricholic Acid, and secondary BAs-ursodeoxycholic acid (UDCA), with similar trends in FMT, while YGYZ decreased NorCA, &#x3b1;-Muricholic acid, Tauro &#x3b1;-Muricholic acid, and UDCA in the fecal BA profile. YGYZ and its FMT dampened the protein expression of IL-6, STAT3, and pSTAT3, but only YGYZ downregulated kruppel-like factor 15 (KLF15).<br><br>CONCLUSION: YGYZ may prevent LM by remodeling the GM and synergistically inhibiting KLF15 to regulate the enterohepatic BA cycle, and suppressing the proliferation and activation of myeloid-derived suppressor cells through the IL-6/STAT3 pathway, thereby improving IME of liver PMN.}, }
@article {pmid41031618, year = {2025}, author = {Xu, F and Yue, Y and Sun, D}, title = {Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis-mediated postoperative cognitive dysfunction in aged mice.}, journal = {The international journal of neuropsychopharmacology}, volume = {28}, number = {10}, pages = {}, pmid = {41031618}, issn = {1469-5111}, mesh = {Animals ; *Sirtuin 1/metabolism ; *Dysbiosis/metabolism/complications ; Male ; Mice ; *Postoperative Cognitive Complications/metabolism/microbiology/etiology ; *Gastrointestinal Microbiome/physiology/drug effects ; *AMP-Activated Protein Kinases/metabolism ; Signal Transduction/drug effects/physiology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Hippocampus/metabolism ; Disease Models, Animal ; Probiotics/pharmacology ; Resveratrol/pharmacology ; Aging ; Carbazoles ; }, abstract = {OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a prevalent complication in older patients who undergo surgery that requires anesthesia. This study explored the role of the adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator factor 2-related enzyme 1 (SIRT1) pathway in gut dysbiosis-mediated POCD in aged mice.<br><br>METHODS: POCD was induced in aged male mice via open tibial fracture surgery under isoflurane anesthesia. Mice then received the probiotic VSL#3, the SIRT1 inhibitor EX527, and the AMPK/SIRT1 activator resveratrol. Fecal microbiota transplantation was conducted in aged POCD mice. Mouse cognitive function was assessed using the Morris water maze and novel object recognition tests. Mouse histopathological changes were observed via hematoxylin-eosin staining. Iba1+/GFAP+ activation was assessed via immunofluorescence, and proinflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-1&#x3b2;, and IL-6) in the hippocampus were determined via enzyme-linked immunosorbent assay. Gut microbiota compositions were detected via 16S rRNA sequencing. Hippocampal pAMPK/AMPK and SIRT1 levels were assessed by western blot.<br><br>RESULTS: Aged POCD mice exhibited prolonged escape latency, reduced platform crossings, and an impaired object discrimination rate on postoperative day 7. Severe hippocampal CA1 damage, increased Iba1+/GFAP+ cell numbers, elevated proinflammatory cytokines, and gut dysbiosis were also observed. The probiotic VSL#3 ameliorated gut dysbiosis, alleviated POCD, and reduced neuroinflammation. Gut microbiota from POCD mice exacerbated cognitive deficits and neuroinflammation in aged mice, while clearance of the gut microbiota improved outcomes. VSL#3 improved POCD in aged mice by balancing the gut microbiota through the AMPK/SIRT1 pathway. The AMPK/SIRT1 pathway activation mitigated POCD.<br><br>CONCLUSION: VSL#3 balanced the gut microbiota and suppressed neuroinflammation in the hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice. Significance Statement Postoperative cognitive dysfunction (POCD) is a common complication in older adults after surgery, causing memory loss and difficulty thinking. In this study, using aged male mice (Mus musculus) we found that an imbalance in gut bacteria can worsen POCD by increasing brain inflammation. Treatment with the probiotic VSL#3 restored healthy gut bacteria, reduced brain inflammation, and improved memory through the AMPK/SIRT1 pathway. These findings suggest that targeting the gut-brain connection may help prevent POCD in older surgical patients.}, }
@article {pmid41032750, year = {2026}, author = {Gurer Kluge, EE and Meedt, E and Feicht, J and Cao, K and Hiergeist, A and Mamilos, A and Hirsch, D and Hoepting, M and Kattner, AS and Matos, C and Bülow, S and Thiele Orberg, E and Beckhove, P and Kandulski, A and Evert, M and Hildner, K and Kreutz, M and Edinger, M and Wolff, D and Herr, W and Poeck, H and Gessner, A and Weber, D and Kehr, B and Holler, E and Ghimire, S}, title = {Mucosal calprotectin is associated with severity of aGI-GVHD and poor outcomes after allogeneic stem cell transplantation.}, journal = {Blood}, volume = {147}, number = {8}, pages = {886-896}, pmid = {41032750}, issn = {1528-0020}, mesh = {Humans ; Male ; *Leukocyte L1 Antigen Complex/metabolism/genetics ; Female ; *Graft vs Host Disease/metabolism/pathology/etiology/mortality ; Middle Aged ; Adult ; Calgranulin A/genetics/metabolism ; Calgranulin B/genetics/metabolism ; *Intestinal Mucosa/metabolism/pathology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Toll-Like Receptor 4/metabolism/genetics ; Transplantation, Homologous ; Aged ; Severity of Illness Index ; Biomarkers/metabolism ; Young Adult ; Adolescent ; RNA, Messenger/genetics ; Toll-Like Receptor 2 ; }, abstract = {Calprotectin, a calcium- and zinc-binding protein that comprises the subunits S100A8 and S100A9, has been extensively studied as a biomarker of gastrointestinal (GI) inflammation through fecal and serum analyses. However, its role in intestinal tissue remains poorly understood because of the limited availability of biopsy specimens. In this study, we analyzed S100A8 and S100A9 messenger RNA (mRNA) expression in 579 intestinal biopsy specimens from allogeneic stem cell transplantation recipients and observed a strong association with acute GI graft-versus-host disease (aGI-GVHD; P< .001). Neutrophil infiltration correlated with the severity of aGI-GVHD (P< .001), and calprotectin expression was strongly linked to Toll-like receptor 4 (TLR4; P< .001) and TLR2 (P< .001) expression. Both TLR4 and aGI-GVHD were associated with elevated calprotectin mRNA levels (P< .001). When patients received broad-spectrum antibiotics at disease onset, calprotectin expression was suppressed (S100A8, P = .001; S100A9, P = .01). GI site-specific differences in calprotectin expression were identified: during severe aGI-GVHD, levels increased up to 30-fold in the small intestine and up to fivefold in the large intestine with respect to mild or no aGI-GVHD, whereas under homeostasis, the large intestine exhibited higher baseline calprotectin (P = .001). The high clinical relevance of this finding is evident from the observation that calprotectin expression was prognostic for transplant-related mortality. Our study suggests that (1) calprotectin is a potential biopsy biomarker in aGI-GvHD and (2) calprotectin expression and neutrophil infiltration possibly indicate translocation of microbiota, which (3) may be modulated by antibiotics.}, }
@article {pmid41033511, year = {2025}, author = {Bian, S and Zhu, S and Lu, J and Iqbal, M and Jamil, T and Kiani, FA and Dong, H and Dai, H and Zhang, X and Liu, F and Li, A}, title = {Targeting gut microbiota in non-alcoholic fatty liver disease (NAFLD): Pathogenesis and therapeutic insights: A review.}, journal = {International journal of biological macromolecules}, volume = {330}, number = {Pt 3}, pages = {147995}, doi = {10.1016/j.ijbiomac.2025.147995}, pmid = {41033511}, issn = {1879-0003}, mesh = {*Non-alcoholic Fatty Liver Disease/therapy/microbiology/pathology/etiology ; Humans ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Dysbiosis/microbiology ; Medicine, Chinese Traditional ; Lipid Metabolism ; Prebiotics ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by hepatic steatosis associated with insulin resistance, oxidative stress, inflammatory responses, and other factors. A precise pathogenesis of NAFLD remains unclear. Although it has emerged as a global health burden, current therapeutic options for example, probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT) have shown promising but varied efficacy. The use of traditional Chinese medicine (TCM) in NAFLD patients, has gained growing attention for its multi-targeted regulatory properties and the beneficial impacts of several natural product-formulations on gut microbiota, lipid metabolism and hepatic health. This article highlights the role of gut microbiota dysbiosis in the pathogenesis of NAFLD and explores the therapeutic strategies emphasizing the need of personalized multimodal approaches and robust clinical trials to validate these interventions.}, }
@article {pmid41033875, year = {2025}, author = {Kopple, JD and Bross, R and Ekramzadeh, M and Markovic, D and Lyzlov, A and Lodebo, BT and Mehrotra, R and Shah, AP}, title = {Lanthanum carbonate lowers serum phosphorus without altering body phosphorus burden in maintenance peritoneal dialysis patients: a randomized crossover trial.}, journal = {The American journal of clinical nutrition}, volume = {122}, number = {6}, pages = {1858-1868}, doi = {10.1016/j.ajcnut.2025.08.015}, pmid = {41033875}, issn = {1938-3207}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Chelating Agents/therapeutic use ; Cross-Over Studies ; Feces/chemistry ; *Hyperphosphatemia/drug therapy/etiology/blood ; *Kidney Failure, Chronic/therapy/complications/blood ; *Lanthanum/therapeutic use/pharmacology/administration &amp; dosage ; *Peritoneal Dialysis ; Phosphates/metabolism ; *Phosphorus/blood/urine/metabolism ; }, abstract = {BACKGROUND: Many studies show that intestinal phosphate binders reduce serum phosphorus concentrations in hyperphosphatemic patients with chronic kidney failure. To our knowledge, there are virtually no studies of the effect of these binders on fecal phosphate or body phosphate.<br><br>OBJECTIVES: This study examined the hypothesis that phosphate binders increase fecal phosphate and reduce body phosphorus burden.<br><br>METHODS: Seven adult patients undergoing maintenance peritoneal dialysis underwent full metabolic balance studies for phosphorus in a research ward while they ate a constant phosphorus diet. Patients were studied during a baseline period without phosphate binders and while they received, in random order, 3 doses of lanthanum carbonate (La2(CO3)3), 1.5, 3.0, and 4.5 g/d, in 3 divided daily doses for &#x223c;12-14 d each. The total duration of study was 47-49 d in each patient. Dialysate, urine, and feces were collected continuously and serum intermittently for phosphorus measurements.<br><br>RESULTS: Serum phosphorus concentrations fell progressively and significantly as the La2(CO3)3 dose was increased (r = -0.47, P < 0.001). Fecal phosphorus concentrations rose progressively as La2(CO3)3 increased (r = 46.4, P < 0.001). However, there was a negative correlation between both dialysate (r = -17.2, P = 0.002) and urine (r = -18.5, P < 0.001) phosphorus and La2(CO3)3 dose. This decline in dialysate and urine phosphorus correlated with the fall in serum phosphorus concentration as the La2(CO3)3 dose increased. As the La2(CO3)3 dose rose, the increase in fecal phosphorus concentration was essentially counterbalanced by the fall in dialysate and urine phosphorus. Hence, body phosphorus balance did not change with increasing La2(CO3)3 doses.<br><br>CONCLUSIONS: La2(CO3)3 treatment lowered serum phosphorus concentration but did not change body phosphorus content. This trial was registered at clinicaltrials.gov as NCT01581996.}, }
@article {pmid41035224, year = {2025}, author = {Farini, A and Strati, F and Molinaro, M and Mostosi, D and Saccone, S and Tripodi, L and Troisi, J and Landolfi, A and Amoroso, C and Cassani, B and Blanco-Míguez, A and Leonetti, E and Bazzani, D and Bolzan, M and Fortunato, F and Caprioli, F and Facciotti, F and Torrente, Y}, title = {Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {5}, pages = {e70054}, pmid = {41035224}, issn = {2190-6009}, support = {M6/C2_CALL 2022//PNRR/ ; FRRB-2022//Unmet Medical Needs, Fondazione Regionale per la Ricerca Biomedica/ ; GJC21084//Cariplo Telethon Alliance GJC2021-2022/ ; //NextGenerationEU/ ; //MUR/ ; PR-0394//Gruppo familiari beta-sarcoglicanopatie/ ; PNC-E3-2022-23683266-CUP: C43C22001630001//Hub Life Science-Diagnostica Avanzata/ ; //Associazione Centro Dino Ferrari/ ; }, mesh = {Animals ; *Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology ; Mice ; Gastrointestinal Microbiome/drug effects ; *Proteasome Inhibitors/pharmacology/therapeutic use ; *Muscle, Skeletal/drug effects/metabolism ; Disease Models, Animal ; Mice, Inbred mdx ; Male ; *Proteasome Endopeptidase Complex/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Duchenne Muscular Dystrophy (DMD) features immune-muscle crosstalk, where muscle fibre degeneration enhances pro-inflammatory macrophage infiltration, worsening inflammation and impairing regeneration.<br><br>METHODS: We investigated the impact of immunoproteasome (IP) inhibition on the gut-muscle axis in mdx mice, a well-established model of DMD. We employed microbiota perturbation models, including broad-spectrum antibiotic treatment (ABX) and faecal microbiota transplantation (FMT) from IP-inhibited mdx mice. IP inhibition effects were assessed by analysing gut microbiota composition, intestinal inflammation, muscle integrity and associated metabolic and inflammatory pathways.<br><br>RESULTS: IP inhibitor ONX-0914 significantly impacted the intestinal inflammatory microenvironment and gut microbiota of mdx mice. ONX-0914 treatment increased gastrointestinal transit (increased wet/dry faecal weights, p&#x2009;=&#x2009;0.0486 and p&#x2009;=&#x2009;0.0112, respectively) and partially restored intestinal barrier integrity (reduced FITC-dextran leakage, p&#x2009;=&#x2009;0.0449). JAM-A was significantly upregulated (p&#x2009;<&#x2009;0.0001). Colonic CD206+ M2 macrophages increased, while CD68&#x2009;+&#x2009;M1 cells partially decreased. ONX-0914 downregulated IP isoforms in macrophages (PSMB8: p&#x2009;=&#x2009;0.0022; PSMB9: p&#x2009;=&#x2009;0.0186) as well as FOXO-1 (p&#x2009;=&#x2009;0.0380) and TNF-&#x3b1; (p&#x2009;=&#x2009;0.0487). Antibiotic-induced microbiota depletion abrogated these effects. Metagenomic analysis revealed significant differences in microbiota composition between C57Bl controls and mdx mice (PERMANOVA p&#x2009;<&#x2009;0.001), with ONX-0914 inducing enrichment of stachyose degradation pathways. Metabolomic analysis showed enrichment of bacterial metabolites, fatty acid and sugar metabolism pathways, with increased glutathione, galactose, glycerol, glyceraldehyde and TCA cycle intermediates. ONX-0914 improved mitochondrial activity in skeletal muscle, as increased expression of ETC complexes (mdx vs. mdx+ONX: Complex II, p&#x2009;=&#x2009;0.0338; Complex IV, p&#x2009;=&#x2009;0.0023) and TCA enzymes (mdx vs. FTMmdx+ONX: IDH p&#x2009;=&#x2009;0.0258; FH p&#x2009;=&#x2009;0.0366). This led to a shift towards oxidative muscle fibres and improved muscle morphology (increased fibre size, p&#x2009;<&#x2009;0.0001 mdx vs. mdx+ONX and mdx vs. FTMmdx+ONX). Muscle performance was enhanced with reduced CPK levels (p&#x2009;=&#x2009;0.0015 mdx vs. mdx+ONX) and fibrosis (decreased TGF&#x3b2;: mdx vs. mdx+ONX, p&#x2009;=&#x2009;0.0248; mdx vs. FTMmdx+ONX, p&#x2009;=&#x2009;0.0279). ONX-0914 reduced CD68+ (mdx vs. mdx+ONX, p&#x2009;=&#x2009;0.0024; mdx vs. FTMmdx+ONX, p&#x2009;<&#x2009;0.0001) and increased CD206+ (mdx vs. FTMmdx+ONX: p&#x2009;=&#x2009;0.0083) macrophages in muscle, downregulated inflammatory genes (mdx vs. mdx+ONX: ccl2 p&#x2009;=&#x2009;0.0327, vcam-1p&#x2009;=&#x2009;0.0378) and reduced pro-inflammatory proteins (MCP1, mdx vs. mdx+ONX, p&#x2009;=&#x2009;0.0442). Inflammatory cytokines and endothelial vessel density in ONX-0914 treated mdx were restored to wild type mice. These data demonstrate that ONX-0914 enhances muscle function through microbiota-dependent mechanisms.<br><br>CONCLUSIONS: Our study advances the understanding of the role of dysbiosis in DMD disease and identifies IP inhibition as a potential therapeutic strategy to modulate the dystrophic gut-muscle axis, offering new perspectives for microbiota-targeted therapies.}, }
@article {pmid41035378, year = {2026}, author = {Zhang, Q and Cui, J and Hou, Y and Guo, L and Li, H and Zhou, G and Wang, X and Zhu, B and Shi, K and Zhang, Y and Bi, Y and Li, Y and Sun, L and Feng, Y and Yuan, J and Wang, X}, title = {Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {63}, number = {4}, pages = {538-556}, pmid = {41035378}, issn = {1365-2036}, support = {7232272//the Beijing Municipal Natural Science Foundation/ ; BJZYYB-2023-06//the Beijing Traditional Chinese Medicine Technology Development Fund Project/ ; 81774234//the National Natural Science Foundation of China/ ; }, mesh = {*Hypertension, Portal/microbiology/metabolism ; Humans ; *Gastrointestinal Microbiome/physiology ; Disease Progression ; Animals ; Male ; *Liver Cirrhosis/microbiology/metabolism/complications ; Mice ; Female ; Middle Aged ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Dysbiosis/microbiology ; Adult ; Mice, Inbred C57BL ; Anti-Bacterial Agents ; Aged ; }, abstract = {BACKGROUND: Although gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear.<br><br>AIMS: To investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH.<br><br>METHODS: We collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH-characteristic bacterial transplantation and antibacterial experiments in mice.<br><br>RESULTS: Microbial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide-producing bacteria and decreased abundance of anti-inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH-associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N-dimethylnitrosamine in mice.<br><br>CONCLUSIONS: Our study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome-based treatment for CPH.}, }
@article {pmid41035652, year = {2025}, author = {Kalopedis, EA and Zorgani, A and Zinovkin, DA and Barri, M and Wood, CD and Pranjol, MZI}, title = {Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1631522}, pmid = {41035652}, issn = {1664-3224}, mesh = {Humans ; Female ; *Endometriosis/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/complications/immunology/microbiology/therapy ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Biomarkers/analysis ; Animals ; Immunologic Factors/metabolism ; }, abstract = {Endometriosis (EMS) is an oestrogen-dependent condition characterised by ectopic endometrial-like tissue growth with a chronic and inflammatory nature leading to severe symptoms and reduced quality of life. Emerging evidence implicates gut microbiome dysbiosis in EMS pathogenesis, driving chronic inflammation, immune dysfunction, and altered bacterial taxa within patient gut microbiome. This review examines the intricate relationship between gut dysbiosis and EMS, with a focus on immunomodulatory mechanisms and the downstream consequences of the bacterial contamination theory. It evaluates recent findings regarding microbial imbalances and microbial diversity, pinpointing gaps in current research that mandate further understanding. For example, while microbial markers like Lactobacillus depletion and elevated Escherichia coli have been observed in patients, their diagnostic potential remains poorly defined. Additionally, it addresses the broader implications of EMS, including its physical, mental and healthcare burdens. Simultaneously, critiquing current drawbacks in diagnostic and therapeutic strategies such as their invasiveness and limited efficacy. The review further evaluates novel microbiome-based strategies namely Lactobacillus-based probiotics and faecal microbiota transplantation (FMT), assessing their potential in modulating immune responses and alleviating EMS symptoms while considering associated challenges. Lastly, it highlights the emerging role of metabolomics in identifying non-invasive and diagnostic biomarkers like short-chain fatty acids (SCFAs), implicated in the interplay between microbial metabolites and immune signalling pathways in EMS.}, }
@article {pmid41035886, year = {2025}, author = {Tayyab, M and Zhao, Y and Zhang, Y}, title = {Microbiome engineering to enhance disease resistance in aquaculture: current strategies and future directions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1625265}, pmid = {41035886}, issn = {1664-302X}, abstract = {Aquaculture, a cornerstone of global food security, faces critical threats from disease outbreaks, antimicrobial resistance, and ecological disruption. Through a narrative analysis of over 160 studies, this review synthesizes advances in microbiome engineering-a sustainable approach to enhancing disease resistance in aquatic animals-addressing key gaps: the inconsistent efficacy of conventional probiotics and prebiotics under field conditions, and the need for climate-resilient solutions. Critically, we highlight the emergence of precision microbiome engineering as a transformative paradigm. We integrate findings from genomics, metabolomics, clustered regularly interspaced short palindromic repeats, and artificial intelligence to identify microbial strategies that enhance host resilience. Genomic and multi-omics methods reveal health-associated microbes and metabolites, such as Vibrio-dominated dysbiosis markers in shrimp and butyrate-mediated immunity. Guided by these biomarkers, we describe precision-tailored probiotics-host-derived or genome-edited Bacillus subtilis strains whose adhesion factors, metabolic outputs (e.g., butyrate, bacteriocins), and heat stress tolerance are matched to the target species' gut niche. These are combined with complementary prebiotics (e.g., chitosan oligosaccharides) and synbiotics (e.g., Lactiplantibacillus plantarum plus king oyster mushroom extracts) that suppress pathogens through competitive exclusion and immune modulation. Ecologically rational innovations-interventions explicitly grounded in ecological theory (niche complementarity, K-selection) to stabilize resource-efficient microbiomes-such as fecal microbiota transplantation and synthetic consortia, demonstrate further disease control potential. Our synthesis reveals that translating microbiome engineering from laboratory to farm requires overcoming host-microbiome compatibility challenges and ecological risks. Policy alignment with the United Nations Sustainable Development Goals-Zero Hunger (Sustainable Development Goal 2), Climate Action (Sustainable Development Goal 13), and Life Below Water (Sustainable Development Goal 14)-is critical for sustainable adoption.}, }
@article {pmid41036224, year = {2025}, author = {Liu, T and Ou, G and Wu, J and Wang, S and Wang, H and Wu, Z and Jiang, Y and Chen, Y and Xu, H and Deng, L and Chen, X and Xu, L}, title = {Pingwei Powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1628488}, pmid = {41036224}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Fatty Acids, Volatile/metabolism ; Colon/pathology/drug effects/microbiology ; *Colitis, Ulcerative/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Cytokines/metabolism ; Disease Models, Animal ; Signal Transduction/drug effects ; Powders ; Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics ; Inflammation/drug therapy ; RNA, Ribosomal, 16S/genetics ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; }, abstract = {BACKGROUND: Pingwei Powder (PWP), a renowned traditional Chinese medicine (TCM) formula, it has demonstrated excellent therapeutic effects in ulcerative colitis (UC), yet its underlying pharmacological mechanisms remain unclear. This study aims to investigate the therapeutic effect of PWP on the aggravation of colonic inflammation induced by a high-fat diet and particularly focuses on its regulatory mechanisms on gut microbiota, which are closely related to UC.<br><br>METHODS: Network pharmacology analysis was employed to screen potential pharmacological targets of PWP for UC. Histological changes in colonic tissue were observed using hematoxylin and eosin (H&amp;E) staining, and immunofluorescence staining was performed to evaluate the expression of tight junction proteins (ZO1 and Occludin). Western blotting was used to detect the expression levels of proteins related to the PI3K/AKT/mTOR pathway, ZO1, and Occludin. qRT-PCR was conducted to measure the relative expression of inflammatory cytokines (IL-1&#x3b2;, IL-17, IL-6, and TNF-&#x3b1;) in colonic tissue. Additionally, 16S rDNA sequencing was performed to analyze gut microbiota alterations, and GC/MS was used to quantify short-chain fatty acids (SCFAs) in gut contents. The gutMgene database was utilized to validate the mediating roles of gut microbiota metabolites in the pharmacological effects of PWP. And their mediating role in PWP efficacy was verified by fecal microbiota transplantation (FMT) and butyrate supplementation.<br><br>RESULTS: Network pharmacology analysis predicted that PWP may regulate the PI3K/AKT pathway to exert therapeutic effects in UC. Experimental validation showed that PWP significantly downregulated the levels of PI3K, pAKT/AKT, and pmTOR/mTOR in colonic tissue, thereby enhancing autophagy in colonic epithelial cells, as evidenced by decreased levels of P62 and increased LC3B-II/LC3B-I ratios. Furthermore, 16S rDNA sequencing combined with targeted SCFAs analysis of gut contents revealed that the pharmacological effects of PWP may be mediated by increasing the abundance of SCFAs-producing gut microbiota (Alistipes and Parabacteroides) and elevating the levels of SCFAs in the gut.<br><br>CONCLUSION: PWP enhances the abundance of SCFAs-producing bacteria (Alistipes and Parabacteroides) in the gut, increases the levels of butyrate, and inhibits the PI3K/AKT/mTOR pathway in the colon. These effects promote colonic autophagy and contribute to the resolution of colonic inflammation.}, }
@article {pmid41036738, year = {2025}, author = {Li, Y and Dong, J and Wang, S and Xiong, R and Kang, X}, title = {High flavonoid diet alleviates chronic stress in cancer patients by optimization of the gut microbiota.}, journal = {Food &amp; function}, volume = {16}, number = {20}, pages = {8233-8247}, doi = {10.1039/d5fo02560e}, pmid = {41036738}, issn = {2042-650X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Flavonoids/administration &amp; dosage ; Humans ; Mice ; Male ; *Stress, Psychological/diet therapy ; *Neoplasms/psychology/microbiology/diet therapy ; Middle Aged ; Female ; Quality of Life ; Diet ; Adult ; Depression/diet therapy ; Anxiety/diet therapy ; Aged ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {Scope: Cancer patients face long-term psychological stress due to the fear of death, economic burden, and pain caused by the disease. The aim of this study is to explore the effects of flavonoid diets on chronic stress in cancer patients. Methods and results: In this study, cancer patients were subjected to a high flavonoid diet (n = 15) or normal diet (n = 15). Their chronic stress status, quality of life and immune function were evaluated at the beginning and end of a 12-week diet intervention. The high flavonoid diet significantly alleviated anxiety, depression, and perceived stress in cancer patients (p < 0.05). The stress indicators in their plasma and saliva also decreased after the flavonoid diet (p < 0.05). The anxiety and depression behaviors of mice improved after receiving fecal microbiota transplantation from cancer patients receiving a high flavonoid diet (p < 0.05). The distribution of the gut microbiota changed, and butyric acid levels increased significantly in the FMT mice from the high flavonoid group (p < 0.05). The selected components of flavonoid (quercetin) caused similar changes in the behavioral experiments and gut microbiota of chronic stress mice. Conclusion: High levels of flavonoid intake can significantly improve the chronic stress status and quality of life of cancer patients, and the effects may be mediated by the optimization of the gut microbiota and their metabolites.}, }
@article {pmid41036798, year = {2025}, author = {Nobel, YR and Park, H and Tillman, AM and Seeram, D and Moallem, DH and Intara, A and Nandakumar, R and Annavajhala, MK and Gomez-Simmonds, A and Verna, EC and Uhlemann, AC}, title = {Fecal Microbiota and Bile Acid Profiles in Early-Stage Hepatocellular Carcinoma: A Matched Case-Control Study.}, journal = {Clinical and translational gastroenterology}, volume = {16}, number = {12}, pages = {e00928}, pmid = {41036798}, issn = {2155-384X}, support = {K24-AI183182d//National Institute of Allergy and Infectious Diseases (NIH)/ ; Transplant Innovation Award//Columbia University Nelson Family Award/ ; Clinical Research Award//American College of Gastroenterology/ ; R01-AI116939//National Institute of Allergy and Infectious Diseases (NIH)/ ; K24 AI183182/AI/NIAID NIH HHS/United States ; R01 AI116939/AI/NIAID NIH HHS/United States ; Daland Fellowship in Clinical Investigation//American Philosophical Society/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/diagnosis/microbiology/pathology ; *Liver Neoplasms/microbiology/diagnosis/pathology ; Case-Control Studies ; Male ; Middle Aged ; Female ; *Bile Acids and Salts/metabolism/analysis ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; Aged ; *Liver Cirrhosis/microbiology/complications ; Early Detection of Cancer/methods ; Neoplasm Staging ; Severity of Illness Index ; }, abstract = {INTRODUCTION: Early identification of hepatocellular carcinoma (HCC) is critical to reduce mortality. Diagnostic tools are limited for early disease. Intestinal microbiota may contribute to HCC risk directly and through metabolites, particularly bile acids (BAs), offering potential noninvasive biomarkers.<br><br>METHODS: This was a case-control study of patients with cirrhosis with or without early-stage HCC, matched based on liver disease severity. Comprehensive analyses of fecal microbiota composition and function were performed.<br><br>RESULTS: There were 98 patients in the study (49 patients per group). Subjects with HCC were older (median 64 vs 60 years, P < 0.01) and more likely to have hepatitis C (78% vs 43%, P < 0.01). Alpha diversity, beta diversity, and genes and pathways related to BA metabolism did not differ between groups overall, but alpha diversity did differ within the subset of patients with metabolic-associated steatotic liver disease. There was differential abundance of multiple taxa between groups, including higher abundance of Klebsiella pneumoniae in cases. Increased concentration of secondary BA, which are microbiota-dependent, was associated with higher odds of HCC (adjusted odds ratio 2.4, P = 0.02); however, addition of microbial or BA features to a model with clinical data alone did not improve HCC prediction.<br><br>DISCUSSION: When accounting for liver disease severity, there were limited differences in intestinal microbiota composition and BA metabolism between subjects with or without early-stage HCC. Promising areas for future study of microbiota-based HCC biomarkers were identified, including a focus on the subpopulation of patients with metabolic-associated steatotic liver disease.}, }
@article {pmid41037658, year = {2025}, author = {Sun, W and Ma, L and Feng, X and Fan, Y and Cai, Y and Li, X}, title = {Efficacy of gut microbiota-based therapy for autism Spectrum Disorder and attention Deficit Hyperactivity Disorder: a systematic review and meta-analysis.}, journal = {Psychology, health &amp; medicine}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/13548506.2025.2565181}, pmid = {41037658}, issn = {1465-3966}, abstract = {The gut-brain axis is an emerging therapeutic target for neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, the overall efficacy of gut microbiome-based interventions remains unclear. This systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed to synthesize the evidence on these interventions. Fifteen randomized controlled trials (RCTs) were identified from 1,080 records across PubMed, Embase, Web of Science, Cochrane, PsycInfo, MEDLINE, and ClinicalTrials.gov through August 2024. Interventions included probiotics, prebiotics, dietary changes, and fecal transplants. Using random-effects models, pooled analysis showed a small but significant overall benefit of gut microbiota-based interventions (Standardized Mean Difference, SMD = -0.12; 95% Confidence Interval, CI: -0.19 to -0.04), with low heterogeneity (I[2] = 5.9%). Effects differed by disorder: ADHD demonstrated greater improvement (SMD = -0.24; 95% CI: -0.42 to -0.06; I[2] = 50.4%) compared to ASD (SMD = -0.05; 95% CI: -0.15 to 0.04; I[2] = 0%). Duration-specific effects emerged: 8-week interventions showed significant outcomes (SMD = -0.32; 95% CI: -0.58 to -0.06), while shorter or longer durations lacked significance. Acceptability analysis from eight studies revealed comparable dropout rates between intervention and control groups (ASD: Risk Ratio, RR = 1.002; ADHD: RR = 0.943), with no serious adverse events reported. Subgroup analyses identified participant age, diagnosis type, and geographic location as heterogeneity sources. Despite methodological limitations and small sample sizes, findings suggest gut microbiome modulation may offer a safe adjunctive therapy, particularly for ADHD, with optimal effects emerging at 8 weeks. The gut-brain axis appears promising for neurodevelopmental disorders, but current evidence remains preliminary. Future research should prioritize large-scale RCTs with standardized protocols, mechanistic investigations, and long-term follow-up to establish clinical guidelines and clarify biological pathways. Findings underscore the need to tailor interventions to specific disorders and optimize treatment duration.}, }
@article {pmid41038145, year = {2025}, author = {Guo, L and Yi, J and Zhang, A and Zheng, X and Wang, M and Yang, F and Kong, X and Meng, J}, title = {Zhenqi Fuzheng Granule targets the SCFAs-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157312}, doi = {10.1016/j.phymed.2025.157312}, pmid = {41038145}, issn = {1618-095X}, mesh = {Animals ; *Colorectal Neoplasms/drug therapy/metabolism/immunology ; *Receptors, G-Protein-Coupled/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Mice ; Humans ; Programmed Cell Death 1 Receptor ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Cell Line, Tumor ; *Immune Checkpoint Inhibitors/pharmacology ; Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs), particularly PD-1 antibodies, represent a breakthrough in colorectal cancer (CRC) treatment. However, their clinical efficacy remains limited by tumour-induced immunosuppression. Traditional Chinese medicine (TCM) has attracted growing interest as a potential adjuvant to immunotherapy. Zhenqi Fuzheng Granule (ZQFZ) is a clinically approved herbal prescription widely used as an adjuvant therapy for CRC, yet its mechanistic underpinnings remain elusive.<br><br>OBJECTIVE: To investigate how ZQFZ improves the efficacy in CRC, with emphasis on gut microbiota modulation, SCFAs production, and downstream immunometabolic pathways involving GPR109A, and confirms that butyrate plays an important role in colorectal cancer inhibition.<br><br>METHODS: Phytochemical analysis of ZQFZ was conducted using LC-MS/MS and UPLC-MS/MS, identifying and quantifying seven major compounds. In vivo experiments, AOM/DSS-induced CRC mouse models were treated with ZQFZ, PD-1 antibody, or their combination. Tumour progression, body weight, and survival were monitored. Gut microbial composition and colonic SCFAs levels were assessed via 16S rRNA sequencing and gas chromatography. RT-qPCR was employed to validate the expression of key genes associated with the GPR109A/AKT/mTOR/HIF-1&#x3b1; signaling pathway. Molecular changes in the GPR109A/AKT/mTOR/HIF-1&#x3b1; pathway were evaluated through Western blotting, transcriptomic, and proteomic analyses. Immune cell infiltration and phenotypes were analyzed by flow cytometry. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and structural stability between GPR109A and AKT1. The interactions between GPR109A and AKT1, as well as between butyrate and GPR109A, were further validated in vitro using microscale thermophoresis (MST) assays. To evaluate the microbial basis of ZQFZ activity, antibiotic-pretreated mice received ZQFZ-derived fecal microbiota transplantation (FMT). In vitro experiments, to investigate the mechanism by which sodium butyrate (NaB), the major gut microbial metabolite of ZQFZ, inhibits glycolysis in colorectal cancer under hypoxic conditions, CCK-8 assays, flow cytometry, lactate measurements, and Western blotting were performed to assess cell viability, apoptosis, lactate production, and the expression of AKT/mTOR/HIF-1&#x3b1; and glycolysis-related proteins.<br><br>RESULTS: LC-MS/MS profiling identified multiple bioactive constituents in ZQFZ. Targeted UPLC-MS/MS quantification revealed that the formulation contained Adenosine (0.87mg/g), Salidroside (0.11 mg/g), Astragaloside IV (0.07 mg/g), Calycosin (0.03 mg/g), Formononetin (6.7 &#x3bc;g /g), Chlorogenic acid (1.4 &#x3bc;g/g), Apigenin (0.5 &#x3bc;g/g). In vivo studies, both ZQFZ and PD-1 antibody inhibited tumour growth, with the combination treatment exerting the most pronounced antitumour effects. ZQFZ reshaped the gut microbiota, increased the levels of short-chain fatty acids (SCFAs), particularly butyrate, and activated the GPR109A pathway, leading to downregulation of the AKT/mTOR/HIF-1&#x3b1; signaling axis, suppression of HK2 expression and lactate production, and consequent inhibition of glycolysis. Immune remodeling was also observed, including reduced infiltration of myeloid-derived suppressor cells (MDSCs), polarization of macrophages toward the M1 phenotype, restoration of the CD4&#x207a;/CD8&#x207a; T cell ratio, and modulation of serum cytokines including upregulation of IL-2, IL-12, and IFN-&#x3b3;, along with downregulation of IL-4 and IL-10. ZQFZ-derived FMT significantly inhibited tumour growth, suppressed glycolysis-related markers (PKM2, GLUT1, HIF-1&#x3b1;, LDHA), and remodeled the immune microenvironment by reducing MDSCs and enhancing M1 macrophages and CD8&#x207a; T cell infiltration. In hypoxia-mimicking in vitro experiments, sodium butyrate (NaB), the principal gut microbial metabolite of ZQFZ, suppressed colorectal cancer cell viability and induced apoptosis. Through activation of GPR109A, NaB inhibited the AKT/mTOR/HIF-1&#x3b1; pathway and glycolysis-related enzymes, reduced lactate production, and further suppressed glycolysis. Molecular docking and dynamics simulations suggested a stable interaction between GPR109A and AKT1, which was confirmed in vitro by MST showing high-affinity binding (Kd=74.5 &#xb1; 20.8 nM); MST also verified moderate-affinity binding between GPR109A and sodium butyrate (Kd=43.3 &#xb1; 6.5 &#x3bc;M), supporting a dual interaction model wherein butyrate activates GPR109A, which in turn directly binds AKT1 to inhibit downstream glycolytic signaling.<br><br>CONCLUSION: This study uncovers a novel integrated mechanism whereby ZQFZ enhances PD-1 antibody efficacy via the gut microbiota-SCFAs-GPR109A axis, and NaB-mediated glycolysis inhibition under hypoxia further confirms its immunometabolic mechanism against CRC.}, }
@article {pmid41038146, year = {2025}, author = {Du, Y and Xu, J and Jia, J and Nong, Y and Lin, Y and Ye, Y and Zhong, Y and Tan, Q and Wei, Y and Huang, G and Mao, D and Huang, G and Lu, L and Peng, Y and Huang, H and Huang, J}, title = {Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157348}, doi = {10.1016/j.phymed.2025.157348}, pmid = {41038146}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; Animals ; *Drugs, Chinese Herbal/pharmacology ; *Fatty Acids, Volatile/metabolism ; Male ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; *Bile Acids and Salts/metabolism ; Rats ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Liver/drug effects ; }, abstract = {BACKGROUND: Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota-bile acid-short-chain fatty acid (GM-BA-SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.<br><br>PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.<br><br>STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.<br><br>METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.<br><br>RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.<br><br>CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.}, }
@article {pmid41038411, year = {2025}, author = {Taoum, C and Devaux, A and Rouanet, P and Colombo, PE and Boucher, D and Bonnet, M}, title = {Gut microbiota and chemoradiotherapy response in rectal cancer: Biomarker opportunities.}, journal = {Critical reviews in oncology/hematology}, volume = {216}, number = {}, pages = {104974}, doi = {10.1016/j.critrevonc.2025.104974}, pmid = {41038411}, issn = {1879-0461}, mesh = {Animals ; Humans ; Biomarkers, Tumor ; *Chemoradiotherapy ; Fusobacterium nucleatum ; *Gastrointestinal Microbiome ; *Rectal Neoplasms/microbiology/therapy ; Treatment Outcome ; Burkholderiales ; }, abstract = {The gut microbiota is increasingly recognized as a key factor in rectal carcinogenesis. This review synthesizes current clinical and preclinical evidence linking specific microbial signatures, such as Fusobacterium nucleatum, Duodenibacillus massiliensis and colibactin-producing Escherichia coli (CoPEC) to chemoradiotherapy (CRT) treatment efficacy and resistance. Microbiota-driven mechanisms include immune modulation, inflammation, and drug metabolism. We highlight emerging microbial biomarkers and therapeutic strategies such as antibiotics, probiotics, and fecal microbiota transplantation. Integrating microbiome profiling into clinical workflows could refine patient stratification and enhance CRT efficacy in rectal cancer. Ongoing clinical trials aim to validate these associations and establish robust microbial biomarkers for CRT response prediction in rectal cancer.}, }
@article {pmid41038971, year = {2025}, author = {Bahar Halpern, K and Kent, I and Yakubovsky, O and Ben-Moshe, S and Barkai, T and Fine, M and Novoselsky, R and Israeli, A and Nachmany, I and Itzkovitz, S}, title = {Stool shed cell transcriptomics mirrors tumor biology and enables colorectal cancer diagnosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {34413}, pmid = {41038971}, issn = {2045-2322}, support = {768956/ERC_/European Research Council/International ; }, mesh = {Humans ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; *Feces/cytology ; Female ; *Transcriptome ; Male ; *Gene Expression Profiling/methods ; Aged ; Middle Aged ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Early Detection of Cancer/methods ; }, abstract = {Screening and molecular characterization of human intestinal pathologies such as colorectal cancer (CRC) currently depends on colonoscopy, an invasive procedure associated with risks and poor adherence. A non-invasive method that captures host molecular changes could improve early detection and monitoring of intestinal diseases. Transcriptomic profiling of shed intestinal cells in stool has shown potential in neonates but is limited in adults by the dominance of bacterial RNA. To address this, we combined microbial ribosomal RNA (rRNA) depletion with unique molecular identifier (UMI)-based RNA sequencing to enrich and quantify human transcripts in stool. Applying this method to samples from 54 CRC patients and 24 healthy controls, we profiled thousands of human genes per sample. Stool-derived gene expression distinguished CRC from control samples with high accuracy (AUC = 0.86) and strongly correlated with matched tumor tissue signatures. Notably, stool transcriptomes reverted to control-like patterns after tumor resection. Our approach offers a powerful, non-invasive alternative to current CRC diagnostics and enables molecular insights into tumor biology. This method could complement or replace existing screening tools and may be applicable to other gastrointestinal diseases.}, }
@article {pmid41039079, year = {2025}, author = {Barkai, T and Yakubovsky, O and Korem Kohanim, Y and Bahar Halpern, K and Shir, S and Oren, N and Fine, M and Kelmer, P and Talmon, A and Israeli, A and Pencovich, N and Pery, R and Nachmany, I and Itzkovitz, S}, title = {Transcriptomic profiling of shed cells enables spatial mapping of cellular turnover in human organs.}, journal = {Molecular systems biology}, volume = {21}, number = {12}, pages = {1778-1792}, pmid = {41039079}, issn = {1744-4292}, support = {768956//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; 908/21//Israeli Science Foundation/ ; 3663/21//Israeli Science Foundation/ ; }, mesh = {Humans ; *Gene Expression Profiling/methods ; *Transcriptome ; Single-Cell Analysis/methods ; Colon/cytology/metabolism ; Esophagus/cytology/metabolism ; Stomach/cytology ; Sequence Analysis, RNA ; }, abstract = {Single-cell atlases provide valuable insights into gene expression states but lack information on cellular dynamics. Understanding cell turnover rates-the time between a cell's birth and death-can shed light on stemness potential and susceptibility to damage. However, measuring turnover rates in human organs has been a significant challenge. In this study, we integrate transcriptomic data from both tissue and shed cells to assign turnover scores to individual cells, leveraging their expression profiles in spatially resolved expression atlases. By performing RNA sequencing on shed cells from the upper gastrointestinal tract, collected via nasogastric tubes, we infer turnover rates in the human esophagus, stomach, and small intestine. In addition, we analyze colonic fecal washes to map turnover patterns in the human large intestine. Our findings reveal a subset of short-lived, interferon-stimulated colonocytes within a distinct pro-inflammatory microenvironment. Our approach introduces a dynamic dimension to single-cell atlases, offering broad applicability across different organs and diseases.}, }
@article {pmid41039216, year = {2025}, author = {Ma, Y and Wang, D and Yu, X and Fan, Y and Yang, Z and Gao, X and Huang, X and Meng, J and Cheng, P and Liu, X and Liu, Z and Li, X}, title = {Moderate altitude exposure induced gut microbiota enterotype shifts impacting host serum metabolome and phenome.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {591}, pmid = {41039216}, issn = {1471-2180}, support = {2023YFE0114300//National key research and development program intergovernmental key projects/ ; No.2024A1515012697//Guangdong Provincial Basic and Applied Basic Research Fund Project/ ; No. 202206010044//Science and Technology Program of Guangzhou, China/ ; No. U24A20652//The Joint Funds of the Natural Science Foundation of China/ ; No. 82272246//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Consistent patterns of gut microbiota variations, particularly in relative abundance, have been identified in the adult human gut. Enterotype, another general measure of the gut microbiota, is a valuable approach for categorizing the human gut microbiota into distinct clusters. The impact of different enterotypes on human health varies, and the changes induced by moderate altitude exposure remain unclear. This study aimed to conduct a comprehensive investigation of the cascade effects triggered by enterotype shifts following moderate altitude exposure.<br><br>RESULTS: Using shotgun metagenome sequencing, participants before and after moderate-altitude exposure were classified into cluster BL (dominated by Blautia) and cluster BA (dominated by Bacteroides). Relative to cluster BL, cluster BA consisted predominantly of individuals exposed to moderate altitude. Compared to cluster BL, Cluster BA exhibited rewired metabolism of serum metabolites (i.e., amino acids, fatty acids and bile acids) and gut microbiota, lower inflammatory factor levels (i.e., tumor necrosis factor-&#x3b1; (TNF-&#x3b1;)), and sparser correlations among these parameters. Individuals with baseline BL enterotype who transitioned to the BA enterotype following moderate-altitude exposure showed prominent improvement in fasting blood glucose (FBG) levels, with higher abundance of Bacteroidetes species (e.g., Bacteroides thetaiotaomicron, and Bacteroides uniformis), but lower Proteobacteria species abundance (e.g., Escherichia coli) and decreased L-Glutamic acid levels. Furthermore, fecal microbiota transplantation (FMT) from moderate-altitude exposed individuals to high-fat diet (HFD) fed mice confirmed increased Bacteroides abundance shifts associated with improvements in glucose homeostasis regulation and rewired amino acid metabolism. In addition, significant increases in alanine aminotransferase (ALT) levels but decreased serum creatinine (Scr), arterial oxygen saturation (SaO2), 4-Hydroxyproline, L-Glutamic acid, L-Asparagine, L-Threonine, L-Citrulline, L-Lysine and Isovaleric acid levels were identified as potentially important signals for individuals upon moderate altitude exposure, regardless of the gut microbiota enterotype.<br><br>CONCLUSIONS: Moderate altitude exposure could induce enterotype switching, and a Bacteroides-dominant enterotype may be a beneficial pattern of the gut microbiome related to host metabolism. Moderate-altitude exposure has potential implications for glycemic control, suggesting new avenues for managing FBG levels in future.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04245-4.}, }
@article {pmid41039491, year = {2025}, author = {Song, J and Yang, X and Liu, X and Li, J}, title = {Gut bacteria: protective mediators, pathogenic contributors and novel therapeutic targets in Candida albicans infections.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {77}, pmid = {41039491}, issn = {1757-4749}, support = {24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; }, abstract = {Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.}, }
@article {pmid41040884, year = {2025}, author = {Zhang, S and Zhang, T and Zhang, Y and Ye, C and Mu, L and He, Q and Huang, T and Wang, G and Li, Y and Xie, S and Tang, X}, title = {Akkermansia muciniphila regulates the gut microenvironment and alleviate periodontal inflammmation in mice with periodontitis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643691}, pmid = {41040884}, issn = {1664-302X}, abstract = {OBJECTIVE: Akkermansia muciniphila (A. muciniphila) is an emerging gut commensal known for its roles in host metabolism and immune modulation. While its involvement in metabolic and inflammatory disorders is well characterized, its potential association with oral diseases such as periodontitis remains poorly understood. This study aimed to explore whether modulation of the gut microbiota via fecal microbiota transplantation (FMT) from periodontally healthy donors could influence the abundance of A. muciniphila and contribute to the alleviation of periodontitis.<br><br>METHODS: Fecal samples were collected from human donors, including periodontally healthy individuals (H group, n&#x202f;=&#x202f;16), untreated patients with severe periodontitis (P group, n&#x202f;=&#x202f;12), and the same patients at two weeks (P2W) and three months (P3M) after periodontal therapy. Quantitative PCR was used to assess A. muciniphila abundance in these human samples. A germ-free mouse model of periodontitis was then established, and the mice received FMT using samples from human donor groups (P-PBS, P-H, and P-P). Gut microbiota composition, periodontal inflammation, gut barrier proteins (MUC2, ZO-1), and inflammatory cytokines (IL-6, TNF-&#x3b1;) were evaluated in the mice.<br><br>RESULTS: Compared to groups H, P2W, and P3M, the abundance of A. muciniphila in the gut was significantly lower in patients with severe periodontitis, but it was increased after periodontal therapy. In mice, FMT from healthy donors (P-H group) significantly enriched A. muciniphila, improved expression of gut barrier proteins, reduced inflammatory cytokine levels, and alleviated periodontal inflammation compared to other groups.<br><br>CONCLUSION: These findings suggest a previously underrecognized link between gut microbial composition particularly A. muciniphila and periodontal health. Targeting the gut microbiota via FMT may represent a novel strategy for modulating systemic and oral inflammation and supporting the prevention or adjunctive treatment of periodontitis.}, }
@article {pmid41041075, year = {2025}, author = {Zhu, S and Li, X and Yu, Y and Han, X and Yang, F and Lu, M and Dai, G and Guo, L and Xu, D}, title = {EZH2-mediated H3K27me3 links microbial inosine loss to depression: a gut-brain epigenetic switch.}, journal = {Theranostics}, volume = {15}, number = {18}, pages = {9969-9986}, pmid = {41041075}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics/physiology ; Mice ; *Enhancer of Zeste Homolog 2 Protein/metabolism/genetics ; *Epigenesis, Genetic ; *Depression/microbiology/metabolism/genetics ; *Histones/metabolism ; *Inosine/metabolism ; *Brain/metabolism ; Male ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Apoptosis ; }, abstract = {Background: Depression, the second most prevalent neurological disorder globally, affects over 300 million people and presents an urgent public health challenge. While gut microbiota dysbiosis is increasingly recognized as a key contributor to depression, the molecular mechanisms linking microbial imbalance to brain dysfunction remain poorly defined. Methods: We investigated the role of EZH2 in gut microbiota-induced depressive behaviors in mice using the chronic unpredictable mild stress (CUMS), fecal microbiota transplantation, and conditional knockout of EZH2. CUT&amp;Tag sequencing was employed to analyze EZH2-mediated H3K27me3 epigenetic reprogramming. Untargeted metabolomics and luciferase reporter assays were used to identify metabolites that upregulate EZH2 expression. 16S rRNA sequencing combined with metabolic tracing was conducted to trace the microbial origin of inosine. Additionally, natural compound screening identified coumaric acid (CA) as a novel EZH2-targeting degrader. Results: Conditional knockout of neuronal Ezh2 abolishes microbiota-induced depressive behaviors and neuronal apoptosis. Mechanistically, reduced abundance of specific microbiota (f_Lachnospiraceae, f_Oscillospiraceae, and f_Erysipelotricaceae) leads to inosine depletion. This depletion subsequently elevates EZH2 transcriptional activity by increasing H3K9ac modification at its locus, mediated through attenuation of the A2aR-cAMP-PKA-CREB-HDAC3 signaling axis. Subsequently, EZH2 silences serotonergic synapse-related genes (e.g., Tph2, Htr2a, Htr6) via H3K27me3 reprogramming, ultimately driving depressive behaviors and neuronal apoptosis in mice. Importantly, CA is identified as a first-in-class EZH2 degrader that binds lysine residues K623/K646 and recruits UBE3A for proteasomal degradation. CA treatment restores synaptic integrity and reverses depressive behaviors with minimal toxicity. Conclusions: Collectively, these findings define a novel "microbiota-inosine-EZH2" axis in depression pathogenesis and highlight EZH2 degradation as a promising therapeutic strategy for microbiota-associated neuropsychiatric disorders.}, }
@article {pmid41041667, year = {2025}, author = {Tariq, H and Ramakrishnan, M and Portocarrero, P and Gupta, M and Herrera, N and Klein, J and Gupta, A and Cibrik, D}, title = {Fecal Impaction: An Unusual Cause of Acute Kidney Injury in a Kidney Transplant Recipient.}, journal = {Case reports in transplantation}, volume = {2025}, number = {}, pages = {5726025}, pmid = {41041667}, issn = {2090-6943}, abstract = {Acute kidney injury (AKI) is common in kidney transplant recipients, and the etiology varies depending on the time since transplantation. We present an uncommon case of AKI from obstructive uropathy 7 years posttransplant in a 47-year-old Caucasian male with moderate intellectual disability and end-stage kidney disease secondary to glomerulonephritis who received a deceased donor kidney transplant. He presented with abdominal pain, lethargy, hypercalcemia, and AKI. However, though his serum calcium level improved with intravenous fluid resuscitation, the AKI did not improve. Kidney transplant ultrasound showed hydronephrosis of the transplant ureter, and a noncontrast abdominal and pelvic computed tomography scan showed fecal impaction as the cause of obstruction of the transplanted ureter. The patient underwent fecal disimpaction resulting in the resolution of his hydronephrosis and return of his kidney function to baseline. Although a few case reports have been published of fecal impaction causing AKI due to obstruction of native ureters, to our knowledge, this is the first case describing AKI from fecal impaction in an adult kidney transplant recipient.}, }
@article {pmid41041846, year = {2025}, author = {Zhao, Y and Yu, C and Zhang, J and Yao, Q and Zhu, X and Zhou, X}, title = {The gut‑skin axis: Emerging insights in understanding and treating skin diseases through gut microbiome modulation (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {6}, pages = {}, pmid = {41041846}, issn = {1791-244X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Skin Diseases/therapy/microbiology ; *Skin/microbiology/pathology ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Emerging evidence indicates a significant association between the composition and functionality of the gut microbiome and various skin disorders, including psoriasis, atopic dermatitis, acne and several dermatological conditions. The gut‑skin axis theory describes a complex bidirectional communication network between the gut and the skin, providing mechanistic insights into the pathogenesis of certain cutaneous diseases. Specifically, the gut microbiome influences skin health through the regulation of systemic immunity, inflammatory responses and metabolic pathways. Advances in high‑throughput sequencing and bioinformatics technologies have substantially enhanced the understanding of the role of the gut microbiome in skin pathology. Clinical and preclinical studies have demonstrated that restoring gut microbial homeostasis via interventions such as faecal microbiota transplantation, probiotics and prebiotics can ameliorate symptoms of skin diseases. Furthermore, personalized microbiome‑based therapies, next‑generation probiotics and dietary modifications hold promise for refining gut‑skin interactions and advancing precision medicine in dermatology. Therapeutic strategies targeting the gut‑skin axis offer novel avenues for innovative dermatological treatments, with future breakthroughs potentially involving microbial community engineering, postbiotics and artificial intelligence in microbiome‑related diagnostics. This narrative review summarizes recent advances in gut‑skin axis research, explores its potential in the prevention and management of selected dermatoses and discusses future trends and scientific developments in the field.}, }
@article {pmid41043062, year = {2025}, author = {Malogan, J and Hallowell, HA and Francis, B and Suez, J}, title = {Supplementation and Elimination of Microbiome-Produced Metabolites in the Treatment of Human Disease.}, journal = {Annals of the New York Academy of Sciences}, volume = {1553}, number = {1}, pages = {50-68}, doi = {10.1111/nyas.70103}, pmid = {41043062}, issn = {1749-6632}, mesh = {Humans ; *Probiotics/therapeutic use/administration &amp; dosage ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation/methods ; Dietary Supplements ; Animals ; }, abstract = {The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.}, }
@article {pmid41043575, year = {2025}, author = {Ahmed, LA and Al-Massri, KF}, title = {Insights into the role of gut microbiota modulation in the management of various cardiovascular diseases: A new approach for improving the efficacy of current cardiovascular medications.}, journal = {European journal of pharmacology}, volume = {1007}, number = {}, pages = {178210}, doi = {10.1016/j.ejphar.2025.178210}, pmid = {41043575}, issn = {1879-0712}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Cardiovascular Diseases/microbiology/drug therapy/therapy ; Animals ; *Cardiovascular Agents/therapeutic use/pharmacology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis ; Prebiotics ; }, abstract = {Gut microbiome is an emerging contributor to various cardiovascular diseases (CVDs) where gut dysbiosis increases the risk of development and progression of atherosclerosis, coronary artery diseases, hypertension, and heart failure. Microbiota can also affect the metabolism of medications including cardiovascular drugs, resulting in alteration of their pharmacokinetics and pharmacodynamics or producing metabolites which can interfere with response of these drugs. Importantly, CVDs require prolonged pharmacological interventions with medications which may have impacts on the diversity and composition of gut microbiota. Gut microbiota modulation using diets, prebiotics, probiotics, fecal microbiota transplantation, antibiotics, and microbial trimethylamine-lyase inhibitors, has also shown benefits in the management of CVDs where gut microbiota and their metabolites have recently been studied as potential targets for the management of these diseases. Specifically, using innovative microbiota therapies in combination with traditional pharmacological agents have been evaluated for additional benefits in various CVDs. However, assessing the interactions among host factors, gut microbiome, and drug response will be essential for the development of new therapeutic targets for cardiovascular disorders, ultimately hoping better prognosis and patient's quality of life for those affected with CVDs.}, }
@article {pmid41043596, year = {2025}, author = {Nasare, D and Bagade, S}, title = {The gut-lung axis in tuberculosis: A new frontier in immunomodulation and microbiota-directed therapeutic strategies.}, journal = {Microbial pathogenesis}, volume = {209}, number = {}, pages = {108087}, doi = {10.1016/j.micpath.2025.108087}, pmid = {41043596}, issn = {1096-1208}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lung/microbiology/immunology ; Dysbiosis/therapy/microbiology/immunology ; Mycobacterium tuberculosis/immunology/pathogenicity ; Probiotics/therapeutic use ; *Immunomodulation ; *Tuberculosis/therapy/microbiology/immunology ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Animals ; }, abstract = {Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.}, }
@article {pmid41045390, year = {2025}, author = {Senthilkumar, H and Chauhan, SC and Arumugam, M}, title = {Unraveling the multifactorial pathophysiology of polycystic ovary syndrome: exploring lifestyle, prenatal influences, neuroendocrine dysfunction, and post-translational modifications.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {980}, pmid = {41045390}, issn = {1573-4978}, mesh = {Humans ; *Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology ; Female ; *Protein Processing, Post-Translational ; Life Style ; Pregnancy ; Neurosecretory Systems/metabolism/physiopathology ; Insulin Resistance/physiology ; Animals ; Oxidative Stress ; }, abstract = {Polycystic ovary syndrome (PCOS) is a complex, multifactorial metabolic and endocrine disorder in reproductive-age women. This review discusses the interlinked roles of lifestyle, metabolic dysregulation, insulin resistance, neuroendocrine impairment, genetic predisposition, and post-translational modifications (PTMs) in PCOS pathogenesis. Lifestyle components, especially those leading to obesity and insulin resistance, worsen the hyperandrogenism, ovulatory dysfunction, and inflammation. Dietary treatments such as, DASH diet and caloric restriction, particularly along with metformin, have been proven to improve metabolic and reproductive parameters. Environmental toxins, such as endocrine-disrupting chemicals (EDCs) and advanced glycation end-products (AGEs), further compromise ovarian function and hormone regulation. Oxidative stress and insulin resistance, driven by mitochondrial malfunction and chronic inflammation, create a self-perpetuating vicious cycle that compromises oocyte quality and worsens metabolic imbalance. Neuroendocrine disruption, characterized by increased GnRH and LH pulsatility, is initiated by dysregulated kisspeptin, dynorphin, and neurokinin B signaling in KNDy neurons, modified GABAergic input, and increased AMH and androgens. PTMs such as phosphorylation, methylation, acetylation, and ubiquitination also play essential roles in granulosa cell function, AR signaling, insulin sensitivity, and oocyte maturation. Current and novel treatment options vary from lifestyle modifications and pharmacological interventions (e.g., metformin, GLP-1 receptor agonists, myoinositol, vitamin D, and statins) to regenerative measures like mesenchymal stem cells and fecal microbiota transplantation. Newer therapies focusing on PTMs and neuroendocrine regulators remain the future hope. Multidisciplinary individualized management is critical for successful PCOS therapy and averting long-term complications.}, }
@article {pmid41046274, year = {2025}, author = {Sadeghloo, Z and Ebrahimi, S and Hakemi-Vala, M and Totonchi, M and Sadeghi, A and Fatemi, N}, title = {Fusobacterium nucleatum and non-coding RNAs: orchestrating oncogenic pathways in colorectal cancer.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {78}, pmid = {41046274}, issn = {1757-4749}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with mounting evidence implicating the gut microbiome in its pathogenesis. Among the microbial agents, Fusobacterium nucleatum has emerged as a prominent contributor, frequently detected in CRC tissues and associated with advanced disease stages and poor prognosis. This review highlights the complex interplay between F. nucleatum and host non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in modulating CRC biology. F. nucleatum influences the expression of several ncRNAs, which in turn regulate key signaling pathways such as Wnt/β-catenin (e.g., miR-1246, miR-135b), PI3K/AKT (e.g., miR-22, miR-135b), and TLR4/NF-κB (e.g., miR-31, lnc-NEAT1). Through these mechanisms, F. nucleatum contributes to tumor cell proliferation, immune evasion, metastasis, and chemoresistance. Additionally, its impact on ncRNA expression is implicated in reduced efficacy of standard chemotherapy. Emerging microbiota-based therapies, including probiotics and fecal microbiota transplantation, show promise in modulating gut flora and potentially reversing ncRNA dysregulation; however, their mechanistic effects on the F. nucleatum-ncRNA axis require further investigation. This review underscores the critical role of F. nucleatum-regulated ncRNAs in CRC and presents new opportunities for biomarker discovery and targeted therapeutics.}, }
@article {pmid41046337, year = {2025}, author = {Vogel, GF and Kathemann, S and Pietrobattista, A and Maggiore, G and Aldrian, D and Sciveres, M and Verkade, HJ and Sokal, E and Jannone, G and Salcedo, M and Rauschkolb, P and Maucksch, C and Valcheva, V and Lainka, E}, title = {Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {81}, number = {6}, pages = {1410-1421}, pmid = {41046337}, issn = {1536-4801}, support = {//Ipsen/ ; }, mesh = {Humans ; *Liver Transplantation/adverse effects ; Male ; *Cholestasis, Intrahepatic/surgery/drug therapy ; Retrospective Studies ; Child ; *Diarrhea/drug therapy/etiology ; *Fatty Liver/drug therapy/etiology ; Adolescent ; Child, Preschool ; *Postoperative Complications/drug therapy/etiology ; Treatment Outcome ; Infant ; }, abstract = {OBJECTIVES: Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT.<br><br>METHODS: Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology.<br><br>RESULTS: Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120&#x2009;&#xb5;g/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two.<br><br>CONCLUSIONS: Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.}, }
@article {pmid41047724, year = {2025}, author = {de Groen, P and Fuhri Snethlage, CM and Wortelboer, K and Tokgöz, S and Davids, M and Verdoes, X and Westerbeke, FHM and Meijer, RI and Gotthardt, M and de Vos, WM and Herrema, H and Nieuwdorp, M and Hanssen, NMJ}, title = {Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2563155}, pmid = {41047724}, issn = {1949-0984}, mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy ; *Insulin-Secreting Cells/physiology/metabolism ; Male ; Female ; Adult ; *Feces/microbiology ; Pilot Projects ; Capsules/administration &amp; dosage ; *Fecal Microbiota Transplantation/adverse effects/methods ; Young Adult ; Middle Aged ; C-Peptide/blood/metabolism ; Adolescent ; Gastrointestinal Microbiome ; }, abstract = {This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.}, }
@article {pmid41047993, year = {2026}, author = {Paaske, SE and Baunwall, SMD and Rubak, T and Rågård, N and Kelsen, J and Hansen, MM and Lødrup, AB and Lyhne, S and Glavind, E and Fernis, CMC and Hald, S and Erikstrup, LT and Vinter-Jensen, L and Lal, S and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Improving Clinical Outcomes of Encapsulated Faecal Microbiota Transplantation for Clostridioides difficile Infection Through Empirical Donor Selection and Optimised Dosing: A Quality Improvement Study.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {63}, number = {2}, pages = {276-287}, pmid = {41047993}, issn = {1365-2036}, support = {8056-00006B//Innovationsfonden/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy ; Female ; Male ; Middle Aged ; Quality Improvement ; Aged ; Treatment Outcome ; *Donor Selection ; Denmark ; Clostridioides difficile ; Adult ; Aged, 80 and over ; Diarrhea/therapy ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected.<br><br>AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen.<br><br>METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8&#x2009;weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors.<br><br>RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.}, }
@article {pmid41048505, year = {2025}, author = {Yang, W and Jin, Q and Xiao, D and Li, X and Huang, D}, title = {Interaction mechanism and intervention strategy between metabolic dysfunction-associated steatotic liver disease and intestinal microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1597995}, pmid = {41048505}, issn = {1664-302X}, abstract = {The interaction between metabolic dysfunction-associated seatotic liver disease (MASLD) and gut microbiota regulates hepatic metabolic homeostasis through the gut-liver axis, and its mechanisms involve intestinal dysbiosis (decreased bacteroidetes, increased ratio of firmicutes/proteobacteria), bile acid metabolism reprogramming (secondary bile acids inhibit FXR signaling), short-chain fatty acid (SCFAs) deficiency, and endotoxin-mediated inflammatory activation (TLR4/NF-κB pathway). Among the intervention strategies, probiotics (such as Bifidobacteria) improved inflammation by regulating microbiota structure and intestinal barrier function, prebiotics such as resistant starch enriched butyric acid-producing bacteria and reduced liver lipid deposition, fecal microbiota transplantation (FMT) could remodel the microbiota but needed to optimize safety, restricted fructose intake and Mediterranean diet reduced liver damage by regulating microbiota metabolism, and metabolic surgery improved fibrosis through microbiota remodeling and bile acid signaling. In the future, it is necessary to combine multi-omics technology to analyze the microbiota-host interaction network, develop precision therapies such as phage targeted clearance or engineering bacterial delivery of metabolites, and promote the clinical transformation of personalized intervention programs.}, }
@article {pmid41052446, year = {2025}, author = {Sacks, HS and , }, title = {In primary CDI, fecal microbiota transplantation was noninferior to vancomycin for clinical cure at 14 d without recurrence at 60 d.}, journal = {Annals of internal medicine}, volume = {178}, number = {10}, pages = {JC117}, doi = {10.7326/ANNALS-25-03648-JC}, pmid = {41052446}, issn = {1539-3704}, abstract = {GIM/FP/GP: [Formula: see text] Gastroenterology: [Formula: see text] Infectious Disease: [Formula: see text].}, }
@article {pmid41052746, year = {2025}, author = {Chen, Y and Yu, L and Zhang, L and Liu, C and You, Y and Guo, H and Li, Z and Yin, X and Hong, T and Ding, L and Fang, Q}, title = {Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.}, journal = {Experimental neurology}, volume = {395}, number = {}, pages = {115488}, doi = {10.1016/j.expneurol.2025.115488}, pmid = {41052746}, issn = {1090-2430}, abstract = {BACKGROUND: Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.<br><br>METHODS: Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1&#x3b2;, IL-6, TNF-&#x3b1;, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.<br><br>RESULT: Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1&#x3b2;, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.<br><br>CONCLUSION: In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1&#x3b2;, and coincides with dysregulation of emotion-related neurotransmitters, collectively contributing to the pathogenesis of PSD.}, }
@article {pmid41052982, year = {2025}, author = {Cao, Y and Fan, X and Zang, T and Qiu, T and Fang, Q and Bai, J and Liu, Y}, title = {Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {383}, pmid = {41052982}, issn = {2158-3188}, support = {2023AFB710//Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Hippocampus/metabolism/pathology/immunology ; Mice ; Pregnancy ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; *Dysbiosis/microbiology/complications ; Humans ; Lipopolysaccharides/blood ; Germ-Free Life ; *Neuroinflammatory Diseases/metabolism/microbiology ; Microglia ; *Pregnancy Complications/microbiology ; Disease Models, Animal ; Behavior, Animal ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.}, }
@article {pmid41055380, year = {2025}, author = {Du, J-Y and Zhang, Z-J and Tan, L and Yang, J-Y and Yang, R-N and Chen, Y-L and Tan, G-F and Li, J and Li, W-J and Yang, L and Cai, J and Shen, D-L and Zhu, H-R and Fan, Z-X and Yuan, M-L and Zhang, W}, title = {Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity.}, journal = {mBio}, volume = {16}, number = {11}, pages = {e0244725}, pmid = {41055380}, issn = {2150-7511}, support = {ZYJC21004//1.3.5 project for disciplines of excellence/ ; 82401769//National Natural Science Foundation of China/ ; 2025ZNSFSC//Department of Science and Technology of Sichuan Province/ ; 2023NSFSC1935//Sichuan science and technology program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/microbiology/complications/metabolism/epidemiology ; *Dysbiosis/microbiology ; Female ; Male ; Adult ; *Major Depressive Disorder/microbiology/complications/metabolism/epidemiology ; *Bile Acids and Salts/metabolism ; Middle Aged ; Feces/microbiology ; Metagenomics ; Comorbidity ; Metabolomics ; }, abstract = {Major depressive disorder (MDD) and irritable bowel syndrome (IBS) exhibit high comorbidity, yet their shared pathophysiology remains unclear. Previous studies have primarily focused on the psychological health in the IBS population, without considering psychiatric diagnoses or stratifying different psychological states, potentially leading to biased findings. This study employed multi-omics approaches to characterize gut microbiota and serum metabolites in 120 MDD patients (47 with IBS and 73 without IBS) and 70 healthy controls (HCs). MDD with IBS patients showed significantly higher depression (Hamilton depression scale [HAMD-17]) and anxiety (Hamilton anxiety scale [HAMA-14]) scores than MDD-only patients (P < 0.05). Metagenomic sequencing of fecal samples revealed increased alpha diversity (Chao1/Shannon indices) and Firmicutes dominance in both MDD groups vs HC, while Actinobacteria enrichment specifically marked MDD with IBS. Functionally, MDD with IBS uniquely activated D-amino acid/glycerolipid metabolism pathways (Kyoto Encyclopedia of Genes and Genomes). Serum metabolomics identified comorbid-specific perturbations: downregulation of bile acids (CDCA, GCDCA, GCDCA-3S) and upregulation of glyceric acid/glutaconic acid. Our study also found that Eggerthella lenta and Clostridium scindens are differentially abundant bacteria that are involved in bile acid metabolism, and that microbial genes (e.g., K03738) are associated with glyceric acid production. These findings implicate gut microbiota-driven bile acid/glyceric acid dysregulation in MDD with IBS comorbidity, supporting the gut-brain axis as a therapeutic target for probiotics or microbiota transplantation.IMPORTANCEMajor depressive disorder (MDD) exhibits a high comorbidity rate with irritable bowel syndrome (IBS). Our study, conducted on 120 MDD patients (47 of whom were comorbid with IBS) and a control group of 70 individuals, revealed that MDD-IBS comorbid patients demonstrated significantly higher depression/anxiety scores. Multi-omics analysis indicated substantial alterations in the gut microbiota (e.g., Firmicutes, Actinobacteria) and serum metabolites (e.g., bile acids, glyceric acid) among MDD-IBS patients, which were associated with specific metabolic pathways. Therefore, the new aspect of this study was the inclusion of patients with MDD but without IBS symptoms, which provided a deeper understanding of the intestinal microbiota dysregulation associated with comorbid IBS and MDD. These findings suggest that there may be involvement of the gut-brain axis, providing new research directions for potential therapeutic targets.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2100041598.}, }
@article {pmid41057955, year = {2025}, author = {Chen, W and Liu, C and Li, X and Yang, X and Liu, Y and Qin, M and Jiang, W and Wang, Y and Sun, H and Li, G and Wen, B and He, S}, title = {5,7-dimethoxyflavone inhibits hepatocellular carcinoma progression via increasing intestinal Akkermansia muciniphila and hepatic CD8[+] T cell infiltration.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {170}, pmid = {41057955}, issn = {1749-8546}, support = {82405072//National Natural Science Foundation of China/ ; 82304927//National Natural Science Foundation of China/ ; 82274286//National Natural Science Foundation of China/ ; 2023A1515110041//Joint Funds of Basic and Applied Basic Research Fund of Guangdong/ ; 2023M741596//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) mainly develops in cases of fibrosis and cirrhosis and is accompanied by intestinal flora disorder. HCC also affects CD8[+] T cell immune function. 5,7-Dimethoxyflavone (DMF), an active flavonoid with anti-tumor effect, is found in Kaempferia parviflora. However, whether DMF can treat HCC remains unclear. This study aims to investigate the effect of DMF on HCC and to explore its possible mechanism, focusing on the gut microbiota regulation and the effect of CD8[+] T cells in a murine model.<br><br>METHODS: The HCC mouse model was induced with diethylnitrosamine/carbon tetrachloride and orally administered DMF. DMF effects on HCC progression were assessed using hematoxylin and eosin staining, immunohistochemistry, and serum biochemical marker levels. The causal relationship between gut microbes and HCC was explored using 16S rRNA genome-derived taxonomic profiling, microbial transplantation, fecal high-throughput targeted metabolomics, and untargeted serum metabolomic analyses. Transcriptome analysis, molecular docking, quantitative real-time polymerase chain reaction, and Western blot were applied to study the genes targeted by DMF. CD8[+] T cell infiltration and tumor-killing factors were studied using flow cytometry and immunofluorescence staining.<br><br>RESULTS: DMF reduced the number of tumors, the largest tumor size, and the liver-to-body ratio while also improving liver function. An antibiotic cocktail lowered the anti-tumor effect of DMF, indicating that DMF inhibition of HCC is partially dependent on the gut microbiota. DMF considerably upregulates Akkermansia muciniphila during chemical hepatocarcinogenesis in mice. DMF-upregulated A. muciniphila leading to intestinal barrier repair, which inhibited HCC progression by enhancing antioxidant capacity through glutathione regulation and 11,12-DIHETrE down-regulation. An untargeted serum metabolomic analysis showed that there existed additional mechanisms underlying DMF anti-tumor effect following its absorption into the bloodstream. DMF enhances the infiltration effect of CD8[+] T cells and upregulates interferon-gamma expression in HCC tissue. Overall, 822 genes, including chemokine (C-C motif) ligand 2 (CCL2), were significantly downregulated by DMF treatment in HCC cells. Notably, DMF binds strongly with nuclear factor kappa-B (NF-&#x3ba;B) and inhibits NF-&#x3ba;B p65 phosphorylation, sequentially suppressing the expression of downstream protein CCL2, which mediate the crosstalk between tumor cells and CD8[+] T cells.<br><br>CONCLUSION: DMF improves A. muciniphila-mediated intestinal barrier repair and inhibits the NF-&#x3ba;B/CCL2 pathway in HCC cells, enhancing the immunity of CD8[+] T cells in the liver. Hence, it may serve as a potential candidate for HCC treatment.}, }
@article {pmid41059058, year = {2025}, author = {Wang, Y and Bai, Z and Liu, Y and Wang, Y and Xu, J and Lai, Z}, title = {Influence of the gut microbiota on the pharmacokinetics of tacrolimus in liver transplant recipients: insights from microbiome analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1616985}, pmid = {41059058}, issn = {1664-302X}, abstract = {INTRODUCTION: Tacrolimus is crucial for immunosuppression after liver transplantation, but its pharmacokinetics vary markedly among individuals. Emerging evidence suggests that the gut microbiota may influence its metabolism, although the underlying mechanisms remain unclear.<br><br>METHODS: This study analyzed the fecal microbiota from 38 postliver transplant patients and 31 healthy controls via 16S rDNA amplicon and shotgun metagenomic sequencing. Patients were stratified into three groups on the basis of oral tacrolimus dosage and blood concentration: LDLBC (low dose, low blood concentration), LDHBC (low dose, high blood concentration), and SDLBC (standard dose, low blood concentration).<br><br>RESULTS: Posttransplant patients presented significantly reduced gut microbial diversity. Specific bacterial taxa, including Enterococcus raffinosus, Intestinibacter bartlettii, and Bacteroides fragilis, were enriched in patients with lower tacrolimus blood concentrations. In contrast, Phascolarctobacterium faecium and Streptococcus salivarius were associated with increased drug levels. Functional analysis revealed differences between patient subgroups in ATP-binding cassette (ABC) transporters and drug efflux pumps, suggesting a potential microbial influence on tacrolimus absorption and metabolism. Additionally, antibiotic resistance genes were more abundant in patients with lower tacrolimus blood concentrations, particularly in the Escherichia coli-enriched groups.<br><br>DISCUSSION: These findings underscore the influence of the gut microbiota on tacrolimus pharmacokinetics and support the potential of microbial composition as a biomarker for optimizing immunosuppressive therapy.}, }
@article {pmid41061376, year = {2025}, author = {Wekking, D and Ende, TVD and Bijlsma, MF and Vidal-Itriago, A and Nieuwdorp, M and van Laarhoven, HWM}, title = {Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review.}, journal = {Cancer treatment reviews}, volume = {140}, number = {}, pages = {103025}, doi = {10.1016/j.ctrv.2025.103025}, pmid = {41061376}, issn = {1532-1967}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Neoplasms/therapy ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.<br><br>METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.<br><br>RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.<br><br>CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.}, }
@article {pmid41061446, year = {2025}, author = {Zhang, J and Lv, Y and Yang, S and Li, H and Luo, Y and Tang, X and Xu, J and Liu, X}, title = {Deciphering the regulatory role of selenium on cadmium bioavailability and toxicity: From the perspective of gut microbiota.}, journal = {Ecotoxicology and environmental safety}, volume = {305}, number = {}, pages = {119193}, doi = {10.1016/j.ecoenv.2025.119193}, pmid = {41061446}, issn = {1090-2414}, mesh = {Animals ; *Selenium/pharmacology ; *Cadmium/toxicity/pharmacokinetics ; *Gastrointestinal Microbiome/drug effects ; Mice ; Biological Availability ; Liver/drug effects/metabolism ; Male ; Oryza/chemistry ; }, abstract = {Residents in areas naturally rich in cadmium (Cd) and selenium (Se) frequently exhibit exceptional longevity, raising intriguing questions about the interplay between the two elements. However, whether co-exposure affects the bioavailability of Cd remains unclear. Meanwhile, it is necessary to unclose the antagonistic mechanisms between Se and Cd. Here, a mouse bioassay was conducted to assess the impact of Se addition at low (0.1 mg/kg), medium (0.5 mg/kg) and high (2 mg/kg) doses, and duration (10 and 30 d) on Cd bioavailability of rice and Cd-induced hepatic toxicity. Results showed that Se cannot reduce Cd bioavailability. Medium Se addition for a duration of 10 days (MSe10) exhibited the highest efficacy in attenuating hepatic inflammation, as evidenced by augmented antioxidant enzyme activity, alleviated pathological damage, and increased levels of anti-inflammatory metabolites within the liver. The benefit was associated with its restoration of the gut microbiota and changes in key metabolic pathways. Notably, MSe10 increased the abundance of Faecalibaculum and Dubosiella, and enhanced the levels of secondary bile acids. Neither 0.1 mg/kg, 2 mg/kg nor long time addition of Se was beneficial for liver recovery. The hepatic lesions were fecal microbiota-dependent, as supported by fecal microbiota transplantation. Microbiota from MSe10 were capable to ameliorate hepatic inflammation, strengthen the intestinal barrier, and inhibit lipopolysaccharides (LPS) accumulation in blood. Additionally, the study provided insights into Se as an intervention for Cd toxicity, highlighting the appropriate dosage and its potential to reduce health risks.}, }
@article {pmid41063317, year = {2025}, author = {Gong, K and Zhang, S and Pan, Y and Cai, Q and Wu, M and Yin, X and Ma, J and Ji, H and Wang, Z and Wu, W and Zheng, H}, title = {Alternate day fasting alleviates neuroinflammation in diabetic mice by regulating δ-valerobetaine-carnitine-microglia axis via enrichment of Akkermansia muciniphila.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {202}, pmid = {41063317}, issn = {2049-2618}, support = {22074106//National Natural Science Foundation of China/ ; LY23H090008//Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Carnitine/metabolism ; Gastrointestinal Microbiome/physiology ; *Fasting ; *Microglia/metabolism ; Akkermansia ; *Neuroinflammatory Diseases/metabolism ; *Diabetes Mellitus, Type 1/microbiology/metabolism ; *Verrucomicrobia ; Mice, Inbred C57BL ; *Diabetes Mellitus, Experimental/microbiology ; Male ; *Betaine/metabolism/analogs &amp; derivatives ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Alternate day fasting (ADF) as a healthy dietary pattern has been reported to improve brain functions and behaviors, but the effect of ADF on diabetes-related brain disorders and the potential mechanisms remain unclear. In this study, we investigated the impact of ADF on neuroinflammation and exploratory behavior in type 1 diabetic (T1D) mice and explored the specific molecular mechanisms from the perspective of the gut microbiota and host metabolism.<br><br>RESULTS: ADF can effectively relieve neuroinflammation and exploratory behavioral disorders in T1D mice. According to fecal microbiota transplant and bacterial supplementation, we demonstrated that ADF-driven enrichment of Akkermansia muciniphila (AKK) was necessary for boosting exploratory behavior in T1D mice. The gut microbiota-derived metabolite &#x3b4;-valerobetaine (VB) reduced hepatic carnitine synthesis by inhibiting BBOX, and caused exploratory behavioral disorders in mice. In vitro and in vivo studies revealed that AKK bacteria had the ability to consume VB, and thereby increased systemic carnitine level. In addition, carnitine was found to deplete lipid droplet accumulation in microglia by enhancing fatty acid oxidation and lipolysis, reduce neuroinflammation and neuron injury, and then increase exploratory behavior in T1D mice.<br><br>CONCLUSIONS: Our study sheds light on the gut-liver-brain metabolic axis mechanism on the protective role of ADF in T1D-associated neuroinflammation and exploratory behavioral disorders and AKK bacteria exert as a key mediator. Video Abstract.}, }
@article {pmid41064515, year = {2025}, author = {Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Issariyakulkarn, N and Gamnarai, P and Bongkotvirawan, P and Wongcha-Um, A and Mahachai, V and Vilaichone, RK}, title = {Efficacy of encapsulated fecal microbiota transplantation and FMT via rectal enema for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial (CAP-ENEMA FMT Trial).}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1648944}, pmid = {41064515}, issn = {2296-858X}, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a functional bowel disorder. Gut dysbiosis involves in pathogenesis of IBS. Limited studies compared efficacy of fecal microbiota transplantation (FMT) via different routes of administration. This study aimed to compare efficacy of encapsulated FMT, FMT via rectal enema, and placebo in IBS patients.<br><br>METHODS: In this double-blind, randomized, placebo-controlled study, we enrolled patients aged 18-70 years with IBS defined by Rome IV criteria at Thammasat university, Thailand. Patients were randomized into three groups: (1) encapsulated FMT (six capsules twice daily for two consecutive days, total 50 g of stool), (2) FMT via rectal enema (50 g of stool in 200 mL of isotonic saline), or (3) placebo. Primary endpoint was clinical response defined by &#x2265;50-point decrease in IBS-symptom severity score (IBS-SSS) at 4 weeks. Secondary outcomes were quality of life and changes of fecal microbiota composition after treatment. The study was registered with ClinicalTrials.gov, number NCT06201182.<br><br>RESULTS: From August 20, 2020, to February 15, 2024, 45 patients were randomized to receive encapsulated FMT (n = 15), FMT via rectal enema (n = 15), or placebo (n = 15). There was no difference in patient characteristics and baseline IBS-SSS between groups. Encapsulated FMT provided significantly improved IBS-SSS (166.7 &#xb1; 73.7 vs. 269.3 &#xb1; 69.5, p = 0.001), clinical response (86.7 vs. 26.7%, p = 0.001), and quality of life (31.7 &#xb1; 4.8 vs. 25.1 &#xb1; 5.2, p < 0.001) at 4 weeks compared with placebo. FMT via rectal enema demonstrated better IBS-SSS (168.7 &#xb1; 101.9 vs. 269.3 &#xb1; 69.5, p = 0.004), clinical response (73.3 vs. 26.7%, p = 0.011), and quality of life (30.2 &#xb1; 5.0 vs. 21.0 &#xb1; 7.4, p < 0.001) than placebo. Clinical response and quality of life between encapsulated FMT and FMT via rectal enema were not different. No serious adverse event was observed. Minor adverse events such as bloating and diarrhea were not different between all groups.<br><br>CONCLUSIONS: Higher clinical response and quality of life were demonstrated in both FMT groups than placebo. Either encapsulated FMT or FMT via rectal enema was safe and could provide favorable outcomes for IBS patients.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06201182, Identifier: NCT06201182.}, }
@article {pmid41065216, year = {2025}, author = {Heer, P and Fernandez Elviro, C and Koutsokera, A and Mornand, A and Rochat, I and Regamey, N and Blanchon, S}, title = {Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251376211}, pmid = {41065216}, issn = {1753-4666}, mesh = {Humans ; *Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism ; *Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects ; Male ; Female ; *Aminophenols/therapeutic use/adverse effects ; *Benzodioxoles/therapeutic use/adverse effects ; *Quinolones/therapeutic use/adverse effects ; Prospective Studies ; Child ; Biomarkers/metabolism/blood ; Adolescent ; Treatment Outcome ; *Aminopyridines/therapeutic use ; Time Factors ; *Indoles/therapeutic use/adverse effects ; *Chloride Channel Agonists/therapeutic use/adverse effects ; Drug Combinations ; Young Adult ; *Pyrazoles/therapeutic use ; Sweat/chemistry ; Adult ; Pyrrolidines/therapeutic use ; }, abstract = {BACKGROUND: There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.<br><br>OBJECTIVES: To identify early parameters measured within 7 to 14&#x2009;days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.<br><br>STUDY DESIGN: Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).<br><br>METHODS: Standardized measurements were taken within 2&#x2009;months prior to and 7 to 14&#x2009;days after starting CFTR modulator treatment.<br><br>RESULTS: ETI treatment was started on 47 patients [median age: 12&#x2009;years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n&#x2009;=&#x2009;8) or tezacaftor/ivacaftor (n&#x2009;=&#x2009;4) to ETI. A significant early treatment effect was observed for BMI z-score (p&#x2009;<&#x2009;0.001) and inflammatory parameters (white blood cells (p&#x2009;=&#x2009;0.006), neutrophils (p&#x2009;=&#x2009;0.006), immunoglobulin G (p&#x2009;=&#x2009;0.012), and fecal calprotectin (p&#x2009;=&#x2009;0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [&#x394;low-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p&#x2009;<&#x2009;0.001). Improvement was also observed in lung function (FVC, FEV1, MMEF25-75, LCI2.5%) (all p&#x2009;<&#x2009;0.001). No changes were found for blood pressure, SpO2, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.<br><br>CONCLUSION: This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.}, }
@article {pmid41066868, year = {2025}, author = {Zeng, Z and Li, H and Yang, W and Li, L and Ni, P and Chen, Q and Zhou, W and Peng, J and Huang, L}, title = {Probiotic VSL#3 alleviates intrahepatic cholestasis of pregnancy by upregulating farnesoid X receptor-fibroblast growth factor 15 through regulation of the gut microbiota.}, journal = {Journal of reproductive immunology}, volume = {172}, number = {}, pages = {104653}, doi = {10.1016/j.jri.2025.104653}, pmid = {41066868}, issn = {1872-7603}, mesh = {Female ; *Gastrointestinal Microbiome/immunology/drug effects ; Pregnancy ; Animals ; *Cholestasis, Intrahepatic/therapy/immunology/microbiology ; Humans ; *Fibroblast Growth Factors/metabolism ; Mice ; *Receptors, Cytoplasmic and Nuclear/metabolism ; *Pregnancy Complications/therapy/immunology/microbiology ; *Probiotics/therapeutic use ; Adult ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Up-Regulation ; Bile Acids and Salts ; Liver/pathology ; Receptor, Farnesoid X-Activated ; }, abstract = {Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to both maternal and fetal health, and treatment options remain limited. This study investigated the efficacy and underlying mechanisms of VSL#3 in alleviating ICP. Clinical fecal and blood samples were collected from 26 patients with ICP and 21 healthy pregnant women. The gut microbiota composition was analyzed using 16S rRNA sequencing. To further explore causality, we established a fecal microbiota transplantation-ICP mouse model using fecal samples from ICP patients, as well as an estrogen-induced ICP mouse model. Compared with healthy pregnant women, ICP patients exhibited a distinct gut microbiota profile, characterized by an increased abundance of Bacteroides and Alistipes. Serum FGF19 levels were significantly lower in ICP patients, showing a negative correlation with liver function markers, such as serum total bile acid (TBA), and a positive correlation with beneficial genera including Bifidobacterium, Ruminococcus, Blautia, Dorea, Eubacterium (hallii group) and Ruminococcus (torques group). VSL#3 treatment in mice alleviated ICP manifestations by improving liver histopathology, reducing TBA and alanine aminotransferase levels, increasing FGF15 concentrations, and enhancing fetal outcomes. These beneficial effects were abolished by co-administration of the FXR antagonist Z-guggulsterone, confirming the role of FXR signaling. In conclusion, VSL#3 alleviated ICP by modulating the gut microbiota to activate the FXR-FGF15 axis, thereby reducing bile acid synthesis and improving maternal and fetal outcomes.}, }
@article {pmid41067200, year = {2025}, author = {Ding, L and Li, Q and Qi, K and Chen, Y and Hu, N and Hu, S and Fang, T and Guan, S and Wang, J and Qiu, J and Deng, X and Xu, L}, title = {Phloretin alleviates Salmonella pullorum infection by modulating gut microbiota-derived 3-phenylpropionic acid and AhR/IL-22/STAT-3 axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157350}, doi = {10.1016/j.phymed.2025.157350}, pmid = {41067200}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Chickens ; *Phloretin/pharmacology ; *Propionates/metabolism ; STAT3 Transcription Factor/metabolism ; *Poultry Diseases/drug therapy/microbiology ; Fecal Microbiota Transplantation ; *Salmonella Infections, Animal/drug therapy/microbiology ; *Salmonella/drug effects ; }, abstract = {BACKGROUND: Salmonella pullorum (S. pullorum) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate gut microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated.<br><br>PURPOSE: This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks.<br><br>METHODS: H&amp;E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum-infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection.<br><br>RESULTS: Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum-infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium, and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum-induced intestinal barrier damage and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis.<br><br>CONCLUSION: These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum-infected chicks.}, }
@article {pmid41067318, year = {2026}, author = {Zhao, H and Li, Y and Liu, N and Chen, P and Yu, X and Li, G and Deng, B and Li, D and Yang, F and Wang, G}, title = {Ganoderma lucidum polysaccharides alleviate non-alcoholic fatty liver disease by modulating gut microbiota against TLR4/NF-κB/MAPK pathway and activating AMPK pathway.}, journal = {Journal of ethnopharmacology}, volume = {355}, number = {Pt B}, pages = {120723}, doi = {10.1016/j.jep.2025.120723}, pmid = {41067318}, issn = {1872-7573}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Reishi/chemistry ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Mice ; Male ; Mice, Inbred C57BL ; AMP-Activated Protein Kinases/metabolism ; *Polysaccharides/pharmacology/isolation &amp; purification/therapeutic use ; Disease Models, Animal ; Liver/drug effects/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; Signal Transduction/drug effects ; *Fungal Polysaccharides/pharmacology ; }, abstract = {Ganoderma lucidum (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, G. lucidum polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of G. lucidum polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.<br><br>AIMS OF THE STUDY: This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from G. lucidum in the treatment of NAFLD and to elucidate its underlying mechanisms.<br><br>MATERIALS AND METHODS: The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.<br><br>RESULTS: The backbone of EPGLa consists of the following glycosidic linkages: &#x2192;6)-&#x3b2;-D-Glcp-(1&#x2192;, &#x2192;3)-&#x3b2;-D-Glcp-(1&#x2192;, &#x2192;4,6)-&#x3b1;-D-Glcp-(1&#x2192;, &#x2192;3,6)-&#x3b2;-D-Manp-(1&#x2192;, &#x2192;2)-&#x3b1;-D-Manp-(1&#x2192;, and &#x2192;4)-&#x3b2;-D-Galp-(1&#xa0;&#x2192;&#xa0;. Its branches are composed of &#x3b2;-D-Glcp-(1&#x2192;, &#x3b2;-D-Glcp-(1&#xa0;&#x2192;&#xa0;3)-&#x3b2;-D-Glcp-(1&#x2192;, and &#x3b1;-L-Fucp-(1&#xa0;&#x2192;&#xa0;. In vivo results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-&#x3ba;B)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.<br><br>CONCLUSION: Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.}, }
@article {pmid41071393, year = {2025}, author = {Wasim, R}, title = {The gut immune axis in ulcerative colitis: insights from microbiome research.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {1006}, pmid = {41071393}, issn = {1573-4978}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/immunology ; Probiotics/therapeutic use ; Intestinal Mucosa/immunology/microbiology ; Prebiotics ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD) marked by inflammation of the colonic mucosa. While its precise aetiology remains unclear, emerging evidence underscores the pivotal role of gut microbiota in UC pathogenesis. In healthy individuals, the gut microbiota contributes to immune modulation, nutrient absorption, and maintenance of intestinal barrier integrity. In contrast, individuals with UC exhibit gut dysbiosis-characterized by a reduction in beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium, and an increase in potentially pathogenic microbes like Escherichia coli. This microbial imbalance disrupts mucosal homeostasis, promotes persistent inflammation, and impairs epithelial healing. Contributing factors include genetic predisposition, antibiotic exposure, diet, and environmental influences. Novel microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT)-are being actively explored, with promising preliminary outcomes in symptom relief and microbiome restoration. However, challenges persist in defining a "healthy" microbiome and standardizing therapeutic protocols. This study highlights the potential of microbiome modulation as a transformative approach in UC management and calls for further research into host-microbe interactions to advance precision-based, microbiota-oriented therapies.}, }
@article {pmid41072600, year = {2025}, author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H}, title = {The "Butterfly Effect" of heart failure: Induced by the combination of polylactic acid nanoplastics and copper from the perspective of gut microbiome.}, journal = {Chemico-biological interactions}, volume = {421}, number = {}, pages = {111769}, doi = {10.1016/j.cbi.2025.111769}, pmid = {41072600}, issn = {1872-7786}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Heart Failure/chemically induced/pathology/microbiology ; *Copper/toxicity ; Male ; *Polyesters/chemistry/toxicity ; Mice, Inbred C57BL ; Mice ; *Microplastics/toxicity/chemistry ; Dysbiosis ; Myocardium/pathology ; *Nanoparticles/toxicity/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Plastic and heavy metal pollution have received extensive attention, but there is relatively little research on the damage to the gut-heart axis induced by the co-exposure to plastics and heavy metals. This study investigated the impact of the co-exposure of Polylactic acid nanoplastics (PLA-NPs) and copper (Cu) on heart failure (HF) in mice and explored the role of the gut microbiota in mediating this adverse outcome. Male C57BL/6J mice were divided into four groups: the Control group, the PLA-NPs group, the Cu group, and the Co-exposure group (PLA-NPs + Cu group). A 28-day exposure experiment was conducted. The research results indicate that, compared with the Single-exposure groups (PLA-NPs and Cu groups), the mice of Co-exposure group exhibited more severe toxic effects, including more pronounced myocardial hypertrophy and more severe myocardial fibrosis. These damages might be caused by increasing the heart's sensitivity to ferroptosis. Additionally, the co-exposure caused significant damage to the gut barrier and remarkable dysbiosis in the gut microbiota, such as a reduction in the abundances of beneficial bacteria like Lactobacillus. The fecal Microbiota Transplantation experiment confirmed that the alterations in gut microbiota play a pivotal role in the synergistic toxicity induced by PLA-NPs and Cu. This study for the first time reveals the mechanism of the combined effect of PLA-NPs and Cu on cardiac damage and emphasizes the crucial role of gut microbiota in this process.}, }
@article {pmid41072839, year = {2025}, author = {Yu, G and Xie, W and Xiang, J and Ke, Y and Wang, Z and Tu, F and Wu, W and Hong, H and Lin, X}, title = {Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2/NLRP3 pathway.}, journal = {European journal of pharmacology}, volume = {1007}, number = {}, pages = {178229}, doi = {10.1016/j.ejphar.2025.178229}, pmid = {41072839}, issn = {1879-0712}, mesh = {*Gastrointestinal Microbiome/drug effects ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Animals ; *Sepsis/microbiology/therapy/metabolism ; *Acetic Acid/metabolism/pharmacology/blood ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Male ; Mice ; Humans ; Aged ; Mice, Inbred C57BL ; Female ; Inflammasomes/metabolism ; Signal Transduction ; Middle Aged ; Dysbiosis ; Disease Models, Animal ; }, abstract = {BACKGROUND: Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice.<br><br>RESULTS: Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis.<br><br>CONCLUSION: Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.}, }
@article {pmid41074196, year = {2025}, author = {Liu, Y and Dong, B and Yang, YL and Zhang, YQ and Zhang, Y and Pan, D and Du, EZ and Zhu, SJ and Wang, B and Huang, YW}, title = {Intestinal microbiota dynamics in piglets: the interplay with swine enteric coronavirus infections and implications for disease control.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {107}, pmid = {41074196}, issn = {2524-4671}, support = {32302873//National Natural Science Foundation of China/ ; U22A20521//National Natural Science Foundation of China/ ; }, abstract = {Infections of swine enteric coronavirus (SECoV), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), cause severe diarrhea in piglets and result in substantial losses to the pig industry. The intestinal microbiota plays a crucial role in SECoV disease progression and outcomes, yet current research largely focuses on specific age groups or intestinal segments. This review provides a comprehensive analysis of the dynamic microbiota changes in piglets after SECoV infections across different ages and intestinal regions. It discusses differential microbiota analyses, functional changes, metabolic products, alongside their effects on immune responses. Additionally, we explore fecal bacterial transplantation as a potential intervention and highlight the role of the microbiota in either promoting or inhibiting SECoV infections. The development of advanced research tools, including culturomics, sequencing technologies, and multi-omics approaches, is pivotal in understanding the intricate relationship between the porcine intestinal microbiota and SECoV infections, offering potential strategies for preventing and controlling SECoV-related diseases.}, }
@article {pmid41075520, year = {2025}, author = {Gong, S and Xu, Y and Zhao, R and Yu, J and Bao, L and Zhang, Y and Li, F and Jiao, L and Kou, J}, title = {Xinqingning tablet attenuates ischemic stroke complicated by gut dysbiosis through regulating the miR-126-driven gut-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157356}, doi = {10.1016/j.phymed.2025.157356}, pmid = {41075520}, issn = {1618-095X}, mesh = {Animals ; *MicroRNAs/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Ischemic Stroke/drug therapy/complications ; *Dysbiosis/drug therapy/complications ; Male ; Mice ; *Neuroprotective Agents/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Blood-Brain Barrier/drug effects/metabolism ; Brain/drug effects/metabolism ; NF-kappa B/metabolism ; Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Tablets ; *Brain-Gut Axis/drug effects ; }, abstract = {BACKGROUND: Ischemic stroke (IS), the predominant clinical stroke subtype, is increasingly linked to dysregulation of the gut-brain axis (GBA)-a bidirectional neuroendocrine-immune interface connecting intestinal homeostasis with cerebrovascular pathophysiology. Xinqingning Tablet (XQNT) demonstrates neuroprotective potential in IS complicated by gut dysbiosis (GD), yet its mechanisms of GBA modulation remain unclear.<br><br>METHODS: A dual-hit IS-GD mouse model was established via fecal slurry transplantation and permanent middle cerebral artery occlusion (pMCAO) surgery. Gut function was evaluated by constipation indices and histopathological changes, while the neuroprotective efficacy of XQNT (0.36, 0.48, and 0.61 g kg&#x207b;&#xb9;) was assessed via TTC staining, neurological deficit scores, cerebral water content, and Evans blue (EB) extravasation assays. Additionally, Western blot was employed to quantify blood-brain barrier (BBB) and inflammation-associated proteins. microRNA sequencing was used to screen the differentially expressed miRNAs. miR-126 expression levels were measured by RT-qPCR, while concentrations of LPS, IL-6 and IL-10 were determined by ELISA. Finally, mechanistic validation employed intravenous miR-126 agonism/antagonism coupled with phenotypic rescue experiments.<br><br>RESULTS: XQNT conferred robust survival benefits, while concurrently ameliorating intestinal dysfunction and neurovascular injury. Mechanistically, XQNT elevated miR-126 expression, suppressing NF-&#x3ba;B-driven neuroinflammation. Additionally, miR-126 agonism phenocopied XQNT efficacy, whereas miR-126 inhibition abrogated therapeutic benefits.<br><br>CONCLUSIONS: This study provides early evidence that XQNT functions as a dual-target GBA modulator that alleviates IS with GD via regulation of the miR-126/NF-&#x3ba;B axis. By simultaneously promoting barrier restoration and inflammatory resolution, XQNT offers a promising therapeutic approach that links regulation of the gastrointestinal system with cerebrovascular protection.}, }
@article {pmid41075893, year = {2025}, author = {Huang, J and Yu, L and Zhang, C and Fang, Y and Zhou, X and Wang, R and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Zhang, Y and Wang, Y}, title = {Water-soluble Poria cocos polysaccharide improves alcoholic liver disease via modulation of gut microbiota-mediated intestinal bile acids-farnesoid X receptor.}, journal = {International journal of biological macromolecules}, volume = {330}, number = {Pt 4}, pages = {148202}, doi = {10.1016/j.ijbiomac.2025.148202}, pmid = {41075893}, issn = {1879-0003}, mesh = {*Wolfiporia/chemistry ; *Polysaccharides/chemistry/pharmacology ; Water/chemistry ; Solubility ; *Liver Diseases, Alcoholic/drug therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects ; *Bile Acids and Salts/metabolism ; *Receptor, Farnesoid X-Activated/metabolism ; Intestinal Barrier Function/drug effects ; Fecal Microbiota Transplantation ; Signal Transduction/drug effects ; Fibroblast Growth Factors/metabolism ; Cholesterol 7-alpha-Hydroxylase/metabolism ; *Intestines/drug effects/metabolism/microbiology ; }, abstract = {Alcoholic liver disease (ALD) is characterized by gut microbiota dysbiosis. This study aimed to elucidate the mechanism by which water-soluble Poria cocos polysaccharide (PCP) ameliorates ALD through modulation of the gut microbiota. PCP administration alleviated hepatic injury, reduced lipid accumulation, and attenuated inflammation in ALD mice. It also enhanced intestinal barrier integrity, as indicated by upregulation of tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced lipopolysaccharide (LPS) levels. Additionally, PCP treatment remodeled the gut microbiota profile, characterized by a marked enrichment of Parabacteroides distasonis, which is associated with bile acid metabolism. Targeted metabolomics revealed PCP increased intestinal chenodeoxycholic acid (CDCA) and cholic acid (CA) levels, activating the intestinal farnesoid X receptor/fibroblast growth factor 15 (FXR/FGF15) axis while suppressing hepatic Cholesterol 7α-hydroxylase (CYP7A1), ultimately reducing systemic bile acids. Fecal microbiota transplantation (FMT) confirmed gut microbiota-mediated protection, while intestinal FXR inhibition with glycine-β-muricholic acid (Gly-β-MCA) abolished PCP's therapeutic effects. These findings reveal that PCP ameliorates ALD by regulating the gut microbiota-bile acid-FXR axis, PCP as a promising natural therapeutic for ALD.}, }
@article {pmid41075966, year = {2026}, author = {Wang, T and Huang, X and Lu, L and Luo, X and Wang, Y and Ma, Y and Tong, X and Zou, H and Gu, J and Liu, X and Bian, J and Liu, Z and Yuan, Y}, title = {The dysbiosis of gut microbiota attributes to the impairment of blood-brain barrier in rats triggered by cadmium.}, journal = {Toxicology}, volume = {519}, number = {}, pages = {154303}, doi = {10.1016/j.tox.2025.154303}, pmid = {41075966}, issn = {1879-3185}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/chemically induced/microbiology/metabolism ; *Blood-Brain Barrier/drug effects/metabolism/pathology ; Male ; *Cadmium/toxicity ; Rats ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Oxidative Stress/drug effects ; }, abstract = {Cadmium (Cd) is a non-biodegradable heavy metal with a long biological half-life that is detrimental to human health. As Cd can increase blood-brain barrier (BBB) permeability and disturb the gut microbiota, the relationship between the BBB and gut microbiota disturbance induced by Cd consumption remains unclear. This study aims to identify whether Cd-induced gut microbiota dysbiosis is associated with rat BBB injury and investigate the possible mechanism. Here, we conducted analyses of variations in the composition of the gut microbiota and its metabolites, as well as BBB permeability and the results of the Morris water maze test, in rats treated with Cd by gavage. Fecal microbiota transplantation was performed to verify the role of the microbiota in altering BBB permeability induced by Cd. The results showed that Cd disturbed the gut microbiota, decreasing the levels of short-chain fatty acids (SCFAs). Furthermore, Cd-induced BBB permeability was substantiated by FITC-dextran leakage, ultrastructural observations, and diminished Claudin-5, Occludin, and ZO-1 protein expression, all of which were mitigated by FMT. In vitro, sodium butyrate (SOB) alleviated Cd-induced oxidative stress and increased the expression levels of GPX4 and FTH. Taken together, these findings suggest that Cd disrupts the microbiota and SCFAs components in rats, thereby contributing to BBB damage. SOB prevents Cd-induced BBB damage by suppressing ferroptosis in microvascular endothelial cells. This exhaustive study considerably enhances our comprehension of the health hazards posed by Cd to the central nervous system via the gut-brain axis.}, }
@article {pmid41076730, year = {2026}, author = {Hull, MA and Sun, H}, title = {Omega-3 polyunsaturated fatty acids and gut microbiota.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {29}, number = {2}, pages = {123-130}, pmid = {41076730}, issn = {1473-6519}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Fatty Acids, Omega-3/pharmacology/administration &amp; dosage ; Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: Oral intake of n (omega)-3 polyunsaturated fatty acids (PUFAs) is associated with changes to gut microbiota. We review recent findings from 2024 onwards, which build the scientific case that changes to bacterial abundance, and their metabolites, contribute to the health benefits associated with n -3 PUFAs.<br><br>RECENT FINDINGS: There are now multiple studies in rodent disease models that demonstrate that n -3 PUFAs do not significantly alter bacterial diversity but, instead, alter abundance of several species that are implicated in short-chain fatty acid synthesis, in a model-specific manner. Limited intervention studies in humans, backed by larger observational studies, concur with the preclinical findings. Importantly, faecal transplantation experiments have confirmed that n -3 PUFA-induced changes to gut microbiota are causally related to reversal of the disease phenotype in two rodent models. In-vitro colonic models are now being used to understand the mechanism(s) underlying n -3 PUFA-induced changes to the gut microbiota and metabolome.<br><br>SUMMARY: Despite emerging proof that the gut microbiota contributes to n -3 PUFA activity in animal models, human data are sparse. It remains unclear how n -3 PUFAs affect changes to the gut microbiota or whether n -3 PUFA metabolism by gut microbes contributes to the host metabolome.}, }
@article {pmid41076929, year = {2025}, author = {Shi, W and Xi, M and Zhang, K and Yang, J and Cheng, X and Zang, H and Fan, W}, title = {Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.}, journal = {International immunopharmacology}, volume = {167}, number = {}, pages = {115671}, doi = {10.1016/j.intimp.2025.115671}, pmid = {41076929}, issn = {1878-1705}, mesh = {Animals ; *Hydrogen/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; NF-E2-Related Factor 2/metabolism ; *Colitis/chemically induced/immunology/microbiology/drug therapy ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Signal Transduction/drug effects ; Mice ; Mice, Inbred C57BL ; Dextran Sulfate ; Male ; Dysbiosis/chemically induced ; Colon/pathology/drug effects/microbiology ; Disease Models, Animal ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing autoimmune disorder of the gastrointestinal tract with incompletely elucidated pathogenesis and limited therapeutic options. Although hydrogen gas (H2) has demonstrated therapeutic efficacy in various diseases including IBD, its mechanisms of action, particularly its interaction with the gut microbiota, remain poorly characterized. This study reveals that H2 inhalation effectively reversed dextran sulfate sodium (DSS)-induced dysbiosis by suppressing the expansion of potential pathogenic bacteria (e.g., Enterobacteriaceae and Escherichia-Shigella) and promoting potential beneficial microbes (e.g., Bacteroides and Lactobacillaceae), thereby restoring microbial homeostasis. Furthermore, H2 inhalation enhanced goblet cell density and mucus production, upregulated tight junction proteins (ZO-1 and occludin), and repaired intestinal barrier integrity. It also rebalanced the Treg/Th17 cell ratio, correcting immune dysregulation. At the molecular level, H2 inhalation suppressed the TLR4/NF-κB signaling pathway and activated the Keap1/Nrf2 antioxidant axis, leading to reduced production of pro-inflammatory cytokines and oxidative stress markers, alongside elevated antioxidant enzymes, collectively ameliorating colonic injury. In brief, the ameliorative effects of H2 are likely mediated through remodeling of the gut microbiota, restoration of the epithelial barrier, suppression of inflammatory signaling, and activation of antioxidant pathways. These findings were further validated by fecal microbiota transplantation (FMT) experiments. Collectively, this study links the therapeutic effects of H2 to structural and functional reprogramming of the gut microbiome, indicating that microbial ecological restoration is a central mechanism through which H2 alleviates colitis, thereby providing a mechanistic foundation for the therapeutic application of H2 inhalation in IBD.}, }
@article {pmid41077329, year = {2025}, author = {González-Rico, C and Hernández, M and Rodríguez-Grande, J and Fernández-Luis, S and Bermúdez Rodríguez, A and González-Huerta, AJ and Llaneza Velasco, E and Vázquez López, L and García García, I and Arnaiz de Las Revillas, F and Fariñas-Álvarez, C and Calvo Montes, J and Ocampo-Sosa, A and Fernández-Martínez, M and Fariñas, MC and , }, title = {Changes in the bacterial profile and diversity of the gut microbiota in allogeneic hematopoietic stem cell transplant recipients.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {161}, number = {}, pages = {108117}, doi = {10.1016/j.ijid.2025.108117}, pmid = {41077329}, issn = {1878-3511}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/genetics ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; Transplantation, Homologous ; Graft vs Host Disease/microbiology ; Feces/microbiology ; Young Adult ; Aged ; Spain ; }, abstract = {OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with significant alterations in gut microbiota (GM) composition, affecting transplant success. This study aimed to correlate these GM changes with post-transplant (post-HSCT) outcomes.<br><br>METHODS: A prospective multicentre cohort study was conducted between June 2017 and December 2021 in three Spanish hospitals. Stool samples from allo-HSCT recipients were collected before HSCT, and at 14-, 30-, 60-, and 100-days post-HSCT. Bacterial 16S rRNA gene sequences were characterized and microbial diversity assessed.<br><br>RESULTS: Analysis of 409 samples from 95 patients revealed significant longitudinal GM shifts. Alpha diversity significantly decreased at days 14 (P < 0.001), 30 (P < 0.001), and 60 (P = 0.002) compared to baseline. A distinct shift in dominant taxonomic profiles was observed, notably a significant decrease in Blautia abundance (P < 0.001). Patients with acute gastrointestinal graft-versus-host disease (GI-GVHD) (P = 0.009), bacteraemia (P = 0.014), or death (P < 0.001) exhibited significantly lower Blautia levels. LEfSe analysis identified 22 differential taxa between deceased and surviving patients; the former showed higher abundance of potential pathogens such as Enterococcus_H (P = 0.026), Enterococcus_A (P = 0.019), and Staphylococcus (P = 0.009).<br><br>CONCLUSIONS: Significant variations in the GM's taxonomic profiles and relative abundances post-HSCT, particularly the decrease in Blautia and the increase in certain pathogens, are associated with poorer clinical outcomes.}, }
@article {pmid41077430, year = {2025}, author = {Polster, SP}, title = {The Role of the Microbiome and the Neurovascular Unit.}, journal = {The Surgical clinics of North America}, volume = {105}, number = {5}, pages = {857-869}, doi = {10.1016/j.suc.2025.06.008}, pmid = {41077430}, issn = {1558-3171}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Blood-Brain Barrier ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The gut-brain axis plays a crucial role in neurovascular diseases, linking gut microbiota to blood-brain barrier integrity, neuroinflammation, and disease progression. Conditions such as cerebral cavernous malformations, traumatic brain injury, radiation-induced damage, and stroke exhibit microbiome-driven modulation that may be relevant to explain disease variance. Microbial metabolites have been shown to influence endothelial function and secondary brain injury mechanisms. Emerging interventions of dietary modifications, probiotics, fecal microbiota transplantation, and metabolite-based therapies show promise in mitigating neurovascular damage. Future research should focus on microbiome-targeted treatments, biomarker discovery, and personalized strategies to optimize neurovascular health through gut microbiome modulation.}, }
@article {pmid41077742, year = {2025}, author = {Gweon, TG}, title = {Is Fecal Microbiota Transplantation Applicable for the Treatment of Irritable Bowel Syndrome? Time for Precision Medicine.}, journal = {Journal of neurogastroenterology and motility}, volume = {31}, number = {4}, pages = {403-404}, pmid = {41077742}, issn = {2093-0879}, }
@article {pmid41077748, year = {2025}, author = {Lee, HK and Shin, CM and Chang, YH and Jo, H and Choi, J and Choi, Y and Jun, YK and Yoon, H and Park, YS and Kim, N and Lee, DH}, title = {Predictors of Treatment Response to Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Pilot Study.}, journal = {Journal of neurogastroenterology and motility}, volume = {31}, number = {4}, pages = {462-476}, pmid = {41077748}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: We aim to investigate the effectiveness, safety, and predictors of treatment response to fecal microbiota transplantation (FMT) in Korean irritable bowel syndrome (IBS) patients.<br><br>METHODS: Patients with moderate to severe diarrhea-predominant IBS (IBS-D) or mixed-type IBS (IBS-M) received FMT from one healthy donor via esophagogastroduodenoscopy. IBS-symptom severity score (IBS-SSS), Bristol stool form scale (BSFS), IBS Quality of Life (IBS-QoL) questionnaires, Hospital Anxiety and Depression Scale (HADS), and gut microbiome profiles were assessed at baseline, 4 weeks and 12 weeks post-FMT.<br><br>RESULTS: Among the 46 enrolled IBS patients, 37 patients (IBS-D:IBS-M = 28:9) completed a 12-week follow-up. Significant improvements were observed in IBS-SSS, IBS-QoL, and BSFS after 12 weeks. FMT led to increased microbial diversity and a sustained increase in beneficial bacterial genera, including Holdemanella, Ruminococcus, and Faecalibacterium. In terms of &#x3b2;-diversity, the distance between the patient's gut microbiome and that of the donor decreased after FMT; greater reduction in distance to donor microbiota was associated with greater symptom improvement (Unweighted UniFrac distance, P < 0.05). Responders (IBS-SSS reduction > 50 points) exhibited lower baseline relative abundances of Roseburia and Subdoligranulum, and more profound microbiome shifts toward the donor profile after FMT.<br><br>CONCLUSIONS: FMT appears to be a potentially effective treatment for moderate to severe IBS, with significant symptom relief and gut microbiota changes. Lower baseline abundances of Roseburia and Subdoligranulum and greater shifts of gut microbiome profile toward donor microbiota after FMT may predict favorable FMT response. Long-term follow-up is on the way to assessing the durability of these effects.}, }
@article {pmid41078065, year = {2026}, author = {Doukas, PG and Doukas, SG and Broder, A}, title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Ulcerative Colitis Treatment: A Systematic Review and Meta-Analysis.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {44}, number = {1}, pages = {85-98}, doi = {10.1159/000548568}, pmid = {41078065}, issn = {1421-9875}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Colitis, Ulcerative/therapy ; Treatment Outcome ; Remission Induction ; }, abstract = {INTRODUCTION: Despite advances in pharmaceuticals, managing ulcerative colitis (UC) remains challenging. Interest in fecal microbiota transplantation (FMT) for UC is growing, but varying formulations and endpoints in trials complicate safety and efficacy assessment. This systematic review and meta-analysis offer a validated, up-to-date overview of FMT's efficacy and safety in UC.<br><br>METHODS: We searched four electronic databases and analyzed only randomized clinical trials that investigated the clinical and endoscopic efficacy of FMT in UC, regardless of administration route or dose. Clinical and endoscopic remission was assessed by comparing the odds ratio (OR) and 95% confidence interval.<br><br>RESULTS: The initial search yielded 6,737 studies with 15 meeting inclusion criteria after duplicate removal and screening. The meta-analysis showed clinical remission in 62% receiving FMT vs. 50.5% in controls (OR 2.65; 1.76, 4.00). The endoscopic response was 42% in the FMT group vs. 22% in controls (OR 2.00; 1.09; 3.68). Heterogeneity was assessed as low (by I2 index and &#x3c4;2).<br><br>CONCLUSION: Our data show that FMT significantly improves clinical and endoscopic remission rates, offering a promising nonpharmacological option for UC patients unresponsive to conventional treatments. Further prospective studies are needed to optimize the formulation, dosing, while also address the safety profile of FMT in UC.}, }
@article {pmid41078360, year = {2025}, author = {Gu, X and Tang, J and Chen, C}, title = {Efficacy of gut microbiota-targeted therapies in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1627406}, pmid = {41078360}, issn = {2235-2988}, mesh = {Humans ; *Parkinson Disease/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Randomized Controlled Trials as Topic ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; Synbiotics/administration &amp; dosage ; }, abstract = {OBJECTIVE: This study aimed to investigate the efficacy of gut microbiota (GM)-targeted therapies in treating Parkinson's disease (PD).<br><br>METHODS: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane, and WOS from database inception to June 2025. The eligible RCTs employed GM-targeted therapies, including antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT), as adjunct treatments for PD. Data were pooled using a random-effects model, and the effect sizes were expressed as standardized mean differences (SMDs). In addition, the quality of evidence for all outcomes was assessed using the GRADE framework.<br><br>RESULTS: This study demonstrated that GM-targeted therapies significantly improved PD outcomes, including Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) III (SMD: -0.34, 95%CI: -0.57 to -0.11, P = 0.004), bowel movements (BMs) (SMD: 1.27, 95%CI: 0.35 to 2.2), use of laxatives (SMD: -0.33, 95% CI: -0.65 to -0.02), malondialdehyde (MDA) (SMD: -0.69, 95%CI: -1.23 to -0.15) indicators. However, there were no significant improvements in MDS-UPDRS I (SMD: -0.64, 95%CI: -1.42 to 0.13), MDS-UPDRS II (SMD: -0.28, 95%CI: -0.70 to 0.14), MDS-UPDRS IV (SMD: -0.08, 95% CI: -0.82 to 0.66), Mini-Mental State Examination (MMSE) (SMD: -0.01, 95% CI: -0.30 to 0.29), Montreal Cognitive Assessment (MoCA) (SMD: 0.04, 95%CI: -0.53 to 0.60), non-motor symptom scale (NMSS) (SMD: -0.11, 95%CI: -0.94 to 0.72), Parkinson's Disease Questionnaire-39 (PDQ-39) (SMD: -0.19, 95%CI: -0.58 to 0.20), total antioxidant capacity (TAC) (SMD: 0.29, 95%CI: -0.04 to 0.62), glutathione (GSH) (SMD: 0.51, 95%CI: -0.02 to 1.03), and Geriatric Depression Scale-15 (GDS-15) (SMD: -0.37, 95%CI: -0.87 to 0.12).<br><br>CONCLUSION: GM-targeted therapies may improve motor symptom scores (as measured by MDS-UPDRS III), alleviate constipation, and reduce blood malondialdehyde levels in PD patients. However, they did not significantly impact the scores for cognitive function, PD neuropsychiatric, behavioral, and emotional symptoms, and activities of daily living in this analysis. Given the inherent limitations of the included studies (such as small sample sizes and heterogeneity), future large-scale and rigorously designed RCTs are needed to validate these preliminary findings.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42024606415.}, }
@article {pmid41078364, year = {2025}, author = {Yu, J and Liu, Z and Wang, Y and Zhou, Y and Liu, W and Wang, T and Xie, Q and Tian, H and Xu, Y and Wang, M and Zhao, F and Wang, L and Zhang, G and Chen, D and Gao, L and Pan, T}, title = {Propionic acid mediates the renoprotective effects of fecal microbiota transplantation against ischemia-reperfusion injury via upregulating GPR43.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1616164}, pmid = {41078364}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats, Sprague-Dawley ; *Reperfusion Injury/therapy/prevention &amp; control ; *Propionates/metabolism/pharmacology ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Rats ; Disease Models, Animal ; Kidney/pathology ; Male ; Guinea Pigs ; *Acute Kidney Injury/therapy/prevention &amp; control ; Apoptosis/drug effects ; Up-Regulation ; Signal Transduction ; }, abstract = {INTRODUCTION: Kidney ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), characterized by aggravated inflammation and apoptosis following reperfusion. This study aimed to investigate the protective effects and mechanisms of fecal microbiota transplantation (FMT) in a rat model of kidney IRI.<br><br>METHODS: Sprague-Dawley rats(SDRs) subjected to 45 minutes of bilateral renal ischemia followed by reperfusion were prophylactically treated with FMT derived from guinea pigs or supplemented with propionic acid. Renal function, histopathology, inflammatory markers, apoptosis, proliferation, and gut microbiota composition were systematically evaluated.<br><br>RESULTS: The results demonstrated that FMT attenuated kidney IRI by remodeling the gut microbiota to enhance propionic acid production, which subsequently modulated inflammation and apoptosis via GPR43 signaling.<br><br>CONCLUSIONS: These findings provide novel insights into microbiota-targeted therapeutic strategies for kidney IRI and highlight propionic acid as a potential therapeutic agent.}, }
@article {pmid41078530, year = {2025}, author = {Li, R and Hu, Y and Liu, Y and Tan, X}, title = {Fecal microbiota transplantation augments 5-fluorouracil efficacy in pancreatic cancer via gut microbiota modulation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1548027}, pmid = {41078530}, issn = {1664-302X}, abstract = {BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.<br><br>OBJECTIVES: This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.<br><br>METHODS: One hundred female C57BL/6 mice aged 6-8&#x202f;weeks were randomly divided into five groups (n&#x202f;=&#x202f;20 each): Sham, Model, FMT, 5FU, and FMT&#x202f;+&#x202f;5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2&#x202f;g fecal material) three times per week, starting 2&#x202f;weeks before tumor implantation. 5FU was administered intraperitoneally at 25&#x202f;mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).<br><br>RESULTS: The FMT&#x202f;+&#x202f;5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (p&#x202f;<&#x202f;0.0001) and 5FU groups (p&#x202f;=&#x202f;0.005). FMT alone reduced tumor volume compared to the Model group (p&#x202f;<&#x202f;0.0001). Gut microbiota analysis revealed increased &#x3b1; diversity in the FMT group compared to the Model group (p&#x202f;<&#x202f;0.0001). The FMT&#x202f;+&#x202f;5FU group showed a significant reduction in cytokine levels, including TNF-&#x3b1; (p&#x202f;=&#x202f;0.0001) and IL-6 (p&#x202f;=&#x202f;0.012) and increased IL-10 level (p&#x202f;<&#x202f;0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT&#x202f;+&#x202f;5FU groups relative to the Model group (p&#x202f;<&#x202f;0.001). Additionally, the FMT&#x202f;+&#x202f;5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).<br><br>CONCLUSION: FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.}, }
@article {pmid41078532, year = {2025}, author = {Taha, H and Issa, A and Muhanna, Z and Al-Shehab, M and Wadi, T and Awamleh, S and Ateiwi, YA and Abusido, M and Berggren, V}, title = {Microbiota-based interventions for autism spectrum disorder: a systematic review of efficacy and clinical potential.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1648118}, pmid = {41078532}, issn = {1664-302X}, abstract = {PURPOSE: Autism spectrum disorder (ASD) is increasingly linked to gut microbiota imbalances, influencing both behavioral and gastrointestinal (GI) symptoms. This systematic review assesses the efficacy of microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), in improving ASD-related symptoms, aiming to provide insights into their therapeutic potential and inform future clinical applications.<br><br>METHODS: A comprehensive systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD42024615043). A structured literature search was performed in PubMed, Cochrane Library, and Scopus to identify peer-reviewed English-language studies. Eligible studies included randomized controlled trials (RCTs), non-randomized trials (NRTs), and retrospective studies assessing the impact of microbiota-based interventions on ASD-related behavioral and GI outcomes. Two independent reviewers conducted study selection, data extraction, and quality assessment using standardized risk-of-bias tools.<br><br>RESULTS: 33 studies were included, consisting of 16 RCTs, 14 NRTs, and 3 retrospective studies. Among them, 15 assessed probiotics, 4 prebiotics, 5 synbiotics, and 9 FMT. Probiotics showed moderate behavioral improvements in ASD, with multi-strain formulations being more effective than single strains. Prebiotics and synbiotics yielded mixed results, with some studies indicating benefits in behavioral and GI symptoms. FMT demonstrated the most consistent and sustained improvements in both ASD-related behaviors and GI function. Adverse events were minimal, primarily involving transient GI symptoms.<br><br>CONCLUSION: Microbiota-targeted interventions, particularly FMT, hold promise for managing ASD symptoms, though probiotics, prebiotics, and synbiotics present variable efficacy. Standardized protocols, larger controlled trials, and personalized microbiome-based approaches are necessary to refine these therapeutic strategies and enhance clinical applicability.<br><br>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024615043, identifier CRD42024615043.}, }
@article {pmid41080149, year = {2025}, author = {Xu, H and Li, S and Liu, S and Zuo, YG}, title = {A Conceptual Review of Gut, Skin, and Oral Microbiota in Autoimmune Bullous Diseases: From Dysbiosis to Therapeutic Potential.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {13925-13943}, pmid = {41080149}, issn = {1178-7031}, abstract = {Autoimmune bullous diseases (AIBDs), including pemphigus and bullous pemphigoid, are chronic inflammatory skin disorders characterized by dysregulated immune responses mediated by autoantibodies that target adhesion molecules in the skin and mucous membranes. Emerging evidence highlights the pivotal role of host microbiota dysbiosis in AIBDs pathogenesis, offering novel insights into disease mechanisms and therapeutic strategies. This review systematically synthesizes the current findings on gut, skin, and oral microbiota alterations in AIBDs, emphasizing their contributions via the gut-skin axis, microbial metabolites, and pathogen-host interactions. Key innovations include uncovering how specific pathogenic and commensal microbiota influence disease progression through intriguing skin inflammation and direct barrier impairment. Notably, while some microbiota changes overlap with other dermatoses, AIBDs exhibit distinct microbial signatures associated with their unique autoimmune mechanisms targeting adhesion molecules. Furthermore, we explore microbiota-targeted therapies, such as antibiotics, probiotics, and fecal microbiota transplantation, and demonstrate their potential to restore microbial homeostasis and improve clinical outcomes. By integrating multi-omics evidence and clinical data, this review bridges mechanistic insights with translational applications, proposing microbiota modulation as a promising adjunctive therapy for AIBDs. Our analysis identifies critical research gaps, including the need for longitudinal studies and personalized microbial interventions, positioning this review at the forefront of microbiome-inflammation-autoimmunity research.}, }
@article {pmid41080326, year = {2025}, author = {Qureshi, U and Bajwa, A and Aslam, Z and Aggrey, A and Nawaz, UH and Ul Ain, Q}, title = {Gut Microbiota Modulation in Type 2 Diabetes and Cardiometabolic Risk: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92020}, pmid = {41080326}, issn = {2168-8184}, abstract = {Cardiometabolic complications related to type 2 diabetes mellitus (T2DM) are often due to changes in the gut microbiota. The review analyzed studies looking at the effects of probiotics, prebiotics, high-fiber diets, and fecal microbiota transplantation (FMT) on glucose levels and heart and metabolic health in individuals either having T2DM or being at risk. The review followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The literature was searched using text terms and controlled vocabulary, employing Boolean operators "AND," "OR," and various combinations across PubMed, Embase, and the Cochrane Library. Open-access, full-text English papers from 2005 to 2025, including those authored by people, were searched. The quality was assessed using the Risk of Bias 2.0 (RoB 2.0) tool, and the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Fifteen randomized controlled trials (RCTs) were analyzed for methodological quality, with three categorized as having a high risk of bias (RoB). The GRADE tool categorized two high RoB RCTs as "low quality." However, two RCTs had low RoB and were classified as "high quality." Ten RCTs had uncertain RoB, lowering the evidence by one point to "moderate quality." A comprehensive review of RCTs was conducted to assess outcomes related to glycemic parameters (e.g., glycated hemoglobin (HbA1c), fasting glucose), lipid profiles, inflammatory markers, anthropometric measures, and gut microbiota composition. Interventions included probiotic and prebiotic supplementation, high-fiber or Mediterranean-style diets, and FMT. Probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis significantly improved lipid profiles by reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol. High-fiber diets consistently lowered fasting blood glucose, HbA1c, triglycerides, and LDL-C while elevating high-density lipoprotein cholesterol (HDL-C) and beneficial short-chain fatty acid (SCFA)-producing bacteria. Anti-inflammatory effects were observed across interventions, notably with probiotics and polyphenol-rich Mediterranean diets, which reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and other inflammatory cytokines. The Green-Mediterranean diet significantly improved weight, insulin resistance, and Framingham risk scores. Novel mechanisms involving SCFAs and bile acid metabolism were also identified as key modulators of host metabolic response. Microbiota-based interventions offer promising avenues for glycemic control and cardiometabolic risk reduction in patients with T2DM.}, }
@article {pmid41080562, year = {2025}, author = {Zhu, Z and Cheng, Y and Liu, X and Xu, X and Ding, W and Ling, Z and Liu, J and Cai, G}, title = {The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1644160}, pmid = {41080562}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Depression/therapy/microbiology/metabolism/etiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {Depression, a highly prevalent and relapsing mental disorder, exacts profound personal and socioeconomic tolls globally, warranting urgent scientific and clinical attention. Emerging evidence from both preclinical models and human clinical investigations has established the microbiota-gut-brain axis (MGBA) as a critical determinant in depression pathogenesis. This intricate bidirectional network integrates gut microbiota with central nervous system function, influencing mental health through mechanisms previously underrecognized. This review systematically synthesizes gut microbiota alterations associated with depression and their impacts on neuroendocrine, neuroimmune, and metabolic pathways. Advanced therapeutic strategies targeting the MGBA are discussed, including probiotics, fecal microbiota transplantation, and artificial intelligence-enabled microbiome interventions for depression management. While challenges in standardization, mechanistic understanding, efficacy and safety remain, MGBA-centered approaches offer a promising shift toward microbiota-based diagnostics and personalized treatments for depression.}, }
@article {pmid41080577, year = {2025}, author = {Wang, Z and Yu, J and Liu, Y and Gong, J and Hu, Z and Liu, Z}, title = {Role of the microbiota-gut-lung axis in the pathogenesis of pulmonary disease in children and novel therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1636876}, pmid = {41080577}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Child ; *Lung/immunology/microbiology/metabolism ; *Lung Diseases/therapy/microbiology/immunology/etiology/metabolism ; Dysbiosis ; Animals ; Fatty Acids, Volatile/metabolism ; }, abstract = {Emerging evidence highlights the microbiota-gut-lung axis (MGLA) as a pivotal regulator of pediatric respiratory health, yet mechanistic insights are lacking and therapeutic applications remain unclear. This review synthesizes cutting-edge findings to delineate how gut microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), orchestrate pulmonary immunity and disease pathogenesis in children. Leveraging multi-omics integration (metagenomics, metabolomics, transcriptomics), emerging studies have uncovered novel microbe-host interactions driving immune dysregulation in asthma, pneumonia, and cystic fibrosis. A comprehensive map of gut-lung crosstalk has been established across these conditions. Current studies suggest that early-life gut dysbiosis, shaped by delivery mode, antibiotics, and diet, disrupts SCFA-mediated immune homeostasis, amplifying T-helper 2 cell inflammation and impairing alveolar macrophage function. Crucially, we identified disease-specific microbial signatures (e.g., depletion of Lachnospira and Faecalibacterium in asthma) and demonstrated that fecal microbiota transplantation and probiotic interventions restore microbial balance, attenuating airway inflammation in preclinical models. This work pioneers the translation of MGLA insights into precision medicine strategies, highlighting dietary modulation and microbial therapeutics as viable alternatives to conventional treatments. By bridging microbial ecology and immune dynamics, our findings provide actionable biomarkers for early diagnosis and personalized interventions, addressing critical gaps in pediatric respiratory disease management. The integration of multi-omics frameworks not only advances mechanistic understanding but also positions the MGLA as a transformative target in reducing global childhood morbidity. Future research must prioritize longitudinal studies and clinical trials to validate these innovations, ultimately redefining therapeutic paradigms for GLA-driven pathologies.}, }
@article {pmid41081080, year = {2025}, author = {Bzdyra, M and Tulewicz-Marti, EM and Przepióra, A and Lewandowski, K and Rydzewska, G}, title = {Efficacy and safety of faecal microbiota transplantation (FMT) in recurrent Clostridioides difficile infection: results of a single-centre retrospective study.}, journal = {Przeglad gastroenterologiczny}, volume = {20}, number = {3}, pages = {330-334}, pmid = {41081080}, issn = {1895-5770}, abstract = {INTRODUCTION: Studies have indicated the high effectiveness of faecal microbiota transplantation (FMT) in the treatment of recurrent Clostridioides difficile infection (rCDI). However, there is still a lack of data from different subpopulations regarding FMT and the factors related to it.<br><br>AIM: The aim of the study was to retrospectively evaluate the efficacy and safety of FMT in rCDI.<br><br>MATERIAL AND METHODS: In all cases, FMT was performed using a nasoenteric tube. A good response following a single FMT was considered an improvement, whereas requiring more than one FMT was considered a suboptimal response.<br><br>RESULTS: In the analysed period, FMT was performed on a total of 98 patients, including 74 with rCDI (of whom 23 received 2 FMTs, 6 received 3 FMTs, and 1 received 5 FMTs). The average age of the patients was 68 years. 42 (56%) patients were women, 41 (55.4%) had previously used antibiotics, 2 (2.7%) had used steroids, and 4 (5.4%) had used proton pump inhibitors (PPI). Following the first FMT procedure, clinical improvement was observed in 44 (59.4%) patients. The odds of a suboptimal effect of the therapy (needing more than 1 FMT) were associated with prior use of metronidazole. Among all analysed factors, cardiovascular risk factors (such as hypertension and hyperlipidaemia) were associated with a threefold increased likelihood of requiring more than 1 FMT (p = 0.038).<br><br>CONCLUSIONS: In our study, FMT was found to be an effective and safe treatment of recurrent CDI. Use of metronidazole was identified as a risk factor for a suboptimal response to FMT in the studied cohort.}, }
@article {pmid41081988, year = {2026}, author = {Bhat, A and Mansoor, A and Fatima, M and Kumar, A and Mari, T and Ali, A and Bakht, K and Dad, A and Zahra, R and Makhija, V and Southwick, FS}, title = {Safety and efficacy of fecal microbiota transplantation versus antibiotics for treating clostridioides difficile infection: systematic review and meta-analysis.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {45}, number = {1}, pages = {57-68}, pmid = {41081988}, issn = {1435-4373}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridium Infections/therapy/drug therapy/microbiology ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; Treatment Outcome ; Clostridioides difficile ; Vancomycin/therapeutic use ; Recurrence ; Randomized Controlled Trials as Topic ; Fidaxomicin/therapeutic use ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is a persistent clinical challenge due to the high rate of relapse following treatment with standard antibiotics. Fecal microbiota transplantation (FMT) has emerged as a promising alternative, with comparable results. Aiming to restore intestinal microbial balance and reduce recurrence. Comparative evidence on the efficacy and safety of FMT versus antibiotics remains variable across studies, warranting a comprehensive synthesis to guide clinical decision-making.<br><br>AIM: This systematic review and meta-analysis aims to present an updated comparison of the effectiveness and safety of FMT versus Vancomycin/ fidaxomicin in patients with CDI.<br><br>METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials comparing FMT with standard antibiotic therapy for recurrent CDI. Primary outcomes included resolution of infection, recurrence, mortality, and adverse events. A random-effects model was used to calculate risk ratios with 95% confidence intervals. Statistical heterogeneity was assessed using the I-squared statistic. The quality of the included studies was evaluated using the Cochrane Risk of Bias version 2 and ROBINS-1 tools.<br><br>RESULTS: A total of 9 clinical trials involving 759 patients were included. FMT was significantly more effective in resolving CDI compared to antibiotic therapy, with a risk ratio (RR) of 1.51 (95% CI: 1.29 to 1.78). Recurrence rates were significantly lower in the FMT group, with a RR of 0.38 (95% CI: 0.29 to 0.50). Mortality did not differ significantly between groups (RR&#x2009;=&#x2009;0.95). Adverse events (AEs) were comparable between FMT and antibiotics, and no serious AEs directly related to FMT were reported. In the subgroup analysis, the lower GI route adminstration showed significant results (p&#x2009;=&#x2009;0.02) for both recurrence and resolution of CDI.<br><br>CONCLUSION: FMT is more effective than standard antibiotic therapy for achieving resolution and reducing recurrence in patients with recurrent CDI.}, }
@article {pmid41082373, year = {2025}, author = {Chen, K and Geng, H and Zheng, Y and Xie, H and Qin, R and Chen, J and Ye, C}, title = {Disruption of Gut Microbiota-Mediated De Novo NAD[+] Synthesis Contributes to the Development of Polycystic Ovary Syndrome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {45}, pages = {e06497}, pmid = {41082373}, issn = {2198-3844}, support = {20240402019GH//Jilin Province Science and Technology Development Plan project/ ; 2024SCZ07//Health Research Talents of Jilin Province/ ; 2024CL04//Spring-Bud Plan Construction Project of China-Japan Union Hospital of Jilin University/ ; }, mesh = {*Polycystic Ovary Syndrome/metabolism/microbiology ; Female ; *Gastrointestinal Microbiome/physiology ; Animals ; Mice ; Humans ; *NAD/biosynthesis/metabolism ; *Dysbiosis/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Polycystic ovary syndrome (PCOS) is a severe disorder that compromises female ovarian health and elevates the risk of various diseases, including endometrial cancer. The pathogenesis of PCOS remains poorly understood, which has hindered the development of effective interventions. In this study, it is demonstrated that patients with PCOS exhibit significant gut dysbiosis. FMT from PCOS patients (P-FMT) into mice induced PCOS-associated symptoms and histological alterations. Notably, both PCOS patients and P-FMT mice exhibit distinct metabolic profiles in the gut, suggesting a gut microbiota-mediated metabolic reprogramming. Furthermore, impaired tryptophan metabolism, particularly reduced levels of 3-hydroxyanthranilic acid (3-HAA), is observed in both PCOS patients and P-FMT mice. Administration of 3-HAA to mice alleviated DHEA-induced PCOS. Mechanistically, 3-HAA promoted NAD[+] synthesis via the de novo biosynthesis pathway, thereby inhibiting DHEA-induced ferroptosis by modulating the mitochondrial DNA-cGAS-STING axis. Collectively, these findings reveal the critical role of gut microbiota-mediated NAD[+] synthesis in the pathogenesis of PCOS, underscoring the potential of targeting gut microbiota and NAD[+] homeostasis as a therapeutic strategy for PCOS prevention and management.}, }
@article {pmid41085348, year = {2025}, author = {Zhang, S and Wu, Z and Zhang, S and Ru, Y and Wang, Q and Tong, H and Qin, Q and Yan, Q and Li, Z and Wu, G}, title = {The intricate microbial-gut-brain axis in Alzheimer's disease: a review of microbiota-targeted strategies.}, journal = {Food &amp; function}, volume = {16}, number = {21}, pages = {8320-8344}, doi = {10.1039/d5fo03139g}, pmid = {41085348}, issn = {2042-650X}, mesh = {Humans ; *Alzheimer Disease/microbiology ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage ; *Brain/metabolism ; Prebiotics/administration &amp; dosage ; Animals ; }, abstract = {The microbiome-gut-brain axis (MGBA) has emerged as a potential focus for the enhancement of cognitive abilities and the improvement of Alzheimer's disease (AD). Probiotics and prebiotics can improve the imbalance of gut microbiota to alleviate AD symptoms. Current research on probiotics/prebiotics and brain function mainly focuses on metabolic pathways such as those involving microbial metabolites like lipopolysaccharides and short-chain fatty acids, as well as immune pathways that regulate inflammation in the gut and brain. However, the roles played by endocrine and neural pathways remain less explored and warrant further attention. This review explores the intricate mechanisms of gut-brain communication within the MGBA, and especially systematically elaborates on the specific mechanisms of the endocrine pathway (impact of gut-derived and exogenous hormones on brain function) and the neural pathway (regulation of brain function by the sympathetic and parasympathetic systems). It also emphasizes the specific changes in gut microbiota noted in individuals with AD. Additionally, it examines the beneficial effects of probiotics, prebiotics, synbiotics, and postbiotics for cognitive function, reviewing their advancements in preclinical research, clinical trials, and commercial applications. Furthermore, this review delves into novel gut microbiota-related strategies to promote brain health, including antibiotics, certain gut-targeted inhibitors or agonists, fecal microbiota transplantation, whole microbiome transplantation, viral microbiota transplantation, genetically engineered bacteria, and bacteriophage-based in situ intestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD.}, }
@article {pmid41086122, year = {2026}, author = {Peng, W and Fan, X and Shi, H and Jiang, Y and Fan, L and Xing, Y and Peng, Y and He, Y and Zou, W and Jiang, M}, title = {Gut Microbiota and Chemotherapy-Induced Gastrointestinal Toxicity: Mechanisms and Intervention Strategies.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {44}, number = {1}, pages = {99-110}, doi = {10.1159/000548922}, pmid = {41086122}, issn = {1421-9875}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Antineoplastic Agents/adverse effects ; *Gastrointestinal Diseases/chemically induced/microbiology/therapy ; Probiotics/therapeutic use ; *Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Cancer remains a leading cause of mortality worldwide. Chemotherapy serves as a cornerstone of cancer treatment, providing significant benefits in tumor control and survival. However, its therapeutic efficacy is often compromised by gastrointestinal toxicity, which impairs quality of life and may necessitate treatment modifications. Disruption of the gut microbiota has been recognized as a key factor in the development of these toxicities.<br><br>SUMMARY: This review synthesizes evidence on how chemotherapeutic agents disrupt gut microbial balance and exacerbate gastrointestinal toxicity through epithelial barrier damage, inflammatory activation, and metabolic disturbance. It also examines diverse interventions, including dietary modifications, probiotics, prebiotics, synbiotics, traditional herbal medicines, and fecal microbiota transplantation, that aim to restore microbial homeostasis and reduce gastrointestinal injury.<br><br>KEY MESSAGES: This review provides a symptom-oriented framework linking specific clinical manifestations of chemotherapy-related gastrointestinal toxicity with underlying microbial alterations. It further integrates emerging evidence across nutritional, microbial, and herbal approaches, emphasizing shared therapeutic pathways and highlighting prospects for personalized microbiota-based strategies to improve treatment tolerance and patient outcomes.}, }
@article {pmid41087029, year = {2026}, author = {Tu, D and Lu, C and Guo, J and Chen, Q and Li, X and Wang, Y and Cheng, L and Jiang, H and Jian, J and Ge, Y and Hou, Z and Feng, X and Feng, Y and Zhou, J and Lei, Y and Diao, H and Ran, L and Zhou, Y and Xu, Z and Zhou, J and Tang, B and Yang, S}, title = {Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.}, journal = {Clinical and molecular hepatology}, volume = {32}, number = {1}, pages = {221-238}, pmid = {41087029}, issn = {2287-285X}, support = {82370586//National Natural Science Foundation of China/ ; 82030020//National Natural Science Foundation of China/ ; }, mesh = {*Berberine/analogs &amp; derivatives/therapeutic use/metabolism/pharmacology ; *Gastrointestinal Microbiome ; Animals ; *Serotonin/metabolism/biosynthesis ; Humans ; Mice ; *Cholestasis/drug therapy/pathology/metabolism ; Male ; Disease Models, Animal ; Tryptophan Hydroxylase/metabolism/genetics ; Female ; Mice, Inbred C57BL ; Middle Aged ; Fecal Microbiota Transplantation ; Liver/pathology/metabolism ; }, abstract = {BACKGROUND/AIMS: Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.<br><br>METHODS: We administered berberine (BBR) or dihydroberberine (dhBBR) in bile duct ligation-, ANIT-, and mdr2-/- CLD mouse models to evaluate the anti-CLD effect. We conducted fecal microbiota transplantation to determine the role of gut microbiota in BBR's effect. We conducted a randomized, controlled clinical trial to evaluate the effects of BBR in patients with CLD.<br><br>RESULTS: Oral BBR alleviates cholestatic liver injury in multiple mouse models. Gut microbes can transform BBR into dhBBR, which suppresses 5-hydroxytryptamine (5-HT) production in gut enterochromaffin cells by antagonizing tryptophan hydroxylase 1 (TPH1) activity and downregulating Tph1 transcription. This further ameliorates CLD by interrupting the 5-HT/5-HTR axis. A clinical study validated that BBR improved blood biochemical indicators in patients with CLD and decreased 5-HT levels.<br><br>CONCLUSIONS: BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.}, }
@article {pmid41087864, year = {2025}, author = {Chen, H and Wang, Z and Su, W and Li, S and Ye, Q and Zhang, G and Zhou, X}, title = {Helicobacter pylori infection impairs glucose homeostasis through gut microbiota dysbiosis.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {663}, pmid = {41087864}, issn = {1471-2180}, support = {82100594//National Natural Science Foundation of China,China/ ; }, mesh = {*Homeostasis ; *Helicobacter pylori/physiology ; *Helicobacter Infections/complications/metabolism/microbiology ; *Glucose/metabolism ; *Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Diabetes Mellitus, Type 2/metabolism/microbiology ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Diabetes Mellitus, Experimental/metabolism/microbiology ; Feces/microbiology ; Glucagon-Like Peptide 1/metabolism ; Colitis/metabolism/microbiology/therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Epidemiological data show that Helicobacter pylori (H. pylori) infection is not only the most important risk factor for gastric cancer, but is also associated with poor glycemic control in patients with diabetes. However, the direct causal and functional relationship between H. pylori infection and dysglycemia is unclear.<br><br>METHOD: A retrospective cohort study was conducted to examine the association between H. pylori infection and glycemic levels in individuals with Type 2 diabetes. C57BL/6 diabetic mice were infected with H. pylori, and the resulting changes in colonic inflammation and intestinal Glucagon-like peptide-1 (GLP-1) secretion were thoroughly examined using immunohistochemistry, RNA sequencing, metagenomic sequencing, and targeted metabolomics. The microbial and metabolomics profiles were analyzed and compared in antibiotic-treated mice through fecal transfer experiments.<br><br>RESULTS: H. pylori infection aggravated insulin resistance in diabetic individuals and mice. We identified a unique H. pylori-induced epithelial inflammation and reduced intestinal GLP-1 secretion in the colon. H. pylori infection also interrupts the normal microbial composition in the colon, leading to a decrease in SCFA-producing bacteria and a reduction in acetic and propionate acids. Similar changes were observed in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. In vitro studies revealed that the intestinal flora of H. pylori-positive diabetic mice inhibited proglucagon transcription, cAMP levels, and GLP-1 secretion in colonic endocrine cells, with SCFA supplementation reversing this effect on GLP-1 production. These microbial, metabolic, and GLP-1 alterations were also seen in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. H. pylori eradication with antibiotics improved glucose metabolism and GLP-1 secretion to levels comparable to uninfected controls.<br><br>CONCLUSION: Our studies offer evidence that H. pylori infection significantly contributes to the progression of glucose impairment and insulin resistance. Therefore, incorporating H. pylori status into preventive strategies for diabetes should be taken into account. (Chinese Clinical Trial Registry Center, ChiCTR2200063489, Registered 08 September 2022, https://www.chictr.org.cn/showproj.html?proj=178102).}, }
@article {pmid41088420, year = {2025}, author = {Zhu, JH and Wu, LP and Deng, L and Zang, SG and Li, XB and Chen, X and Yu, JX}, title = {Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {971}, pmid = {41088420}, issn = {2047-783X}, support = {No.YK2023130//The Medical Research Project of Yancheng Health Commission/ ; No.2024LZ006//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; 2024LZ008//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; No.YCBE202475//The Special Fund Project of Yancheng Science and Technology Bureau/ ; }, mesh = {Humans ; *Lupus Erythematosus, Systemic/metabolism/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/metabolism/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement, with pathogenesis closely linked to that of gut dysbiosis and metabolic disturbances. Studies indicate that SLE patients exhibit significantly reduced gut microbial diversity, increased abundance of pathogenic bacteria, and decreased beneficial bacteria. Dysbiosis exacerbates disease progression by disrupting the intestinal barrier, triggering autoimmune responses, and promoting proinflammatory cytokine release. Metabolomic analyses further reveal that SLE is associated with dysregulated amino acid metabolism, reduced short-chain fatty acids, and disrupted lipid homeostasis, which correlate with disease activity, renal injury, and increased atherosclerosis risk. Emerging microbiota-targeted interventions, such as fecal microbiota transplantation (FMT), probiotics/prebiotics, phage therapy, and dietary modifications, demonstrate promising therapeutic potential by restoring microbial balance, enhancing immune regulation, and improving metabolic homeostasis. This review systematically summarizes the alterations in gut microbiota and metabolism in SLE, their critical roles in disease progression, diagnosis, and pathogenesis, and explores the clinical value of microbial-targeted strategies in improving SLE outcomes.}, }
@article {pmid41089403, year = {2025}, author = {Wang, J and Zhang, X and Cui, C and Li, M and Xie, Z and Yang, L and Ding, D and Li, X and Zhao, M}, title = {Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {14059-14073}, pmid = {41089403}, issn = {1178-7031}, abstract = {BACKGROUND: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.<br><br>METHODS: In this study, a skin transplantation mouse model was established to explore the effects of tacrolimus on gut microbiota and its metabolites. Additionally, we investigated the protective effect and potential mechanism of feces from mice treated with tacrolimus on skin allografts.<br><br>RESULTS: Tacrolimus did not significantly affect gut microbiota &#x3b1;-diversity but altered &#x3b2;-diversity, with specific changes in microbial composition. LEfSe analysis identified 19 microbial taxa with reduced and 12 with elevated relative abundance in the Tac group (mice treated with tacrolimus) compared to the Ctrl group (mice with no treatment). Metabolomic analysis identified 33 differential fecal metabolites (17 upregulated and 16 downregulated) in the Tac group compared to the Ctrl group. FMT from tacrolimus-treated mice significantly prolonged skin allograft survival, reduced inflammatory cell infiltration, and improved graft histopathology. This protective effect was associated with increased Treg cell proportions and decreased Th17 cell proportions in draining lymph nodes and mesenteric lymph node.<br><br>CONCLUSION: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.}, }
@article {pmid41089551, year = {2025}, author = {Hearn, J and Malik, G and Stukalin, I and Panaccione, R and Ingram, RJM and Ma, C}, title = {Refractory Immune Checkpoint Inhibitor Colitis Treated With Biologics, Janus Kinase Inhibition, Plasma Exchange, and Fecal Microbiota Transplantation.}, journal = {ACG case reports journal}, volume = {12}, number = {10}, pages = {e01847}, pmid = {41089551}, issn = {2326-3253}, abstract = {Enterocolitis is a common immune-related adverse event associated with cancer immunotherapy. Current guidelines inform first-line pharmacologic management of immune checkpoint inhibitor-related enterocolitis; however, treatment in refractory cases is uncertain. We present a case of a 45-year-old woman with refractory immune checkpoint inhibitor-related enterocolitis requiring treatment with a combination of janus kinase inhibition, therapeutic plasma exchange, and fecal microbiota transplantation after failure of several lines of therapy. This is the first report of the combination of upadacitinib, plasma exchange, and fecal microbiota transplant for refractory enterocolitis.}, }
@article {pmid41089557, year = {2025}, author = {Chen, N and Zhang, M and Shi, B and Luo, X and Huang, R and Luo, Z and He, J and Xue, S and Li, N and Ling, Z and Guo, H and Xu, R and Liu, Y}, title = {Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites.}, journal = {Journal of orthopaedic translation}, volume = {55}, number = {}, pages = {280-292}, pmid = {41089557}, issn = {2214-031X}, abstract = {BACKGROUND: As a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, Tirzepatide (TZP) is a recently approved medication for treating type 2 diabetes mellitus (T2DM) and obesity; however, the effect of TZP in bone remodeling remains unclear.<br><br>METHODS: 1. The effect of Tirzepatide on osteoblasts and osteoclasts was observed by inducing differentiation of bone marrow mesenchymal cells (BMSCs) in vitro. 2. Db/db mice were used as a pathological model to investigate the role of TZP on bone metabolism. After TZP intervention, the feces in the intestinal tract of mice were collected for 16s rRNA gene sequencing to select the candidate gut microbiota most related to bone mass, and the effects of gut microbiota on bone metabolism were verified through subsequent microbiota supplementation experiments. 3. Metabolomics was used to analyze the difference of fecal metabolites between mice with the candidate microbiota supplement and those without, and the effect of candidate metabolites on bone metabolism was verified by the in vitro intervention of differential metabolites in BMSCs induction differentiation experiments.<br><br>RESULTS: We found that TZP intervention resulted in a significant decrease in bone mass accrual in vivo. TZP was not indispensable to the differentiation of osteoblasts and osteoclasts in vitro. Bone and fat homeostasis were modulated by gut microbiota. We further demonstrated that the biodiversity of the gut microbiota in db/db mice was strikingly altered after TZP treatment. Lachnospiraceae, a key pro-osteogenic component of gut microbiota was significantly reduced. As a main metabolite of Lachnospiraceae, evodiamine played a role in suppressing osteoclastogenesis in vitro. Based on this, the transplantation of the Lachnospiraceae effectively ameliorated bone loss that was seen in db/db mice due to TZP treatment.<br><br>CONCLUSION: TZP administration leads to bone loss in the context of diabetes and obesity, and targeting the composition of gut microbiota may provide a potential way to protect bone health in type 2 diabetic patients treating with TZP.<br><br>This study indicates that TZP has a negative impact on bone mass, suggesting that clinical attention should be paid to the risk of further decline in bone mass after Tirzepatide treatment, and it is necessary to follow up on their bone metabolism. Additionally, the gut microbiota plays an important role in bone metabolism regulation, and supplementing with certain probiotics may have a preventive effect on bone mass reduction associated with TZP treatment. Our research provides a reference for the prevention and treatment of drug-related osteoporosis in patients with T2DM in the future.}, }
@article {pmid41090697, year = {2025}, author = {Moore, JE and Millar, BC}, title = {Improving health literacy and patient-directed knowledge of fecal microbiota transplantation (FMT) through analysis of readability: a cross-sectional infodemiology study.}, journal = {Expert opinion on biological therapy}, volume = {25}, number = {10}, pages = {1135-1143}, doi = {10.1080/14712598.2025.2576509}, pmid = {41090697}, issn = {1744-7682}, mesh = {Humans ; *Health Literacy ; *Comprehension ; *Fecal Microbiota Transplantation ; Cross-Sectional Studies ; *Patient Education as Topic ; *Health Knowledge, Attitudes, Practice ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information.<br><br>RESEARCH DESIGN AND METHODS: Readability was calculated using Readable software, examining (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index, and (iv) SMOG Index and two text metrics [words/sentence, syllables/word] for 234 sources of FMT information, from four categories (abstracts/hospital information/patient-facing information/clinical trials).<br><br>RESULTS: Mean readability scores of FMT information for FRE and FKGL were 22.2&#x2009;&#xb1;&#x2009;1.2 (SEM) (target&#x2009;>&#x2009;60) and 14.8&#x2009;&#xb1;&#x2009;0.2 (target&#x2009;<&#x2009;8), respectively, with mean words/sentence and syllables/word of 19.2&#x2009;&#xb1;&#x2009;0.4 and 2.0, respectively. There was no significant difference in readability between scientific abstracts and lay summaries. No information was found that had a readability of less than 7th grade (12-13&#x2009;year olds).<br><br>CONCLUSION: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.}, }
@article {pmid41090775, year = {2025}, author = {Baek, JS and Ma, X and Park, HS and Lee, DY and Kim, DH}, title = {Bifidobacterium longum P77 and Lactiplantibacillus plantarum P72 and Their Mix-Live or Heat-Treated-Mitigate Sleeplessness and Depression in Mice: Involvement of Serotonergic and GABAergic Systems.}, journal = {Cells}, volume = {14}, number = {19}, pages = {}, pmid = {41090775}, issn = {2073-4409}, support = {RS-2024-00486802//the Commercialization Promotion Agency for R&amp;D Outcomes (COMPA) grant/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Animals ; *Depression/therapy ; Mice ; *Serotonin/metabolism ; Humans ; Male ; *Bifidobacterium longum/physiology ; Probiotics/pharmacology ; Anxiety ; Hot Temperature ; gamma-Aminobutyric Acid/metabolism ; Mice, Inbred C57BL ; Stress, Psychological ; }, abstract = {Sleeplessness (insomnia) is a significant symptom associated with stress-induced depression/anxiety. In the present study, we selected Bifidobacterium longum P77, which increased serotonin production in corticosterone-stimulated SH-SY5Y cells, from the fecal bacteria collection of healthy volunteers and examined the effects of B. longum on depression, anxiety, and sleeplessness induced by immobilization stress or by transplantation of cultured fecal microbiota (cFM) from patients with depression. Orally administered B. longum P77 decreased depression/anxiety- and sleeplessness-like behaviors in immobilization stress-exposed mice. B. longum P77 reduced immobilization stress-induced corticosterone, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression and the cell population of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)[+] in the prefrontal cortex, while the expression levels of immobilization stress-suppressed IL-10, γ-aminobutyric acid (GABA), its receptor GABAARα1, serotonin, and its receptor 5-HT1AR increased. B. longum P77 also alleviated immobilization stress-induced colitis: it decreased TNF-α and IL-6 expression and increased IL-10 expression in the colon. Furthermore, B. longum P77, Lactiplantibacillus plantarum P72, and their combination decreased cFM- or immobilization stress-induced depression-, anxiety-, and sleeplessness-like behaviors. They also decreased cFM-induced, corticosterone, TNF-α, and IL-6 expression levels in the prefrontal cortex and colon, while increasing cFM- or immobilization stress-suppressed GABA, GABAARα1, serotonin, and 5-HT1AR expression levels in the prefrontal cortex. In particular, the combination of B. longum P77 and L. plantarum P72 (P7277) additively or synergistically alleviated depression-, anxiety-, and sleeplessness-like behaviors, along with their associated biomarkers. Heat-killed P7277 also alleviated immobilization stress-induced depression/anxiety- and sleeplessness-like symptoms. These results imply that L. plantarum P72 and/or B. longum P77 can mitigate depression/anxiety and sleeplessness by upregulating GABAergic and serotonergic systems, along with the suppression of NF-κB activation.}, }
@article {pmid41094491, year = {2025}, author = {Wang, Z and Zhou, L and Zheng, Y and Zhong, X and Huang, R and Sun, W and Wang, S and Li, W}, title = {Nuclear receptor Nr1d1 links sleep deprivation to intestinal homeostasis via microbiota-derived taurine.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1106}, pmid = {41094491}, issn = {1479-5876}, support = {2023YFC2705400//National Key R&amp;D Rrogram of China/ ; 2021B1515420004//Guangdong Basic and Applied Basic Research Foundation/ ; 2025A03J4164//Huadu District Basic and Applied Basic Research Joint Funding Project/ ; GKLBCN-202501-01//Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University/ ; 202201020363//Science and Technology Projects in Guangzhou/ ; 2020A1515011031//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Animals ; *Sleep Deprivation/microbiology/metabolism ; *Homeostasis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Taurine/metabolism/pharmacology ; *Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism ; Male ; Mice, Inbred C57BL ; Intestinal Mucosa/pathology/metabolism ; *Intestines/microbiology/pathology ; Mice ; Fecal Microbiota Transplantation ; Colon/pathology ; }, abstract = {BACKGROUND: Sleep deficiency significantly compromises human health, with the gut being particularly susceptible. However, the molecular mechanisms by which gut microbiota mediate sleep deprivation-induced intestinal dysfunction remain largely undefined. In this study, we employed a chronic sleep deprivation (CSD) mouse model to investigate the impact of sleep loss on intestinal integrity and microbial composition.<br><br>METHODS: The CSD mouse model was established using the modified multiple platform (rotating rod) method. Colon histomorphology was assessed by hematoxylin and eosin (HE) staining. Expression levels of barrier proteins (Occludin, Claudin-1) and circadian regulators (Nr1d1, Bmal1) were evaluated via Western blot or immunohistochemistry (IHC). Gut microbiota composition and stability were analyzed by 16S rRNA gene sequencing, and the causal role of microbiota in CSD-induced barrier damage was assessed through fecal microbiota transplantation (FMT). RNA sequencing (RNA-seq) of intestinal epithelial tissues identified differentially expressed genes and enriched pathways. Untargeted metabolomics was employed to investigate key differential metabolites (Taurine). Additionally, taurine was supplemented in vivo to explore its efficacy and mechanism in alleviating intestinal barrier damage in CSD mice.<br><br>RESULTS: CSD led to pronounced colon shortening and significant downregulation of the epithelial barrier proteins Occludin and Claudin-1, indicative of impaired intestinal barrier function. Moreover, CSD exacerbated symptoms of chemically induced colitis and induced gut microbiota dysbiosis. Mechanistically, FMT from CSD mice into antibiotic-treated recipients recapitulated intestinal inflammation, confirming the pathogenic role of the altered microbiota. Transcriptomic analysis revealed significant enrichment of genes involved in circadian rhythm pathways, notably a marked suppression of the circadian nuclear receptor Nr1d1, a key regulator of intestinal homeostasis. Complementary untargeted metabolomic profiling identified taurine as a microbiota-derived metabolite significantly reduced by CSD. In vivo taurine supplementation restored Nr1d1 expression, reinforced epithelial barrier integrity, and decreased pro-inflammatory cytokine production.<br><br>CONCLUSION: Together, these findings reveal a gut microbiota-taurine-Nr1d1 axis underlying sleep deprivation-induced intestinal barrier dysfunction, and suggest that therapeutic modulation of taurine levels or circadian pathways may offer novel strategies to prevent or treat sleep-related gastrointestinal disorders.}, }
@article {pmid41095952, year = {2025}, author = {Soares Ferreira Júnior, A and Rodrigues da Silva, BF and Luiz da Silva, J and Trovão da Silva, M and Feliciano, JVP and Colturato, I and Barros, GMN and Scheinberg, P and Chao, NJA and de Oliveira, GLV}, title = {Unraveling the Intestinal Microbiota Conundrum in Allogeneic Hematopoietic Stem Cell Transplantation: Fingerprints, Clinical Implications and Future Directions.}, journal = {Journal of clinical medicine}, volume = {14}, number = {19}, pages = {}, pmid = {41095952}, issn = {2077-0383}, support = {#2022/12989-6//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #2023/08142-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; }, abstract = {Intestinal dysbiosis represents a critical determinant of clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Distinct microbiota patterns represent potential prognostic biomarkers and therapeutic targets. However, the exponential growth in microbiota research and analytical complexity has created significant interpretive challenges for clinicians. This review provides a synthesis of current literature examining microbiota fingerprints and their clinical implications. We analyzed key studies evaluating the clinical implications of intestinal microbiota fingerprints in allo-HSCT. Additionally, we examined current therapeutic strategies for microbiota modulation and approaches for translating research findings into clinical practice. We identified three major microbiota fingerprints: (1) decreased intestinal microbiota diversity, (2) reduced abundance of short-chain fatty acid-producing bacteria, and (3) Enterococcus domination. These fingerprints are associated with critical clinical outcomes including overall survival, Graft-versus-host disease, transplant-related mortality, and infection-related complications. While fecal microbiota transplantation and dietary interventions appear promising, current studies suffer from limited sample sizes and lack standardized protocols. Despite significant advances in microbiota research, biological, methodological, and logistical challenges continue to hinder its clinical translation. Understanding microbiota fingerprints represents a promising avenue for improving allo-HSCT outcomes. However, successful clinical implementation requires standardized methodologies, mechanistic studies, and multi-center collaborations to translate research into actionable clinical tools.}, }
@article {pmid41096928, year = {2025}, author = {Yang, B and Wu, J and Hou, X and Bai, T and Liu, S}, title = {Memory in Misfire: The Gut Microbiome-Trained Immunity Circuit in Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {19}, pages = {}, pmid = {41096928}, issn = {1422-0067}, support = {2022YFC2504005//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Animals ; *Immunologic Memory ; Immunity, Innate ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Trained Immunity ; }, abstract = {Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. "Trained immunity"-the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors-maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut-bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome-immune-neuronal axis interactions, and host genetic variants modulating microbiome-immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions.}, }
@article {pmid41097199, year = {2025}, author = {Dey, P}, title = {All That Glitters Ain't Gold: The Myths and Scientific Realities About the Gut Microbiota.}, journal = {Nutrients}, volume = {17}, number = {19}, pages = {}, pmid = {41097199}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Dysbiosis/microbiology ; Probiotics ; Diet ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as 'good' or 'bad', and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome-drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies.}, }
@article {pmid41097970, year = {2025}, author = {Ma, Y and Huang, J and Zhuo, Q and Shen, S and Zhang, B and Wang, H and Zhang, J and Wang, O}, title = {[Impact of high-fat diet on intestinal fat absorption and fatty acid metabolism in rats transplanted with gut microbiota from hypertriglyceridemic individuals].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {54}, number = {5}, pages = {757-762}, doi = {10.19813/j.cnki.weishengyanjiu.2025.05.008}, pmid = {41097970}, issn = {1000-8020}, mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; *Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; *Intestinal Absorption ; *Hypertriglyceridemia/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Humans ; Feces/microbiology ; Lipid Metabolism ; }, abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on fat absorption rate, fatty acid metabolic flux, and short-chain fatty acid production in germ-free Sprague-Dawley(SD) rats.<br><br>METHODS: Ten-week-old male germ-free SD rats were randomly grouped(5-6 rats/group) by body weight. Blank control: saline gavaged + germ-free basal diet. Normal control: colonized with normal-TG(&#x2264;1.7 mmol/L) human gut microbiota + germ-free basal diet. Two other groups: colonized with high-TG(>1.7 mmol/L) human gut microbiota, one on germ-free basal diet and the other on high-fat diet(40.5% fat energy). Day 0 marked colonization start. On Days 0, 2, 4, rats were gavaged with fecal bacteria(1 mL/100 g body weight). After 10-day adaptation, high-fat group started high-fat diet on Day 14. Feces were induced and collected aseptically on Days 0, 14, 21, 56, 77 for total fat(fat absorption rate), fatty acid profile, and short-chain fatty acids like butyric acid.<br><br>RESULTS: On Day 77, compared to blank control, normal control had lower body weight, fat absorption rate, and fecal palmitoleic and linoleic acids(P<0.05), but higher butyric, palmitic, arachidic, oleic, DHA, and stearic acids(P<0.05). High-TG group had higher body weight, fat absorption rate, and fecal palmitoleic and linoleic acids than normal control(P<0.05), with lower butyric, three saturated, and oleic acids(P<0.05). High-fat group had higher body weight, fat absorption rate, and fecal fatty acids than high-TG group(P<0.05). After Day 21, &#x3b1;-linolenic acid was undetectable in all groups.<br><br>CONCLUSION: In contrast to the positive regulation of lipid metabolism in rats by colonization with non-high-TG microbiota, colonization with high-TG microbiota disrupts lipid metabolism balance, inhibits the excretion of saturated fatty acids and oleic acid, reduces butyrate production, increases fat absorption rate, elevates the risk of obesity, and may synergize with a high-fat diet to exacerbate intestinal lipid metabolism disorders.}, }
@article {pmid41098769, year = {2025}, author = {Li, Y and Xin, Y and Zong, W and Li, X}, title = {The role of oral microbiota in digestive system diseases: current advances and perspectives.}, journal = {Journal of oral microbiology}, volume = {17}, number = {1}, pages = {2566403}, pmid = {41098769}, issn = {2000-2297}, abstract = {The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.}, }
@article {pmid41100443, year = {2025}, author = {Shi, F and Zou, D and Zhang, L and Guo, N and Yu, J and Degen, AA and Tang, X and Ren, S and Ru, Y and Zheng, S and Zhang, Y and Wang, D}, title = {Increased urea nitrogen salvaging by a remodeled gut microbiota helps nonhibernating pikas maintain protein homeostasis during winter.}, journal = {PLoS biology}, volume = {23}, number = {10}, pages = {e3003436}, pmid = {41100443}, issn = {1545-7885}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Nitrogen/metabolism ; *Urea/metabolism ; Seasons ; *Lagomorpha/metabolism/microbiology/physiology ; Homeostasis ; *Proteostasis/physiology ; Feces/microbiology ; Diet, Protein-Restricted ; Male ; Liver/metabolism ; Herbivory ; Fecal Microbiota Transplantation ; }, abstract = {Nitrogen balance is a major challenge for herbivores when consuming a low-nitrogen diet. Gut microbiota-mediated urea nitrogen recycling facilitates protein homeostasis during times of nitrogen deficiency, yet its relevance to wild nonhibernating small mammals remains unclear. Here, through a combination of isotope tracing, metagenomics, targeted short-chain fatty acid analysis, and fecal microbiota transplantation, we investigated the effects of protein restriction in winter on urea nitrogen recycling in plateau pikas (Ochotona curzoniae) of the Qinghai-Tibetan Plateau. Hepatic urea-cycle metabolism was downregulated during winter protein restriction, accompanied by increases in beneficial bacteria with ureolytic capacity (such as the genus Alistipes), gut urease activity, and urea transporters, and acetate production, with a consequent increase in nitrogen reincorporation into the pika's protein pool. Critically, supplementing a low-protein diet with yak fecal microbiota enhanced the ureolytic capacity by increasing Alistipes abundance, revealing a critical mechanism whereby interspecies horizontal microbial transfer between sympatric species enhances host protein homeostasis. Our results reveal a functional role for the gut microbiota in urea nitrogen recycling to maintain protein balance in winter-active herbivorous small mammals and contribute to our understanding of species coexistence and mammalian adaptation to high-altitude environments. Our findings establish that microbiota-driven urea nitrogen recycling is a key adaptive strategy for protein homeostasis in winter-active herbivores. This work provides new insights into the mechanisms of mammalian adaptation to high-altitude environments and the dynamics of interspecies coexistence.}, }
@article {pmid41101217, year = {2026}, author = {Liu, XL and Wu, SY and Zou, ZP and Xian, X and Wang, J and Min, L and Zhou, Y and Houf, K and Yu, Z}, title = {Characterization and intestinal pathogenicity of Proteus mirabilis isolated from broiler carcasses and processing environments.}, journal = {International journal of food microbiology}, volume = {445}, number = {}, pages = {111487}, doi = {10.1016/j.ijfoodmicro.2025.111487}, pmid = {41101217}, issn = {1879-3460}, mesh = {Animals ; *Proteus mirabilis/pathogenicity/genetics/isolation &amp; purification/drug effects ; Chickens/microbiology ; Virulence ; *Intestines/microbiology/pathology ; Mice ; *Proteus Infections/microbiology/veterinary ; Drug Resistance, Multiple, Bacterial ; Anti-Bacterial Agents/pharmacology ; Food Contamination/analysis ; *Meat/microbiology ; Food Microbiology ; Food Handling ; }, abstract = {Proteus mirabilis, a well-known urinary tract pathogen, is increasingly recognized as a food safety concern due to its frequent detection in meat products, particularly poultry. Sporadic reports indicate gastrointestinal symptoms linked to P. mirabilis, but the relationship between its genome, antibiotic resistance, and variable pathogenicity remains unclear. In this study, 142 P. mirabilis isolates were collected from broiler carcasses and processing environments in wet markets and industrial facilities to assess contamination levels. Thirty-six representative isolates were characterized for genomic heterogeneity, antibiotic resistance, and virulence gene profiles using whole-genome sequencing and phenotypic susceptibility testing. Selected strains were further assessed for intestinal pathogenicity in a murine model. Broiler carcasses from wet markets had significantly higher contamination rates (80.77 %, 21/26) than industrial sources (41.67 %, 5/12), with all wet market samples (13/13) testing positive. Overall, 94.4 % of isolates were multidrug-resistant, with carcass isolates showing higher resistance than environmental isolates. Animal experiments demonstrated variable pathogenicity, including intestinal injury, villus disruption, epithelial shedding, goblet cell loss, inflammatory cytokine elevation, and gut dysbiosis. Dysbiosis induced by certain strains (e.g., R638) was linked to intestinal injury, as confirmed by fecal microbiota transplantation. These findings highlight P. mirabilis as a highly heterogeneous foodborne pathogen, emphasizing the need for targeted hygiene practices, particularly in wet market processing environments.}, }
@article {pmid41102296, year = {2025}, author = {Udomkarnjananun, S and Chuaypen, N and Metta, K and Dissayabutra, T and Sodsai, P and Kittiskulnam, P and Tangkijvanich, P}, title = {Dietary composition modulate gut microbiota and related biomarkers in patients with chronic kidney disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {36274}, pmid = {41102296}, issn = {2045-2322}, support = {PMU-B, grant number B36G660010//the NSRF via the Program Management Unit for Human Resources &amp; Institutional Development, Research and Innovation (PMU-B, grant number B36G660010)/ ; }, mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/blood ; *Gastrointestinal Microbiome ; Male ; Female ; *Biomarkers/blood ; Middle Aged ; Methylamines/blood ; Cross-Sectional Studies ; Aged ; Cytokines/blood ; Feces/microbiology ; *Diet ; Dietary Fiber ; Adult ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Emerging evidence indicates gut microbiota is essential to chronic kidney disease (CKD) progression. This study investigated the association between gut microbiota profiles, plasma trimethylamine-N-oxide (TMAO), and circulating inflammatory markers in CKD patients according to dietary patterns, particularly low-protein, high-fiber (LP-HF) versus high-protein, low-fiber (HP-LF) diet. In this cross-sectional study, patients with non-dialysis CKD and healthy subjects were enrolled. Dietary patterns among participants were assessed using three-day diet records with detailed nutrient analysis. The 16 S ribosomal RNA sequencing was conducted to examine fecal gut microbiota composition. Plasma samples were analyzed for TMAO concentration and cytokine levels. A total of 135 CKD patients were recruited. A distinct shift in gut microbiota composition in CKD patients was observed compared to 19 healthy controls, particularly a significant reduction of short-chain fatty acid (SCFA)-producing bacteria. TMAO and several cytokine levels were significantly elevated in CKD patients compared to healthy subjects. Within CKD, patients with LP-HF diet displayed a greater abundance of SCFA-producing bacteria, such as the Lachnospiraceae NK4A136 group and Eubacterium ruminantium group, than those with the HP-LF diet. The HP-LF subgroup showed enriched proteolytic bacterial genera such as Klebsiella. The HP-LF subgroup also exhibited significantly higher plasma levels of TMAO, interleukin (IL)-18, and monocyte chemoattractant protein-1 (MCP-1). CKD patients displayed marked alterations in gut bacterial composition compared to healthy controls. Our results also highlighted the potential advantages of adopting a high fiber-rich and low-protein diet intake in reducing gut dysbiosis in CKD patients.}, }
@article {pmid41103946, year = {2025}, author = {Zhou, L and Li, B and Ren, J and Wang, S and Wang, J}, title = {Microbiome-mediated regulation of chemoradiotherapy response.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1659467}, pmid = {41103946}, issn = {2234-943X}, abstract = {The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.}, }
@article {pmid41104042, year = {2025}, author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK}, title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1667448}, pmid = {41104042}, issn = {1663-4365}, abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.}, }
@article {pmid41105383, year = {2025}, author = {Carlsen, A and Steinsbø, &#xd8; and Kvaløy, JT and Aabakken, L and Bolstad, N and Warren, DJ and Karlsen, L and Lundin, KEA and Omdal, R and Grimstad, T}, title = {Optimizing serum adalimumab levels in maintenance therapy via proactive therapeutic drug monitoring improves markers of disease activity in Crohn's disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {60}, number = {12}, pages = {1214-1225}, doi = {10.1080/00365521.2025.2573725}, pmid = {41105383}, issn = {1502-7708}, mesh = {Humans ; *Adalimumab/blood/therapeutic use/administration &amp; dosage ; *Crohn Disease/drug therapy/blood ; *Drug Monitoring/methods ; Female ; Male ; Adult ; C-Reactive Protein/analysis/metabolism ; Cross-Sectional Studies ; Leukocyte L1 Antigen Complex/analysis ; Biomarkers/blood ; Longitudinal Studies ; Middle Aged ; Feces/chemistry ; Severity of Illness Index ; Young Adult ; Maintenance Chemotherapy ; *Anti-Inflammatory Agents/blood/therapeutic use ; }, abstract = {OBJECTS: The benefit of a proactive therapeutic drug monitoring (TDM) strategy in patients with inflammatory bowel disease receiving biological therapy remains disputed. We aimed to evaluate whether optimizing serum adalimumab levels (s-ADL), guided by proactive TDM, is associated with improved markers of disease activity in patients with Crohn's disease.<br><br>MATERIALS AND METHODS: In this longitudinal cross-sectional study, 72 patients receiving adalimumab maintenance therapy from our outpatient clinic, were included. Patients underwent five study visits at 3-month intervals over one year. Disease activity was assesed using the Harvey-Bradshaw Index, plasma C-reactive protein (CRP), and fecal calprotectin. s-ADL levels were measured at each visit, and dosing was adjusted to maintain a therapeutic target range of 5.0-12.0&#x2009;mg/L.<br><br>RESULTS: At baseline, subtherapeutic s-ADL levels were associated with higher CRP levels (p&#x2009;=&#x2009;0.03), and in these patients' drug levels increased significantly over the study (p&#x2009;=&#x2009;0.001), whereas CRP levels decreased (p&#x2009;=&#x2009;0.03). Longitudinal analysis demonstrated that higher s-ADL levels (&#x2265;5.0&#x2009;mg/L) were associated with lower CRP levels (p&#x2009;=&#x2009;0.008) and lower HBI scores (p&#x2009;=&#x2009;0.03). Additionally, lower CRP- and fecal calprotectin levels at any visit were associated with higher s-ADL levels at the preceding visit (p&#x2009;=&#x2009;0.04 for both). Lower CRP levels were also associated with higher s-ADL levels using 7.0&#x2009;mg/L as the therapeutic threshold in longitudinal analyses (p&#x2009;=&#x2009;0.003).<br><br>CONCLUSION: Proactive TDM-guided optimization of s-ADL levels in Crohn's disease patients on adalimumab maintenance therapy was associated with the modest but significant improvements in markers of disease activity over one year of follow-up.}, }
@article {pmid41106199, year = {2025}, author = {Yu, Z and Wu, J and Han, J and Wang, L and Lu, R and Chen, J and Wang, K and Shi, Z}, title = {Triclosan induced obesity via gut microbiota dysbiosis and butyrate reduction.}, journal = {Ecotoxicology and environmental safety}, volume = {305}, number = {}, pages = {119227}, doi = {10.1016/j.ecoenv.2025.119227}, pmid = {41106199}, issn = {1090-2414}, mesh = {Animals ; *Triclosan/toxicity ; *Gastrointestinal Microbiome/drug effects ; Rats, Sprague-Dawley ; *Dysbiosis/chemically induced ; *Obesity/chemically induced/microbiology/metabolism ; *Butyrates/metabolism ; Rats ; Male ; Energy Metabolism/drug effects ; Thermogenesis/drug effects ; Fecal Microbiota Transplantation ; Adipose Tissue, Brown/drug effects ; }, abstract = {Triclosan (TCS) can influence energy metabolism and is a potential obesogen. However, its underlying mechanisms remain largely unknown. This study investigated how low-dose TCS exposure (0.5 mg/kg/day) disrupts energy metabolism in Sprague-Dawley rats. TCS increased body weight, visceral fat, liver lipid accumulation, and serum triglyceride levels. It also promoted hyperphagia by altering hypothalamic appetite regulation, activating orexigenic neuropeptide Y neurons and suppressing anorexigenic pro-opiomelanocortin neurons. Furthermore, TCS may reduce brown adipose tissue thermogenesis, as indicated by decreased mitochondrial uncoupling protein 1 and tyrosine hydroxylase. These metabolic effects were blocked by subdiaphragmatic vagotomy, confirming gut-brain neural circuit involvement. Mechanistically, TCS reduced gut microbial diversity and butyrate levels. Crucially, both fecal microbiota transplantation from control rats and butyrate supplementation reversed TCS-induced metabolic dysregulation. These findings reveal that TCS-induced gut dysbiosis and butyrate reduction as key drivers of metabolic disturbances and offer insights into the role of environmental chemicals in obesity and potential therapeutic strategies targeting the gut microbiota and butyrate.}, }
@article {pmid41106539, year = {2026}, author = {Wang, R and Tang, D and Wu, L and Ou, L and Ding, L and Jiang, J and Wu, Y}, title = {Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {190}, number = {}, pages = {106873}, doi = {10.1016/j.biocel.2025.106873}, pmid = {41106539}, issn = {1878-5875}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Carcinoma, Hepatocellular/drug therapy/immunology/pathology/microbiology ; Mice ; *Liver Neoplasms/drug therapy/immunology/pathology/microbiology ; Disease Models, Animal ; Male ; Cell Proliferation/drug effects ; }, abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.}, }
@article {pmid41107170, year = {2026}, author = {Taylor, NA and Sivam, S and van Dorst, J and Coffey, MJ and Visser, S and Haber, P and Volovets, A and Ooi, CY}, title = {Stool and symptom testing in ColoREctal Evaluation for Neoplasia in Cystic Fibrosis (SCREEN-CF).}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {25}, number = {1}, pages = {98-103}, doi = {10.1016/j.jcf.2025.09.008}, pmid = {41107170}, issn = {1873-5010}, mesh = {Humans ; Female ; *Cystic Fibrosis/complications/epidemiology ; Male ; *Colorectal Neoplasms/diagnosis/epidemiology/etiology ; *Feces/chemistry ; Middle Aged ; Colonoscopy/methods ; Prospective Studies ; Occult Blood ; *Early Detection of Cancer/methods ; Leukocyte L1 Antigen Complex/analysis ; Adult ; Australia/epidemiology ; Pyruvate Kinase/analysis ; *Adenomatous Polyps/diagnosis ; }, abstract = {BACKGROUND: People with cystic fibrosis (pwCF) have increased colorectal cancer (CRC) risk. Colonoscopy is recommended, yet CF comorbidities increase complexity and risk.<br><br>METHODS: We conducted a prospective, observational study of pwCF meeting colonoscopy screening guidelines at an Australian centre (2019 - 2023). Immunochemical faecal occult blood test (iFOBT), faecal calprotectin (FC), and faecal tumour pyruvate kinase isoenzyme type M2 (TuM2-PK) were evaluated for detecting adenomatous polyps and malignant ileocolonic lesions in pwCF. Stools were collected within 3 months of colonoscopy. Diagnostic performance and optimal cut-offs were calculated.<br><br>RESULTS: Among 49 participants [mean (SD) age 47.8 (8.2) years; 53 % female], 12 (24.5 %) were post-solid organ transplant, 10 (20.4 %) had > 3 months of triple modulator therapy at stool testing, 12 (24.5 %) had adenomatous polyps and 2 (4 %) had ileocolonic malignancy. Malignancies were in non-transplanted individuals, in the terminal ileum (age 43) and hepatic flexure/ascending colon (age 48). Higher BMI (>23.5 kg/m&#xb2;) was associated with abnormal colonoscopy (p = 0.03). iFOBT, FC and TuM2PK demonstrated excellent predictive performance for malignancy (AUC 0.93, 1.00, 0.83; all p < 0.05). Only FC had acceptable predictive performance for pre-malignant lesions (AUC 0.73; p = 0.008). For adenomatous polyps, FC &#x2264;100 &#xb5;g/g achieved a sensitivity of 91.7 % and an NPV of 95.5 %. For ileocolonic malignancy, FC &#x2265;1000 &#xb5;g/g showed 100 % sensitivity and specificity (p = 0.0009).<br><br>CONCLUSION: CRC screening in pwCF is critical given the high prevalence of neoplasia. Alternative non-invasive screening may support risk stratification among individuals with comorbidities, or reluctance, though performance could be influenced by CFTR modulator therapy.}, }
@article {pmid41108334, year = {2026}, author = {Chang, A and Oh, J and Shin, A and Oser, M and Manitius, N and Ghaffari, A and Limketkai, BN}, title = {Similar Symptoms, Distinct Syndromes: Multi-modal Approach to the Patient with an IBD-IBS Overlap.}, journal = {Digestive diseases and sciences}, volume = {71}, number = {3}, pages = {868-879}, pmid = {41108334}, issn = {1573-2568}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis/physiopathology ; *Inflammatory Bowel Diseases/therapy/diagnosis/physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Combined Modality Therapy ; }, abstract = {Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are distinct gastrointestinal conditions, but they frequently share overlapping clinical symptoms such as abdominal pain, bloating, and altered bowel habits. IBD is defined by the presence of chronic immune-mediated inflammation, and IBS is characterized by gastrointestinal symptoms in the absence of endoscopic and histologic inflammation. When patients with IBD continue to experience IBS-like symptoms despite remission of inflammation, this phenomenon is commonly referred to as IBD-IBS overlap. These patients pose diagnostic and therapeutic challenges, as symptom persistence may reflect lingering immune activation, disrupted barrier function, visceral hypersensitivity, gut-brain axis dysfunction, or microbiome alterations. This review synthesizes emerging evidence on the shared mechanisms underlying IBD and IBS and outlines a multimodal treatment approach that includes pharmacologic management, dietary interventions, mind-body therapies, and microbiome-directed strategies such as probiotics and fecal microbiota transplantation.}, }
@article {pmid41109415, year = {2026}, author = {Alasbly, G and Alotaishan, S and Algindan, Y and Khattab, R}, title = {Risk factors for nosocomial Clostridioides difficile infection-induced diarrhoea in patients receiving enteral feeding: a scoping review.}, journal = {The Journal of hospital infection}, volume = {167}, number = {}, pages = {81-90}, doi = {10.1016/j.jhin.2025.10.005}, pmid = {41109415}, issn = {1532-2939}, mesh = {Humans ; *Clostridium Infections/epidemiology/microbiology ; *Cross Infection/epidemiology/microbiology/prevention &amp; control ; Risk Factors ; *Diarrhea/epidemiology/microbiology/etiology ; *Enteral Nutrition/adverse effects ; Gastrointestinal Microbiome ; Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use/adverse effects ; }, abstract = {Nosocomial Clostridioides difficile infection (CDI)-induced diarrhoea is a major healthcare-associated infection, particularly in critically ill patients. Antibiotic use and disruptions in gut microbiota are known risk factors, and the role of enteral feeding (EF) requires further exploration. The aim of this scoping review was to examine risk factors for nosocomial CDI-induced diarrhoea in hospitalized patients receiving enteral feeding and assess the impact of EF-related factors on CDI outcomes. Evidence was synthesized from recent studies evaluating CDI risk in hospitalized patients on EF, focusing on antibiotic exposure, hospitalization duration, EF type, and gut microbiota alterations. Key risk factors identified include prolonged hospitalization, antibiotic use, and feeding tube placement, all of which may facilitate C. difficile colonization. Altered gut microbiota, characterized by reduced bacterial diversity, was associated with prolonged EF and lack of fibre in formulas. Fibre-enriched and polymeric formulas may support microbial balance, while the effects of probiotics on CDI prevention were inconsistent. Management strategies emphasized include antibiotic stewardship, infection control, and optimized nutrition. Faecal microbiota transplantation and bezlotoxumab show promise in reducing recurrence. However, evidence remains limited on whether specific EF modalities (e.g. continuous vs intermittent feeding, polymeric vs elemental formulas) directly affect CDI risk. EF may contribute to CDI risk through its impact on gut microbiota and related factors. While certain EF strategies show potential benefits, further research is needed to determine their role in CDI prevention and to develop evidence-based nutritional guidelines for at-risk patients.}, }
@article {pmid41109531, year = {2025}, author = {Kapoor, HK and Appolon, CB and Bardsley, CA and Kharel, K and Schneider, KR and Sharma, M and Mishra, AK and Dev Kumar, G and Pires, AFA and Dunn, LL and Mishra, A}, title = {Temporal and Environmental Drivers for Survival of Escherichia coli in Florida Soils Amended with Heat-Treated Poultry Pellets and Composted Poultry Litter.}, journal = {Journal of food protection}, volume = {88}, number = {12}, pages = {100639}, doi = {10.1016/j.jfp.2025.100639}, pmid = {41109531}, issn = {1944-9097}, mesh = {*Escherichia coli/growth &amp; development/isolation &amp; purification ; *Soil Microbiology ; Random Allocation ; Onions/growth &amp; development/microbiology ; Colony Count, Microbial ; Florida ; *Fertilizers/microbiology ; Composting ; Poultry/microbiology ; Feces/microbiology ; Hot Temperature ; Soil/chemistry ; Linear Models ; Models, Biological ; Time Factors ; Humidity ; }, abstract = {Previous studies have shown that field environmental conditions influence pathogen survival in the soils amended with biological soil amendments of animal origin (BSAAOs). To address this, a two-year completely randomized design field study in Florida was conducted with plots amended with heat-treated poultry pellets (HTPPs), composted poultry litter (PL), and unamended (UN), all inoculated with E. coli. Onion bulbs were transplanted into selected HTPP plots (O-HTPP) and field cured after harvesting. Soil samples were enumerated for E. coli on days 0, 1, 3, 7, 14, 28, 56, 84, 112, 140, 147 (harvest day), and 161 (after curing). The E. coli data were used to fit a linear mixed effect model (LME) with five weather variables: cumulative rainfall (cmrain4), average air temperature (at601234), relative humidity (RH1234), wind speed (W1), soil temperature (ast1). Overall, E. coli levels were 1.8 and 1.6 log10CFU or MPN/g higher in HTPP than UN plots in Year 1 and Year 2. The LME for soil amendment plots identified weather parameters that significantly influenced E. coli survival; cmrain4 and W1 increased and decreased survival by 0.698 and 0.712 log10CFU or MPN/g (p < 0.01), in Year 1. In the LME that compared plots with and without onions, W1 significantly increased survival in soils by 0.504 log10CFU or MPN/g (p < 0.05) in Year 1 (p < 0.05). These robust LME models (R[2]: 0.88-0.92) can predict the E. coli population in soils amended with poultry-litter-based amendments with or without onions. However, future studies will benefit from frequent samplings at later time points.}, }
@article {pmid41109693, year = {2025}, author = {Wagh, RS and Shasthry, SM and Sarin, SK}, title = {New Approaches to Alcohol-Associated Hepatitis.}, journal = {Clinics in liver disease}, volume = {29}, number = {4}, pages = {595-626}, doi = {10.1016/j.cld.2025.06.012}, pmid = {41109693}, issn = {1557-8224}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Liver Transplantation ; Fecal Microbiota Transplantation ; Plasma Exchange ; Granulocyte Colony-Stimulating Factor/therapeutic use ; }, abstract = {Severe alcohol-associated hepatitis (SAH) remains a difficult-to-treat severe liver ailment with limited therapeutic options and high mortality. The article reviews new data to help identify the steroid non-responders at the baseline to reduce the risk of infections and increased mortality. New information on the use of growth factors, such as granulocyte-colony stimulating factor, plasma exchange, and fecal microbiota transplantation, has been provided to choose as a monotherapy or with steroids for SAH. Early selection for liver transplantation after careful ethical considerations and risks of recidivism post-transplant can help improve survival upto 70% to 80%.}, }
@article {pmid41109696, year = {2025}, author = {Bunchorntavakul, C and Reddy, KR}, title = {Current Status and Future Directions in the Pharmacologic Management of Cirrhosis.}, journal = {Clinics in liver disease}, volume = {29}, number = {4}, pages = {657-672}, doi = {10.1016/j.cld.2025.06.003}, pmid = {41109696}, issn = {1557-8224}, mesh = {Humans ; *Liver Cirrhosis/complications/therapy ; *Liver Failure/etiology/prevention &amp; control ; *Gastrointestinal Agents/therapeutic use ; Hypertension, Portal/drug therapy/etiology ; Adrenergic beta-Antagonists/therapeutic use ; Albumins/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Rifaximin/therapeutic use ; Anticoagulants/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, the necessity for pharmacologic treatments to mitigate the risk of hepatic decompensation has been highlighted, with non-selective beta-blockers identified as the most effective option. However, a significant therapeutic gap persists, and additional or alternative treatments have been proposed, including statins, rifaximin, albumin, anticoagulants, angiotensin receptor blockers, granulocyte-colony stimulating factor, and fecal microbial transplant. According to the data from limited clinical trials, these pharmacotherapies offer promising possibilities; nonetheless, additional investigations, particularly randomized controlled trials, are required, in some instances, prior to their incorporation into routine clinical practice.}, }
@article {pmid41110352, year = {2025}, author = {Yuan, Y and Hu, J and Lu, X and Han, H and Wang, M and Zhang, W and Jiao, Y and Li, Y and Lin, Z and Liang, C and Yu, Y and Xie, C and Li, J and Mao, T}, title = {Oral rhein attenuate nonalcoholic steatohepatitis in mice through the modulation of gut microbiota and Th17 cell differentiation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157409}, doi = {10.1016/j.phymed.2025.157409}, pmid = {41110352}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Non-alcoholic Fatty Liver Disease/drug therapy/microbiology ; *Anthraquinones/pharmacology/administration &amp; dosage ; *Th17 Cells/drug effects ; Cell Differentiation/drug effects ; Mice ; Male ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; Liver/drug effects/pathology ; Administration, Oral ; }, abstract = {BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an important clinical issue and a challenge in the field of global public health. However, there are very few clinically approved drugs that can effectively treat NASH. Rhein is a natural organic compound with anti-inflammatory and antioxidant properties, but the specific role and mechanism on NASH remain unexplored.<br><br>PURPOSE: This study investigated the role and associated mechanism of rhein in NASH mice.<br><br>METHODS: The effects of rhein on lipid accumulation were evaluated in NASH mice through systemic signs of obesity, biochemical parameters, and histological changes. Network pharmacology was employed to determine the main bioactive compounds and key targets of rhein for the NASH treatment. Additionally, antibiotics treatment and fecal microbiota transplantation (FMT) were performed to investigate the role of microbiota in the treatment of NASH with rhein. Bacterial 16S rRNA amplicon sequencing, LC-MS/MS analysis and flow cytometric were employed to investigate the mechanisms underlying rhein's regulatory effects on gut microbiota, BA metabolism and immune balance. Finally, in vitro cell experiments were conducted to explore the effects of metabolites on Th17 cell differentiation.<br><br>RESULTS: Our results showed that mice treated with rhein showed a significant alleviating effect from high-fat diet (HFD)-induced liver lipid accumulation and pathological changes compared to those in HFD group. The protective effects of rhein are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Microbiota transferred from rhein-treated mice displayed a similar role in attenuating hepatic lipid deposition as rhein on NASH in mice, and depletion of the gut microbiota through antibiotics treatments diminished the protective effects of rhein on NASH mice. Moreover, the results from bacterial 16S rRNA sequencing suggested that rhein partially attenuated HFD-induced gut dysbiosis in NASH mice. Network pharmacology analyses was implemented and showed that Th17 cell differentiation might be the potential target in the treatment of rhein against NASH, which was confirmed by flow cytometric analysis showing markedly decrease of the percentage of Th17 cells, corresponded with upregulated Treg cells in rhein-treated NASH mice. Furthermore, targeted bile acid metabolomics analysis showed that supplement with rhein greatly increased the levels of primary bile acids &#x3b2;-MCA and AlloLCA, positively correlated with the relative abundances of Bifidobacterium_choerinum, which may play the key role by which rhein-altered gut microbiota promoted the restoration of Th17/Treg balance in NASH mice. Subsequent in vitro experiments confirmed that AlloLCA directly inhibits Th17 cell differentiation, with suppression of glycolysis potentially serving as the underlying mechanism for the immunomodulatory effects of AlloLCA.<br><br>CONCLUSIONS: Collectively, our results suggested that orally administrated rhein reduced hepatic lipid deposition through the modulation of dysregulated gut microbiota and bile acids metabolism, thus regulating Th17/Treg immune balance. This study uncovers a novel mechanistic axis in NASH pathogenesis and providing new research directions for microbiota-targeted clinical strategies.}, }
@article {pmid41110523, year = {2026}, author = {Li, R and Liu, J and Ye, F and He, S and Huang, J and Zhou, M and Xie, Q and Liu, Z and Cheng, W and Wang, G and Deng, W and Wang, X and Yang, T and Liang, Z and Hu, F and Huang, W and Cai, M and Xie, L and Zhang, W and Gong, S and Chen, Y and Wang, Y and Lin, L and Zhu, K}, title = {Microbial metabolism dysfunction induced by transarterial chemoembolization aggravates postprocedural liver injury in HCC.}, journal = {Journal of hepatology}, volume = {84}, number = {4}, pages = {808-822}, doi = {10.1016/j.jhep.2025.10.008}, pmid = {41110523}, issn = {1600-0641}, mesh = {Animals ; *Carcinoma, Hepatocellular/therapy ; *Chemoembolization, Therapeutic/adverse effects/methods ; *Liver Neoplasms/therapy ; *Gastrointestinal Microbiome/physiology/drug effects ; Rats ; Humans ; Male ; Limosilactobacillus reuteri/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Middle Aged ; }, abstract = {BACKGROUND &amp; AIMS: Transarterial chemoembolization (TACE) is widely used to treat unresectable hepatocellular carcinoma (HCC). Liver injury induced by TACE (TACE-LI) is the most common complication and limits long-term outcomes. Beyond the conventional understanding of direct TACE-induced damage to normal liver tissue, the underlying mechanisms of TACE-LI remain unclear. We aimed to elucidate the relationship between gut microbiota disturbances and TACE-LI.<br><br>METHODS: Microbial multi-omics analysis, genetically engineered bacteria and transcriptomics were used to study microbiota disturbances and host responses in TACE-LI.<br><br>RESULTS: Rats with antibiotic-depleted gut microbiota, as well as rats receiving fecal transplants from donor rats or patients who had undergone TACE, exhibited more severe TACE-LI. Limosilactobacillus reuteri (L. reuteri) abundance was significantly reduced in TACE-treated rats and patients with HCC. Reduced L. reuteri abundance after TACE led to decreased levels of tryptophan metabolite indole-3-lactic acid (ILA), while administration of live L. reuteri or ILA provided effective protection against TACE-LI. Mechanistically, L. reuteri relied on the key enzyme phenyllactate dehydrogenase to generate ILA. ILA inhibits the ATPase activity of heat shock protein 90, thereby deactivating the NOD-like receptor protein 3-inflammasome in macrophages and suppressing hepatic pro-inflammatory responses. Reduced levels of L. reuteri and ILA were correlated with aggravated LI and poorer overall survival in TACE-treated patients with HCC.<br><br>CONCLUSIONS: This is the first study to identify gut microbiota disturbance, i.e. deficiency of L. reuteri metabolite ILA, as a significant cause of TACE-LI. Administration of L. reuteri or ILA may serve as a promising therapeutic strategy to mitigate TACE-related adverse effects and improve prognosis in HCC.<br><br>IMPACT AND IMPLICATIONS: Transarterial chemoembolization (TACE) is widely used to treat unresectable hepatocellular carcinoma (HCC), but its long-term outcomes are limited by liver injury (LI). Beyond direct ischemic- or chemotherapy-induced liver damage, the mechanisms underlying TACE-induced LI (TACE-LI) remain unclear. We found that TACE disturbs the gut microbiota, notably reducing levels of Limosilactobacillus reuteri (L. reuteri) and its metabolite indole-3-lactic acid (ILA). These reductions were associated with aggravated TACE-LI and poorer overall survival in patients with HCC. Administration of L. reuteri or ILA significantly alleviated TACE-LI by suppressing macrophage-driven inflammation. This study is the first to identify gut microbiota disturbances as a key contributor to TACE-LI. Supplementing L. reuteri or ILA represents a safe and promising strategy to prevent TACE-LI, reduce TACE-related adverse effects, and improve prognosis in patients with HCC.}, }
@article {pmid41111149, year = {2025}, author = {Cai, K and Chen, Z and Wu, J and Wang, Q and Zhou, X and Pan, B and Xie, Z and Li, P and Chen, F and Chen, H and Liao, Q}, title = {Qing-Kai-Ling oral liquid alleviates non-alcoholic fatty liver disease via remodeling gut microbiota and activating AMPK/ACC1 axis.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {177}, pmid = {41111149}, issn = {1749-8546}, support = {2023B03J1382//Guangzhou Science and Technology Program/ ; 2022ZD004//Nansha Science and Technology Program/ ; 2024A1515011747//Guangdong Basic and Applied Basic Research Foundation/ ; }, abstract = {BACKGROUND: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, has demonstrated hepatoprotective, lung-protective, and gut microbiota-modulating properties. However, its efficacy in preventing high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and its relationship with gut microbiota and hepatic inflammation remain unclear.<br><br>PURPOSE: The study aims to investigate whether QKL can prevent HFD-induced NAFLD, focusing on the mechanistic role of gut microbiota, microbial metabolites, and hepatic inflammation.<br><br>METHODS: QKL was subjected to extraction and chemical profiling to identify its active compounds. In vivo studies were conducted in HFD-fed mice to assess the effects of QKL on hepatic lipid accumulation, inflammation, gut microbiota composition, SCFAs production, intestinal permeability, body weight, and fat mass.<br><br>RESULTS: Chemical analysis revealed that the major components of QKL are gallic acid, corilagin, and chebulagic acid. QKL administration (12.33 and 24.66&#xa0;mL/kg) for 8&#xa0;weeks significantly reduced hepatic steatosis, serum lipid profiles (TG, LDL-C), and body weight in high-fat diet-induced NAFLD mice, while improving glucose tolerance and intestinal barrier integrity. Gut microbiota analysis revealed QKL enriched beneficial taxa (e.g., Akkermansia, Bacteroides) and suppressed pathobionts (e.g., Lachnospiraceae NK4A136_group), effects replicated through faecal microbiota transplantation from QKL-treated donors. QKL upregulated intestinal gene GPR41/43 and hepatic protein GPR135 expression, enhanced SCFAs production (acetic, propionic, and butyric acids), and activated AMPK/ACC1 signaling to suppress lipogenesis and promote lipid oxidation. Untargeted metabolomics demonstrated QKL restored hepatic fatty acid metabolism by reducing palmitic acid and arachidonic acid accumulation.<br><br>CONCLUSION: These findings established QKL as a microbiota-modulating therapeutic agent for NAFLD through SCFA-AMPK/ACC1 axis activation, providing a foundation for developing QKL-based treatments.}, }
@article {pmid41111893, year = {2025}, author = {Fu, Z and Yu, T and Meng, C and Zhang, G and Huang, S and Li, Y and Fu, L and Deng, Z}, title = {Tortoise Oligopeptides Augment Cyclophosphamide's Antitumor Activity Through Dual Modulation of Therapeutic Efficacy and Hematologic Toxicity.}, journal = {Food science &amp; nutrition}, volume = {13}, number = {10}, pages = {e71078}, pmid = {41111893}, issn = {2048-7177}, abstract = {Cyclophosphamide (CTX) is a widely used chemotherapeutic agent, but its efficacy is often limited by leukopenia, a common adverse effect for which effective preventive strategies are currently lacking. In this study, oligopeptides were prepared from a blend of three edible tortoise species (Cuora trifasciata, Mauremys mutica, and Chinemys reevesii) and evaluated for their potential to alleviate CTX-induced leukopenia. The resulting Tortoise Oligopeptides (TOPs) were characterized primarily as small molecules with molecular weights under 5 kDa and peptide lengths between 4 and 15 amino acids, rich in glycine, glutamic acid, and proline. In a mouse model, TOPs administration significantly ameliorated CTX-induced leukopenia in a dose-dependent manner, attenuated pathological damage in the spleen and femur, and correlated with elevated serum levels of IL-4, IL-1β, TNF-α, and IFN-γ. In CTX-treated tumor-bearing mice, TOPs not only reduced leukopenia but also enhanced the antitumor efficacy of CTX. Correlation analyses linked leukocyte recovery to increased relative abundance of gut microbiota genera such as Colidextribacter, Tyzzerella, Prevotellaceae_UCG_001, and Rikenella. KEGG pathway analysis and fecal microbiota transplantation (FMT) experiments indicated that TOPs alleviate CTX-induced granulocytopenia partly through modulation of the gut microbiota. Additionally, LC-MS/MS sequencing combined with bioinformatic prediction and molecular docking identified several peptides-including PAIPAPPVGPGPK, FSFPTLPF, and PGLPFHP-with high binding affinity to key tumor targets (BCL-2, MDM2, EGFR), suggesting intrinsic antitumor properties. These findings indicate that TOPs may serve as a specialized medical food to mitigate CTX-induced leukopenia through multimodal mechanisms involving immunonutrition, gut microbiota regulation, and direct antitumor peptide effects.}, }
@article {pmid41112042, year = {2025}, author = {Lin, A and Xiong, M and Jiang, A and Huang, L and Wong, HZH and Feng, S and Zhang, C and Li, Y and Chen, L and Chi, H and Zhang, P and Ye, B and Zhang, H and Zhang, N and Zhu, L and Mou, W and Shen, J and Li, K and Xu, W and Ying, H and Zhang, C and Zeng, D and Xie, J and Deng, X and Wang, Q and Xu, J and Shi, W and Qi, C and Qu, C and Huang, X and Hajdu, A and Li, C and Peng, C and Cao, X and Pei, G and Zhang, L and Huo, Y and Xu, J and Glaviano, A and Szöllősi, AG and Bian, S and Li, Z and Tang, H and Tang, B and Liu, Z and Zhang, J and Miao, K and Cheng, Q and Wei, T and Yuan, S and Luo, P}, title = {The microbiome in cancer.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70070}, pmid = {41112042}, issn = {2770-596X}, abstract = {The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ-specific microbiome signatures and highlights their potential as non-invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host-microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment.}, }
@article {pmid41112050, year = {2025}, author = {Wang, W and Bu, N and Cao, H and Chen, N and Chen, W and Cheng, L and Cui, B and Dai, L and Gao, H and Guo, M and He, X and Hu, J and Jiang, C and Jiang, X and Li, J and Li, P and Li, W and Liao, W and Liu, H and Liu, J and Liu, L and Liu, S and Liu, X and Lv, M and Ma, Y and Man, C and Pi, Z and Ren, Q and Sang, L and Sun, Z and Suo, H and Tan, Y and Tao, W and Wang, G and Wang, J and Wang, L and Wang, X and Wang, X and Wang, Y and Wu, K and Wu, R and Wu, Z and Xiao, X and Xiang, B and Yang, S and Yi, H and Yu, H and Yu, J and Zeng, Y and Zhai, H and Zhai, Q and Zhang, C and Zhang, G and Zhang, J and Zhang, W and Zhao, F and Zhao, L and Zhou, H and Zhu, L and Lan, C and Zhang, H and Zhu, S and Zhang, F}, title = {Shaping the future of probiotics, live biotherapeutic products, and fecal microbiota transplantation: 30 scientific recommendations from the CHINAGUT Conference.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70083}, pmid = {41112050}, issn = {2770-596X}, abstract = {The 2025 CHINAGUT Conference has assembled a panel of 63 experts (30 scientists, 26 physicians, and 7 corporate R&amp;D personnel) collaborated in three groups to present 30 scientific recommendations to advance probiotics, live biotherapeutic products, and fecal microbiota transplantation, addressing key issues on standardization, translation, supervision, regulation, and regulatory harmonization. These interdisciplinary guidelines aim to synthesize cutting-edge knowledge and practical needs to transform microbiota-based treatments from applications into precision-driven medical solutions, and serve as reference by scientific researchers, medical educators, pharmaceutical enterprises, clinicians, food and drug administrations, policymakers, and patients.}, }
@article {pmid41112298, year = {2025}, author = {Ma, T and Zhang, T and Peng, C and Liu, K and Xiong, Y and Chen, K and Peng, N and Wei, Z and Kuang, J and Ou, L}, title = {Immune cells: the key mediator between the gut microbiota and osteoporosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1680021}, pmid = {41112298}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Osteoporosis/immunology/microbiology/metabolism/therapy/etiology ; Animals ; Bone and Bones/immunology/metabolism ; Probiotics ; }, abstract = {As the body's largest immunological interface, the intestine harbors a complex ecosystem of gut microbiota (GM) that orchestrates mucosal immune maturation while sustaining local immunological equilibrium. Emerging evidence reveals the gut's influence on skeletal homeostasis via neuro-immune-endocrine pathways-termed the gut-bone axis-though its mechanistic intricacies remain incompletely defined. Since the concept of osteoimmunology was proposed in 2000 by Arron &amp; Choi, immune-skeletal interactions have garnered significant research traction. Immune cells primarily contribute to the maintenance of bone homeostasis through the release of pro- and anti-inflammatory factors. Consequently, the immune system represents a crucial intermediary in understanding the relationship between GM and metabolic bone diseases. This review synthesizes the interrelationships among gut microbiota, immune cells, and osteoporosis, and elucidates how GM modulate bone metabolism in osteoporosis through this critical intermediary. Furthermore, building upon the microbiome-immune-bone axis, we highlight several emerging microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, fecal microbiota transplantation, and engineered microbes-and evaluate their clinical translational potential, with the aim of advancing diagnostic and therapeutic strategies for metabolic bone disorders.}, }
@article {pmid41113141, year = {2025}, author = {Waseem, MH and Abideen, ZU and Shoaib, A and Rehman, N and Osama, M and Sajid, B and Ahmad, R and Fahim, Z and Ansari, MW and Aimen, S and Cheema, AH and Thada, PK}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Journal of central nervous system disease}, volume = {17}, number = {}, pages = {11795735251388781}, pmid = {41113141}, issn = {1179-5735}, abstract = {BACKGROUND: Emerging evidence has indicated gut dysbiosis as a potential modifiable contributor to the pathogenesis of Parkinson's disease (PD). Fecal microbiota transplantation (FMT), a microbiome-centric model aimed at modulating the intestinal microbial taxa, represents a novel therapeutic approach. However, its safety and efficacy profile in improving PD symptoms remains inadequately researched.<br><br>METHODS: PubMed, ScienceDirect, and the Cochrane Central Registry were searched to retrieve relevant articles from inception till February 2025. Risk ratios (RR) and Mean differences (MD), along with 95% confidence intervals (CI), were pooled under the random-effect model for dichotomous and continuous outcomes, respectively. The primary outcomes of interest were change in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1 (MDS-UPDRS 1), change in MDS-UPDRS 2. Secondary endpoints of interest were change in MDS-UPDRS 3 (on medication), change in MDS-UPDRS 3 (off medication), change in MDS-UPDRS 4, change in Irritable Bowel Severity Scoring System (IBS-SSS), change in Montreal Cognitive Assessment (MoCA), change in Parkinson Disease Questionnaire Summary Index (PDQ-39 SI), and GI adverse events. The Cochrane Risk of Bias 2.0 (RoB 2.0) tool was used for the quality assessment of the included randomized controlled trials (RCTs). A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was done for the certainty of evidence.<br><br>RESULTS: This systematic review and meta-analysis included 145 patients across 3 RCTs. FMT and placebo were comparable regarding the primary outcomes that include MDS-UPDRS Part I (MD = -0.36; 95% CI:[-2.18,1.45]; P = .70; I[2] = 33%), Part II (MD = -0.46; 95% CI:[-1.91,0.99]; P = .53; I[2] = 0%). The secondary outcomes, involving MDS-UPDRS Part III on-medication (MD = 1.41; 95% CI:[-2.14,4.42]; P = .50; I[2] = 17%), Part III off-medication (MD = 1.26; 95% CI:[-2.27,4.79]; P = .48; I[2] = 0%), and Part IV (MD = -0.39; 95% CI:[-1.63,0.85]; P = .54; I[2] = 24%) were also comparable between the two groups. No significant changes were observed in IBS-SSS (MD = -15.91; 95% CI:[-63.17,31.89]; P = .51; I[2] = 76%), PDQ-39 SI (MD = -2.13, 95% CI:[-5.62,1.36]; P = .23; I[2] = 0%), and MOCA scores (MD = 0.11; 95% CI:[-1.34,1.57]; P = .88; I[2] = 68%). However, the FMT group had more frequent adverse gastrointestinal events (RR = 3.32; 95% CI: [1.01,10.87]; P = .05; I[2] = 39%).<br><br>CONCLUSION: FMT shows no evidence of superiority compared to placebo. Variations in the findings of existing studies suggest that donor fecal composition, host-microbiota interactions, and methodological heterogeneity may determine outcomes. Further RCTs employing tailored microbiota and standardized endpoint metrics are required to establish a correlation between FMT and PD.}, }
@article {pmid41114029, year = {2025}, author = {Li, X and Liu, Q and Wang, Y and Zhang, H and Wu, Z and Fan, R and Ma, Y and Gong, W and Li, X}, title = {Two modified colonoscopically guided fecal microbiota transplantation catheter placement methods: a retrospective study (with video).}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1641325}, pmid = {41114029}, issn = {2296-858X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) transfers fecal microbiota from a healthy person into a patient for the treatment of various diseases. This study introduces two modified colonoscopically guided fecal microbiota transplantation catheter placement methods and evaluates their effectiveness and safety in clinical use.<br><br>METHODS: This study retrospectively reviewed medical records and corresponding endoscopist operational records of FMT patients at Shenzhen Hospital, Southern Medical University, from January 13, 2022, to July 26, 2024. The study analyzed 117 cases, divided into the Direct Loop Clamping (DLC) group and the Clip Loop Binding (CLB) group. The primary outcome was the catheter placement success rate. The secondary outcomes were operation-related times and adverse events.<br><br>RESULTS: Both groups achieved a 100% success rate in catheter placement. The two methods showed no significant differences in cecal intubation time, withdrawal time, and total operation time. What's more, the CLB group had a slightly shorter time for the first endoscopic clip securement (median 1.8 min vs. 3.7 min, P = 0.006). There were no significant differences in the incidence of adverse events between the two groups, and no severe adverse events were reported.<br><br>CONCLUSION: Both modified colonoscopically guided fecal microbiota transplantation catheter placement methods demonstrated safety and effectiveness in securing the FMT catheter, meeting the needs of patients requiring multiple FMT treatments over a short period. However, further validation through large-scale randomized controlled trials is needed.}, }
@article {pmid41114530, year = {2025}, author = {Xiao, Y and Zhang, X and Shao, B and Wu, Z and Li, X and Yi, D and Li, T and Yang, T and Zhu, J and Huang, T and Deng, Y and Qiu, T and Yang, G and Sun, X and Wang, N}, title = {Hydroxytyrosol Improves Metabolic Dysfunction-Associated Fatty Liver Disease Dependent on the Modulation of Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {43}, pages = {27450-27468}, doi = {10.1021/acs.jafc.5c07003}, pmid = {41114530}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Phenylethyl Alcohol/analogs &amp; derivatives/administration &amp; dosage ; Humans ; Animals ; Male ; Mice ; Bacteria/classification/genetics/isolation &amp; purification/drug effects/metabolism ; Middle Aged ; Female ; Adult ; *Fatty Liver/metabolism/drug therapy/microbiology ; Liver/metabolism/drug effects ; Feces/microbiology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism/drug therapy ; }, abstract = {The global threat of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, but effective measures are still lacking. To explore the potential impact of hydroxytyrosol (HT), a plant polyphenol, in the metabolic outcomes of MAFLD and the mediating role of the gut microbiota, we performed an 8-week randomized placebo-controlled clinical trial in MAFLD patients and collected fecal bacteria for metagenomics analysis and targeted metabolomics. In this population-based trial, we have revealed that HT mitigates liver injury and steatosis in patients with MAFLD, as well as systemic glucolipid metabolism disorder. Through analysis of the differences in bacterial taxon and functional profiles, as well as correlation analysis between species and metabolic indicators, it was found that Fusicatenibacter saccharivorans (F. saccharivorans), the microbial species with the greatest difference after HT intervention, was also the most significantly correlated with metabolic parameters of MAFLD and showed a significant positive correlation with the content of fecal butanoic acid. Butanoic acid was further associated with MAFLD-related metabolic indexes. To confirm the potential causal relationship between alterations in gut microbiota induced by HT intervention and improved MAFLD metabolic phenotypes, fecal microbiota transplantation (FMT) was conducted using a model of pseudogerm-free mice. We have further demonstrated that the fecal microbiota from donors of MAFLD patients receiving HT supplementation can ameliorate liver and systemic phenotypes in western-diet-induced MAFLD mice, interpreting the robust action of gut microbiota remodeled by HT in improving MAFLD. Consequently, HT supplementation may represent a tactic for improving MAFLD by modulating the composition and functionality of the gut microbiota.}, }
@article {pmid41114583, year = {2025}, author = {Xia, Y and Yang, J and Lu, S and Cheng, W and Ren, M and Liu, Z and Yang, L and Shen, Q and Liang, Y and Huang, H and Chen, M and Zhou, X and Yu, M and Ji, F and Xu, C}, title = {Microbial changes resulting from VSG attenuate MASLD by modulating bile acid metabolism and the intestinal FXR-FGF19 axis.}, journal = {mSystems}, volume = {10}, number = {11}, pages = {e0063425}, pmid = {41114583}, issn = {2379-5077}, support = {82370571//National Natural Science Foundation of China/ ; 82370574//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fibroblast Growth Factors/metabolism ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/metabolism ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Rats ; Male ; *Gastrectomy/methods ; Fecal Microbiota Transplantation ; Signal Transduction ; Humans ; Rats, Sprague-Dawley ; Amidohydrolases/metabolism ; Mice ; Receptor, Farnesoid X-Activated ; }, abstract = {UNLABELLED: Vertical sleeve gastrectomy (VSG) is a highly effective intervention for metabolic dysfunction-associated steatotic liver disease (MASLD) and is associated with significant alterations in the gut microbiota. However, the precise mechanisms underlying its metabolic benefits remain poorly understood. In this study, we revealed that VSG mitigates MASLD by reshaping gut microbiota-mediated bile acid metabolism. Through integrated 16S rRNA sequencing, targeted metabolomics, and functional validation experiments, we demonstrated that VSG markedly enhances bile salt hydrolase (BSH) activity within the gut microbiota, resulting in elevated levels of unconjugated bile acids. These unconjugated bile acids serve as potent agonists for the intestinal farnesoid X receptor (FXR), thereby activating the intestinal FXR-fibroblast growth factor 19 signaling pathway. This activation leads to significant improvements in metabolic health, including enhanced glucose regulation and attenuated hepatic lipid accumulation. Fecal microbiota transplantation (FMT) from VSG-treated rats replicated these metabolic improvements, whereas antibiotic treatment abolished these beneficial effects, highlighting the indispensable role of the gut microbiota in mediating the anti-MASLD effects of VSG. Importantly, inhibition of intestinal FXR signaling negated the metabolic benefits of FMT, further emphasizing the critical role of the gut microbiota-BSH-FXR axis. Our findings reveal a novel mechanism by which VSG alleviates MASLD through gut microbiota-dependent activation of intestinal FXR, offering new perspectives for microbiome-targeted therapeutic strategies in MASLD.<br><br>IMPORTANCE: Fecal transplantation from bariatric surgery patients and mice to germ-free mice has shown that the gut microbiota may contribute to metabolic benefits after bariatric surgery. However, the mechanisms by which the gut microbiota contributes to metabolic benefits after bariatric surgery require further investigation. To address this gap, we investigated the effects of the vertical sleeve gastrectomy (VSG) gut microbiota on metabolic dysfunction-associated steatotic liver disease (MASLD) in vivo and elucidated its underlying mechanisms. Our study demonstrated that VSG significantly improved the gut microbiota, especially by increasing bile salt hydrolase (BSH) activity, in MASLD rats. Increased BSH activity significantly increased the proportion of FXR-agonistic bile acids and further activated the intestinal FXR-FGF19 axis, thereby improving MASLD. These findings explored the key roles and mechanisms of the gut microbiota in the metabolic benefits of VSG, offering new microbiome-based treatment strategies.}, }
@article {pmid41115539, year = {2025}, author = {Meng, M and Zhao, L and Liu, W and Yi, G and Song, Y and Gan, Z and Tan, X and Dou, H and Liu, Y and Zhang, Y}, title = {Effect of polysaccharides from Aconitum pendulum Bush on rheumatoid arthritis.}, journal = {International journal of biological macromolecules}, volume = {331}, number = {Pt 1}, pages = {148405}, doi = {10.1016/j.ijbiomac.2025.148405}, pmid = {41115539}, issn = {1879-0003}, mesh = {*Aconitum/chemistry ; *Polysaccharides/administration &amp; dosage/isolation &amp; purification/pharmacology ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; Animals ; Rats ; *Arthritis, Experimental/therapy ; Gastrointestinal Microbiome/drug effects ; Male ; Rats, Wistar ; Cytokines/blood ; Feces/microbiology ; }, abstract = {The Tibetan people of China have used the roots of Aconitum pendulum Bush as a folk remedy for rheumatoid arthritis (RA). In this study, we investigated the effects of A. pendulum polysaccharides (APPs) on RA. Chemical analysis revealed that APPs were mostly composed of galacturonic acid, glucose, and glucuronic acid. Structural characterization showed that it is an α-glucan with (1 → 4) and (1 → 3,6) glycosidic linkages. Furthermore, we examined the therapeutic potential of APPs (100 and 400 mg/kg) in a rat model of bovine collagen-induced arthritis (CIA). Results indicated that APP administration markedly reduced the critical characteristics of CIA, including foot swelling, thymic and splenic indices, and serum concentrations of pro-inflammatory cytokines. Histopathological analysis further validated that APPs mitigated vascular opacities and synovial inflammation in the ankle joints. Moreover, initial analysis of fecal samples revealed changes in the abundance of specific intestinal microbial taxa after APP treatment. These findings collectively establish an experimental basis for the potential of APPs as adjunctive therapeutic agents for RA. However, additional research, encompassing fecal microbiota transplantation and studies in germ-free models, is essential to clarify the potential causal relationship between the observed alterations in gut microbiota and the anti-arthritic effects of APPs.}, }
@article {pmid41115624, year = {2025}, author = {Mishra, R and Harvey, A and Guo, A and Tillotson, G and Feuerstadt, P and Khanna, S and Shannon, WD and Blount, KF}, title = {Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements.}, journal = {Anaerobe}, volume = {96}, number = {}, pages = {103006}, doi = {10.1016/j.anaerobe.2025.103006}, pmid = {41115624}, issn = {1095-8274}, mesh = {Humans ; *Quality of Life ; *Metabolome ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention &amp; control/therapy/microbiology ; Adult ; Aged ; Clostridioides difficile ; }, abstract = {OBJECTIVES: Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.<br><br>METHODS: A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants' fecal microbiome or bile acid compositions.<br><br>RESULTS: Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.<br><br>CONCLUSIONS: The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent C. difficile infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.<br><br>CLINICAL TRIAL REGISTRATION: NCT03244644.}, }
@article {pmid41115965, year = {2025}, author = {Göttert, S and Thiele Orberg, E and Fan, K and Heinrich, P and Matthe, DM and Khalid, O and Klostermeier, L and Suriano, C and Strieder, N and Gebhard, C and Vonbrunn, E and Mamilos, A and Hirsch, D and Meedt, E and Kleigrewe, K and Hiergeist, A and Schwarz, A and Gläsner, J and Ghimire, S and Joachim, L and Voll, F and Neuhaus, K and Janssen, KP and Perl, M and Pielmeier, F and Ruland, J and Kreutz, M and Weber, D and Schmidl, C and Köhler, N and Tschurtschenthaler, M and Hoffmann, P and Edinger, M and Wolff, D and Bassermann, F and Rehli, M and Haller, D and Evert, M and Hildner, K and Büttner-Herold, M and Herr, W and Gessner, A and Heidegger, S and Holler, E and Poeck, H}, title = {The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9282}, pmid = {41115965}, issn = {2041-1723}, support = {324392634//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Animals ; *Graft vs Host Disease/prevention &amp; control ; *Mechanistic Target of Rapamycin Complex 1/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Intestines/physiology/drug effects ; *Membrane Proteins/metabolism/genetics ; *Regeneration/drug effects ; Mice, Inbred C57BL ; *Tyrosine/analogs &amp; derivatives/pharmacology/metabolism ; Male ; Female ; Fecal Microbiota Transplantation ; Transplantation, Homologous ; STING Protein ; }, abstract = {Changes in the intestinal microbiome and microbiota-derived metabolites predict clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report that desaminotyrosine (DAT), a product of bacterial flavonoid metabolism, correlates with improved overall survival and reduced relapse rates in patients receiving allo-HSCT. In preclinical mouse models, treatment with synthetic DAT prevents graft-versus-host disease by protecting the intestinal barrier and promoting intestinal regeneration and contributes to graft-vs.-leukemia responses. DAT´s beneficial effects on intestinal regeneration remain effective despite broad-spectrum antibiotics-induced dysbiosis, also when administered by fecal microbiota transfer with flavonoid-degrading F. plautii. Mechanistically, DAT promotes mTORC1-dependent activation and proliferation of intestinal stem cells, with concomitant engagement of the innate immune receptor STING required to mitigate metabolic stress and maintain an undifferentiated stem cell state independently of type-I interferon responses. Additionally, DAT can skew T cells towards an effector phenotype to modulate graft-versus-leukemia responses. Our data uncover DAT's dual, tissue- and immune-modulating properties and underscore its potential in precision microbiome-based therapies to improve tissue regeneration and minimize immune-mediated side effects.}, }
@article {pmid41118252, year = {2025}, author = {Qi, X and Li, Y and Zhu, Y and Shen, R and Xie, Z}, title = {Rebuilding the gut ecosystem: Emerging strategies targeting the microbiota in antibiotic-associated diarrhea.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {72}, number = {4}, pages = {287-295}, doi = {10.1556/030.2025.02690}, pmid = {41118252}, issn = {1588-2640}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Diarrhea/chemically induced/therapy/microbiology ; *Anti-Bacterial Agents/adverse effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/chemically induced/therapy ; Animals ; }, abstract = {Antibiotic-associated diarrhea (AAD) is a prevalent iatrogenic complication of antibiotic therapy, primarily triggered by dysbiosis and loss of intestinal homeostasis. The traditional interventions, such as empirical probiotic use, have shown a modest and a heterogeneous efficacy. This review integrates the current mechanistic understanding of AAD through the lens of the microbiota-mucosal-immune axis and provides a comprehensive overview of emerging therapeutic strategies. By integrating evidence from metagenomics, metabolomics, and immunology, we highlight next-generation approaches, including rationally engineered probiotics, standardized fecal microbiota transplantation (FMT), and synthetic-biology-derived interventions. Recent progress in multi-omics technologies and machine learning has enabled patient-stratified modulation of the gut microbiota, moving beyond empirical supplementation toward precision ecological reprogramming. These advanced therapies demonstrate superior outcomes in restoring microbial diversity, strengthening epithelial barrier function, and re-establishing immunological homeostasis. Ultimately, the management of AAD requires a systems-biology strategy that leverages real-time microbiome analytics for targeted, accurate, and sustainable restoration of gut health.}, }
@article {pmid41120029, year = {2026}, author = {Liu, J and Bian, X and Bian, X and Zhang, J and Li, Z and Liu, H and Wu, J and Sun, X}, title = {The main active component Kaji-ichigoside F1 of the ethnic medicine Rosa roxburghii Tratt prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.}, journal = {Journal of ethnopharmacology}, volume = {356}, number = {}, pages = {120767}, doi = {10.1016/j.jep.2025.120767}, pmid = {41120029}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Acetaminophen/toxicity ; Male ; Mice ; *Chemical and Drug Induced Liver Injury/prevention &amp; control/microbiology/metabolism ; *Rosa/chemistry ; Mice, Inbred C57BL ; Disease Models, Animal ; Anti-Inflammatory Agents/pharmacology/isolation &amp; purification ; Liver/drug effects/pathology ; *Plant Extracts/pharmacology ; }, abstract = {Kaji-ichigoside F1 (KF1), the main active component of the Guizhou ethnic medicinal material Rosa roxburghii Tratt, is widely used in China due to its anti-inflammatory properties. However, the protective effects of KF1 against drug-induced liver injury and its potential mechanisms are not yet understood.<br><br>AIM OF THE STUDY: We aimed to investigate the effects of KF1 on acute liver injury (ALI) and explore its underlying mechanisms, particularly its role in modulating the gut microbiota to inhibit ALI development.<br><br>MATERIALS AND METHODS: KF1 was prepared via 80&#xa0;% ethanol extraction, silica gel column chromatography, and Sephadex LH-20 column chromatography. Mouse models of ALI were established using acetaminophen (APAP) treatment, with or without KF1 (5 and 10&#xa0;mg/kg). 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to explore the inhibitory effect of KF1 on ALI. Additionally, the role of the gut microbiota was investigated through antibiotic treatment and fecal microbiota transplantation experiments.<br><br>RESULTS: Treatment with KF1 significantly altered the gut microbiota composition, notably increasing the abundance of the probiotic Akkermansia muciniphila (A. muciniphila). Furthermore, A. muciniphila enhanced the levels of beneficial metabolites, including inosine. Notably, inosine significantly suppressed inflammatory factors and improved APAP-induced ALI. Transcriptomic analysis revealed that inosine inhibited key signaling pathways, including MAPK, PI3K-AKT, JAK-STAT3, IL-17, TNF, and cytokine-cytokine receptor interactions. Importantly, the preventive effect of KF1 is dependent on microbial mechanisms.<br><br>CONCLUSION: KF1 protects against ALI by modulating the gut microbiota and associated metabolites, thereby promoting a more favorable state and inhibiting pro-inflammatory pathways.}, }
@article {pmid41120147, year = {2025}, author = {Takeshige-Amano, H and Igami, E and Okuzumi, A and Kamo, R and Iseki, M and Tsuyama, K and Wakamori, R and Okada, H and Taniguchi, D and Ueno, SI and Oji, Y and Ishikawa, KI and Nishikawa, N and Orikasa, M and Odakura, R and Koma, M and Maruyama, T and Nomura, K and Ishikawa, D and Shibuya, T and Nagahara, A and Teramoto, H and Yanagisawa, N and Hatano, T and Hattori, N}, title = {Randomised, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of antibiotic faecal microbiota transplantation in patients with Parkinson's disease (FLORA-PD): a study protocol.}, journal = {BMJ open}, volume = {15}, number = {10}, pages = {e102851}, pmid = {41120147}, issn = {2044-6055}, mesh = {Female ; Humans ; Male ; Middle Aged ; *Anti-Bacterial Agents/administration &amp; dosage ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/drug effects/physiology ; *Parkinson Disease/microbiology/physiopathology/therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: The intestinal microbiota of people with Parkinson's disease (PwP) differs significantly from that of healthy individuals. Given that altered microbiota may play a role in the pathogenesis of Parkinson's disease, faecal microbiota transplantation (FMT) has been proposed as a potential therapeutic approach. However, the efficacy of FMT in improving motor symptoms in PwP has been inconclusive in some pilot randomised controlled trials (RCT). Previous RCTs on PwP employed simple FMT, but our modified approach-pretreatment with antibiotics before FMT (A-FMT)-has been shown to improve the engraftment rate of given species and the beneficial effects of FMT. This study aims to evaluate the efficacy and safety of A-FMT for PwP, particularly in those with motor fluctuations.<br><br>METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, parallel-group study with an 8-week observation period following a single A-FMT. Thirty clinically established PwP with prominent motor fluctuation episodes will be randomised 1:1 to FMT or placebo. Participants in both groups will receive antibiotic treatment prior to colonoscopy for FMT or placebo treatment. Primary and secondary endpoints will include subjective and objective evaluations of motor and non-motor symptoms and will be evaluated before and after antibiotic treatment and at 4 and 8 weeks after the procedure. Exploratory endpoints will include blood and faecal sample analyses, advanced brain MRI and pharmacokinetic assessment of levodopa concentrations during a levodopa challenge test.<br><br>ETHICS AND DISSEMINATION: This study has been approved by the ethical committee of Juntendo University in August 2024 (J24-005) and will be conducted in accordance with the Declaration of Helsinki, the Japan Ministry of Health, Labour and Welfare Clinical Trials Act and related laws and regulations. All patient data will be anonymised to protect privacy and used solely for study purposes. Results will be published in academic journals and presented at conferences.<br><br>TRIAL REGISTRATION NUMBER: jRCTs031240344.}, }
@article {pmid41121479, year = {2026}, author = {Sahoo, A and Singh, J and Alam, K and Alruwaili, NK and Aodah, A and Almalki, WH and Almujri, SS and Alrobaian, M and Barkat, MA and Singh, T and Lal, JA and Rahman, M}, title = {Addressing Unmet Needs in Clostridium difficile Infection: Advances in Diagnosis, Treatment, and Prevention.}, journal = {Current medicinal chemistry}, volume = {33}, number = {10}, pages = {1900-1917}, pmid = {41121479}, issn = {1875-533X}, mesh = {Humans ; *Clostridium Infections/diagnosis/prevention &amp; control/drug therapy/therapy ; *Clostridioides difficile/drug effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Antibodies, Monoclonal/therapeutic use ; }, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) is a serious global health concern characterized by toxin-induced colonic damage, ranging from diarrhea to life-threatening conditions. Despite improved diagnostics and treatments, recurrence rates of up to 30% underscore persistent gaps in effective disease management.<br><br>METHODS: CDI pathogenesis is driven by the disruption of the gut microbiota, often due to broad- -spectrum antibiotic use. Risk factors such as advanced age, hospitalization, IBD, and immunosuppression increase the severity and recurrence of the infection. The hypervirulent ribotype 027 strain has been associated with increased mortality and treatment resistance, necessitating targeted therapies.<br><br>RESULTS: Emerging treatments such as FMT and monoclonal antibodies show promise for CDI management, with FDA approvals marking progress in microbiome restoration. However, hurdles remain in safety, regulation, and donor screening. Advances in diagnostic and scoring tools have aided in the detection and treatment, but differentiating between colonization and infection remains a challenge. Preventive measures and novel agents such as bacteriocins and bacteriophages offer targeted, microbiome-sparing strategies.<br><br>DISCUSSION: Despite recent advances, CDI management remains challenging because of diagnostic uncertainty and frequent recurrences. Innovative treatments such as FMT and monoclonal antibodies are promising but face limitations in safety, access, and cost. Preventive strategies and decision tools help, yet distinguishing colonization from infection remains difficult, underscoring the need for ongoing and multidisciplinary innovation.<br><br>CONCLUSION: This review highlights current approaches to CDI diagnosis, treatment, and prevention, stressing the urgent need for innovative strategies to reduce recurrence. Targeted research and policy efforts are vital to improving outcomes and quality of life for those affected.}, }
@article {pmid41122746, year = {2025}, author = {Zhang, X and Li, Y and Guo, Y and Sun, J and Yang, Y}, title = {Clinical efficacy of fecal microbiota transplantation in alleviating depressive symptoms: a meta-analysis of randomized trials.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1656969}, pmid = {41122746}, issn = {1664-0640}, abstract = {BACKGROUND: Depressive symptoms are common in neuropsychiatric disorders, significantly affecting quality of life and posing challenges to treatment. While pharmacological and psychological therapies remain standard, many patients show limited response. Fecal microbiota transplantation (FMT), which aims to restore gut microbial balance, has emerged as a novel approach for alleviating depressive symptoms by modulating the gut-brain axis. This study aims to conduct a comprehensive synthesis and quantitative evaluation of current evidence to elucidate the therapeutic potential of FMT in the management of depressive symptomatology.<br><br>METHODS: Following PRISMA guidelines, we conducted a systematic search across PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL from January 1, 2000, to December 31, 2024. 12 randomized controlled trials (RCTs) with 681 participants were included. The standardized mean difference (SMD) was calculated to evaluate FMT's effect on depressive symptoms. Subgroup analyses examined effects by delivery routes, follow-up duration, and clinical population.<br><br>RESULTS: FMT significantly reduced depressive symptoms (SMD = -1.21; 95% CI: -1.87 to -0.55; p = 0.0003). Sensitivity analysis confirmed statistical significance (SMD = -0.56; 95% CI: -0.86 to -0.26; p = 0.001). Both oral capsule and direct gastrointestinal administration were effective, with greater effects seen in direct gastrointestinal delivery (SMD = -1.06 vs. -1.29). Improvements were most notable in the short- to mid-term; effects diminished by 6 months. Subgroup analysis showed stronger effects in patients with irritable bowel syndrome (IBS) (SMD = -1.06) than in those with neurological/psychiatric-related conditions (SMD = -0.67), with moderate heterogeneity (I&#xb2; = 47%).<br><br>CONCLUSIONS: This meta-analysis supports FMT as an effective adjunctive therapy for depressive symptoms, especially in individuals with IBS. Endoscopic or enema routes appear more efficacious than oral capsules. While short- and mid-term benefits are evident, sustained effects require further investigation through long-term, high-quality RCTs.<br><br>https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025638185.}, }
@article {pmid41123497, year = {2026}, author = {Mali, J and Salusjärvi, J and Leppäniemi, A and Mentula, P and Sallinen, V}, title = {Comparison of classification systems for acute diverticulitis and updating of Helsinki staging.}, journal = {The journal of trauma and acute care surgery}, volume = {100}, number = {1}, pages = {129-135}, doi = {10.1097/TA.0000000000004795}, pmid = {41123497}, issn = {2163-0763}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Diverticulitis, Colonic/classification/complications/diagnosis/surgery ; Middle Aged ; Aged ; Acute Disease ; Peritonitis/etiology ; Prognosis ; Finland ; ROC Curve ; Severity of Illness Index ; Intensive Care Units/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Helsinki classification for acute colonic diverticulitis, based on radiological and clinical parameters, stratifies patients according to their prognosis and recommended treatment into five stages. This study aims to update Helsinki classification to improve it in patients with abscesses and peritonitis and validate the classification by comparing it with other classifications of diverticulitis.<br><br>METHODS: This was a retrospective cohort study. Patients treated for acute colonic diverticulitis of any stage between 2011 and 2017 and for stages 4 and 5 between 2006 and 2017 in Helsinki University Hospital were included. Performance of classifications was tested with area under the receiver operating characteristic curve analysis.<br><br>RESULTS: In total, 2,361 patients were included. Receiver operating characteristic curve analysis showed the highest specificity and sensitivity for abscess cutoff point 50 mm in intensive care unit (ICU) admissions, discharge within 14 days, and operative treatment. Patients with Helsinki stage 4 fecal peritonitis had significantly more ICU admissions (38% vs. 12%, p = 0.005) and less ICU-free days (median, 24 vs. 26; p < 0.03), and fewer were discharged within 14 days (48% vs. 72%, p = 0.03) than patients with Helsinki stage 4 purulent peritonitis. Outcomes were similar between stage 4 fecal subgroup and stage 5 patients. Based on these findings, in the updated Helsinki 2.0 classification, abscess diameter cutoff between Helsinki stages 2 and 3 was changed to 50 mm, and fecal peritonitis was defined as belonging to Helsinki stage 5 diverticulitis. Helsinki 2.0 classification had generally at least equal area under the curve (AUC) values (AUC, 0.89-0.95) for mortality and morbidity compared with other classifications of diverticulitis (AUC, 0.83-0.95).<br><br>CONCLUSION: Updated Helsinki 2.0 classification is an easy-to-use robust pre- and intraoperative classification for acute diverticulitis accurately predicting outcomes and guiding treatment choices.<br><br>LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level III.}, }
@article {pmid41123566, year = {2026}, author = {Omar, TM and Al-Hussainy, AF and Jyothi, SR and Priyadarshini Nayak, P and Bethanney Janney, J and Singh, G and Polatova, D and Sameer, HN and Salih, RM and Adil, M and Salajegheh, P}, title = {Invisible influencers: the tumor microbiome's impact on immunotherapy in colorectal cancer (CRC).}, journal = {Expert review of anticancer therapy}, volume = {26}, number = {2}, pages = {161-178}, doi = {10.1080/14737140.2025.2579656}, pmid = {41123566}, issn = {1744-8328}, mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology/immunology/pathology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; *Immune Checkpoint Inhibitors/pharmacology/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; Probiotics/administration &amp; dosage ; Animals ; Precision Medicine/methods ; Disease Progression ; Drug Resistance, Neoplasm ; Gastrointestinal Microbiome/immunology ; Microbiota/immunology ; }, abstract = {INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology.<br><br>AREAS COVERED: This review examines the tumor microbiome's impact on CRC immunotherapy, focusing on immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 and anti-CTLA-4. It explores microbial composition, their immune-modulatory mechanisms, and metabolite-driven resistance pathways, including short-chain fatty acids and polyamines. Emerging strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted antibiotics are discussed, alongside challenges in personalizing microbiome-based therapies. Literature was sourced from peer-reviewed studies on tumor microbiome dynamics and immunotherapy resistance.<br><br>EXPERT OPINION: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.}, }
@article {pmid41123835, year = {2026}, author = {Saha, J and Goswami, R}, title = {Modulation of Innate Immunity by Short-Chain Fatty Acids in Probiotic and Fecal Microbiota Transplantation Therapies for the Treatment of Colon Disorders.}, journal = {Probiotics and antimicrobial proteins}, volume = {18}, number = {3}, pages = {3781-3807}, pmid = {41123835}, issn = {1867-1314}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Fatty Acids, Volatile/metabolism ; *Probiotics/administration &amp; dosage ; *Immunity, Innate/drug effects ; Gastrointestinal Microbiome ; Animals ; *Colonic Diseases/therapy/immunology/microbiology ; *Inflammatory Bowel Diseases/therapy/immunology/microbiology ; }, abstract = {Short-chain fatty acids (SCFAs) are produced by microbes in the gut from macronutrient fermentation. As the key bacterial metabolites, three SCFAs-acetate, propionate, and butyrate-are abundant in the gut and are presently linked to a number of homeostatic and pathophysiologic immune regulatory processes. The significance of these metabolites in the control of numerous immunological processes is currently being closely examined especially in gut immunity in gut-liver and gut-brain axes. Besides affecting cell metabolism and functions that confer immunity to the host, interestingly, SCFAs are currently in the spotlight for their role in innate immune cell maturation and differentiation having potential translational benefits. Dysbiosis in the gut leading to alterations of gut microbe population affects wide array of physiologic functions including both local and systemic immune regulation. Affecting millions worldwide, inflammatory bowel disease (IBD) and colorectal cancer (CRC) are the major gut diseases where the etiology can be partially attributed to gut dysbiosis and short-chain fatty acid alterations. We closely monitored the impact of intervention strategies of IBD and CRC by alteration of gut microbiota through probiotic administration and fecal microbiota transplantation on innate immunity. Although ongoing studies underscore the implications of these strategies in combatting gut inflammation but the importance of SCFA metabolism on innate immunity needs to be addressed. With the current narrative, we aim to connect the dots and find any missing links, between how probiotic administration and fecal microbiota transplantation as therapies impact gut inflammation via innate immune cell regulation through SCFAs as gut microbial metabolites.}, }
@article {pmid41123871, year = {2025}, author = {Krawczyk, A and Kasperski, T and Gosiewski, T and Nikiforuk, A and Potasiewicz, A and Arent, Z and Salamon, D}, title = {Effects of fecal microbiota transplantation on the abundance and diversity of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.}, journal = {Pharmacological reports : PR}, volume = {77}, number = {6}, pages = {1546-1556}, pmid = {41123871}, issn = {2299-5684}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; Rats ; *Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; Female ; *Schizophrenia/therapy/microbiology/chemically induced ; *Archaea/isolation &amp; purification ; Pilot Projects ; Male ; Methylazoxymethanol Acetate ; Pregnancy ; *Fungi/isolation &amp; purification ; Feces/microbiology ; }, abstract = {BACKGROUND: The gut microbiome has been increasingly recognized for its potential role in schizophrenia through gut-brain interactions involving immune, neural, and metabolic pathways. This pilot study evaluated the impact of fecal microbiota transplantation (FMT) on the abundance and variability of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.<br><br>METHODS: Sprague-Dawley rats using as a prenatal methylazoxymethanol acetate (MAM-E17) model of schizophrenia underwent FMT or placebo. Fecal DNA was extracted and analyzed via quantitative Real-Time PCR (qPCR) to quantify selected fungi (Candida tropicalis, Malassezia spp., Cryptococcus neoformans) and archaea (Methanobrevibacter smithii, Methanosphaera stadtmanae) before and after intervention RESULTS: A slightly higher prevalence of C. tropicalis was noted in MAM-exposed rats compared to healthy controls (19% vs. 10%). Post-FMT, C. tropicalis colonization increased to nearly 100% across all groups, irrespective of transplantation source, indicating natural microbiome maturation rather than FMT effect. Malassezia spp. were commonly present before treatment, with their abundance significantly declining after both FMT and placebo administration, suggesting procedural impacts rather than specific FMT effects. C. neoformans and methanogenic archaea were absent.<br><br>CONCLUSIONS: Overall, the results suggest that FMT has limited impact on gut fungal populations, possibly due to the developmental stage of microbiome maturation or procedural interventions. The absence of archaea underscores the complexity of the microbiome's role in neurodevelopmental disorders, highlighting the necessity for continued research into microbial influences on schizophrenia pathophysiology.}, }
@article {pmid41125958, year = {2025}, author = {Fan, Y and Ni, M and Aggarwala, V and Mead, EA and Ksiezarek, M and Cao, L and Kamm, MA and Borody, TJ and Paramsothy, S and Kaakoush, NO and Grinspan, A and Faith, JJ and Fang, G}, title = {Long-read metagenomics for strain tracking after faecal microbiota transplant.}, journal = {Nature microbiology}, volume = {10}, number = {12}, pages = {3258-3271}, pmid = {41125958}, issn = {2058-5276}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, mesh = {*Fecal Microbiota Transplantation ; *Metagenomics/methods ; Humans ; Clostridium Infections/therapy/microbiology ; Feces/microbiology ; Clostridioides difficile/genetics/classification/isolation &amp; purification ; Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {Accurate tracking of bacterial strains that stably engraft in faecal microbiota transplant (FMT) recipients is critical for understanding the determinants of strain engraftment, evaluating correlations with clinical outcomes and guiding the development of therapeutic consortia. While short-read sequencing has advanced FMT research, it faces challenges in strain-level de novo metagenomic assembly. Here we describe LongTrack, a method that uses long-read metagenomic assemblies for FMT strain tracking. LongTrack shows higher precision and specificity than short-read approaches, especially when multiple strains co-exist in the same sample. We uncovered 648 engrafted strains across six FMT cases involving patients with recurrent Clostridioides difficile infection and inflammatory bowel disease. Furthermore, long reads enabled assessment of the genomic and epigenomic stability of engrafted strains at the 5-year follow-up timepoint, revealing structural variations that may be associated with strain adaptation in a new host environment. Our findings support the use of long-read metagenomics to track microbial strains and their adaptations.}, }
@article {pmid41126356, year = {2025}, author = {Ba, F and Wang, W and Huang, Y and Zhang, S and Qiu, B and Xie, S and Xu, L and Gao, W and Zhang, X and Wen, Z and Wang, Q and Gao, H and Sheng, G and Berglund, B and Li, P and Li, L and Yao, M}, title = {Improving fecal transplantation precision for enhanced maturation of intestinal function in germ-free mice through microencapsulation and probiotic intervention.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {212}, pmid = {41126356}, issn = {2049-2618}, support = {2024YFA1307100//National Key Research and Development Program of China/ ; 2023YFC2506005, 2022YFA1303801//National Key Research and Development Program of China/ ; LR22C200005//Outstanding Youth Project of Zhejiang Natural Science Foundation/ ; SYS202202//Shandong Provincial Laboratory Project/ ; 2019-I2M-5-045//CAMS Innovation Fund for Medical Sciences/ ; 32372339//National Natural Science Foundation of China/ ; LY22C200014//Zhejiang Provincial Natural Science Foundation of China/ ; 2025ZFJH03//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; *Germ-Free Life ; Models, Animal ; *Probiotics/administration &amp; dosage ; *Gastrointestinal Microbiome/genetics/physiology ; Feces/microbiology ; *Pediococcus pentosaceus ; Bacteria/classification/genetics/isolation &amp; purification ; Humans ; Mice, Inbred C57BL ; Male ; Animals ; Mice ; RNA, Ribosomal, 16S/genetics ; DNA, Bacterial/isolation &amp; purification ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a widely used treatment for various diseases. While previous efforts have focused on selecting "super donors", the precise modulation of donor microbiota to enhance FMT efficacy remains a critical challenge. This study aimed to develop strategies to modify donor microbiota to promote gastrointestinal development and maturation in germ-free mice. Probiotic Pediococcus pentosaceus Li05 (Li05) was used as gut microbiota modulator to establish a healthier donor fecal microbiota, and a microencapsulation method was applied to ensure high bacterial viability during gastrointestinal tract transition.<br><br>RESULTS: Probiotic intervention initially altered the stability of the gut microbiota but eventually fostered a more complex bacterial interaction network and established a new equilibrium within 14&#xa0;days. Transplantation of encapsulated Li05-modulated fecal microbiota significantly promoted epithelial development, improved barrier function, and altered the colonic transcriptome profile. These effects were found to be more dependent on the abundance of some bacterial genera instead of their co-occurrence network, and the key functional bacterial genera associated with these benefits were believed to be Parabacteroides, Parasutterella, Lachnoclostridium, Muribaculum and Desulfovibrio. Notably, both encapsulation and probiotic modulation played critical roles in enhancing the functional efficacy of these key bacterial genera, and the community composed of key functional bacteria demonstrated an antagonistic relationship with other bacterial communities. Moreover, encapsulated Li05-modulated fecal microbiota induced dramatical changes in host lipid metabolism, especially the bile acids and their derives. Sporobiota gained the function of promoting epithelium development gene expression only after Li05-modulation since high abundance of Lachnoclostridium was introduced.<br><br>CONCLUSION: These findings underscore the importance of encapsulation and donor microbiota modulation in FMT and provide valuable strategies for improving transplantation precision and outcomes.}, }
@article {pmid41126840, year = {2025}, author = {Liu, T and Li, Y and Xiong, X and Lai, X and Xu, X}, title = {The Microbiota-gut-brain axis in vascular cognitive impairment: unraveling the mysterious link and therapeutic prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1648800}, pmid = {41126840}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain/metabolism ; *Cognitive Dysfunction/microbiology/therapy/etiology ; *Brain-Gut Axis ; *Dementia, Vascular/microbiology/therapy/etiology ; Medicine, Chinese Traditional ; Animals ; }, abstract = {BACKGROUND: Vascular cognitive impairment (VCI) exhibits particularly high prevalence in East Asian populations. However, its pathogenesis remains elusive due to its multifactorial and complex nature. Emerging evidence highlights the microbiota-gut-brain axis as a novel and promising paradigm for elucidating VCI mechanisms and developing therapeutic interventions. This systematic review aims to synthesize recent advances in this field, offering critical perspectives to guide future research on VCI through the lens of gut-brain interactions. Notably, given Traditional Chinese Medicine's (TCM) holistic and multi-target therapeutic advantages, we incorporate TCM studies to complement conventional approaches.<br><br>METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database for relevant studies from their inception to March 31, 2025, and conducted a comprehensive review.<br><br>RESULTS: A total of 22 relevant studies were included in the final review. Current research primarily focused on analyzing the altered gut microbiota in VCI patients, with findings indicating significant changes in both the structure and abundance of gut microbiota. Enterobacteriaceae exhibited potential as a diagnostic biomarker for post-stroke cognitive impairment (PSCI) (AUC=0.629), while distinct microbial signatures involving Bifidobacterium, Lactobacillus gasseri, and Anaerostipes hadrus may effectively differentiated PSCI patients from stroke survivors without cognitive deficits (AUC values of 0.785, 0.792, and 0.750, respectively). Furthermore, multiple interventional studies from both basic and clinical research systematically explored the microbiota-gut-brain axis as a promising therapeutic target for VCI. They evaluated the efficacy of diverse approaches-such as fecal microbiota transplantation, aerobic exercise, pharmacological interventions, and acupuncture-on key outcome including gut microbiota composition, cognitive function, hippocampal integrity, and inflammatory markers. Basic experimental studies revealed that Prevotella histicola, Clostridium butyricum, aerobic exercise, and TCM improved cognitive function, whereas trimethylamine N-oxide exacerbated cognitive impairment. The efficacy of TCM was further confirmed by clinical studies.<br><br>CONCLUSION: Research is in its early stages, but the microbiota-gut-brain axis already offers promising prospects for a deeper understanding and discovery of potential new therapeutic targets for VCI.<br><br>https://www.crd.york.ac.uk/prospero, identifier CRD42024560293.}, }
@article {pmid41128412, year = {2025}, author = {Peng, L and Song, H and Shi, H and Wu, L and Ma, Y and Fan, X and Wu, M and Duan, L and Li, Z and Yuan, H}, title = {Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis.}, journal = {ACS nano}, volume = {19}, number = {43}, pages = {37758-37782}, pmid = {41128412}, issn = {1936-086X}, mesh = {Animals ; *Manganese/chemistry/administration &amp; dosage/pharmacology ; *Sepsis/complications/drug therapy/metabolism ; Mice ; *Carbon/chemistry/administration &amp; dosage/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Lung Injury/drug therapy/etiology/metabolism/pathology ; Administration, Oral ; Male ; *Quantum Dots/chemistry/administration &amp; dosage ; Lung/drug effects/metabolism ; }, abstract = {Sepsis-induced pulmonary injury represents a life-threatening global health challenge due to poorly defined pathological mechanisms. The gut-lung axis has been proven to be widely involved in sepsis-induced lung injury, yet effective interventions targeting gut microbiota homeostasis remain unknown. Single-cell sequencing revealed increased alveolar apoptosis and impaired macrophage efferocytosis during sepsis pathogenesis. Thus, we designed oral manganese-doped carbon dots (Mn-CDs) to alleviate septic lung injury by remodeling gut microbiota homeostasis and targeting the gut-lung axis. Biochemical characterization demonstrated Mn-CDs possess multienzyme mimetic activities (SOD-, CAT-, POD-, GPx-like) and potent ROS scavenging capacity. In murine sepsis models, Mn-CDs significantly improved systemic indices and were associated with macrophage anti-inflammatory states with enhanced efferocytosis, as evidenced by transcriptomic profiling. Integrated metagenomic/metabolomic analyses identified Mn-CDs-mediated enrichment of g_Clostridium and g_Bacteroides, concomitant with elevated indole-3-propionic acid (IPA) production. Subsequent in vitro studies demonstrate that IPA likely binds primarily to the aryl hydrocarbon receptor (AHR), promoting both efferocytosis and anti-inflammatory polarization in macrophages, thereby mitigating septic lung injury. Notably, the fecal microbiota transplantation (FMT) from Mn-CDs-treated mice not only alleviated systemic symptoms but also effectively promoted efferocytic polarization of pulmonary macrophages in septic mice. Depletion of the gut microbiota resulted in a significant loss of the protective efficacy of Mn-CDs in a murine model of septic lung injury. Collectively, the gut-lung axis mediated by microbiota-derived IPA and macrophage efferocytosis contributes to the remediation of septic lung injury, highlighting the potential of Mn-CDs in microbiome-directed critical care.}, }
@article {pmid41129310, year = {2025}, author = {Mao, ZH and Liu, Y and Pan, S and Zhang, Q and Qiao, Y and Zhang, X and Li, D and Chen, J and Liu, D and Feng, Q and Liu, Z}, title = {The Gut-Kidney Dialogue: Unraveling the Microbial Symphony in Renal Fibrosis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {20}, pages = {e71179}, doi = {10.1096/fj.202502675R}, pmid = {41129310}, issn = {1530-6860}, support = {U21A20348//National Natural Science Foundation of China (NSFC)/ ; 82200796//National Natural Science Young Scientists Foundation of China/ ; LHGJ20230165//Medical Science and Technology Research Project of Henan Province/ ; LHGJ20240215//Medical Science and Technology Research Project of Henan Province/ ; 252300421112//Natural Science Foundation of Henan Province/ ; YQRC2024011//Young and Middle-aged Innovation Talents of Health Science and Technology Project in Henan Province/ ; 242102310009//Key R&amp;D and Promotion Special Projects of Henan Province/ ; 242102310098//Key R&amp;D and Promotion Special Projects of Henan Province/ ; //Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; Fibrosis/microbiology ; *Renal Insufficiency, Chronic/microbiology/pathology ; *Kidney/pathology/microbiology ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Mice ; Probiotics/therapeutic use ; }, abstract = {Renal fibrosis is a maladaptive pathological endpoint common to the diverse etiologies of chronic kidney disease (CKD), resulting in irreversible nephron loss and functional decline. Emerging evidence has highlighted the potential role of the gut microbiota in renal fibrosis through bidirectional interactions between the gut and kidney. In animal models, broad-spectrum antibiotic regimens have been confirmed to attenuate renal fibrosis, whereas fecal microbiota transplantation from fibrotic donors transmits renal disease in recipient germ-free mice, providing rudimentary evidence of microbial causality. Human-based studies have demonstrated that, in patients with CKD exhibiting progressive fibrosis, there are modifications in the composition of the gut microbiota, including decreased microbial variety and shifts in the distribution of specific bacterial groups. Furthermore, metabolomic profiling revealed that the severity of fibrosis was independently predicted by increased levels of circulating trimethylamine N-oxide and indoxyl sulfate. Preliminary clinical studies exploring the therapeutic potential of regulating the gut microbiota have demonstrated promising results. Interventions, such as high-purity probiotic formulations, result in improved renal function and decreased levels of fibrotic markers. These findings suggest a potential correlation between gut microbiota dysbiosis and renal fibrosis. However, further research is necessary to determine the causal correlations, elucidate the underlying mechanisms, and identify specific microbial species and metabolites related to the regulation of renal fibrosis. This review provides a systematic summary of the current understanding of the important connection between gut microbiota dysbiosis and renal fibrosis. Understanding the influence of gut microbiota on renal fibrosis may open new avenues for the development of innovative therapeutic strategies to prevent or manage renal fibrosis and its associated complications.}, }
@article {pmid41130528, year = {2025}, author = {Wang, J and Luo, Y and Wang, S and Zhou, Y and Gan, G and Xie, J and Cheng, ASK}, title = {Gut microbiota and late-life depression: from mechanistic insights to clinical rehabilitation.}, journal = {Life sciences}, volume = {382}, number = {}, pages = {124041}, doi = {10.1016/j.lfs.2025.124041}, pmid = {41130528}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Depression/microbiology/therapy/rehabilitation ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {Emerging evidence identifies the gut microbiota as a promising therapeutic target for late-life depression, yet its mechanisms and clinical applications remain insufficiently defined in aging populations. This review synthesizes findings from animal studies and clinical trials to examine how the gut microbiota contributes to late-life depression and to evaluate potential intervention. We first outline the association between microbial ecosystem alterations and mental health, emphasizing their relevance for late-life depression. Mechanistic pathways are then discussed in sequence: disruption of intestinal microbial networks that impair barrier integrity, dysregulation of microbial metabolites that disturb gut-brain communication, and maladaptive immune activation and signal transduction at the host-microbe interface. Building on these insights, we assess the therapeutic approaches, including dietary interventions, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Recovery outcomes are also summarized, covering microbial composition, metabolite changes, neurological biomarkers and neuroimaging findings. Finally, we address major translational challenges, including individual variability, dynamic monitoring, technological limitations, and safety concerns. We highlight the methodological gaps that limit current research and propose future directions to advance mechanistic understanding and clinical translation. By integrating ecological balance with personalized strategies, gut microbiota-based interventions hold potential to improve prevention and treatment of late-life depression.}, }
@article {pmid41130540, year = {2025}, author = {Li, J and Yue, Y and Pan, J and Liang, F}, title = {Research progress on gut microbiota in colorectal cancer immunotherapy.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1880}, number = {6}, pages = {189476}, doi = {10.1016/j.bbcan.2025.189476}, pmid = {41130540}, issn = {1879-2561}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Colorectal Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Fecal Microbiota Transplantation/methods ; Tumor Microenvironment/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical benefits in treating various malignancies. However, their therapeutic efficacy exhibits considerable interindividual variability in patients with colorectal cancer (CRC). In recent years, growing attention has been focused on the regulatory role of the gut microbiota and its metabolic microenvironment in modulating ICIs responses. This article systematically reviews key advances in understanding how the gut microbiota and its metabolites influence ICIs efficacy. For example: Specific bacterial species (e.g., Lactobacillus paracasei and Fusobacterium nucleatum) may regulate ICIs efficacy by modulating antigen presentation or the tumor immune microenvironment. Microbial metabolites, such as short-chain fatty acids (SCFAs), can enhance immune function and thereby improve ICIs outcomes. Potential microbiome-targeted interventions-including probiotic/prebiotic combinations, optimized antibiotic administration timing, refined fecal microbiota transplantation (FMT) protocols, and engineered synthetic biology-based bacterial therapies-are also discussed. By synthesizing current evidence, this review provides a theoretical foundation for developing novel personalized immunotherapy strategies for CRC, with a focus on microbiome modulation to optimize ICIs treatment efficacy.}, }
@article {pmid41131460, year = {2025}, author = {Li, G and Hou, Y and Zhang, L and Chen, L and Yang, Y and Yu, D}, title = {Gut microbiota and metabolomic profiles of tacrolimus-induced DILI in renal transplant recipients: a population-based case control study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {684}, pmid = {41131460}, issn = {1471-2180}, support = {2025ZNSFSC0718//Sichuan Science and Technology Support Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Kidney Transplantation/adverse effects ; Male ; Female ; Middle Aged ; *Tacrolimus/adverse effects ; Case-Control Studies ; Adult ; *Immunosuppressive Agents/adverse effects ; *Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Transplant Recipients ; *Chemical and Drug Induced Liver Injury/microbiology/metabolism/etiology ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics ; *Metabolome ; Aged ; }, abstract = {BACKGROUND: In clinical practice, cases of drug-induced liver injury (DILI) often occur in renal transplant recipients treated with tacrolimus (Tac) as an immunosuppressive therapy. Numerous studies have confirmed the close relationship between gut microbiota (GM) and DILI. However, systematic studies on the GM and metabolomic characteristics of Tac-associated DILI are lacking, and the role of GM and its metabolites in DILI remains incompletely understood.<br><br>METHODS: Renal transplant recipients receiving Tac at the Organ Transplantation Center of Sichuan Provincial People's Hospital were enrolled. Patients with DILI were assigned to the DILI group, and those with stable liver function to the control group. Stool samples were analyzed by 16&#xa0;S rRNA gene sequencing and LC-MS non-targeted metabolomics, and blood samples were collected to measure Tac trough concentrations.<br><br>RESULTS: Seventy-two renal transplant recipients were included, comprising 32 DILI patients and 40 controls. Oscillibacter and Ruminococcus gnavus group were significantly enriched in the DILI group, whereas Bacteroides, Lachnospiraceae NK4A136 group, Anaerostipes, Subdoligranulum, Eubacterium coprostanoligenes group, and Megamonas were significantly decreased in the DILI group. Metabolites such as icosadienoic acid and 1-acyl-sn-glycerol-3-phosphate were significantly elevated in the DILI group, while glycyrrhetinate, S-adenosylmethionine, and other related metabolites were significantly reduced.<br><br>CONCLUSIONS: In renal transplant recipients, distinct GM and enteric metabolic profiles differentiate patients with DILI from those with stable liver function. Key microbial taxa-including Oscillibacter, Bacteroides, Ruminococcus gnavus group, and Lachnospiraceae NK4A136 group-potentially contribute to DILI pathogenesis through modulation of bile acid metabolism and inflammatory signaling pathways.}, }
@article {pmid41132492, year = {2025}, author = {Zhang, L and Xu, T and Chen, W and Chai, Y and Wu, Y and Du, X}, title = {The potential of the microbiome as a target for prevention and treatment of carbapenem-resistant Enterobacteriaceae infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1674534}, pmid = {41132492}, issn = {2235-2988}, mesh = {Humans ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology ; *Enterobacteriaceae Infections/prevention &amp; control/microbiology/therapy ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use/administration &amp; dosage ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; Dysbiosis ; Carbapenems/pharmacology ; Fatty Acids, Volatile ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) present an escalating threat to global health due to their high transmissibility, limited treatment options, and high mortality rates. The gastrointestinal tract serves as both a major reservoir and a transmission hub for CRE, especially under conditions of antibiotic-induced dysbiosis. This review highlights the growing interest in the gut microbiome as a potential target for preventing and managing CRE infections. Building upon the understanding of CRE pathogenesis, we examine how commensal microbiota contribute to colonization resistance through mechanisms such as nutrient competition, spatial niche exclusion, immune modulation, and the production of antimicrobial metabolites. We further discuss microbiome-based therapeutic strategies, including probiotic administration, fecal microbiota transplantation (FMT), and supplementation with short-chain fatty acids (SCFAs), that have shown encouraging results in reducing intestinal CRE colonization. In addition, we explore emerging microbiome engineering approaches, particularly CRISPR-Cas9-mediated systems, which enable the selective elimination of resistant strains while maintaining microbial homeostasis. Current microbiome-based approaches have shown promise in the treatment and prevention of CRE infections, but further research is still needed to clarify their mechanisms, evaluate long-term safety, and determine their effectiveness in different clinical settings. With continued studies and thoughtful integration into existing infection control and antibiotic stewardship practices, these strategies may gradually contribute to a more practical and sustainable way to manage CRE.}, }
@article {pmid41132656, year = {2025}, author = {Hu, Y and Yang, Y and Li, Y and Zhang, Q and Zhang, W and Jia, J and Han, Z and Wang, J}, title = {Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1651063}, pmid = {41132656}, issn = {1664-3224}, mesh = {Humans ; *Th17 Cells/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy/metabolism ; Animals ; Dysbiosis/immunology ; Cytokines/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic and recurrent intestinal inflammation, primarily including Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is closely linked to abnormal immune responses, particularly T-cell mediated immune reactions. Th17 cells promote persistent intestinal inflammation by secreting pro-inflammatory cytokines such as IL-17, while regulatory T (Treg) cells help maintain immune homeostasis by secreting anti-inflammatory cytokines like IL-10 and TGF-β. In patients with IBD, Th17 cell function is enhanced, whereas Treg cell function is impaired or their numbers are reduced, leading to an imbalance in the immune system and exacerbating intestinal inflammation. The gut microbiota plays a crucial role in the immune regulation of IBD. Dysbiosis can lead to excessive activation of Th17 cells and suppression of Treg cell function, further aggravating clinical symptoms. Studies have shown that restoring gut microbiota balance through probiotics, antibiotics, dietary interventions, or fecal microbiota transplantation can not only improve immune responses but also restore the balance between Th17 and Treg cells, which has a positive impact on IBD treatment. This review summarizes how gut microbiota modulates the Th17/Treg cell balance to influence IBD immune responses and explores therapeutic strategies targeting Th17/Treg balance, including cytokine antagonists and immunosuppressive agents, which provide new directions and approaches for clinical IBD treatment.}, }
@article {pmid41133047, year = {2025}, author = {Al-Juhani, A and Desoky, MS and Almuhaimid, AA and Zaheer, M and Alhaqbani, HF and Abalkhail, EA and Alanazi, SA and Alzahrani, RS and Alrefaai, M and Desoky, R}, title = {Efficacy of Gut Microbiome-Targeted Therapies in Modulating Systemic Inflammation and Low-Grade Chronic Inflammatory States in Adults With Metabolic Disorders: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92881}, pmid = {41133047}, issn = {2168-8184}, abstract = {Gut microbiome-targeted therapies have shown promise in promoting the outcomes of metabolic inflammation-related disease management. This review aims to assess the effectiveness of microbiome-targeted interventions and pinpoint the most promising therapies for clinical implementation. Following the PRISMA 2020 standards, we searched four main databases: PubMed, EMBASE, Scopus, and the Cochrane Library. We integrated medical subject headings (MeSH) and free-text keywords search pertinent to gut microbiome-targeted interventions, along with related outcomes such as inflammation and insulin resistance. English studies were conducted on primary adults with a metabolic disease diagnosis or deemed a high risk, and were mandated to report at least one outcome pertinent to metabolic health or systemic inflammation. To assess the risk bias, data were extracted, and the Cochrane Risk of Bias (RoB) 2.0 tool was employed. Fifteen studies fulfilled the inclusion criteria. A narrative synthesis was conducted. We found that probiotics significantly enhanced insulin resistance (HOMA-IR), reduced circulating endotoxin levels, decreased visceral fat, BMI, and fat mass, and increased beneficial taxa with obesity-associated bacteria reduction. However, inconsistent outcomes were shown for lipid parameters. Prebiotic therapies showed significant decreases in fasting glucose in overweight people, and insulin levels and HOMA-IR in patients with metabolic syndrome, enhanced anti-inflammatory effects (31% C-reactive protein (CRP) reduction, decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and lipopolysaccharide (LPS) levels), and promoted butyrate-producing bacteria. Synbiotic interventions showed complementary benefits for glucose metabolism and body composition. Fecal microbiota transplantation (FMT) studies indicated improved insulin sensitivity and donor microbiota engraftment in responders. Fiber-rich diet trials markedly improved HbA1c levels in diabetic and prediabetic individuals. In conclusion, prebiotics demonstrated the most consistent metabolic and anti-inflammatory benefits across multiple parameters. Probiotics showed targeted effects on insulin resistance and body composition but inconsistent lipid outcomes. FMT and synbiotics require further investigation to establish clinical efficacy. This evidence supports prebiotics as a priority intervention for metabolic disease management through microbiome modulation.}, }
@article {pmid41133095, year = {2025}, author = {Cui, X and Yuan, Q and Long, J and Zhou, J}, title = {Recent advances in gut microbiota-mediated regulation of fat deposition and metabolic disorders.}, journal = {Microbiome research reports}, volume = {4}, number = {3}, pages = {31}, pmid = {41133095}, issn = {2771-5965}, abstract = {The gut microbiota critically regulates lipid metabolism through microbial metabolites and host signaling pathways. Short-chain fatty acids (SCFAs), derived from dietary fiber fermentation, suppress hepatic lipogenesis via inhibition of SREBP-1c and enhance mitochondrial β-oxidation through GPR41/43 activation. Microbial enzymes convert primary bile acids into secondary bile acids, which activate FXR to inhibit lipogenesis and TGR5 to promote adipose thermogenesis. Lipopolysaccharide (LPS) from dysbiotic microbiota triggers TLR4-NF-κB signaling, exacerbating insulin resistance and adipose inflammation. Branched-chain amino acids (BCAAs), metabolized by gut microbes, drive adipogenesis via mTORC1-PPARγ signaling, with elevated circulating BCAAs linked to obesity. In livestock, microbiota modulation optimizes fat deposition: probiotics in pigs enhance intramuscular fat via Lactobacillus-enriched communities, while dietary succinate or coated sodium propionate reduces abdominal fat in broilers by reshaping cecal microbiota. Fecal microbiota transplantation confirms microbial causality in transferring fat phenotypes. Dysbiosis-associated mechanisms are conserved across species, where SCFAs and bile acids ameliorate metabolic inflammation, whereas LPS and BCAA imbalances worsen lipid dysregulation. Metabolic disorders, including obesity, type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD), are tightly linked to gut microbiota perturbations. Dysbiosis drives LPS translocation and barrier impairment. These changes, along with altered metabolites, promote inflammation and fat deposition. Future strategies should integrate multi-omics and precision engineering of microbial consortia to advance therapies for both livestock and human metabolic health.}, }
@article {pmid41133518, year = {2025}, author = {Abdullah, IA and Khan, S and Hassan, FE}, title = {Gut-Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {41133518}, issn = {2076-3271}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Postoperative Cognitive Complications/microbiology/etiology/prevention &amp; control ; *Brain ; *Neurosurgical Procedures/adverse effects ; Dysbiosis ; Animals ; Probiotics/therapeutic use ; }, abstract = {Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut-brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood-brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this.}, }
@article {pmid41134466, year = {2025}, author = {Strzępa, A and Szczepanik, M}, title = {The role of microbiota modulation in preventing Alzheimer's disease- a review.}, journal = {Pharmacological reports : PR}, volume = {77}, number = {6}, pages = {1468-1490}, pmid = {41134466}, issn = {2299-5684}, support = {N43/DBS/000345//Polish Ministry of Science and Higher Education/ ; }, abstract = {Alzheimer’s disease (AD) is the most common form of dementia, and its incidence is projected to triple worldwide over the next 25 years. The most prevalent form, late-onset Alzheimer’s disease (LOAD), develops in genetically predisposed individuals exposed to environmental risk factors. Hallmarks of AD include accumulation of amyloid-β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, and mitochondrial dysfunction, resulting in oxidative stress, impaired glucose metabolism, and cognitive decline. Such metabolic disruptions result in early cerebral glucose hypometabolism and other metabolic disruptions, including altered lipid and branched-chain amino acid profiles. Recent evidence suggests that gut microbiota alterations, although individually variable, are a consistent and influential factor in AD progression via inflammatory and metabolic pathways. This narrative review explores therapeutic interventions targeting the gut-brain axis, including fecal microbiota transplantation (FMT), probiotic and antibiotic treatments, and dietary strategies such as the ketogenic and Mediterranean diets, as well as nutritional compounds such as omega-3 fatty acids. The aim is to evaluate the latest findings in both preclinical and clinical studies to identify multi-targeted, microbiota-based approaches for the prevention and management of AD.}, }
@article {pmid41136355, year = {2025}, author = {Chen, D and Yang, X and Jiao, D and Chen, X and Xiao, W and Zheng, J and Li, YX and Bao, C and Li, Y and Xu, B and Yuan, M}, title = {Electroacupuncture ameliorates Autism Spectrum Disorder via modulating the gut-brain axis depending on the integrity of vagus nerve.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {428}, pmid = {41136355}, issn = {2158-3188}, mesh = {Animals ; *Autism Spectrum Disorder/therapy/chemically induced ; *Electroacupuncture ; *Gastrointestinal Microbiome/physiology ; Mice ; *Vagus Nerve/physiopathology ; Disease Models, Animal ; Male ; Microglia/metabolism ; Female ; *Brain-Gut Axis/physiology ; Behavior, Animal/physiology ; Mice, Inbred C57BL ; Brain ; Fecal Microbiota Transplantation ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by behavioral and neurological abnormalities. Numerous pieces of evidence indicate a strong association between ASD and neuroinflammation mediated by gut microbiota and microglial activation. Previous studies have shown that the therapeutic effects of an acupuncture protocol targeting the bacteria-gut-brain axis in a well-established ASD mouse model induced by prenatal exposure to valproic acid (VPA). We demonstrated that electroacupuncture significantly alleviates behavioral symptoms in VPA model. However, the precise mechanisms remain insufficiently elucidated. In this study, we confirmed that electroacupuncture markedly improved behavioral symptoms in ASD mice. We conducted gut microbiota transplantation from electroacupuncture-treated mice to untreated ASD mice, improving behavioral outcomes in untreated ASD mice. Conversely, by transplanting gut microbiota from ASD mice into electroacupuncture-treated mice, we successfully mitigated the beneficial behavioral effects of acupuncture. We analyzed inflammatory markers in the microglial activation from cerebral cortex and hippocampus tissues, revealing that acupuncture exerts robust anti-neuroinflammatory effects in ASD mice. To further validate the mechanism, we performed vagotomy in ASD mice, which abolished the therapeutic benefits of acupuncture. Our findings establish that the behavioral improvements observed in ASD mice are intricately linked to the diversity and abundance of gut microbiota. Furthermore, regulatory effects of electroacupuncture on ASD behaviors are mediated via bacteria-gut-brain axis, dependent on intact vagus nerve signaling. This study provides compelling evidence for the potential of acupuncture to modulate central neuroinflammation through vagus nerve-mediated gut microbiota regulation, offering novel avenue into its therapeutic application for neurodevelopmental disorders such as ASD.}, }
@article {pmid41137517, year = {2025}, author = {Bayne, J and Charavaryamath, C and Hu, Y and Yousefi, F and Murphy, M and Law, A and Michael, A and Muyyarikkandy, MS and Nibbering, B and Smits, WK and Kuijper, E and Opriessnig, T and Sauer, M and Scaria, J and Sponseller, B and Ramirez, A and Mooyottu, S}, title = {The swine IsoLoop model of the gut host-microbiota interface enables intra-animal treatment comparisons to advance 3R principles.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2568706}, pmid = {41137517}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Swine ; Ileum/microbiology/surgery ; *Host Microbial Interactions ; Humans ; Feces/microbiology ; Clostridioides difficile/physiology ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation &amp; purification ; Models, Animal ; Disease Models, Animal ; }, abstract = {Understanding gut-host microbiota interactions requires models that replicate human physiology while providing region-specific resolution, translational precision, and minimal animal use. To this end, we developed the IsoLoop model, a swine gut loop platform enabling intra-animal, multi-treatment comparisons. Microbiota-depleted ileal loops were surgically created in pigs, maintaining neurovascular integrity while isolating them from the anastomosed digestive tract. In Experiment 1, loops were inoculated with human fecal microbiota (HFM) or HFM combined with Peptacetobacter hiranonis. In Experiment 2, they were inoculated with Clostridioides difficile. Host-microbiota interactions were compared with respective controls in each experiment. The IsoLoop model reduced animal use by 75% compared to conventional whole-animal designs. Following antibiotic-induced depletion, loops re-established microbial diversity by day 5, despite reduced richness and loss of taxa, including Lactobacillus. HFM transplantation in microbiota-depleted loops induced robust transcriptomic recovery, enriched Akkermansia and Bifidobacterium, and restored specific metabolic pathways, although taxonomic and metabolic restoration remained incomplete and divergent. P. hiranonis promoted normal ileum-like metagenomic functional convergence, activated epithelial repair pathways, and increased specific secondary bile acids. C. difficile challenge recapitulated early infection pathology in IsoLoops. The IsoLoop model offers an ethical and precise platform for investigating host-microbiota crosstalk, localized enteric pathologies, and therapeutic interventions.}, }
@article {pmid41140006, year = {2026}, author = {Shearer, J and Scantlebury, MH and Erome-Utunedi, O and Choudhary, A and Thompson, JA and Ohland, C and McCoy, KD and Mu, C}, title = {Role of Acid-Sensing Ion Channels 1a in the Regulation of Obesity and the Gut Microbiota.}, journal = {Obesity (Silver Spring, Md.)}, volume = {34}, number = {2}, pages = {372-381}, pmid = {41140006}, issn = {1930-739X}, support = {RGPIN-2018-04238//Natural Sciences and Engineering Research Council of Canada/ ; //Cumming School of Medicine Research Enhancement Program/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/genetics ; *Acid Sensing Ion Channels/genetics/metabolism ; Male ; *Obesity/metabolism/microbiology/genetics ; Female ; Rats ; Diet, High-Fat/adverse effects ; Mice ; Fecal Microbiota Transplantation ; Insulin Resistance ; Mice, Knockout ; Feces/microbiology ; }, abstract = {OBJECTIVE: Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of Asic1a influences obesity, metabolic, and gut-based outcomes.<br><br>METHODS: Employing male and female rats with systemic Asic1a deletion (Asic1a [-/-]), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high-fat diet administration for 8&#x2009;weeks. Fecal microbiota transplantation into germ-free mice was carried out as a proof-of-concept approach to assess the gut microbiota's direct impact.<br><br>RESULTS: On a chow diet, Asic1a deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild-type controls. These effects were exacerbated with high-fat diet administration. Asic1a [-/-] reshaped the gut microbiota, characterized by the enrichment of Bacteroides and Akkermansia. Microbiota transplantation from Asic1a [-/-] rats to recipient germ-free mice increased body weight gain relative to those from wild-type rats, implicating the potential role of gut microbiota.<br><br>CONCLUSIONS: Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.}, }
@article {pmid41140403, year = {2025}, author = {Scarpellini, E and Abenavoli, L and Falalyeyeva, T and Kobyliak, N and Bendriss, G}, title = {Editorial: Fecal Microbiota Transplants: challenges in translating microbiome research to clinical applications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1704947}, pmid = {41140403}, issn = {1664-302X}, }
@article {pmid41140407, year = {2025}, author = {Li, D and Li, Z and Liu, W}, title = {The gut-kidney axis in urolithiasis: roles of gut microbiota, metabolites, and therapeutic implications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1655808}, pmid = {41140407}, issn = {1664-302X}, abstract = {Urolithiasis affects 2-20% of the global population and recurs frequently. Emerging evidence positions the gut-kidney axis as a central driver of stone formation. This review synthesizes epidemiological data, comparative metagenomic analyzes, and mechanistic studies to demonstrate that stone formers exhibit reduced α-diversity, depletion of oxalate-degrading taxa (e.g., Oxalobacter, Lactobacillus, Bifidobacterium), and enrichment of pro-inflammatory genera (Escherichia, Bacteroides). Microbial metabolites-oxalate, short-chain fatty acids, p-cresol, and secondary bile acids-modulate intestinal oxalate transport, systemic inflammation, and renal crystal nucleation. Therapeutic modulation via targeted probiotics, prebiotics, engineered Lactobacillus, or fecal microbiota transplantation restores oxalate homeostasis and attenuates nephrolithiasis in rodent models; however, human efficacy remains preliminary. Large-scale multi-omics cohorts and randomized controlled intervention trials are imperative to translate gut-centric strategies into precision urology.}, }
@article {pmid41140755, year = {2026}, author = {Santos-Ferreira, N and Zhang, X and Corneillie, L and Van Dycke, J and Chiu, W and Montpellier, C and Neyts, J and Cocquerel, L and Kaptein, SJF and Rocha-Pereira, J}, title = {Proliferative Cell Targeting and Epithelial Cell Turnover Fuels Hepatitis E Virus Replication in Human Intestinal Enteroids.}, journal = {Gastro hep advances}, volume = {5}, number = {1}, pages = {100769}, pmid = {41140755}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Hepatitis E virus (HEV) is a leading pathogen causing acute viral hepatitis globally. While HEV is primarily spread fecal-orally, the role of the gut in HEV pathogenesis remains largely unexplored, including how HEV disseminates from gut to liver, and whether the gut is an HEV reservoir. We here aimed to illuminate HEV biology in the gut using human intestinal enteroids (HIEs).<br><br>METHODS: Three strategies were explored to establish an HEV-HIE model - three-dimensional (3D) HIEs, two-dimensional HIEs in transwell, and HEV RNA-electroporated HIEs. HEV particles produced by electroporated HIEs were characterized by western blot and gradient centrifugation. The intestinal tropism of HEV was investigated through confocal fluorescent microscopy and gene expression analysis.<br><br>RESULTS: HEV infection in 3D-HIEs and two-dimensional-HIEs showed limited replication, whereas HIEs electroporation led to a sustained increase in the release of nonenveloped infectious virions. These virions could reinfect new 3D-HIEs, yielding a &#x223c;2 log10 increase in HEV RNA over time. In electroporated HIEs, high expression of the infectious open reading frame 2 capsid form was observed in the supernatant. Importantly, 70% of all HEV-infected cells were identified as proliferative cells (leucine-rich-repeat-containing G-protein-coupled receptor 5 intestinal stem cells and transit-amplifying progenitor cells). Open reading frame 2 staining was also observed in absorptive enterocytes, goblet, and enteroendocrine cells.<br><br>CONCLUSION: Overall, we established a robust HEV-HIE model that yields high titers of infectious nonenveloped virions. Proliferative cells and the fast intestinal epithelial cell turnover are important features that facilitate efficient HEV replication, and likely also its dissemination. This study suggests that the gut is an HEV reservoir, capable of producing some of the nonenveloped HEV shed in the feces.}, }
@article {pmid41143926, year = {2025}, author = {Shi, Y and Ma, H and Li, H and Wang, Y and Wang, C and Zhang, N and Luo, G and Wang, Y and Gao, X}, title = {Sennoside A alleviating cognitive impairment in APP/PS1 mice via balancing microbiome metabolism.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {108}, number = {4}, pages = {1659-1676}, doi = {10.1177/13872877251389922}, pmid = {41143926}, issn = {1875-8908}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Cognitive Dysfunction/drug therapy/metabolism ; *Sennosides/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy/metabolism ; Male ; Mice, Transgenic ; Disease Models, Animal ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/genetics ; Brain/drug effects/pathology/metabolism ; }, abstract = {BackgroundThe progression of Alzheimer's disease (AD) is associated with constipation, potentially mediated by gut microbiota. Laxatives have shown potential in improving the cognitive function of AD, but the specific mechanism remains underexplored. Sennoside A (SA), a well-established laxative, is commonly used for treating constipation.ObjectiveThis work used SA as a probe to explore the therapeutic effects and potential mechanisms of laxatives on AD via the gut-brain axis.MethodsFollowing a two-month treatment, behavioral experiments were used to assess the cognitive function. The central pathologies and neuroinflammation were evaluated by histopathology and ELISA. 16S rRNA sequencing, fecal microbiota transplantation and antibiotic treatment were conducted to verify whether SA exerts anti-AD effects via gut microbiota. Further, non-targeted metabolomics coupled with Spearman correlation analysis was employed to elucidate the underlying mechanisms.ResultsSA significantly countered cognitive dysfunction and central pathological damage in APP/PS1 mice. Besides, SA ameliorated gut dysbiosis and affected the metabolic functions of the flora. Furthermore, the therapeutic effects of SA decrease with the depletion of gut microbes and could be transferred with the microbiota. Intriguingly, amino acid metabolism and aminoacyl-tRNA biosynthesis were the main metabolic pathways regulated by SA, consistent with the predicted functions of gut bacteria. Finally, correlation analysis revealed a strong correlation between gut microbes, fecal metabolites, and cognitive ability affected by SA.ConclusionsThe study investigated the efficacy and mechanisms of laxatives represented by SA for AD from the perspective of the gut-brain axis.}, }
@article {pmid41144501, year = {2026}, author = {Jiang, T and Li, C and Pan, Z and Wang, Y and Chen, X and Song, J and Zhu, K and Yang, Y and Hou, Y and Sun, L and Zhao, H and Liu, J and Gu, Y and Tao, B}, title = {Gut Microbiota-Decanoic Acid-Interleukin-17A Axis Orchestrates Hyperglycemia-Induced Osteoporosis in Male Mice.}, journal = {Diabetes}, volume = {75}, number = {1}, pages = {154-165}, doi = {10.2337/db25-0471}, pmid = {41144501}, issn = {1939-327X}, support = {22YF1440000//Shanghai Sailing Program/ ; 82070865//National Natural Science Foundation of China/ ; 82201396//National Natural Science Foundation of China/ ; 82270931//National Natural Science Foundation of China/ ; 82301005//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Interleukin-17/metabolism ; *Gastrointestinal Microbiome/physiology ; *Osteoporosis/metabolism/etiology/microbiology ; Mice ; *Hyperglycemia/complications/metabolism/microbiology ; Male ; Fecal Microbiota Transplantation ; Dysbiosis/metabolism/microbiology ; Mice, Inbred C57BL ; Th17 Cells ; }, abstract = {UNLABELLED: Hyperglycemia (HG) is a well-established risk factor for secondary osteoporosis, primarily due to suppressed osteoblast activity. While gut microbiota (GM) dysbiosis has been implicated in various diseases, its role in HG-induced osteoporosis remains poorly understood. Here, we demonstrate that HG mice develop low-turnover osteoporosis accompanied by reduced GM diversity. Fecal microbiota transplantation (FMT) from HG mice (GMHG-FMT) induced osteoporosis in recipient mice, independent of blood glucose levels. A depletion of Bifidobacterium pseudolongum was associated with bone loss, whereas supplementation with either microbiota of normoglycemic mice or B. pseudolongum alleviated osteoporosis in HG mice. Both HG and GMHG-FMT recipient mice exhibited elevated serum interleukin-17A (IL-17A) levels, and anti-IL-17A antibody treatment mitigated osteoporosis in the GMHG-FMT model. Furthermore, decanoic acid levels were elevated in the feces of HG mice and the serum of GMHG-FMT recipients. Decanoic acid promoted the differentiation of naive CD4+ T cells into T helper17 cells, leading to increased IL-17A production. These findings reveal a microbiome dysbiosis-driven decanoic acid/IL-17A axis in HG-induced osteoporosis and highlight the therapeutic potential of microbiome-associated targets.<br><br>ARTICLE HIGHLIGHTS: This study investigated the role of gut microbiota dysbiosis in hyperglycemia-induced osteoporosis, a condition with unclear mechanisms. We explored whether gut microbiota dysbiosis drives bone loss in hyperglycemia and identified key microbial and molecular pathways. Hyperglycemic mice showed disturbed gut microbiota symbiosis, decreased Bifidobacterium pseudolongum, and elevated decanoic acid, which promoted T helper 17 differentiation and interleukin-17A (IL-17A) production, leading to osteoporosis. Fecal microbiota transplantation from control mice, B. pseudolongum supplementation, and IL-17A blockade alleviated bone loss, highlighting both B. pseudolongum supplementation and IL-17A inhibition as potential therapeutic strategies for hyperglycemia-induced osteoporosis.}, }
@article {pmid41144632, year = {2025}, author = {Vermeijden, NK and Oorthuys, A and Groen, J and Thapar, N and Vlieger, A and Puoti, MG and Borrelli, O and Benninga, M}, title = {Current and novel therapeutic strategies in pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified.}, journal = {Expert opinion on pharmacotherapy}, volume = {26}, number = {16}, pages = {1649-1663}, doi = {10.1080/14656566.2025.2582017}, pmid = {41144632}, issn = {1744-7666}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/physiopathology/psychology ; *Abdominal Pain/therapy/physiopathology/psychology ; Child ; Cognitive Behavioral Therapy/methods ; Hypnosis/methods ; Quality of Life ; Fecal Microbiota Transplantation/methods ; }, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS) are amongst the most common disorders affecting children worldwide, often associated with a lower quality of live, anxiety, and depression. The underlying mechanisms of these conditions remain poorly understood, posing significant challenges to effective treatment. Consequently, many children receive inadequate care. This highlights the urgent need for accessible and effective treatment strategies.<br><br>AREA COVERED: Data were identified using CENTRAL, MEDLINE, and PUBMED databases up to 1 December 2024. This review will explore existing treatment approaches, from first-line reassurance to a spectrum of non-pharmacological and pharmacological interventions. We also discuss emerging therapies and future directions.<br><br>EXPERT OPINION: IBS and FAP-NOS are now named disorders of gut-brain interaction in the Rome IV criteria, highlighting the complex interplay between central and peripheral gastrointestinal alterations. Psychological interventions, such as cognitive behavior therapy and gut hypnotherapy, have proven to be the most successful therapies in pediatric IBS and FAP-NOS, whilst the evidence for the efficacy of pharmacological interventions is mostly lacking due to poor quality of available studies and high placebo responses. Future studies are needed to investigate the value of novel treatment strategies such as fecal microbiota transplantation and open label placebo's.}, }
@article {pmid41144719, year = {2026}, author = {Liu, M and Sun, J and Jia, Z and Cui, Y and Zhu, X and Wang, Z and Sun, H and Liu, B and Shi, Y}, title = {Medicago Sativa L. Saponin-Driven Lactobacillus Intestinalis Restores Intestinal Stemness in Naturally Aged Mice via the Bile Acid-FXR-Wnt Signaling Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {4}, pages = {e15370}, pmid = {41144719}, issn = {2198-3844}, support = {CARS-34//Modern Agro-industry Technology Research System of China/ ; 244200510010//Science and Technology Innovation Leading Talent in Central Plains/ ; }, mesh = {Animals ; *Saponins/pharmacology ; Mice ; *Medicago sativa/chemistry ; *Bile Acids and Salts/metabolism ; Gastrointestinal Microbiome/drug effects ; *Wnt Signaling Pathway/drug effects ; *Stem Cells/metabolism/drug effects ; *Aging/drug effects ; *Intestines/drug effects ; Mice, Inbred C57BL ; *Lactobacillus ; Male ; }, abstract = {Aging is recognized as a significant risk factor for chronic diseases. The decline in intestinal stem cells function is a critical contributor to intestinal aging, resulting in impaired intestinal homeostasis and increased vulnerability to age-related diseases. Medicago sativa L. (alfalfa) saponin are plant-derived bioactive compounds that are shown to have benefits in regulating oxidative stress and gut microbiota. However, the potential of alfalfa saponin (AS) to modulate intestinal aging and enhance intestinal stemness to maintain homeostasis remains insufficiently explored. In this study, the effects of AS on intestinal stemness in naturally aged mice and its underlying mechanisms involving gut microbiota regulation are examined. Antibiotic-mediated depletion of intestinal bacteria and fecal microbiota transplantation are employed to determine the specific role of the gut microbiota in mediating the effects of AS. Comprehensive multi-omics analyses revealed that AS significantly increased the abundance of Lactobacillus intestinalis (L. intestinalis). Notably, L. intestinalis is found to possess bile acids metabolic capabilities, producing ursodeoxycholic acid, which functions as an FXR antagonist to activate the Wnt signaling pathway and enhance intestinal stemness, thereby supporting intestinal homeostasis. These findings are validated in both intestinal organoids and naturally aged mice models. This study provides the first identification of a complete functional axis by which the metabolites of AS and L. intestinalis modulate intestinal stemness to mitigate intestinal aging, offering insights for the development of innovative natural product-based therapeutic strategies to promote healthy aging.}, }
@article {pmid41145481, year = {2025}, author = {Yu, Y and Zheng, Y and Zhang, H and Fan, X and Guo, J and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS ameliorates simulated microgravity induced skeletal muscle atrophy via the gut-muscle axis.}, journal = {NPJ microgravity}, volume = {11}, number = {1}, pages = {73}, pmid = {41145481}, issn = {2373-8065}, support = {2025JC-YBMS-046//Natural Science Foundation of Shaanxi Province/ ; 12374442, 11974233//National Natural Science Foundation of China/ ; 12034005//National Natural Science Foundation of China/ ; }, abstract = {Study investigated if abdominal low-intensity pulsed ultrasound (LIPUS) alleviates simulated microgravity (hindlimb unloading, HU)-induced skeletal muscle atrophy by restoring gut microbiota. Mice were divided into control (NC), HU, and HU with daily abdominal LIPUS (HU + LIPUS) groups. Fecal microbiota transplantation (FMT) from LIPUS-treated mice to HU mice was also performed. After 28 days, abdominal LIPUS partially reversed HU-induced gut dysbiosis, restored intestinal barrier integrity, and increased short-chain fatty acid (SCFAs) levels. LIPUS downregulated muscle atrophy genes (MSTN, ActRIIB) and upregulated growth genes (Akt, mTOR) in HU mice, preventing muscle loss. SCFAs levels positively correlated with muscle function. HU mice receiving FMT from LIPUS-treated donors showed similar gut and muscle improvements as direct LIPUS treatment. Results demonstrate abdominal LIPUS ameliorates muscle atrophy by modulating the gut-muscle axis, offering a potential non-invasive strategy for astronauts and patients.}, }
@article {pmid41145520, year = {2025}, author = {Suzuki, TA and Tanja, AS and Waters, JL and Jakob, D and Vu, DL and Ballinger, MA and Di Rienzi, SC and Chang, H and de Araujo, IE and Tyakht, AV and Ley, RE}, title = {Selection and transmission of the gut microbiome alone can shift mammalian behavior.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9482}, pmid = {41145520}, issn = {2041-1723}, support = {101142834//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/genetics ; Male ; Mice ; *Behavior, Animal/physiology ; Feces/microbiology ; *Selection, Genetic ; Locomotion ; Lactobacillus/metabolism ; Mice, Inbred C57BL ; Germ-Free Life ; Fecal Microbiota Transplantation ; }, abstract = {Animals live in partnership with their gut microbiota, and these microbial communities often shift when hosts adapt to new environments. While it is well known that the microbiome can influence traits ranging from metabolism to behavior, a key question remains unresolved: can host traits under natural selection be transmitted solely through the microbiome, without changes to the host genome? Here we experimentally demonstrate that selection on a behavioral trait in mice significantly shifts the host trait over time through microbiome transmission alone. We first identify locomotor activity as transmissible through the gut microbiome, using fecal transfers from wild-derived mouse strains into germ-free male recipients. Building on this, we carry out four rounds of one-sided microbiome selection, serially transferring microbiomes from low-activity donors to independently bred male germ-free mice. Only this selection line, not the randomly chosen control line, shows a decrease in locomotion toward the end of the experiment. Reduced activity is linked to enrichment of Lactobacillus and its metabolite indolelactic acid, and administration of either alone is sufficient to suppress locomotion. These findings demonstrate that microbiome selection and transmission can shape mammalian behavior, independent of host genomic evolution. Our work highlights the role of microbiome-mediated trait inheritance in shaping host ecology and evolution.}, }
@article {pmid41146499, year = {2025}, author = {Lang, Q and Zeng, Y and Yao, H and Dai, N and Fu, X and Fu, B}, title = {[Gut microbiota: new perspective on the treatment of acute pancreatitis and clinical application prospects].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {37}, number = {9}, pages = {797-801}, doi = {10.3760/cma.j.cn121430-20240903-00744}, pmid = {41146499}, issn = {2095-4352}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Pancreatitis/therapy/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Acute Disease ; Anti-Bacterial Agents/therapeutic use ; Enteral Nutrition ; }, abstract = {Acute pancreatitis (AP) is a severe inflammatory disease characterized by self-digestion of pancreatic tissue and inflammatory responses. Recent studies have revealed a close connection between gut microbiota and AP. The gut microbiota community, a complex ecosystem composed of trillions of microorganisms, is closely associated with various physiological activities of the host, including metabolic processes, immune system regulation, and intestinal structure maintenance. However, in patients with AP, dysbiosis of the gut microbiota are believed to play a key role in the occurrence and progression of the disease. This dysbiosis not only impairs the integrity of the intestinal barrier, but may also exacerbate inflammatory responses through multiple mechanisms, thereby affecting the severity of the disease and patient' clinical prognosis. This article reviews the mechanisms of action of gut microbiota in AP, explores how gut microbiota dysbiosis affects disease progression, and evaluates current clinical treatment methods to regulate intestinal flora, including probiotic supplementation, fecal microbiota transplantation, antibiotic therapy, and early enteral nutrition. In addition, this article discusses the efficacy and safety of the aforementioned therapeutic approaches, and outlines future research directions, aiming to provide novel perspectives and strategies for the diagnosis, treatment and prognostic evaluation of AP. Through in-depth understanding the interaction between gut microbiota and AP, it is expected that more precise and personalized therapeutic regimens will be developed to improve patients' quality of life and clinical outcomes.}, }
@article {pmid41148447, year = {2025}, author = {Choo, JM and Kang, WX and Le Leu, R and Manning, SK and Elms, L and Watson, N and Mukherjee, M and Trimingham, C and Coates, PT and Jesudason, S and Rogers, GB and Meade, A}, title = {The capacity of gastrointestinal microbiota in kidney transplant recipients to ferment prebiotic starch.}, journal = {Journal of nephrology}, volume = {38}, number = {9}, pages = {2977-2982}, pmid = {41148447}, issn = {1724-6059}, support = {(2019/07-QA25217)//Kidney Transplant &amp; Diabetes Research Australia/ ; APP1155179//National Health and Medical Research Council/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; Fermentation ; *Kidney Transplantation/adverse effects ; *Prebiotics ; Middle Aged ; Male ; Female ; Adult ; Feces/microbiology ; Zea mays ; *Starch/metabolism ; *Bacteria/metabolism/genetics/growth &amp; development ; Diarrhea/microbiology/prevention &amp; control ; Amylose/metabolism ; Aged ; }, abstract = {BACKGROUND: Disruption of the gut microbiota in kidney transplant recipients has been linked to an increased risk of post-transplant infections and gastrointestinal symptoms, including diarrhoea. Dietary supplementation with resistant starch may mitigate these risks by promoting the growth of commensal gut bacteria that produce beneficial bioactive metabolites.<br><br>METHODS: Faecal microbiome profiles, gastrointestinal symptoms, and dietary habits were assessed in 13 individuals with kidney failure before and after transplantation, using 16S rRNA V4 amplicon sequencing, a modified Gastrointestinal Symptom Rating Scale (mGSRS) and a food frequency screener. The effect of resistant starch supplementation on the gut microbiota pre- and post-transplant was evaluated using a preclinical in vitro fermentation model with high amylose maize starch.<br><br>RESULTS: Gut microbiota diversity (based on richness and Shannon diversity index) declined significantly following kidney transplantation. This loss correlated with a higher frequency of gastrointestinal symptoms, including rectal pain. Significant shifts in microbiota composition were observed, including depletion of butyrate-producing Lachnospiraceae species, a change&#xa0;previously associated with post-transplant diarrhoea. These microbiota changes occurred independently of dietary patterns, which remained consistent throughout the study. Fermentation of high amylose maize starch in vitro by pre- or early post-transplant gut microbiota did not result in significant expansion of commensal bacterial populations.<br><br>CONCLUSIONS: Alterations in the gut microbiota following kidney transplantation are associated with gastrointestinal symptoms. High amylose maize starch supplementation did not produce beneficial effects on the gut microbiota in preclinical model studies, either before or after transplantation.}, }
@article {pmid41148459, year = {2025}, author = {Liang, M and Li, L and Fan, J}, title = {Multi-target Effects of Short-Chain Fatty Acids for Obesity-Related Asthma: Interventional Potential and Challenges.}, journal = {Clinical reviews in allergy &amp; immunology}, volume = {68}, number = {1}, pages = {97}, pmid = {41148459}, issn = {1559-0267}, mesh = {Humans ; *Asthma/etiology/metabolism/therapy/epidemiology ; *Obesity/complications/metabolism ; *Fatty Acids, Volatile/metabolism/therapeutic use ; Gastrointestinal Microbiome ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, the prevalence of obesity and asthma has risen steadily, emerging as two major chronic diseases threatening public health. These conditions exert mutual promotion and may induce pathological superposition effects in obesity-related asthma. Obesity-related asthma represents a distinct asthma phenotype, with pathogenesis involving chronic low-grade inflammation, metabolic dysregulation, mechanical constraints, and genetic predispositions. Critically, four core components, including adipose dysfunction with metabolic dysregulation, gut microbiota dysbiosis with intestinal barrier impairment, systemic chronic inflammation, and pulmonary inflammation with airway hyperresponsiveness, interlock into a self-reinforcing cycle that synergistically amplifies disease progression. Accordingly, obesity-related asthma exhibits a greater clinical burden than classical asthma, including more severe symptoms, higher exacerbation rates, and poorer therapeutic responsiveness. As key metabolites derived from gut microbiota, short-chain fatty acids (SCFAs) demonstrate potential to disrupt this pathological cycle in obesity-related asthma through anti-inflammatory actions, immune-metabolic modulation, and epithelial barrier protection. Furthermore, SCFA levels can be effectively modulated through dietary interventions, microbial preparation supplementation, and fecal microbiota transplantation, positioning them as promising translational targets for obesity-related asthma.}, }
@article {pmid41148568, year = {2026}, author = {Che, Y and Shi, Y and Xu, Y and Guo, S and Liu, H and Yang, J and Liu, J and Niu, J and Shi, W and Guo, L and Wang, X and Zhang, F and Fan, W}, title = {Gut Microbiota Dysbiosis and LPS/NLRP3/GSDMD Pyroptosis Drive Hepatic Fibrosis: Therapeutic Potential of a Synbiotic Intervention.}, journal = {Probiotics and antimicrobial proteins}, volume = {18}, number = {3}, pages = {4906-4924}, pmid = {41148568}, issn = {1867-1314}, support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Dysbiosis/microbiology/therapy ; *Lipopolysaccharides/metabolism ; *Pyroptosis/drug effects ; *Synbiotics/administration &amp; dosage ; *Liver Cirrhosis/microbiology/therapy/metabolism ; Mice ; Male ; Mice, Inbred C57BL ; *Phosphate-Binding Proteins/metabolism/genetics ; Fecal Microbiota Transplantation ; Humans ; Gasdermins ; }, abstract = {Hepatic fibrosis (HF) is the inevitable course from chronic hepatitis to liver cirrhosis with limited treatment options. Our previous studies have found that a synbiotic alleviates autoimmune hepatitis in mice by improving the gut microbiota. However, whether this synbiotic can prevent the progression of HF and its underlying mechanism remains unclear. Therefore, we explored the effects and mechanism of this synbiotic on concanavalin A (ConA)-induced HF in mice. We found that the synbiotic not only reshaped the gut microbiota by increasing beneficial bacteria such as Bifidobacterium and reducing harmful bacteria such as Allobaculum and Dubosiella but also strengthened the intestinal barrier, reduced the hepatic transfer of lipopolysaccharide (LPS), and inhibited the LPS/NLRP3/GSDMD pyroptosis pathway. It also decreased collagen deposition and alleviated HF in mice in vivo and in LX2 cells in vitro. Fecal microbiota transplantation (FMT) experiments showed that microbiota from fibrotic mice exacerbated gut barrier dysfunction and promoted the LPS-induced pyroptosis pathway. In contrast, microbiota depletion with antibiotics alleviated these effects. In conclusion, our study indicates that gut microbiota dysbiosis and the subsequent activation of the LPS/NLRP3/GSDMD pyroptosis pathway are important factors in the progression of HF. The synbiotic, by regulating the gut microecology and inhibiting the LPS-induced pyroptosis pathway, provides a promising therapeutic strategy for inhibiting HF.}, }
@article {pmid41148805, year = {2025}, author = {Baum, S and Hamedi, K and Loftus, C and Loftus, G and Zhou, ER and Arce, S}, title = {From Cytokines to Biomarkers: Mapping the Immunopathology of Inflammatory Bowel Disease.}, journal = {Cells}, volume = {14}, number = {20}, pages = {}, pmid = {41148805}, issn = {2073-4409}, mesh = {Humans ; *Inflammatory Bowel Diseases/immunology/pathology/genetics ; *Biomarkers/metabolism ; *Cytokines/metabolism ; Animals ; Genetic Predisposition to Disease ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT.}, }
@article {pmid41153659, year = {2025}, author = {Lagoa, T and Martins, L and Queiroga, MC}, title = {Microbiota Modulation as an Approach to Prevent the Use of Antimicrobials Associated with Canine Atopic Dermatitis.}, journal = {Biomedicines}, volume = {13}, number = {10}, pages = {}, pmid = {41153659}, issn = {2227-9059}, support = {UIDB/05183/2020 and LA/P/0121/2020//FCT - Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia, Portugal/ ; }, abstract = {Modern lifestyle factors-such as dietary changes, reduced microbial exposure, and genetic susceptibility-profoundly influence the composition and function of the commensal microbiota. Additionally, dysregulation of the gut microbiota has been linked to impaired immune responses and an increased prevalence of skin disorders, including allergies and inflammatory conditions, thereby underscoring the importance of the gut-skin axis. Chronic gastrointestinal and dermatological manifestations frequently lead to excessive antimicrobial use, which in turn fosters the selection and colonization of multidrug-resistant organisms, most notably methicillin-resistant Staphylococcus pseudintermedius (MRSP) in companion animals. Furthermore, the growing threat of antimicrobial resistance (AMR) to both human and animal health reinforces the urgent need for alternative strategies like modulating the gut microbiota, which also contributes to the prevention and management of skin conditions. Against this backdrop, the present review aims to evaluate microbiota modulation as an alternative and complementary approach to antimicrobial therapy, focusing on its ability to restore microbial balance, strengthen epithelial barrier integrity, and improve overall health outcomes in dogs affected by atopic dermatitis (cAD). Promising interventions-including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation-are highlighted for their potential role in mitigating AMR and warrant further investigation as sustainable therapeutic strategies.}, }
@article {pmid41153953, year = {2025}, author = {Zhang, Z and Chen, K and Zhang, S and He, Y and Lei, G and Zhao, Y and Liang, J}, title = {Identification of Fecal Microbiota and Related Metabolites Associated with Feed Efficiency in DLY Pigs.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {20}, pages = {}, pmid = {41153953}, issn = {2076-2615}, abstract = {Improving feed efficiency (FE) is essential for enhancing productivity, reducing production costs, and minimizing environmental impacts in the swine industry. Fecal microbiota and their metabolites play important roles in nutrient metabolism and energy utilization. This study aimed to investigate the fecal microbiota and associated metabolites in pigs with divergent feed conversion ratios (FCR). Fecal samples were collected from 20 Duroc × (Landrace × Yorkshire) (DLY) commercial pigs exhibiting extremely high (HFCR, n = 10) and low (LFCR, n = 10) FCR for analysis using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). The microbiota analysis revealed significantly higher abundances of Ruminococcus, Prevotella, Akkermansia, and Eubacterium in LFCR pigs (p < 0.05), while pathogenic bacteria predominated in HFCR pigs (p < 0.05). LC-MS metabolomics identified significant variations in metabolites involved in steroid hormone biosynthesis and primary bile acid metabolism between the two groups (p < 0.05). Spearman correlation analysis further demonstrated significant positive correlations between Ruminococcaceae_NK4A214_group and [Eubacterium]_coprostanogenes_group with bile acid metabolites, as well as between Akkermansia and steroid hormone synthesis (p < 0.05). These findings suggest a potential role for specific microbes and metabolites that are associated with feed efficiency, and warrant validation in pig feeding trials and fecal microbiota transplantation (FMT).}, }
@article {pmid41154477, year = {2025}, author = {Hsu, CN and Hou, CY and Tzeng, HT and Wu, KLH and Lee, WC and Chang-Chien, GP and Lin, SF and Tain, YL}, title = {Maternal Fecal Microbiota Transplantation Mitigates Hypertension in Offspring Exposed to a High-Fructose Diet.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {41154477}, issn = {2076-3921}, support = {CMRPG8M0711, CMRPG8M0721, and CORPG8P0533//Kaohsiung Chang Gung Memorial Hospital, Taiwan/ ; }, abstract = {Excessive maternal fructose intake contributes to the developmental programming of hypertension in offspring, partly via gut microbiota dysbiosis and oxidative stress. Fecal microbiota transplantation (FMT) may restore microbial balance and modulate short-chain fatty acid (SCFA) production. We investigated whether maternal FMT from healthy donors could prevent hypertension in offspring exposed to a high-fructose (HF) diet. Pregnant Sprague Dawley rats (n = 12) were fed normal chow (ND) or a 60% HF diet from mating to delivery. Cross-FMT was performed: HF dams received FMT from ND donors, and ND dams received FMT from HF donors. Male offspring (n = 8/group) were assigned to ND, HF, ND + HF-FMT, or HF + ND-FMT groups. Offspring of HF dams developed higher systolic blood pressure (+13 mmHg vs. ND, p < 0.05). Maternal FMT from ND donors reduced this elevation by ~8 mmHg (p < 0.05). Protective effects were accompanied by higher plasma butyrate, increased expression of SCFA receptors (GPR41, GPR43), reduced renal oxidative stress markers (8-OHdG), and distinct gut microbiota profiles. Maternal FMT generated four enterotypes in offspring, each associated with differential blood pressure outcomes. These findings suggest that maternal microbiota-targeted interventions, such as FMT, can mitigate hypertension of developmental origin by restoring gut microbial and metabolic homeostasis.}, }
@article {pmid41155291, year = {2025}, author = {Watai, K and Taniguchi, M and Azuma, K}, title = {The Gut-Brain-Immune Axis in Environmental Sensitivity Illnesses: Microbiome-Centered Narrative Review of Fibromyalgia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Multiple Chemical Sensitivity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, pmid = {41155291}, issn = {1422-0067}, mesh = {Humans ; *Fibromyalgia/microbiology/immunology/therapy ; *Fatigue Syndrome, Chronic/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Multiple Chemical Sensitivity/microbiology/immunology/therapy ; *Brain/immunology/metabolism ; Animals ; *Brain-Gut Axis/immunology ; }, abstract = {Environmental sensitivity illnesses-including fibromyalgia syndrome (FMS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and multiple chemical sensitivity (MCS)-are chronic, disabling disorders characterized by hypersensitivity to environmental stimuli, persistent fatigue, widespread pain, and neurocognitive and autonomic dysfunction. Although their diagnostic criteria differ, increasing evidence suggests overlapping clinical features and shared biological mechanisms. A unifying hypothesis highlights the gut-brain-immune axis, where alterations in the intestinal microbiome, epithelial barrier dysfunction, and aberrant immune signaling interact with central sensitization and systemic metabolic dysregulation. Recent studies demonstrate reduced microbial diversity, depletion of anti-inflammatory taxa (e.g., Faecalibacterium prausnitzii, Bifidobacterium), and enrichment of pro-inflammatory Clostridium species across these conditions. These shifts likely alter production of short-chain fatty acids, amino acid metabolites, and complex lipids, with downstream effects on mitochondrial function, neuroinflammation, and host energy metabolism. Moreover, emerging clinical interventions-including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation-suggest a potential role for microbiome-targeted therapies, though controlled evidence remains limited. This review synthesizes current knowledge on microbiome alterations in FMS, ME/CFS, and MCS, emphasizing their convergence on metabolic and immune pathways. By integrating microbial, immunological, and neurophysiological perspectives, we propose a microbiome-centered framework for understanding environmental sensitivity illnesses and highlight avenues for translational research and therapeutic innovation.}, }
@article {pmid41155411, year = {2025}, author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M}, title = {Microbiome and Long COVID-19: Current Evidence and Insights.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, pmid = {41155411}, issn = {1422-0067}, support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; }, mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.}, }
@article {pmid41156565, year = {2025}, author = {Komorniak, N and Gaweł, K and Deskur, A and Pawlus, J and Stachowska, E}, title = {The Impact of Diet on the Fecal Microbiota Transplantation Success in Patients with Gastrointestinal Diseases-A Literature Review.}, journal = {Nutrients}, volume = {17}, number = {20}, pages = {}, pmid = {41156565}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Gastrointestinal Diseases/therapy/microbiology ; *Diet ; Dietary Fiber/administration &amp; dosage ; Treatment Outcome ; Feces/microbiology ; }, abstract = {Background: Fecal microbiota transplantation (FMT) is a therapeutic method involving the administration of appropriately prepared feces from a healthy donor to the gastrointestinal tract of a recipient. This literature review aims to summarize and critically evaluate the available evidence on the impact of different dietary patterns and nutrients on the efficacy of FMT. Methods: The present literature review focuses on the impact of diet on the gut microbiota in the context of the effectiveness of fecal microbiota transplantation. A literature review was conducted based on the PubMed Database. Results: More and more data confirm the close link between diet and gut microbiota and suggest that proper nutrition before and after FMT may support the effectiveness of this procedure. It appears that increased fiber intake significantly delays the loss of diversity in the transplanted microbiota, thereby enhancing the beneficial clinical effects following FMT. Additionally, the use of an anti-inflammatory components in the diet combination with FMT could be effective in achieving clinical remission in patients with ulcerative colitis. Conclusions: Based on the literature review, it appears that the most optimal nutritional model (through its beneficial effect on the composition of the gut microbiota, short-chain fatty acids production, and intestinal barrier integrity) to support the effectiveness of FMT is an anti-inflammatory diet rich in dietary fiber (for both the donor and the recipient).}, }
@article {pmid41156627, year = {2025}, author = {Rodak, K and Mnichowska-Polanowska, M and Waloryszak, A and Ptaszyński, K and Wójcik, J and Wojtyś, ME}, title = {An Unusual Case of Anterior Mediastinal Cystic Echinococcosis Successfully Resolved with Multidisciplinary Approach.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {41156627}, issn = {2076-0817}, mesh = {Animals ; Humans ; *Echinococcosis/diagnosis/parasitology/pathology/drug therapy ; Echinococcus granulosus/isolation &amp; purification ; Echinococcus multilocularis/isolation &amp; purification ; *Mediastinum/parasitology/pathology/diagnostic imaging ; }, abstract = {Human echinococcosis is a zoonotic disease caused by accidental ingestion of tapeworm eggs of the genus Echinococcus, shed in the feces of animal definitive host. In the human duodenum, these eggs release oncospheres, which penetrate the intestinal wall and via the bloodstream reach the liver-the most common site for development of cysts. However, it is important to remember that any other organ can be affected via the bloodstream, due to larvae size. In Europe, the most diagnostically relevant species are Echinococcus granulosus, with a median incidence of 0.6 cases per 100,000 inhabitants, and Echinococcus multilocularis, with 0.1 cases per 100,000 inhabitants. This article aims to describe an exceptionally unusual location of human cystic echinococcosis in the anterior mediastinum. We describe the role of multidisciplinary diagnostics in establishing the definitive diagnosis. The pathomorphological examination, radiological imaging and serological testing for diagnosing cystic echinococcosis are hereby described. It is particularly important to avoid reporting unspecified Echinococcus (NOS) if possible, as the management and treatment of patients with echinococcosis varies depending on the species.}, }
@article {pmid41156706, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {The Gut Microbiome in Enteric Viral Infections: Underlying Mechanisms and Therapeutic Approaches.}, journal = {Microorganisms}, volume = {13}, number = {10}, pages = {}, pmid = {41156706}, issn = {2076-2607}, abstract = {Despite growing recognition of the role of the gut microbiome in host health and in modulating pathogen activity, the dynamic and reciprocal relationship between enteric viruses and the gut microbial ecosystem remains insufficiently defined and requires further exploration. This comprehensive review examines the bidirectional interplay between the gut microbiome and enteric viral infections by addressing (i) viruses associated with gastrointestinal alterations, (ii) how enteric viral infections alter the composition and function of the gut microbiome, (iii) how the gut microbiome modulates viral infectivity and host susceptibility, and (iv) current microbial-based approaches for preventing or treating enteric viral infections. Gastrointestinal viral infections induce gut microbiome dysbiosis, marked by reductions in beneficial bacteria and increases in potentially pathogenic populations. Specific gut microorganisms can modulate host susceptibility, with certain bacterial genera increasing or decreasing infection risk and disease severity. Pattern recognition receptors in the intestinal epithelium detect microbial signals and trigger antimicrobial peptides, mucus, and interferon responses to control viral replication while maintaining tolerance to commensal bacteria. The gut microbiome can indirectly facilitate viral infections by creating a tolerogenic environment, suppressing antiviral antibody responses, and modulating interferon signaling, or directly enhance viral replication by stabilizing virions, promoting host cell attachment, and facilitating coinfection and viral recombination. In turn, commensal gut bacteria can inhibit viral entry, enhance host antiviral responses, and strengthen mucosal barrier function, contributing to protection against gastrointestinal viral infections. Probiotics and fecal microbiota transplantation constitute potential microbial-based therapeutics that support antiviral defenses, preserve epithelial integrity, and restore microbial balance. In conclusion, the role of the gut microbiome in modulating enteric viral infections represents a promising area of future investigation. Therefore, integrating microbiome insights with virology and immunology could enable predictive and personalized strategies for prevention and treatment.}, }
@article {pmid41156796, year = {2025}, author = {Chukhlovin, AB and Goloshchapov, OV and Shchukina, OB and Kharitidis, AM and Zhloba, AA and Subbotina, TF and Kusakin, AV and Kosarev, OV and Tsai, VV and Kalinin, RS and Eismont, YA and Glotov, OS}, title = {Changes in Gut Phageome and Bacteriome Following Fecal Microbiota Transfer in Patients with Intestinal Graft-Versus-Host Disease and Crohn's Disease.}, journal = {Microorganisms}, volume = {13}, number = {10}, pages = {}, pmid = {41156796}, issn = {2076-2607}, abstract = {Intestinal bacterial dysbiosis develops in a number of immune-mediated disorders. Fecal microbiota transfer (FMT) is considered a potentially efficient tool for restoration of the patient's gut microbiota. The aim of our study was to trace the time course of dominant bacterial populations and some Enterobacteria phages in patients with GVHD and Crohn's disease after FMT procedure. Patients and methods: We observed 12 patients with intestinal graft-versus-host disease (GVHD), and 15 persons with Crohn's disease after massive anti-infectious treatment. FMT was performed by a standard protocol using oral capsules administered for 2 days. Fecal bacteriome was assessed by 16S rRNA sequencing. Viral sequences were identified by NGS with a customized primer set. Plasma citrulline levels were measured in order to assess enterocyte damage in the patients. Results: Complete clinical response to FMT was observed in 5 of 12 GVHD patients and 10 of 15 Crohn's disease cases. Before FMT, most anaerobic Bacillota were exhausted in both Crohn's disease patients and GVHD. Following FMT, Akkermansia ratios tended to decrease within 30 days in Crohn's disease, along with higher Faecalibacteria, Romboutsia, and Dialister ratios than in GVHD, thus suggesting lesser damage to anaerobic microbiota in Crohn's disease. Increased contents of facultative anaerobes (Enterococcus and E. coli) was detected in GVHD patients after FMT. Fecal virome changes in Crohn's disease after FMT included early transient decrease in Caudoviricetes with a rise in Lederbergvirus and Eganvirus ratios at later terms. In GVHD patients, reverse correlations were revealed between E. coli and E. coli-hosted Eganvirus species. Intestinal damage assessed by low plasma citrulline levels was associated with fecal Klebsiella expansion, being more pronounced in GVHD than in Crohn's disease. Clinical response to FMT in GVHD patients correlated with increased plasma citrulline and lower Eganvirus abundance. Future studies will concern specific relations between fecal bacteriome and virome reconstitution following FMT in gut GVHD and other immune-mediated intestinal disorders.}, }
@article {pmid41157257, year = {2025}, author = {Eghdami, S and Saeidi, M and Gunturu, S and Boroon, M and Shalbafan, M}, title = {Gut Microbiota and Obsessive-Compulsive Disorder: A Systematic Review of Mechanistic Links, Evidence from Human and Preclinical Studies, and Therapeutic Prospects.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, pmid = {41157257}, issn = {2075-1729}, abstract = {Obsessive-compulsive disorder (OCD) is a multifactorial condition, and interest in gut-brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress circuitry, to clarify plausible mechanisms. Step 2 synthesized evidence from human and preclinical studies that measured or manipulated microbiota. Searches across PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane (September 2025) yielded 357 biological and 20 microbiota-focused studies. Risk of bias was assessed using the Joanna Briggs Institute checklist for human studies and SYRCLE's tool for animal studies. Although taxonomic findings in human cohorts were heterogeneous, functional patterns converged: reduced short-chain fatty acid capacity, enrichment of pro-inflammatory pathways, and host markers of barrier disruption and inflammation correlating with OCD severity. Transferring patient microbiota to mice induced OCD-like behaviors with neuroinflammatory changes, partly rescued by metabolites or barrier-supporting strains. Mendelian randomization suggested possible causal contributions at higher taxonomic levels. Diet, especially fiber intake, and psychotropic exposure were major sources of heterogeneity. Evidence supports the microbiota as a modifiable co-factor in a subset of OCD, motivating diet-controlled, stratified clinical trials with composite host-microbe endpoints.}, }
@article {pmid41160105, year = {2025}, author = {Singh, LS and Singha, LS and Singh, WS and Singh, YR and Marak, GK}, title = {Microbiome modulation as a therapeutic strategy for alcohol-induced gut dysbiosis and associated disorders.}, journal = {Antonie van Leeuwenhoek}, volume = {118}, number = {12}, pages = {182}, pmid = {41160105}, issn = {1572-9699}, mesh = {*Dysbiosis/therapy/microbiology/chemically induced ; Humans ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Ethanol/adverse effects ; *Alcoholism/microbiology/therapy ; }, abstract = {Chronic alcohol consumption alters the composition of the gut microbiota, leading to dysbiosis, increased intestinal permeability, and systemic inflammation, which collectively contribute significantly to the pathogenesis of alcohol-related disorders, encompassing hepatic disease, metabolic abnormalities, immune dysfunction, and neuropsychiatric conditions. The complex interactions of alcohol with the gut ecosystem illuminate the fundamental mechanisms that result in the disruption of the gut-liver axis, the imbalance of microbial metabolites, and the emergence of leaky gut syndrome. The bidirectional gut-brain axis is similarly impaired, intensifying concerns related to addiction and cognitive deficits. Therapeutic strategies, encompassing probiotics, prebiotics, synbiotics, postbiotics, dietary alterations, and fecal microbiota transplantation, offer promising modalities for reinstating microbial balance and alleviating alcohol-induced damage. Cutting-edge treatments such as paraprobiotics and bacteriophage therapy further highlight the potential of microbiome modulation as a viable therapeutic strategy. This review underscores the urgent need for precision-targeted, microbiota-based interventions and calls for expanded clinical research to translate these insights into effective treatments for alcohol-associated disorders.}, }
@article {pmid41160345, year = {2025}, author = {Beswick, G and Major, N and Hendrickson, C and Kumar, V and Waller, M and Durrani, Z and Hotchkiss, S and Bala, A and Taylor, VH}, title = {A Scoping Review on the Role of the Microbiome as a Factor in the Bidirectional Association Between Obesity and Depression.}, journal = {Current diabetes reports}, volume = {25}, number = {1}, pages = {56}, pmid = {41160345}, issn = {1539-0829}, mesh = {Humans ; *Obesity/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; *Depression/microbiology ; Inflammation/microbiology ; }, abstract = {PURPOSE OF REVIEW: Obesity is a chronic illness highly comorbid with mental health conditions, particularly depression. Among the factors involved in this association, inflammation is a consistently identified link. This review explores the emerging role of the gut microbiota as a modulator of inflammation and its potential involvement in the pathophysiological processes linking obesity and depression.<br><br>RECENT FINDINGS: Chronic low-grade inflammation is observed in both obesity and depressive disorders. Alterations in gut microbiota are increasingly implicated in inflammatory mechanisms, including increased intestinal permeability, immune activation, and short-chain fatty acid (SCFA) production, influencing leukocyte function and cytokine production. Additionally, both obesity and depression are associated with altered microbial composition. The gut microbiome contributes to chronic inflammation relevant to the pathophysiology of both obesity and depression. Accumulating evidence highlights the need for further research into how gut microbiota influences inflammatory mechanisms observed in both obesity and depression.}, }
@article {pmid41161092, year = {2025}, author = {Gu, M and Peng, X and Dai, X and Ma, X and Ge, W and Yang, S and Wei, W}, title = {Tannic acid decreased the synthesis and secretion of sIgA in the small intestine of Brandt's voles (Lasiopodomys brandtii) by modifying gut microbiota.}, journal = {Biochemical and biophysical research communications}, volume = {789}, number = {}, pages = {152846}, doi = {10.1016/j.bbrc.2025.152846}, pmid = {41161092}, issn = {1090-2104}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arvicolinae/microbiology/immunology ; *Intestine, Small/drug effects/microbiology/metabolism/immunology ; *Tannins/pharmacology ; *Immunoglobulin A, Secretory/metabolism/biosynthesis ; Male ; Fecal Microbiota Transplantation ; Polyphenols ; }, abstract = {Tannic acid (TA), a representative plant secondary metabolite, impairs intestinal immune function and alters intestinal microbiota abundance of Brandt's voles. Whether TA reduces intestinal immune function by modifying the gut microbiota remains unknown. In this study, Brandt's voles were divided into three groups for microbiota transplantation (FMT): normal saline (Ab), microbiota from normal saline administration (R-Con), and microbiota from TA administration (R-TA). Then, the intestinal morphology, immune indices, gut flora, and microbiota metabolites were measured after FMT. The findings showed that the sIgA content of small intestine of voles in the R-TA group were lower than in the R-con group. Additionally, the voles in the R-con group exhibited higher mRNA levels of PIgR, J-chain, BAFF, and APRIL than in the R-TA group. The ANOSIM results showed significant structural differentiation, reflecting that the β-diversity of the cecal microbiome was altered. Moreover, the voles in the R-con group had a higher concentration of butyric acid in the cecum compared to both the Ab and R-TA groups. In the experiment 2, the sIgA content in the duodenum and ileum of Brandt's voles in the TBA group (1200 mg•kg[-1]d[-1] TA + butyrate) was significantly higher than that in the TNS group (1200 mg•kg[-1]d[-1] TA + normal saline). To summarize, the "TA microbiota" decreased the slgA secretion and synthesis in the small intestine by reducing butyric acid content, thus lowering the intestinal immune capacity of Brandt's voles. The findings provide the experimental basis to prove the critical role of gut microorganisms in controlling animal physiological processes.}, }
@article {pmid41161186, year = {2025}, author = {He, J and Lian, H and Wang, J and Wu, B and Liu, X and Zhang, Z and Yin, W and Gao, P and Wu, X and Cao, J and Li, H and Huang, X and Wang, S}, title = {Xiaoer Qixing Cha alleviates functional constipation via regulating gut microbiota and short-chain fatty acids in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157417}, doi = {10.1016/j.phymed.2025.157417}, pmid = {41161186}, issn = {1618-095X}, mesh = {Animals ; *Constipation/drug therapy/microbiology/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/chemistry ; Mice ; Male ; *Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Loperamide ; Feces/microbiology ; Mice, Inbred C57BL ; Dysbiosis ; }, abstract = {BACKGROUND: Constipation is a prevalent gastrointestinal disorder associated with gut microbiota dysbiosis. Conventional pharmacological treatments, while effective for short-term symptom relief, are limited by adverse effects, high recurrence rates after discontinuation, and risks of dependency with prolonged use. Xiaoer Qixing Cha (XQC), a well-established Chinese herbal prescription, is widely utilized in pediatric care for addressing dyspepsia, diminished appetite, and constipation. However, its therapeutic mechanisms remain poorly elucidated.<br><br>PURPOSE: This study was designed to comprehensively explore the therapeutic efficacy and elucidate the mechanistic basis of XQC in murine constipation models.<br><br>STUDY DESIGN AND METHODS: The chemical composition of XQC was comprehensively characterized using high-resolution mass spectrometry. The therapeutic efficacy of XQC (200, 400, and 800 mg/kg) was investigated in loperamide-induced constipated mice. Changes in fecal microbiota were evaluated via 16S rRNA sequencing. Both untargeted and targeted metabolomic analyses were carried out to explore the metabolomic profiles of mice treated with XQC. Additionally, fecal microbiota transplantation (FMT) was performed to evaluate the functional role of gut microbiota mediated by XQC in constipation.<br><br>RESULTS: High-resolution mass spectrometry identified 141 distinct compounds in XQC. Oral administration of XQC significantly alleviated loperamide-induced constipation in mice, as evidenced by improved fecal output, increased fecal water content, enhanced intestinal motility, accelerated whole-gut transit, and modulated inflammatory cytokine levels and mucin 2 expression. Furthermore, XQC selectively restored the gut microbiota, reversing loperamide-induced microbial dysbiosis and enriching beneficial bacterial taxa, including norank_f__Muribaculaceae and Bacteroides. FMT experiments confirmed that the therapeutic effects of XQC were at least partially mediated by gut microbiota. Notably, XQC restored short-chain fatty acid (SCFA) levels, particularly butyrate and isobutyrate. Exogenous butyrate supplementation further alleviated constipation symptoms in mice, supporting its role in XQC's mechanism of action.<br><br>CONCLUSION: These findings underscore XQC's dual therapeutic role in mitigating constipation and restoring gut microbial balance, positioning it as a viable alternative to conventional therapies. Furthermore, this study establishes a theoretical foundation and clinical framework for the evidence-based application of XQC in constipation management, advancing its rational integration into pediatric and gastroenterological practice.}, }
@article {pmid41163076, year = {2025}, author = {Xu, B and Qin, W and Chen, Y and Yan, Z and Tang, Y and Zhou, S and Huang, J and Ma, L and Yan, X}, title = {Gut microbiota-derived short-chain fatty acids promote follicular maturation via gWAT-ovary axis in mammals.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {220}, pmid = {41163076}, issn = {2049-2618}, support = {LQN25C170003//Zhejiang Provincial Natural Science Foundation of China/ ; 2024LFR079//Research and Development Project of Zhejiang Agricultural and Forestry University/ ; 32230099//National Natural Science Foundation of China/ ; 2021hszd018//Foundation of Hubei Hongshan Laboratory/ ; 2022YFD130015//National Key Research and Development Program of China/ ; 2662023DKPY002//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; Swine ; *Fatty Acids, Volatile/metabolism ; *Ovarian Follicle/growth &amp; development/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/metabolism/genetics/isolation &amp; purification ; *Ovary/metabolism ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {BACKGROUND: Previous studies have demonstrated that gut microbiota regulates reproductive performance in mammals. Our prior research identified the gut microbiota-ovary axis as an important contributor to the superior follicular development observed in Chinese indigenous Meishan sows, yet the underlying mechanisms remain unclear. This study aims to elucidate the mechanism through which gut microbiota regulates follicular development.<br><br>RESULTS: Fecal microbiota transplantation (FMT) from Meishan sows promoted follicular maturation in recipient Landrace&#x2009;&#xd7;&#x2009;Yorkshire sows, evidenced by increased numbers of antral follicles, secondary follicles, and corpora lutea, accompanied by decreased atretic follicles. Additionally, FMT altered reproductive hormone profiles, significantly elevating estradiol secretion during the estrous cycle prior to sampling. Multi-omics analyses identified four key bacterial species of Fibrobacter intestinalis, Lactobacillus mucosae, Bifidobacterium thermophilum, and Ruminococcin flavefaciens, along with short-chain fatty acids (SCFAs), that are closely associated with follicular maturation. These microbial species and their shared metabolites SCFAs promoted follicular maturation and ovulation rate by inhibiting apoptosis of ovarian granulosa cells, thus reducing follicular atresia. Mechanistically, SCFAs activated G-protein-coupled receptor 43 (GPR43), which is&#xa0;highly expressed in peri-ovarian&#xa0;gonadal white adipose tissue (gWAT). This&#xa0;SCFAs-mediated activation of GPR43 stimulated leptin secretion from gWAT in a concentration-dependent manner, consequently suppressing granulosa cell apoptosis and promoting follicular maturation. Furthermore, in a large-scale validation trial, dietary SCFAs&#xa0;supplementation increased litter size by approximately 5.91%.<br><br>CONCLUSION: Collectively, gut microbiota-derived SCFAs&#xa0;promote follicular maturation and increase litter size in sows by stimulating leptin secretion from peri-ovarian gWAT, thus providing novel insights into enhancing reproductive outcomes in mammals. Video Abstract.}, }
@article {pmid41163775, year = {2025}, author = {Ma, J and Gao, H and Zeng, G and Huda, N and Jiang, Y and Thoudam, T and Yang, Z and Liangpunsakul, S}, title = {Alcohol-Associated Hepatitis: Translating Pathophysiology into Targeted Clinical Trials.}, journal = {Current hepatology reports}, volume = {24}, number = {1}, pages = {34}, pmid = {41163775}, issn = {2195-9595}, support = {U01 AA026917/AA/NIAAA NIH HHS/United States ; K99 AA031067/AA/NIAAA NIH HHS/United States ; R01 AA030993/AA/NIAAA NIH HHS/United States ; UM1 TR004402/TR/NCATS NIH HHS/United States ; UH2 AA026903/AA/NIAAA NIH HHS/United States ; R01 AA030312/AA/NIAAA NIH HHS/United States ; R00 AA031067/AA/NIAAA NIH HHS/United States ; I01 CX000361/CX/CSRD VA/United States ; I01 BX006202/BX/BLRD VA/United States ; }, abstract = {PURPOSE OF REVIEW: Alcohol-associated hepatitis (AH) is a severe manifestation of alcohol-associated liver disease with high short-term mortality and limited treatment options. This review synthesizes mechanistic insights into AH pathogenesis and evaluates both failed and emerging clinical trials to guide targeted therapeutic development.<br><br>RECENT FINDINGS: AH arises from intertwined mechanisms including hepatotoxicity, oxidative stress, inflammation, impaired regeneration, and gut-liver axis disruption. Trials targeting inflammatory cytokines or apoptosis pathways have not demonstrated survival benefit and raised safety concerns. Current investigations emphasize therapies that mitigate oxidative stress, enhance hepatocyte regeneration, and restore gut-liver integrity. Novel agents such as interleukin-22 (IL-22), granulocyte colony-stimulating factor (G-CSF), probiotics, fecal microbiota transplantation (FMT), larsucosterol, and farnesoid X receptor (FXR) agonists are under evaluation.<br><br>SUMMARY: Although no effective pharmacologic therapy is yet available, advances in understanding AH biology provide a framework for mechanism-based strategies. Integrating hepatology with addiction medicine and incorporating stratified trial designs will be essential to advance effective therapies.}, }
@article {pmid41164228, year = {2025}, author = {Wei, S and Yin, H and Hu, X and Chi, Y and Zhang, L and Zhang, B and Qian, K and Xu, W}, title = {Detection of antimicrobial peptides from fecal samples of FMT donors using deep learning.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1689589}, pmid = {41164228}, issn = {2297-1769}, abstract = {INTRODUCTION: Antimicrobial peptides (AMPs) represent a class of short peptides that are widely distributed in organisms and are regarded as an effective means to tackle bacterial resistance, potentially functioning as substitutes for onventional antibiotics.<br><br>METHODS: We employed metagenomics in combination with deep learning to mine AMPs from the 120 fecal microbiota transplantation (FMT) donor metagenome. Subsequently, a comprehensive analysis of the candidate AMPs was conducted through metaproteomic cross-validation, solubility analysis, cross-validation with other prediction tools, correlation analysis, and molecular dynamics simulations. Finally, four candidate AMPs were selected for chemical synthesis, and experimental validation identified two with broad-spectrum antimicrobial activity. Furthermore, molecular docking was utilized to further analyze the antimicrobial mechanisms of the candidate AMPs.<br><br>RESULTS: Our approach successfully predicted 2,820,488 potential AMPs. After a comprehensive analysis, four candidate AMPs were selected for synthesis, two of which exhibited broad-spectrum antimicrobial activity. Molecular docking provided further insight into the binding mechanisms of these peptides.<br><br>DISCUSSION: This study demonstrates the feasibility of discovering functional AMPs from the human fecal microbiome using computational and experimental approaches, highlights the potential of mining novel AMPs from the fecal microbiome, and provides new insights into the therapeutic mechanisms of FMT.}, }
@article {pmid41164289, year = {2025}, author = {Mishra, P and Logan, AC and Prescott, SL}, title = {Reimagining criminal accountability: microbial and omics perspectives in the evolution of legal responsibility.}, journal = {Journal of law and the biosciences}, volume = {12}, number = {2}, pages = {lsaf022}, doi = {10.1093/jlb/lsaf022}, pmid = {41164289}, issn = {2053-9711}, abstract = {Recent advances in microbiome science and omics technologies are reshaping our understanding of human behavior, suggesting that microbial communities significantly influence cognition, impulse control, and aggression. Emerging studies in neuromicrobiology, including fecal transplant studies, are pointing toward a causal role for gut microbes and their metabolites in human cognition and behavior. This essay introduces the legalome-a framework integrating microbial perspectives, including microbiome and omics sciences, into the courts and larger criminal justice system. We argue that the legalome is on a trajectory that will move the field of neurolaw forward, and challenge traditional doctrines of mens rea and culpability. Drawing on recent court decisions related to auto-brewery syndrome, and neuro-microbiological research, we examine how subtle biological processes influence behavior in ways overlooked by current legal standards. Recent findings raise questions about criminal intent, biological determinism, and equitable access to scientific defenses. At the same time, emergent research also suggests potential for microbiome-based rehabilitative interventions. Despite methodological challenges, we advocate for interdisciplinary collaboration to harmonize biological research with legal principles, creating a more nuanced framework for justice in the twenty-first century. The legalome provides concrete implementation protocols and assessment tools that demonstrate practical utility for courts, practitioners, and policymakers.}, }
@article {pmid41166910, year = {2025}, author = {Mao, YQ and Song, SY and Xu, Q and Zang, TT and Wang, LS and Shen, L and Ge, JB}, title = {Dietary fiber pectin supplement attenuates atherosclerosis through promoting Akkermansia-related acetic acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157373}, doi = {10.1016/j.phymed.2025.157373}, pmid = {41166910}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Atherosclerosis/drug therapy/microbiology ; *Pectins/pharmacology ; *Dietary Fiber/pharmacology ; Male ; Mice ; *Acetic Acid/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Dietary Supplements ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Knockout, ApoE ; Mice, Knockout ; }, abstract = {BACKGROUND: Atherosclerosis (AS) is a vascular disease caused by chronic inflammation, and its incidence and mortality rates are still on the rise. Recent studies have revealed that the structure and function of gut microbiota are significantly correlated with the occurrence and development of AS, providing novel insights into the mechanisms of cardiovascular diseases. Multiple studies have clarified that dietary fiber pectin alter the structure and function of the gut microbiota. At the same time, it has also been found that dietary fiber pectin can alleviate atherosclerosis.<br><br>PURPOSE: The aim is to explore whether the gut microbiota mediates the anti-atherosclerotic effects of pectin, and to elucidate the underlying molecular mechanisms.<br><br>METHODS: We established an atherosclerosis model in ApoE[-/-] mice by feeding a high-fat and high-cholesterol diet. We combined antibiotic depleted gut microbiota and transplanted the fecal microbiota to demonstrate that the effect of dietary fiber pectin in alleviating atherosclerosis depends on the gut microbiota. Subsequently, we explored the material basis of the anti-atherosclerotic effect mediated by the gut microbiota through 16 s rRNA sequencing, targeted metabolomics detection, and bacterial culture methods.<br><br>RESULTS: We conducted experiments on ApoE[-/-] mice to deplete gut microbiota with antibiotics and then perform fecal microbiota transplantation, and the results showed that supplementation with dietary fiber pectin attenuates atherosclerosis in a gut microbiome dependent manner. Through 16S rRNA sequencing, we found that supplementation of dietary fiber pectin could enrich the abundance of Akkermansia (Akk). In addition, administration with Akk was sufficient to prevent the progression of atherosclerosis in a diet-induced model. Mechanistically, Akk produced acetic acid through fermentation of pectin, and then inhibited the proliferation of Lactococcus lactis (l.lactis) in arterial plaque to exert anti-atherosclerosis effect.<br><br>CONCLUSIONS: Our results suggest that dietary fiber pectin enriches the abundance of Akk, which inhibits the proliferation of the atherosclerotic-related bacterium, l.lactis, by producing acetic acid in ApoE[-/-] mice. Our findings first reveal that pectin prevents the development of atherosclerosis through gut microbiota. Additionally, based on the theory of the "gut-vessel" axis, we demonstrate that dietary fiber pectin enriched the abundance of Akk in the gut, which elevated the level of acetic acid and further inhibit the abundance of l. within atherosclerotic plaques. These data provide new clues and strategies for the clinical treatment of atherosclerosis.}, }
@article {pmid41167427, year = {2026}, author = {Prossomariti, D and Merrick, B and Goldenberg, SD}, title = {Should faecal microbiota transplant donors be screened for Candidozyma auris?.}, journal = {The Journal of hospital infection}, volume = {167}, number = {}, pages = {34-35}, doi = {10.1016/j.jhin.2025.10.015}, pmid = {41167427}, issn = {1532-2939}, }
@article {pmid41168141, year = {2025}, author = {Vollebregt, PF and Baeten, CIM and Drewes, AM and Marinello, F and Martelluci, J and Mekhael, M and Nugent, K and Rink, AD and Rosen, H and Scott, SM and Slattenschek, PE and Zerbib, F and Christensen, P and , }, title = {Transanal irrigation: Bridging the gap in treatment for chronic constipation and/or faecal incontinence-A systematic review and management guidance.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {11}, pages = {e70274}, pmid = {41168141}, issn = {1463-1318}, support = {//Coloplast/ ; }, mesh = {Humans ; *Constipation/therapy ; *Fecal Incontinence/therapy ; *Therapeutic Irrigation/methods/standards ; Chronic Disease/therapy ; Treatment Outcome ; Anal Canal ; Female ; Practice Guidelines as Topic ; Male ; Quality of Life ; }, abstract = {AIM: The aims of the study were to: (1) update a systematic review on the efficacy of transanal irrigation (TAI) in patients with chronic constipation (CC) and/or faecal incontinence (FI); (2) provide guidance on the position of TAI in the treatment pathway of CC and FI; and (3) discuss knowledge gaps and areas of future research.<br><br>METHOD: A collaborative of 11 experts (gastroenterologists, colorectal surgeons, and clinical scientists) from eight European countries was established. The expert group was divided into three main groups, with each group leading a specific section (systematic review, treatment pathway, and knowledge gaps). A previously published systematic review on TAI was updated by conducting an additional search on 12 April 2025. Studies on TAI in specific subgroups (neurogenic bowel dysfunction, low anterior resection syndrome) were excluded.<br><br>RESULTS: Sixteen studies involving 1567 (range 16-507) patients were included. Only one underpowered randomised trial was performed, which demonstrated that high-volume TAI may be more effective than low-volume TAI in patients with CC. Most other studies (observational) showed improvement in symptoms and/or quality of life to some extent, with a large variation in outcomes used. Treatment discontinuation was reported in 3-57% of patients. The position of TAI in the treatment pathway of CC and FI was proposed, and 13 knowledge gaps were provided.<br><br>CONCLUSION: TAI may be an effective treatment in patients with CC and/or FI. There is a need for randomised controlled trials to study its efficacy and current knowledge gaps.}, }
@article {pmid41168195, year = {2025}, author = {Shan, L and Guo, X and Hu, Y and Zhou, H and Meng, X and Liu, K and Shi, L and Hu, F and Liu, Y and Zhang, T and Zhou, Y}, title = {L-citrulline protects testicular Sertoli cell function by mitigating DNA damage via the gut-testis axis of sheep fed a high-concentrate diet.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {202}, pmid = {41168195}, issn = {2055-5008}, support = {YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2023ZD0407504//Biological Breeding-National Science and Technology Major Project/ ; 2023ZD0407504//Biological Breeding-National Science and Technology Major Project/ ; 2023YFHH0114//Inner Mongolia Autonomous Region Science and Technology Plan/ ; 32260180//the National Natural Science Foundation of China/ ; 32260181//the National Natural Science Foundation of China/ ; 2024SKYPT0068//the Science and Technology Major Project of Inner Mongolia Autonomous Region of China to the State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock/ ; }, mesh = {Male ; Animals ; *DNA Damage/drug effects ; *Sertoli Cells/drug effects/metabolism/physiology ; *Gastrointestinal Microbiome/drug effects ; *Citrulline/metabolism/pharmacology ; Sheep ; *Testis/drug effects ; Fecal Microbiota Transplantation ; Blood-Testis Barrier/drug effects ; Metabolomics ; *Diet/adverse effects ; Infertility, Male ; Dysbiosis ; }, abstract = {Mounting evidence underscores that high-concentrate diets (HCD) significantly impair male reproductive health, leading to infertility, and are closely associated with dysregulation of the gut microbiome and metabolome. However, effective therapeutic strategies targeting these alterations remain elusive. Notably, compelling evidence implicates the gut-testis axis as a critical mediator in the etiology of poor semen quality. Gut-derived metabolites, as key players in the gut-testis axis, warrant in-depth investigation as potential therapeutic targets for addressing male infertility caused by environmental factors, particularly dietary stressors. In this study, through an integrated multi-omics approach employing 10× Genomics single-cell mRNA sequencing, 16S ribosomal DNA sequencing and metabolomic profiling, we demonstrate that HCD induces DNA damage in Sertoli cells and disrupts the integrity of the blood-testis barrier (BTB), resulting in a significant decline in spermatozoa quality. Moreover, HCD impairs gut microbiota homeostasis and arginine biosynthesis, particularly leading to a remarkable decrease in L-citrulline levels. Additionally, fecal microbiota transplantation (FMT) experiments confirm that gut microbiota dysbiosis contributes to Sertoli cell DNA damage and BTB dysfunction. Interestingly, the effect of HCD-induced aberrant Sertoli cells function can be rescued by supplementation with L-citrulline. Collectively, these findings highlight the therapeutic potential of L-citrulline in protecting male reproductive health under dietary stress conditions, particularly through its action on the gut-testis axis.}, }
@article {pmid41169365, year = {2025}, author = {Fu, W and Peng, N and Geng, Y}, title = {Fecal microbiota transplantation as salvage therapy for disseminated strongyloidiasis in an immunosuppressed patient: a case report.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1676906}, pmid = {41169365}, issn = {1664-3224}, mesh = {Humans ; *Strongyloidiasis/therapy/immunology ; Male ; *Fecal Microbiota Transplantation/methods ; Aged ; *Immunocompromised Host ; Animals ; *Strongyloides stercoralis ; *Salvage Therapy/methods ; Treatment Outcome ; Diarrhea/therapy ; }, abstract = {BACKGROUND: Disseminated strongyloidiasis carries high mortality in immunosuppressed populations. We report a case of refractory Strongyloides stercoralis-induced severe diarrhea and sepsis successfully treated with fecal microbiota transplantation (FMT).<br><br>CASE PRESENTATION: A 68-year-old male with nephrotic syndrome on long-term glucocorticoids developed hyperinfection syndrome manifesting as septic shock, multiorgan dysfunction, and intractable diarrhea (>30 episodes/day). Conventional therapies including antiparasitics (albendazole), antibiotics, and probiotics failed. FMT achieved rapid symptom resolution and microbiota restoration.<br><br>CONCLUSION: This case highlights FMT's potential in modulating gut-parasite interactions and suggests its role as adjunctive therapy for parasitic hyperinfection syndromes.}, }
@article {pmid41170420, year = {2025}, author = {Guo, Y and Zhang, N and Pei, D}, title = {Gut microbiota heterogeneity in non-alcoholic fatty liver disease: a narrative review of drivers, mechanisms, and clinical relevance.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1645298}, pmid = {41170420}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD), a prevalent metabolic disorder, is increasingly recognized as a complex condition influenced by gut microbiota dysbiosis. However, the heterogeneity in findings across studies has hindered the clinical translation of microbiota-based interventions. In this narrative review, we synthesize current evidence on gut microbial alterations in patients with NAFLD, with a focus on the sources of variability that contribute to inconsistent results. We included human studies (2000-2024) that compared gut microbiota profiles between NAFLD patients and healthy controls using 16S rRNA or metagenomic sequencing; key drivers of microbial changes include clinical factors (metabolic comorbidities, disease progression), biological variables (diet, genetics), and methodological biases (sequencing platform differences, diagnostic criteria variability). Emerging evidence highlights the role of non-bacterial components (fungi, viruses) in modulating bacterial communities and disrupting host metabolic pathways, exacerbating hepatic inflammation and lipid accumulation. To overcome current limitations, we propose integrating multi-omics approaches (metagenomics, metabolomics, and proteomics) with a longitudinal study design to capture dynamic microbiota-host interactions. Precision microbiota therapies, including strain-specific probiotics, engineered microbial consortia, and fecal microbiota transplantation tailored to individual dysbiosis profiles, are emerging as promising strategies for targeted interventions. Addressing these challenges is essential to identifying reliable microbial biomarkers and developing personalized strategies for NAFLD prevention and treatment. Future research should harmonize methodologies, validate causal mechanisms, and optimize microbiota-based therapies to bridge experimental findings and clinical application.}, }
@article {pmid41171006, year = {2025}, author = {Zhou, Y and Wang, B and Wang, Q and Wang, F and Mou, X and Gong, L and Li, W}, title = {Lactobacillus plantarum Lac16 alleviates dextran sodium sulfate-induced colitis in mice by suppressing NLRP3 inflammasome overactivation through microbiota-derived isobutyric acid.}, journal = {mBio}, volume = {16}, number = {12}, pages = {e0239225}, pmid = {41171006}, issn = {2150-7511}, support = {LZ20C170002//Natural Science Foundation of Zhejiang Province/ ; 32072766//National Natural Science Foundation of China/ ; 31672460//National Natural Science Foundation of China/ ; 31472128//National Natural Science Foundation of China/ ; 2020A1515110819//Basic and Applied Basic Research Foundation of Guangdong Province/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Dextran Sulfate/adverse effects ; Mice ; *Colitis/chemically induced/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Lactiplantibacillus plantarum/physiology ; *Inflammasomes/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; *Probiotics/administration &amp; dosage ; Colon/pathology/microbiology ; Butyrates ; }, abstract = {UNLABELLED: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder characterized by immune dysregulation. Therapeutic strategies targeting gut microbiota modulation have been proven to be effective against IBD. This study sought to explore the protective effects of Lactobacillus plantarum Lac16 against dextran sulfate sodium (DSS)-induced colitis and to elucidate its underlying mechanisms. Results illustrated that Lac16 administration significantly ameliorated colitis symptoms, as evidenced by reduced weight loss, attenuated colon shortening, and decreased disease activity index scores. Furthermore, Lac16 treatment restored intestinal barrier integrity, modulated inflammatory cytokine levels, promoted macrophage polarization toward an anti-inflammatory phenotype, and suppressed NOD-like receptor protein 3 (NLRP3) inflammasome overactivation in the colon. Lac16 treatment effectively remodeled gut microbiota composition by significantly increasing the abundance of beneficial bacteria, particularly Alloprevotella and Dubosiella, while reducing the abundance of potentially pathogenic bacteria such as Bacteroides and Helicobacter. It also elevated acetic acid and isobutyric acid levels among microbiota-derived short-chain fatty acids. The pseudo-germ-free mouse model confirmed that Lac16 inhibits NLRP3 inflammasome overactivation and ameliorates colitis symptoms by modulating the gut microbiota. Moreover, the fecal microbiota transplantation (FMT) mouse model demonstrated that these protective benefits are transferable through FMT. Subsequently, isobutyric acid was found to suppress NLRP3 inflammasome overactivation and ameliorate colitis in vivo while also attenuating inflammatory injury in vitro. Collectively, these findings illustrate that Lac16 alleviates colitis and provides gastrointestinal protection by suppressing NLRP3 inflammasome overactivation through a gut microbiota-dependent mechanism, with microbiota-derived isobutyric acid identified as the pivotal mediator in this protective process.<br><br>IMPORTANCE: This study establishes that Lactobacillus plantarum Lac16 alleviates DSS-induced colitis through gut microbiota-dependent mechanisms. Lac16 administration significantly ameliorated colitis symptoms while restoring intestinal barrier integrity, promoting anti-inflammatory macrophage polarization, and suppressing NLRP3 inflammasome overactivation. The pseudo-germ-free mouse model provided definitive evidence that Lac16's suppression of NLRP3 inflammasome overactivation requires gut microbiota. Fecal microbiota transplantation verified the causal role of microbiota in mediating Lac16's therapeutic benefits. Notably, Lac16 reshaped microbial composition, elevating beneficial genera (Alloprevotella and Dubosiella) while suppressing pathogenic genera (Bacteroides and Helicobacter). Crucially, Lac16 increased microbiota-derived short-chain fatty acids, particularly isobutyric acid. Both in vivo and in vitro experiments confirmed that isobutyric acid significantly contributes to anticolitic effects and suppresses NLRP3 activation. These findings elucidate a novel mechanism by which Lac16 ameliorates colitis via (i) microbiota-dependent NLRP3 inflammasome modulation and (ii) isobutyric acid-mediated protective effects. This work provides important insights into probiotic mechanisms and supports targeting microbial metabolic networks for IBD intervention.}, }
@article {pmid41171386, year = {2025}, author = {Singh, S and Kriti, M and Sharma, P and Pal, N and Sarma, DK and Verma, V and Tiwari, RR and Kumar, M}, title = {From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {32}, number = {12}, pages = {3816-3832}, pmid = {41171386}, issn = {1933-7205}, mesh = {Humans ; *Reproductive Health ; *Gastrointestinal Microbiome/physiology ; Female ; Probiotics/therapeutic use ; Dysbiosis/therapy/microbiology ; Fecal Microbiota Transplantation ; Pregnancy ; Animals ; Male ; Prebiotics/administration &amp; dosage ; }, abstract = {Recent advances in microbiome research have illuminated the complex bidirectional interactions between gut health and reproductive well-being. Understanding the gut microbiome's influence on the reproductive system and vice versa reveals how both of them can affect hormone production, immune function, and ultimately overall reproductive health. Dysbiosis, an imbalance in the gut microbial community, has been linked with a range of reproductive issues, including decreased sperm count and motility, erectile dysfunction, polycystic ovary syndrome (PCOS), endometriosis, infertility, and adverse pregnancy outcomes. This review critically evaluates emerging therapeutic interventions aimed at restoring microbial balance and enhancing reproductive health, such as use of prebiotics, probiotics, bacteriophage therapy, and fecal microbiota transplantation (FMT). By exploring the intricate interplay between gut microbiota and reproductive health, this review also emphasizes the need for integrated approaches in research and clinical practice to develop effective microbiome-based therapies for better reproductive health outcomes.}, }
@article {pmid41172243, year = {2025}, author = {Hovmand, KA and Nielsen, FD and Jochumsen, EA and Kjeldsen, J and Holm, DK and Nilsson, AC and Justesen, US and Kragsnaes, MS}, title = {Impact of storage conditions on live bacteria in partially processed faecal microbiota transplantation products using culturomics.}, journal = {Letters in applied microbiology}, volume = {78}, number = {11}, pages = {}, doi = {10.1093/lambio/ovaf126}, pmid = {41172243}, issn = {1472-765X}, support = {//Novo Nordisk Foundation/ ; //Odense University Hospital/ ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Bacteria/isolation &amp; purification/growth &amp; development/genetics ; Microbial Viability ; *Feces/microbiology ; Clostridium Infections/therapy ; Glycerol ; Cryopreservation ; }, abstract = {Faecal microbiota transplantation (FMT) is an effective treatment for Clostridioides difficile infection, but current FMT product manufacturing protocols are time-sensitive, labour-intensive, and require specialized staff. Delays can compromise microbial viability and product quality. Efficient storage methods for partially processed FMT material could therefore improve flexibility and streamline production. Therefore, this feasibility study evaluated the impact of storage conditions on live bacteria in partially processed donations containing glycerol as a cryoprotectant. Using culturomics, we assessed the concentration and composition of live bacteria immediately after half-way processing (reference, 0 h) or after storage at 5°C (refrigerator) or -80°C (freezer) for up to 72 h. Each FMT product was initially processed from one faecal donation provided by one of four screened donors. Storage at -80°C preserved the amount and composition of live bacteria in partially processed products. In contrast, storage at 5°C led to reduced bacterial concentrations and compositional shifts, particularly affecting the abundance of Bacteroides spp. These results highlight the potential adverse effects of refrigerator storage on bacterial viability, suggesting it may not be suitable for maintaining the quality of partially processed encapsulated FMT products. Freezer storage, however, emerged as a reliable method to preserve the content of live bacteria for at least 72 h.}, }
@article {pmid41174753, year = {2025}, author = {Xing, Y and Liu, C and Zhang, C and Zhou, D and Hu, B and Jiang, Q and Chen, J and Lin, Z and Wang, T and Yan, H and Liu, A and Lu, W and Ben, X and Yang, K and Yuan, JX and Zhan, W and Wang, J}, title = {Antibiotic-driven and microbiota-targeted therapy for advanced management of pulmonary hypertension.}, journal = {Respiratory research}, volume = {26}, number = {1}, pages = {303}, pmid = {41174753}, issn = {1465-993X}, support = {82120108001//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Hypertension, Pulmonary/drug therapy/microbiology/physiopathology ; *Anti-Bacterial Agents/therapeutic use/pharmacology/administration &amp; dosage ; Male ; Retrospective Studies ; Rats ; Humans ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Aged ; Rats, Sprague-Dawley ; *Disease Management ; Cohort Studies ; *Microbiota/drug effects ; }, abstract = {BACKGROUND: Pulmonary hypertension (PH), particularly secondary to hypoxic lung diseases like chronic obstructive pulmonary disease (COPD), lacks effective targeted therapies. Emerging evidence suggests that microbiota imbalances contribute to PH progression, raising the possibility of microbiome-targeted interventions. This study explores the role of antibiotics in modulating microbiota and ameliorating PH.<br><br>METHODS: A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care (MIMIC) database to assess changes in mean pulmonary artery pressure (mPAP) after antibiotic treatment. Subsequently, clinical data of 220 PH patients (including group 1, 3, and 4 PH) from single clinical center were analyzed, with 16S rRNA sequencing performed on pharyngeal and fecal samples to evaluate microbiota composition. A hypoxia-induced PH rat model was used to investigate the effects of antibiotic treatment on hemodynamics, pulmonary vascular remodeling, and gut microbiota.<br><br>RESULTS: Antibiotic use was associated with reduced mPAP in PH patients, particularly in hypoxic associated PH. Microbiota diversity decreased with antibiotic treatment, but probiotic species like Lactobacillus were enriched. In hypoxia-induced PH rats, antibiotics attenuated right ventricular systolic pressure (RVSP), reduced pulmonary vascular thickening, and preserved gut villi integrity. Lactobacillus and Anaerostipes correlated negatively with PH severity, suggesting a protective role.<br><br>CONCLUSION: Antibiotic-driven microbiota modulation may alleviate PH progression by targeting dysbiosis and reducing inflammation. These findings support further investigation into optimized antibiotic regimens as a therapeutic strategy for PH, particularly in hypoxic lung disease-associated cases.}, }
@article {pmid41175583, year = {2025}, author = {Ning, F and Luo, S and Nong, T and Lu, L and Yin, Z and Qin, Z and Huang, M and Jin, J}, title = {Total tanshinones extract alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying intestinal flora and suppressing the LPS-TLR4 axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157458}, doi = {10.1016/j.phymed.2025.157458}, pmid = {41175583}, issn = {1618-095X}, mesh = {Male ; *Toll-Like Receptor 4/metabolism ; Animals ; *Prostatitis/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Lipopolysaccharides/metabolism ; *Abietanes/pharmacology ; *Pelvic Pain/drug therapy/microbiology ; Rats, Sprague-Dawley ; Rats ; Salvia miltiorrhiza/chemistry ; Plant Extracts/pharmacology ; Disease Models, Animal ; Anti-Inflammatory Agents/pharmacology ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: Total tanshinones (T-Tan) extract, a class of lipophilic abietane diterpenes isolated from Salvia miltiorrhiza Bunge, exhibits anti-inflammatory effects. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urologic disorder. Dysbiosis of gut microbiota is closely related to CP/CPPS. However, whether T-Tan extract can regulate the intestinal flora to improve CP/CPPS remains unclear.<br><br>PURPOSE: The aim of this study was to investigate the effect of T-Tan extract on CP/CPPS and elucidate the mechanisms through which T-Tan extract modulates gut microbiota to ameliorate CP/CPPS.<br><br>METHODS: The pseudo-germ-free model was established by administering antibiotics (abx) water, and the experimental autoimmune prostatitis (EAP) model was induced via subcutaneous injections of prostate protein extract emulsified with Freund's adjuvant. The 16S rDNA method was used to analyze the structure and differential species of rat intestinal flora. Chronic pelvic pain was assessed by applying von Frey filaments. Inflammatory factors were detected by ELISA, qPCR and IHC. HE staining was used to evaluate histopathology. Immune cell markers were localized using IF. The expression levels of TLR4 pathway were detected by WB, IHC and qPCR. The graphical abstract is made by Figdraw.<br><br>RESULTS: T-Tan extract and its major compound tanshinone IIA (Tan IIA) alleviated abnormal pain and reduced inflammation. Moreover, they restored intestinal flora composition, reduced LPS levels, and downregulated the TLR4 pathway. In addition, fecal microbiota transplantation (FMT) preserved the protective effects of T-Tan extract, reduced inguinal pain, attenuated inflammatory responses, and inhibited the LPS-TLR4 signaling axis. Besides, we further confirmed that the role of intestinal flora in the treatment of CP/CPPS.<br><br>CONCLUSION: T-Tan extract could alleviate CP/CPPS by modulating the intestinal flora and then inhibiting the LPS-TLR4 axis, which is helpful for developing novel, microbiota-focused therapeutic strategies to treat CP/CPPS.}, }
@article {pmid41175586, year = {2025}, author = {Shang, Z and Zhou, L and Liu, Y and Yang, X and Yao, D and Zhai, F and Liu, B and Chen, Y and Zhu, X and Liu, D and Yi, B}, title = {Tongxie Yaofang attenuates ulcerative colitis by modulating gut microbiota and IL-10RA/NF-κB-mediated macrophage polarization.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157459}, doi = {10.1016/j.phymed.2025.157459}, pmid = {41175586}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/microbiology ; Humans ; *NF-kappa B/metabolism ; Mice ; *Drugs, Chinese Herbal/pharmacology ; Mice, Inbred C57BL ; *Macrophages/drug effects ; Caco-2 Cells ; Fecal Microbiota Transplantation ; Male ; *Interleukin-10 Receptor alpha Subunit/metabolism ; Disease Models, Animal ; Dextran Sulfate ; Coculture Techniques ; }, abstract = {BACKGROUND: Tongxie Yaofang (TXYF), a traditional Chinese herbal formula, has shown therapeutic potential in gastrointestinal disorders. However, its mechanism in ulcerative colitis (UC) remains unclear. This study provides new insights into immune-microbiota crosstalk as a key mechanism driving the protective effects of TXYF.<br><br>METHODS: A DSS-induced colitis mouse model was used to evaluate TXYF's efficacy. Gut microbiota was profiled by 16S rRNA sequencing, while transcriptomics and network pharmacology identified core pathways. In vivo and in vitro assays examined immune regulation and epithelial barrier function. A THP-1/Caco-2 co-culture system explored IL-10RA-dependent immune-epithelial crosstalk, and fecal microbiota transplantation (FMT) tested the functional role of microbial remodeling.<br><br>RESULTS: TXYF alleviated colitis symptoms, improved colon histology, and reduced pro-inflammatory cytokines. It reshaped gut microbiota by enriching SCFA-producing beneficial taxa and suppressing pathogenic bacteria. Transcriptomic analyses identified IL-10RA/NF-&#x3ba;B as a novel regulatory axis, and TXYF enhanced IL-10RA expression, inhibited NF-&#x3ba;B activation, and promoted M2 macrophage polarization. The co-culture model revealed IL-10RA-dependent macrophage-epithelial signaling that strengthened tight junction integrity. Importantly, FMT from TXYF-treated donors yielded these therapeutic benefits, reinforcing the evidence for microbiota-driven causality.<br><br>CONCLUSION: This study is the first to identify IL-10RA/NF-&#x3ba;B as a key immunoregulatory pathway of TXYF, uncover IL-10RA-dependent immune-epithelial communication, and validate gut microbiota as a functional mediator through FMT. Collectively, these findings demonstrate the innovative potential of TXYF as a multi-target herbal therapy for UC.}, }
@article {pmid41175891, year = {2025}, author = {Minari, TP and Pisani, LP}, title = {The Role of Gut Microbiota in Chronic Noncommunicable Diseases: An Overview of the Last Decade.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuaf200}, pmid = {41175891}, issn = {1753-4887}, abstract = {The gut microbiota has emerged as a key modulator of various health outcomes, including chronic noncommunicable diseases (NCDs). Obesity, diabetes, and hypertension represent important clinical challenges. Recent research suggests that gut dysbiosis may contribute to the pathophysiology of NCDs through metabolic and inflammatory pathways. This narrative review evaluates current scientific evidence on the role of gut microbiota in NCDs, examining its impact on blood pressure, glucose regulation, and weight control. It also explores interactions with medications, prebiotics, probiotics, fecal transplants, and lifestyle changes while identifying research gaps to advance understanding and inform innovative therapeutic strategies. An extensive review was conducted across multiple scientific databases, including PubMed, Web of Science, CrossRef, Google Scholar, and Scopus. Articles published between 2015 and 2025 were collected. A total of 115 relevant studies were identified and analyzed. The findings demonstrate consistent associations between gut dysbiosis and NCDs. Genera such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Fusicatenibacter were depleted in disease states, while Prevotella and Clostridium sensu stricto 1 were often enriched in obesity, diabetes, and hypertension. Microbial imbalances, including altered Bacillota/Bacteroidota ratios and reduced short-chain fatty acid production, were implicated in low-grade inflammation and metabolic disruption. Current findings suggest that fecal transplantation, prebiotics, postbiotics (bioactive compounds resulting from probiotic activity), and probiotics have limited effectiveness in improving gut microbiota, emphasizing the need for further human studies. Several drugs can positively or negatively alter the composition of the microbiota. Gut microbiota imbalances contribute meaningfully to the onset and progression of major NCDs. Although emerging therapies offer promise, clinical translation requires more robust, longitudinal studies integrating microbiome profiling, metabolic outcomes, and personalized strategies. Advancing microbiota-targeted approaches may help bridge current gaps in NCD prevention and management.}, }
@article {pmid41176272, year = {2026}, author = {Gilbert, MS and Cai, Y and Minderhoud, R and Edens, MGJ and Folkerts, G and Braber, S and Gerrits, WJJ}, title = {Effects of galacto-oligosaccharides and microbiota transfer on lung health and performance of calves.}, journal = {Journal of dairy science}, volume = {109}, number = {1}, pages = {390-405}, doi = {10.3168/jds.2025-27121}, pmid = {41176272}, issn = {1525-3198}, mesh = {Animals ; Cattle ; *Oligosaccharides/pharmacology ; Male ; *Lung/drug effects ; Diet/veterinary ; Microbiota ; Bronchoalveolar Lavage Fluid/chemistry ; Dietary Supplements ; Animal Feed ; }, abstract = {Bovine respiratory disease is a major multifactorial health issue in calves. Our objective was to evaluate the effects of galacto-oligosaccharide supplementation, microbiota transfer, and their interaction on lung health and performance of calves. A total of 180 male Holstein-Friesian calves at 18 ± 3.6 d of age received 1 of 4 treatments according to a 2 × 2 factorial design for 8.5 wk (period 1). Calves received galacto-oligosaccharides (GOS) via the milk replacer or not (CON) and received a microbiota transfer (MT) or not (MOCK). The MT strategy consisted of a combination of an oral rumen microbiota transfer and a fecal microbiota transfer supplied orally and rectally. The MT or MOCK procedure was applied 3 times in the first week after arrival and was repeated within a week after a group antimicrobial treatment. Clinical health was scored weekly, and BW was measured every 4 wk. Bronchoalveolar lavage fluid (BALF) and blood samples were collected biweekly from a subset of calves (n = 108). After period 1, all calves received the same control milk replacer for 4 wk (period 2), during which performance and clinical health were measured. Clinical scores increased from wk 1 to 3, and BALF IL-8 concentrations increased with time in period 1. This high infection pressure resulted in a requirement of 6 group antimicrobial treatments (supplied to all calves). Supplementation with GOS increased the ADG adjusted to equal solid feed intake (+27 g/d) in period 1 and tended to increase it (+45 g/d) in period 2. Supplementation with GOS decreased clinical scores in wk 1 and 3 (in the absence of MT) but tended to increase it in wk 6. Furthermore, GOS tended to decrease rectal temperature in period 2. Cytokine concentrations in BALF and blood were not affected by GOS, but the percentage of lymphocytes in BALF was increased by GOS, accompanied by a decrease in lymphocyte and an increase in neutrophil percentage in plasma. Microbiota transfer reduced plasma white blood cell concentration, related to a relative decrease in plasma neutrophils. Microbiota transfer reduced the percentage of BALF lymphocytes, and in wk 5, it also reduced the BALF concentration of TNFα. However, MT did not affect performance. At the start of period 2, MT even increased clinical scores in the absence of GOS, resulting in a higher individual antimicrobial treatment supply to MT calves in period 2, ultimately reducing the rectal temperature of MT calves at the end of period 2. Hardly any interactions between GOS and MT occurred, suggesting the absence of an additive relation. In conclusion, GOS improved performance and even tended to increase it after GOS supplementation ended, but this was not related to lung health. Microbiota transfer affected some inflammatory parameters, pointing toward reduced systemic and respiratory inflammation, but this was not reflected in clinical health, which even decreased in the carry-over period.}, }
@article {pmid41177025, year = {2025}, author = {Singh, DP and Bijalwan, V and Poonam, J and Lal, R and Palkhade, R and Viramgami, A and Vidhani, H and Kumar, A and Bishnoi, M and Das, S}, title = {Bisphenol-A at an environmentally plausible dose caused gut microbiota-led impaired cognitive performances in adult mice.}, journal = {Journal of hazardous materials}, volume = {499}, number = {}, pages = {140254}, doi = {10.1016/j.jhazmat.2025.140254}, pmid = {41177025}, issn = {1873-3336}, mesh = {Animals ; *Benzhydryl Compounds/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Phenols/toxicity ; Mice ; Male ; *Cognition/drug effects ; Brain/drug effects/metabolism ; Maze Learning/drug effects ; *Cognitive Dysfunction/chemically induced ; Behavior, Animal/drug effects ; Dysbiosis ; Bisphenol A Compounds ; }, abstract = {Omnipresent Bisphenol-A (BPA) exposure is linked to neurobehavioral deficits and gut dysbiosis. However, studies assessed its impact on cognitive performance at environmentally unrealistic doses. Nevertheless, the exact mechanism underlying the neurobehavioral phenotype, linking the role of gut microbiota is poorly understood. Here, we evaluated the effects of environmentally plausible dose of BPA-exposure on cognitive task performances with the functional analysis of gut metagenome to elucidate the role of microflora-gut-brain axis in behavioural regulation. Swiss albino mice were exposed to BPA for 5 weeks assessed for working and spatial navigation task performances. qRT-PCR based gene expression, histological investigation, gut permeability, molecular and biochemical markers of neuro-inflammation, leaky gut, oxido-nitrosative stress and 16 s rRNA gene based metagenomics with functional analysis were performed. BPA exposure altered the cognitive task performances (mean difference for transfer latency in elevated plus maze 20.84 ± 5.64 sec in and -13.12 ± 3.53 in Morris' water maze), changed serotonin levels (-70.95 ± 21.43) and acetylcholinesterase activity (0.0032 ± 0.0008), enhanced ileal permeability (12.36 ± 3.56) and systemic and tissue level inflammation (increased brain LPS, TNF-a, IL-1b, IL-6 and circulating TNF-a and IL-1b), coupled with reduced SCFAs levels (acetate; 32.48 ± 8.48, and butyrate; 28.16 ± 9.86). Faecal microbial transplant cohort replicated similar behavioural, biochemical and molecular patterns, suggesting the role of gut-microbiota in the phenotype determination. Functional pathways prediction suggested altered serotonin, dopamine, SCFAs metabolism and LPS biosynthesis. BPA at a much lower but environmentally relevant dose altered the cognitive performances, which has potential linkage to gut-microbiota mediated pathways.}, }
@article {pmid41177416, year = {2025}, author = {Bashir, B and Gulati, M and Vishwas, S and Hussain, MS and Gupta, G and Kumar, P and Negi, P and Mittal, N and Dua, K and Singh, SK}, title = {Bridging the gap in the management of Alzheimer's disease using fecal microbiota transplantation.}, journal = {Molecular and cellular neurosciences}, volume = {135}, number = {}, pages = {104052}, doi = {10.1016/j.mcn.2025.104052}, pmid = {41177416}, issn = {1095-9327}, mesh = {Humans ; *Alzheimer Disease/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that greatly impairs the health status of human beings and creates significant burdens on individuals, families, and society. AD is characterized by the buildup of pathological proteins and glial cell dysregulated activity. Additional hallmark features include oxidative stress, neuroinflammation, impaired autophagy, cellular senescence, mitochondrial dysfunction, epigenetic alterations, reduced neurogenesis, increased blood-brain barrier permeability, and age-inappropriate intestinal dysbiosis. There is significant evidence that shows that microbiota in the gut affects the development and progression of AD. As a result, gut microbiota modulation has been identified as a new method of clinical management of AD, and more and more efforts have been devoted to identifying new methodologies for its prevention and treatment. This paper will discuss the role of gut microbiome in the etiopathogenesis of AD and consider the possibilities of fecal microbiota extract (FME) supplementation, commonly referred to as fecal microbiota transplantation (FMT). It is both a prophylactic and curative approach. The FMT therapy is grounded on the premise that anti-inflammatory effects, modifications of amyloid β, improved synaptic plasticity, short-chain fatty acids, and histone acetylation are the principles behind the enhancement of AD. The current review will present an overview of the linkage between FMT and AD as well. It further examines and evaluates the effects of FMT on aging-based mechanisms that support the development of AD. It also provides a broad description of the recent clinical and preclinical evidence on the application of FMT to AD.}, }
@article {pmid41178925, year = {2025}, author = {Pacheco-Barcia, V and Mariño-Mendez, A and Hernandez-Jimenez, E and Jimenez-Fonseca, P and Muñoz Martín, AJ and Custodio-Cabello, S and Palka-Kotlowska, M and Gonzalez-Diaz, I and Cabezon-Gutierrez, L}, title = {Gut microbiome and nutritional strategies in gastrointestinal cancers: Clinical implications and therapeutic perspectives.}, journal = {World journal of clinical oncology}, volume = {16}, number = {10}, pages = {107877}, pmid = {41178925}, issn = {2218-4333}, abstract = {Gastrointestinal malignancies, particularly pancreatobiliary and gastroesophageal cancers, are associated with poor prognosis due to their frequent late-stage diagnosis. Many of these tumors contribute to anorexia-cachexia syndrome and malnutrition, further exacerbating disease progression. Inflammation plays a crucial role in tumor proliferation, and growing evidence suggests that gut microbiome significantly influence inflammatory responses and clinical outcomes in these patients. Additionally, the gut microbiome contributes to carcinogenesis through multiple mechanisms, including DNA damage, activation of oncogenic pathways, and modulation of immune responses. The emerging field of nutritional interventions highlight the microbiome's impact on anticancer drug responses, affecting both chemotherapy and molecular-targeted treatments. Given its pivotal role, microbiome modulation through probiotics, fecal microbiome transplantation, and antibiotics represents a promising approach for cancer prevention and treatment. In this review, we explore the intricate interplay between gut microbiome, inflammation, and nutritional status in gastrointestinal cancers, emphasizing potential therapeutic strategies to improve patient outcomes.}, }
@article {pmid41179483, year = {2025}, author = {Fanous, N and Talley, NJ and Chaemsupaphan, T and Lee, E and Rayamajhee, B and Baradaran Ghavami, S and Kazemifard, N and Asadzadeh Aghdaei, H and Chuang, E and Leong, RW}, title = {Microbiota-targeted strategies in IBD: therapeutic promise of 2'-fucosyllactose and beyond.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251386319}, pmid = {41179483}, issn = {1756-283X}, abstract = {Inflammatory bowel diseases (IBD) are chronic and recurrent conditions of the gastrointestinal tract. IBD is often challenging to manage due to the complex etiology and involvement of multiple dysregulated immune pathways. Current treatments, including biologics and immunosuppressants, are associated with significant risks and side effects, highlighting the need for safer alternatives. Human milk oligosaccharides (HMOs), a group of bioactive carbohydrates found in human breast milk, play a crucial role in shaping the infant gut microbiome, modulating microbial metabolism and immune responses, and reducing inflammation. Notably, HMOs have no nutritional value for the infant and travel undigested through the upper gastrointestinal tract, serving as selective substrates for beneficial gut bacteria and supporting intestinal epithelial health. Among these, 2'-fucosyllactose (2'-FL) is the most abundant and well-studied HMO, functioning as a trisaccharide prebiotic. Emerging evidence suggests that the benefits of HMOs extend beyond infancy, with potential therapeutic applications in modulating immune responses, promoting epithelial health, and reducing inflammation in IBD. This review summarizes current research on the role of 2'-FL in inflammation and colitis, exploring its potential role in treating IBD.}, }
@article {pmid41180995, year = {2025}, author = {Anis, MA and Shahid, Y and Majeed, AA and Abid, S}, title = {Microbiome and gut-liver interactions: From mechanisms to therapies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {40}, pages = {111409}, pmid = {41180995}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology/drug effects ; *Dysbiosis/therapy/microbiology/immunology ; *Liver/microbiology/immunology/metabolism/pathology ; Probiotics/therapeutic use ; *Liver Diseases/microbiology/therapy/immunology ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; Anti-Bacterial Agents/therapeutic use ; Precision Medicine/methods ; Animals ; Host Microbial Interactions/immunology ; }, abstract = {The gut-liver axis represents a bidirectional and dynamic communication system between the gastrointestinal tract and liver, critically modulated by gut microbiota, bile acids, immune responses, and metabolic pathways. Disruption of this finely tuned axis contributes to the pathogenesis of several liver diseases, including alcohol-associated hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatic encephalopathy, and cholangiopathies like primary biliary cholangitis and primary sclerosing cholangitis. Dysbiosis, marked by reduced microbial diversity and dominance of pathogenic species, alters bile acid metabolism, increases gut permeability, and fuels hepatic inflammation. In cholangiopathies, the gut microbiome modulates immune dysregulation and fibrosis through complex microbial-host interactions. Emerging therapies targeting the microbiota, such as fecal microbiota transplantation, antibiotics (e.g., rifaximin, vancomycin), bile acid modulators, and probiotics, show promise in restoring microbial equilibrium, improving liver biochemistry, and reducing disease progression. Precision medicine strategies integrating genomics, metabolomics, and microbiomics offer a tailored approach for therapy and prognosis. This review highlights the central role of the gut-liver axis in liver diseases and the potential of microbiome-based interventions to shift management from symptomatic relief toward disease modification and personalized hepatology, underscoring a new frontier in liver disease therapeutics.}, }
@article {pmid41181343, year = {2025}, author = {Jeyaraman, N and Jeyaraman, M and Dhanabal, P and Ramasubramanian, S and Ambrosio, L and Vadalà, G and Muthu, S}, title = {Implications of the gut microbiome in spinal cord injuries.}, journal = {Frontiers in surgery}, volume = {12}, number = {}, pages = {1668225}, pmid = {41181343}, issn = {2296-875X}, abstract = {Spinal cord injuries (SCIs) present complex challenges in medical treatment and rehabilitation, profoundly affecting the patient's physiological and neurological status. Emerging research on the gut microbiome has unveiled its potential role in influencing SCI outcomes and recovery. The gut microbiome undergoes significant changes following SCIs, which influence systemic inflammation and increase susceptibility to secondary complications, such as infections and chronic pain. These effects are linked to altered permeability, immune system dysregulation, and activation of the gut-brain axis, which represent promising therapeutic targets for the treatment of these conditions. Insights into the mechanisms underlying these effects were explored, highlighting the roles of microbial-derived metabolites like short-chain fatty acids, which have been shown to possess anti-inflammatory properties and support neuroprotective responses. The implications of these findings are significant, suggesting that interventions aimed at modulating the gut microbiome, such as the use of probiotics, prebiotics, and faecal microbiota transplantation, could complement existing SCI treatments and support recovery processes. This review aims to synthesise current knowledge on the interplay between the gut microbiome and SCIs, exploring how this relationship can influence immune modulation, inflammation, and neuroplasticity, thereby affecting recovery trajectories and the necessity for interdisciplinary research approaches that integrate neurology, microbiology, and nutrition to develop holistic, effective treatment strategies for SCI patients.}, }
@article {pmid41181478, year = {2025}, author = {Singhal, R and Ghadvaje, G and Karra, N and Gadde, ST and Chandra, P and Voruganti, BKT and Doddareddy, NP and Iftikhar, S and Patel, T}, title = {A narrative review on fecal microbiota transplantation routes in ulcerative colitis: identifying the optimal approach across key parameters.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {10}, pages = {6599-6611}, pmid = {41181478}, issn = {2049-0801}, abstract = {Fecal microbiota transplantation (FMT) has gained increasing attention as a novel therapeutic approach for treating ulcerative colitis (UC), a chronic inflammatory bowel disease that causes an imbalance in the gut microbiota. Although FMT has demonstrated the potential to induce remission in UC patients, the most effective route of administration remains an area of active investigation. This narrative review provides a comprehensive comparison of different FMT delivery methods, such as oral capsules, enemas, colonoscopy, and nasogastric or nasoenteric tubes, across a range of clinically relevant parameters, including efficacy, safety, patient satisfaction, microbiota changes, pretreatment protocols, and cost-effectiveness. Furthermore, we examined how post-FMT dietary interventions may influence microbial engraftment and improve the long-term outcomes in patients with UC. In addition to assessing these practical and clinical factors, this review highlights the importance of patient-centered considerations, such as the tolerability and convenience of each administration route. The integration of these findings can provide valuable insights into how different FMT routes affect disease outcomes and guide clinicians in optimizing the treatment for individual patients. By synthesizing current evidence on these key variables, we aimed to identify the most effective and feasible FMT approach for UC. Establishing standardized protocols for FMT administration, informed by this analysis, will be crucial for ensuring consistency in clinical practice, improving patient outcomes, and minimizing adverse events. The insights from this review will help pave the way for more targeted and individualized FMT strategies, ultimately enhancing the therapeutic landscape of UC management.}, }
@article {pmid41181931, year = {2025}, author = {Khoruts, A}, title = {The challenges and opportunities in the expanding horizons of microbiota transplant therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2559032}, pmid = {41181931}, issn = {1949-0984}, }
@article {pmid41183735, year = {2026}, author = {He, J and Lin, Z and Lin, X and Wang, C and Cao, M and Xia, R and Hong, W}, title = {Targeted fecal microbiota transplantation ameliorates autism-like behaviors via gut-brain axis and excitatory/inhibitory balance restoration in a propionic acid mouse model.}, journal = {Brain, behavior, and immunity}, volume = {131}, number = {}, pages = {106162}, doi = {10.1016/j.bbi.2025.106162}, pmid = {41183735}, issn = {1090-2139}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Mice ; Propionates ; *Autism Spectrum Disorder/therapy/metabolism ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/metabolism ; Behavior, Animal/physiology ; Brain/metabolism ; *Brain-Gut Axis/physiology ; Feces/microbiology ; RNA, Ribosomal, 16S ; Female ; }, abstract = {Autism spectrum disorder (ASD) is characterized by social interaction deficits, repetitive behaviors, and restricted interests. Emerging evidence suggests a role for the gut microbiota in ASD pathophysiology, with fecal microbiota transplantation (FMT) emerging as a potential therapeutic strategy. This study investigated the effects of targeted FMT using processed fecal suspensions from rigorously screened healthy human donors, selected by 16S rRNA sequencing for high Lactobacillus abundance, on a propionic acid (PPA)-induced ASD mouse model. PPA-exposed mice exhibited ASD-like behaviors, including anxiety, repetitive grooming, and social interaction deficits, along with alterations in gut microbiota composition, SCFA levels, and neurotransmitter profiles. Donor selection based on 16S rRNA gene sequencing revealed that FMT from donors with high Lactobacillus abundance was more effective in improving social interaction deficits compared to donors with lower Lactobacillus levels. Targeted FMT intervention restored gut microbiota diversity and enriched beneficial taxa, such as Lactobacillus, Roseburia, and Blautia. Furthermore, targeted FMT reduced PPA levels in both feces and the prefrontal cortex (PFC), and normalized the Glu/GABA ratio in the PFC, suggesting a restoration of E/I balance. Electrophysiological recordings confirmed that FMT corrected the E/I imbalance in PFC pyramidal neurons by reducing sEPSC frequency and increasing sIPSC frequency. These findings demonstrate that FMT can ameliorate ASD-like behaviors in a PPA-induced mouse model by modulating gut microbiota and restoring E/I balance in the brain. Our study provides foundational evidence for the potential of targeted FMT as a therapeutic strategy for ASD, highlighting the importance of donor selection based on gut microbiota composition.}, }
@article {pmid41184709, year = {2025}, author = {Kiecka, A and Szczepanik, M}, title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.}, journal = {Pharmacological reports : PR}, volume = {77}, number = {6}, pages = {1514-1526}, pmid = {41184709}, issn = {2299-5684}, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/therapy/diet therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; Animals ; Prebiotics/administration &amp; dosage ; *Diet ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.}, }
@article {pmid41185751, year = {2025}, author = {Huang, Y and Zhang, Z and Xue, L and Zhang, X and He, C}, title = {Advances in Nanomedicine-Mediated Modulation of the Microbiome for Cancer Therapy.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {13079-13096}, pmid = {41185751}, issn = {1178-2013}, mesh = {Humans ; *Neoplasms/therapy/microbiology/drug therapy ; *Nanomedicine/methods ; Tumor Microenvironment/drug effects ; Animals ; Probiotics/therapeutic use/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; *Microbiota/drug effects ; Liposomes/chemistry ; Drug Delivery Systems ; Antineoplastic Agents/administration &amp; dosage ; Gastrointestinal Microbiome/drug effects ; }, abstract = {The microbiome is closely related to the development of cancer, and it is feasible to modulate the microbiome for cancer therapy. Strategies based on the modulation of the microbiome, such as probiotic therapy and fecal microbiota transplantation (FMT), have achieved certain results in cancer therapy. However, poor targeting and low survival rate of the microbiome limited their further application in cancer therapy. Nanomaterials such as liposomes and micelles are widely used as carriers for drug delivery due to their good biocompatibility and stability. The latest evidence indicates that some nanomedicines can reverse cancer-promoting effects (such as promoting cell proliferation and accelerating tissue inflammation) by eliminating cancer-related microbiota, or increase the proportion of beneficial bacteria, which further enhance the production of beneficial metabolites, facilitate immune cell infiltration, and reshape the tumor microenvironment (TME), thereby inhibit tumor growth. Thus, it is promising to enhance the efficacy of cancer therapy by regulating microbiota through nanomedicines. This review highlights recent advances in the integration of nanomedicine and microbiota modulation for cancer treatment, aiming to provide insights into the design of innovative therapeutic strategies and broaden treatment options for cancer patients.}, }
@article {pmid41186720, year = {2026}, author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P}, title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {399}, number = {4}, pages = {4879-4905}, pmid = {41186720}, issn = {1432-1912}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/drug effects ; Animals ; *Brain/metabolism/drug effects ; Dysbiosis ; *Nervous System Diseases/microbiology/therapy/drug therapy/physiopathology ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.}, }
@article {pmid41187620, year = {2025}, author = {Tian, J and Cheng, J and Yang, H and Niu, Z and Zhao, L and Guan, L and Liu, N and Rong, S and Wang, C and Shi, D and Zheng, H and Cao, N and Li, R and Zhang, Y and Ren, C and Zhang, Z}, title = {Unveiling the gut-vascular connection: Gut microbiota regulates cardiovascular toxicity induced by combined exposure to PM2.5 and high-fat diet via butyric acid/NLRP3 pathway.}, journal = {Journal of hazardous materials}, volume = {499}, number = {}, pages = {140334}, doi = {10.1016/j.jhazmat.2025.140334}, pmid = {41187620}, issn = {1873-3336}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Particulate Matter/toxicity ; Male ; Mice ; *Butyric Acid/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Dysbiosis ; Blood Pressure/drug effects ; }, abstract = {Environmental particulate matter and dietary factors have been found to induce gut microbiota dysbiosis and exert an impact on cardiovascular toxicity. However, the underlying biological connections among them remain unclear. Our results indicated co-exposure to PM2.5 and high-fat diet (HFD) notably elevated blood pressure and blood lipid in mice and serum nitric oxide and endothelin-1 were abnormal. Meanwhile, vascular diameter and end-diastolic velocity (EDV) decreased, while resistance index (RI) increased. There was a synergistic effect of co-exposure on EDV and RI. Furthermore, significant damage to colon was observed. 16S rDNA sequencing of fecal microbiota indicated PM2.5 and HFD led to gut microbiota dysbiosis. Desulfovibrio was positively correlated with blood pressure, while Parabacteroides was negatively correlated. Fecal microbiota transplantation from donor mice exposed to hazardous substances successfully exacerbated cardiovascular toxicity in recipient mice. Further analysis of short chain fatty acids using metabolomics showed exposure to PM2.5 and HFD decreased serum butyric acid. Supplementation with sodium butyrate (SB) successfully alleviated the damage to cardiovascular system. Both in vivo and vitro experiments demonstrated SB supplementation significantly inhibited NLRP3 inflammasome. These findings indicate that modulating gut microbiota and its metabolite butyric acid may prevent the adverse cardiovascular effects of environmental PM2.5 exposure and HFD.}, }
@article {pmid41188912, year = {2025}, author = {Li, X and Hou, M and Lyu, J and Min, X and Han, X and Wang, X and Liu, Z and Leng, Y}, title = {Gut microbiota-derived arginine metabolism mitigates intestinal ischemia-reperfusion injury.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1215}, pmid = {41188912}, issn = {1479-5876}, support = {82260381//Natural Science Foundation of china/ ; }, abstract = {BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a severe pathological condition characterized by disruption of the mucosal barrier, immune dysregulation, and gut microbiota imbalance. However, whether the gut microbiota regulates immune homeostasis and mucosal repair through arginine metabolism remains unclear.<br><br>METHODS: We employed antibiotic-treated and fecal microbiota transplantation (FMT) mouse models, MNK-3 cells, metabolomics, arginine supplementation, and CASTOR1 knockout mice to evaluate intestinal barrier integrity, inflammatory responses, and signaling pathways following I/R injury.<br><br>RESULTS: I/R injury induced significant microbial dysbiosis and decreased fecal arginine levels. FMT demonstrated that microbial alterations reshaped arginine metabolism in recipient mice. Arginine supplementation restored tight junction protein expression, downregulated pro-inflammatory cytokines, enhanced interleukin (IL)-22 secretion, and suppressed IL-17 upregulation. Mechanistically, arginine activated mTORC1 signaling via CASTOR1, thereby promoting IL-22 production, whereas CASTOR1 deficiency or mTORC1 inhibition markedly impaired its protective effects.<br><br>CONCLUSIONS: The gut microbiota functions as an upstream regulator of arginine metabolism during I/R injury. Arginine confers immunoprotection by activating the CASTOR1&#x2013;mTORC1&#x2013;ILC3 axis, enhancing cytokine secretion and promoting mucosal repair. These findings reveal a novel microbiota&#x2013;metabolism&#x2013;immunity interplay and suggest nutrient-sensing pathways as promising therapeutic targets in intestinal injury.}, }
@article {pmid41189008, year = {2025}, author = {Cho, HW and Byeon, HW and Park, SO and Uyangaa, E and Choi, JY and Kim, K and Eo, SK}, title = {The gut microbiota limits systemic inflammation during neurotrophic viral CNS infection by priming tonic type I interferon signaling.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {259}, pmid = {41189008}, issn = {1742-2094}, support = {RS-2025-00513722//National Research Foundation of Korea/ ; RS-2021-NF000550//Korea Basic Science Institute/ ; HI22C0591//Korea Health Industry Development Institute/Republic of Korea ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/immunology/drug effects ; *Interferon Type I/metabolism/immunology ; Mice ; Mice, Inbred C57BL ; *Signal Transduction/physiology ; Fecal Microbiota Transplantation ; Inflammation/microbiology/immunology ; Male ; Encephalitis Virus, Japanese ; *Encephalitis, Japanese/immunology ; Neuroinflammatory Diseases ; }, abstract = {Neurotropic viruses, such as Japanese encephalitis virus (JEV), trigger central nervous system (CNS) inflammation primarily through disruption of the blood-brain barrier (BBB) and infiltration of peripheral immune cells. Although the gut microbiota is known to regulate diverse immunopathological processes, its contribution to CNS neuroinflammation and systemic immune responses during neurotropic viral infection remains poorly understood. Here, we show that depletion of gut microbiota by antibiotic cocktail treatment markedly increases susceptibility to CNS neuroinflammation following JEV infection. Loss of microbiota promoted viral dissemination into extraneural tissues, aggravated systemic inflammation and organ damage, and impaired tonic type I interferon (IFN-I) responses and hematopoietic differentiation during disease progression. Remarkably, fecal microbiota transplantation (FMT) restored resistance to CNS neuroinflammation, highlighting the protective role of the microbiota. Moreover, ampicillin-mediated depletion of specific gram-positive bacteria-including Bifidobacterium, Faecalibaculum, Ligilactobacillus, and Turicibacter-was associated with enhanced viral spread, systemic inflammation, and organ injury, accompanied by distinct shifts in fecal metabolites. Collectively, these findings demonstrate that gut microbiota-driven tonic IFN-I responses limit viral dissemination in extraneural tissues, thereby attenuating systemic inflammation and protecting against CNS neuroinflammation, particularly viral encephalitis.}, }
@article {pmid41189901, year = {2025}, author = {Bautista, J and Maldonado-Noboa, I and Maldonado-Guerrero, D and Reinoso-Quinga, L and López-Cortés, A}, title = {Microbiome influence in gastric cancer progression and therapeutic strategies.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1681824}, pmid = {41189901}, issn = {2296-858X}, abstract = {Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fourth leading cause of cancer-related death worldwide. While Helicobacter pylori is established as the primary microbial risk factor, emerging evidence underscores the broader oncogenic potential of gastric microbiome dysbiosis. This review synthesizes recent advances in understanding how microbial communities, both within the stomach and along the gut-stomach axis, contribute to gastric carcinogenesis. We explore how alterations in microbial diversity, virulence, and metabolic output disrupt mucosal homeostasis, drive chronic inflammation, and reshape local immune surveillance. Special attention is given to the molecular mechanisms by which H. pylori virulence factors cytotoxin-associated gene A (CagA) and VacA, vacuolating cytotoxin, induce epithelial transformation, immune evasion, and epigenetic reprogramming. We also highlight the oncogenic roles of non-H. pylori taxa such as Fusobacterium nucleatum, Streptococcus anginosus, and Lactobacillus fermentum, which synergize with host and environmental factors to sustain tumor-promoting microenvironments. Multi-omics studies reveal microbial signatures predictive of disease progression, therapeutic response, and prognosis, laying the foundation for microbiome-informed precision oncology. Furthermore, we examine how microbiota-targeted interventions, probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, can enhance chemotherapy and immunotherapy efficacy while mitigating treatment-related toxicity. Lastly, we discuss the implications of early H. pylori eradication, the impact of antibiotic resistance, and the need for global surveillance strategies.}, }
@article {pmid41190061, year = {2025}, author = {Ma, C and Wang, J and Song, X and Wang, X and Zong, S}, title = {Molecular mechanisms and clinical applications of gut microbiota-derived bioactive compounds in metabolic dysfunction-associated fatty liver disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1682755}, pmid = {41190061}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Probiotics ; Dysbiosis/metabolism ; Fecal Microbiota Transplantation ; Prebiotics ; *Non-alcoholic Fatty Liver Disease/metabolism/therapy/microbiology ; Lipid Metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide. Its pathogenesis is closely associated with gut microbiota dysbiosis and metabolic disturbances. In recent years, numerous studies have demonstrated that bioactive compounds produced by gut microbial metabolism-such as short-chain fatty acids, secondary bile acids, tryptophan derivatives, and bacterial extracellular vesicles-play critical roles in the development and progression of MAFLD by modulating hepatic lipid metabolism, inflammatory responses, and epigenetic regulation. The characteristic expression patterns of these gut microbiota-derived bioactive compounds provide novel options for differential diagnosis of the disease. Moreover, elucidation of the underlying pathological mechanisms has paved novel avenues for MAFLD treatment. Strategies including dietary interventions, prebiotics, probiotics, and other microbiota-targeted therapies are considered potential approaches to modulate MAFLD progression. This review systematically summarizes the molecular mechanisms underlying the development of MAFLD influenced by gut microbiota-derived bioactive compounds. It also explores the feasibility of utilizing specific gut microbial metabolite profiles for MAFLD diagnosis and highlights potential therapeutic strategies targeting microbiota-host metabolic interactions, including the use of engineered bacteria to produce specific metabolites, probiotic/prebiotic interventions, and the clinical prospects of fecal microbiota transplantation.}, }
@article {pmid41191115, year = {2025}, author = {Habeeb, TAAM and Hussain, A and Bueno-Lledó, J and Giménez, ME and Aiolfi, A and Chiaretti, M and Kryvoruchko, IA and Manangi, MN and Elias, AA and Adam, AAM and Gadallah, MA and Ahmed, SMA and Khyrallh, A and Alsayed, MH and Awad, ETK and Ibrahim, EA and Elshafey, MH and Labib, MF and Badawy, MHM and Teama, SRA and Seleem, A and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Mohamed, BA and Alwadees, A and El-Taher, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Atef, B and Elnemr, M and Khairy, MM and Abdelwanis, AH and Abdelaziz, AM and Mostafa, A and Hamed, AM and Wasefy, T and Heggy, IA and Nawar, AMH}, title = {COVID-19-specific risk factor for early post-appendectomy complications (EPAC) in older patients: a retrospective study.}, journal = {Techniques in coloproctology}, volume = {29}, number = {1}, pages = {188}, pmid = {41191115}, issn = {1128-045X}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Age Factors ; *Appendectomy/adverse effects ; *Appendicitis/surgery ; *COVID-19/complications/epidemiology/diagnosis ; Incidence ; *Postoperative Complications/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; Surgical Wound Infection/epidemiology ; }, abstract = {BACKGROUND: The incidence of acute appendicitis in older patients significantly varies from that in younger adults. The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of early post-appendectomy complications (EPAC). This study aimed to investigate the incidence and risk factors associated with EPAC in older patients after appendectomy and to define active COVID-19 infection during surgery as an associated risk factor for EPAC.<br><br>METHODS: We conducted a retrospective multicenter analysis of older patients aged &#x2265;&#x2009;60 years who underwent appendectomy between April 2020 and December 2024. Logistic regression identified the risk factors associated with EPAC.<br><br>RESULTS: A total of 585 patients aged &#x2265;&#x2009;60&#xa0;years were divided into the EPAC (n&#x2009;=&#x2009;32) and no EPAC (n&#x2009;=&#x2009;553) groups. The incidences of EPAC was 5.5% (32/585), including superficial incisional surgical site infections (SSI) (9/32, 28.1%), deep incisional SSI (2/32, 6.3%), organ/space infection (2/32, 6.3%), intra-abdominal abscess (9/32, 28.1%), ileus (2/32, 6.3%), pneumonia (3/32, 9.4%), acute myocardial infraction (MI) (2/32, 6.3%), fecal fistula (2/32, 6.3%), and acute adhesive intestinal obstruction (1/32, 3.1%). Multivariable analysis identified that active COVID-19 infection during surgery (odds ratio (OR)&#x2009;=&#x2009;25.9; 95% confidence interval (CI) 4.8-139.1; p&#x2009;<&#x2009;0.001), American Society of Anesthesiologists (ASA) score&#x2009;&#x2265;&#x2009;II (OR&#x2009;=&#x2009;4.5; 95% CI 1.2-17.07; p&#x2009;=&#x2009;0.02), open approach (OR&#x2009;=&#x2009;30.6; 95% CI 8.1-115.3; p&#x2009;<&#x2009;0.001), and high-grade appendicitis&#x2009;&#x2265;&#x2009;IV (OR&#x2009;=&#x2009;63.06; 95% CI 7.5-526.4; p&#x2009;<&#x2009;0.001) were significant associated risk factors for EPAC.<br><br>CONCLUSIONS: The incidence of EPAC in older patients after appendectomy is 5.5%. Active COVID-19 infection during surgery is strongly associated with an increased risk of EPAC. COVID-19 should be considered in perioperative risk assessment of EPAC.<br><br>TRIAL REGISTRATION: This study was registered as a clinical trial (NCT06787573). Retrospectively registered.}, }
@article {pmid41192727, year = {2026}, author = {Lai, J and Yang, B and Ju, P and Sun, Y and Sun, X and Cheng, W and Chen, J}, title = {Gut microbiota from adolescents with social anxiety disorder is associated with behavioral alterations and metabolic changes in the medial prefrontal cortex.}, journal = {Journal of affective disorders}, volume = {411}, number = {}, pages = {120597}, doi = {10.1016/j.jad.2025.120597}, pmid = {41192727}, issn = {1573-2517}, mesh = {Animals ; *Prefrontal Cortex/metabolism ; *Phobia, Social/microbiology/metabolism/psychology ; Adolescent ; Rats ; *Gastrointestinal Microbiome/physiology ; Female ; Humans ; Male ; Fecal Microbiota Transplantation ; Feces/microbiology ; Disease Models, Animal ; Anxiety ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Social anxiety disorder (SAD) is a prevalent and burdensome neuropsychiatric disorder characterised by pronounced and persistent fear and anxiety in social situations. While evidence links gut microbiota to neuropsychiatric disorders, its role in SAD remains poorly understood.<br><br>AIM: In this study, we aimed to investigate the potential involvement of gut microbiota in SAD pathophysiology through fecal microbiota transplantation.<br><br>METHOD: We collected demographic data and fecal samples from 40 first-episode, comorbidity-free, and drug-naive adolescent patients with SAD, along with 32 demographically matched healthy controls. Fecal samples underwent 16S rDNA amplicon sequencing and were pooled for transplantation into neonatal rats from postnatal day 1 through late adolescence. Recipient rats were evaluated with behavioral tests, microbiota detection, and non-targeted metabolomics of the medial prefrontal cortex.<br><br>RESULT: Patients with SAD displayed alterations in gut microbiota composition. Rats colonized with SAD-associated microbiota exhibited anxiety-like behaviors and reduced social novelty preference, alongside microbial profiles partially overlapping with those of patients. These behavioral changes were correlated with microbiota differences, and distinct metabolic alterations were detected in the medial prefrontal cortex of SAD-colonized rats.<br><br>CONCLUSION: Gut microbiota from adolescents with SAD is associated with behavioral and metabolic alterations in a rodent model, suggesting a potential role of the gut-brain axis in SAD. Further studies are warranted to establish causality and elucidate underlying mechanisms.}, }
@article {pmid41192778, year = {2026}, author = {Tabata, K and Ikarashi, N and Yoshida, R and Shinozaki, Y and Kato, Y and Kon, R and Iwasaki, Y and Yokoyama, K and Saito, R and Sakai, H and Hosoe, T}, title = {High-fat diet exacerbates atopic dermatitis through alterations in the gut microbiome.}, journal = {The Journal of nutritional biochemistry}, volume = {148}, number = {}, pages = {110164}, doi = {10.1016/j.jnutbio.2025.110164}, pmid = {41192778}, issn = {1873-4847}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Dermatitis, Atopic/microbiology/etiology/metabolism/pathology ; *Diet, High-Fat/adverse effects ; Mice ; Male ; Fatty Acids, Volatile/metabolism ; Skin/metabolism ; Fecal Microbiota Transplantation ; Dinitrochlorobenzene ; }, abstract = {Atopic dermatitis (AD) is a chronic, relapsing skin disorder characterized by pruritic eczema. In addition to genetic predispositions, environmental factors such as diet are thought to contribute to the exacerbation of AD. The aim of this study was to provide scientific evidence on how environmental factors, particularly a high-fat diet (HFD), influence the pathogenesis of AD. AD was induced in NC/Nga mice fed an HFD through the application of 2,4-dinitrochlorobenzene. In the AD-HFD group, the expression levels of inflammatory markers (Tnfa, Il1b, Ptgs2, and Nos2) and AD-related factors (Il4, Ccl17, and Tslp) in the skin were significantly elevated compared with those in the AD group (mice fed a normal diet). Alteration of gut microbiota was observed in the AD-HFD group, characterized by a reduction in the abundances of Bacteroides acidifaciens and Parabacteroides distasonis, bacteria involved in short-chain fatty acid (SCFA) production. Moreover, the levels of acetate, propionate, and butyrate in the cecal contents were significantly decreased in the AD-HFD group. Fecal microbiota transplantation experiments revealed that alterations in the gut microbiota were associated with the exacerbation of AD symptoms. Furthermore, the administration of acetate alleviated the increase in the expression of skin inflammation markers and AD-related factors and the overall exacerbation of AD-like symptoms induced by the HFD. HFD intake exacerbates AD-like symptoms, and this exacerbation is linked to alteration of gut microbiota and a decrease in SCFA levels. These results suggest that acetate and acetate-producing bacteria may serve as potential tools for the prevention and treatment of AD.}, }
@article {pmid41194539, year = {2025}, author = {Rolhion, N and Sokol, H}, title = {Targeting the gut microbiome in inflammatory bowel disease: from concept to clinical reality.}, journal = {Intestinal research}, volume = {23}, number = {4}, pages = {396-404}, pmid = {41194539}, issn = {1598-9100}, support = {ERC-2021-COG-101043802/ERC_/European Research Council/International ; //MSDAVENIR/ ; }, abstract = {The gut microbiota, a complex community of trillions of microorganisms inhabiting the human gastrointestinal tract, has emerged as a critical regulator of immune homeostasis and gastrointestinal health. In the context of inflammatory bowel disease (IBD), comprising primarily Crohn's disease and ulcerative colitis, disruptions to this microbial ecosystem-collectively termed dysbiosis-have been increasingly recognized as central to disease pathogenesis. Recent research has established that alterations in gut microbiota not only reflect disease states but may actively drive immune dysregulation, barrier dysfunction, and mucosal inflammation. This review synthesizes current knowledge on the role of the gut microbiota in IBD and evaluates the therapeutic landscape of microbiota-modulating strategies using selected examples. Fecal microbiota transplantation, while offering proof-of-concept validation, is hindered by standardization challenges and variable clinical outcomes. As a response, microbiome-based therapeutics have evolved toward defined live biotherapeutic products including bacterial consortia and single-strain products, postbiotics, and metabolite-centered approaches targeting specific pathways. Groundbreaking research into rationally designed synthetic microbiomes and next-generation probiotics is driving a paradigm shift in microbiota-based treatment for IBD from empirical to precision-guided interventions.}, }
@article {pmid41195402, year = {2025}, author = {Ruohan, Z and Ruting, W and Hongxi, W and Zhenjin, H and Jiale, L and Rongxin, Z and Feng, J and Yuanbo, S}, title = {Gut microbiota as a novel target for treating anxiety and depression: from mechanisms to multimodal interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1664800}, pmid = {41195402}, issn = {1664-302X}, abstract = {The global prevalence of depression and anxiety continues to rise, with major depressive disorder and anxiety disorders estimated to affect approximately 3.1 and 4.8% of the world's population. Yet current pharmacological treatments demonstrate limited efficacy. This limitation has spurred extensive research into alternative treatment methods. Emerging evidence highlights a complex correlation between gut microbiota (GM) imbalance and mental health disorders. Disruptions in GM may trigger or exacerbate symptoms of anxiety and depression by interfering with communication pathways between the gut and brain. These pathways include neural signaling through the vagus nerve, hormone regulation via the hypothalamic-pituitary-adrenal (HPA) axis, immune responses involving pro-inflammatory cytokines, and metabolic processes related to short-chain fatty acids (SCFAs). Preclinical studies and initial clinical trials indicate promising results for therapeutic interventions targeting gut microbiota. Given that current evidence remains constrained by insufficient depth of understanding regarding underlying mechanisms, this review explores the intricate interactions among the gut microbiota, and brain, highlighting opportunities for advanced therapeutic approaches, focusing on probiotics, prebiotics, postbiotics, synbiotics, dietary modifications, fecal microbiota transplantation (FMT), fecal virome transplantation (FVT), and traditional Chinese medicine (TCM). It elucidates the role of gut microbiota in depression/anxiety and advances therapeutic approaches.}, }
@article {pmid41196286, year = {2026}, author = {Ni, Z and Ye, D}, title = {The impact of gut microbiota modulation on responses to immune checkpoint inhibitors in cancer.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {73}, number = {1}, pages = {13-19}, doi = {10.1556/030.2025.02719}, pmid = {41196286}, issn = {1588-2640}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; *Neoplasms/drug therapy/microbiology/immunology/therapy ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Bacteria/classification/isolation &amp; purification/genetics ; Probiotics ; }, abstract = {The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specific bacterial taxa may influence both efficacy and immune-related adverse events (irAEs). However, the magnitude and consistency of these associations remain unclear. A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted through March 2025. Eligible studies evaluated baseline gut microbiota composition, fecal microbiota transplantation (FMT), probiotic/prebiotic interventions, or antibiotic exposure in cancer patients treated with ICIs. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for response rates and irAEs, were estimated using random-effects models. Across 38 studies involving 5,642 patients were included. Pooled analysis demonstrated that enrichment of Akkermansia muciniphila, Bifidobacterium longum and Faecalibacterium prausnitzii was significantly associated with improved OS (HR 0.62, 95% CI 0.51-0.76) and PFS (HR 0.69, 95% CI 0.55-0.83). Conversely, antibiotic exposure before or during ICI treatment was associated with worse OS (HR 1.84, 95% CI 1.45-2.34). Patients undergoing FMT from responders exhibited higher objective response rates (OR 2.91, 95% CI 1.48-5.73). Microbiota diversity indices were consistently higher in responders than in non-responders. Collectively, gut microbiota composition and its modulation significantly impact the therapeutic efficacy and toxicity profile of ICIs. These findings highlight the translational potential of microbiome-based biomarkers and interventions in optimizing immunotherapy.}, }
@article {pmid41196658, year = {2026}, author = {Verna, G and De Santis, S and Islam, BN and Sommella, EM and Licastro, D and Zhang, L and De Almeida Celio, F and Miller, EN and Merciai, F and Caponigro, V and Xin, W and Campiglia, P and Pizarro, TT and Chieppa, M and Cominelli, F}, title = {A missense mutation in Muc2 promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis.}, journal = {The Journal of clinical investigation}, volume = {136}, number = {1}, pages = {}, pmid = {41196658}, issn = {1558-8238}, support = {R37 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK055812/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Mutation, Missense ; Mice ; *Mucin-2/genetics/metabolism ; *Gastrointestinal Microbiome ; *Metabolome ; *Colitis-Associated Neoplasms/genetics/microbiology/metabolism/pathology ; *Colitis, Ulcerative/genetics/microbiology/metabolism/pathology ; *Colitis/genetics/microbiology/metabolism/pathology ; *Carcinogenesis/genetics/metabolism ; Fecal Microbiota Transplantation ; Humans ; Disease Models, Animal ; Female ; }, abstract = {Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, an ulcerative colitis-like (UC-like) model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie mice showed only mild colitis but no tumorigenesis. By comparison, when re-derived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct proinflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Using either SPF Winnie or WT (Bl/6) donors, fecal microbiota transplantation (FMT) into GF Winnie recipients demonstrated that, while colitis developed regardless of the donor, only FM from SPF Winnie donors resulted in CAC in recipient mice. Our studies present a relevant model of CAC, providing strong evidence that the microbiome plays a key role in its pathogenesis, thus challenging the concept of colon cancer as a strictly nontransmissible disease.}, }
@article {pmid41197688, year = {2026}, author = {Mela, V and Ortiz Samur, NS and Vijaya, AK and Gálvez, VJ and García-Martín, ML and Bandera, B and Martínez-Montoro, JI and Gómez-Pérez, AM and Moreno-Indias, I and Tinahones, FJ}, title = {Ketogenic diet is less effective in ameliorating depression and anxiety in obesity than Mediterranean diet: A pilot study for exploring the GUT-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {131}, number = {}, pages = {106167}, doi = {10.1016/j.bbi.2025.106167}, pmid = {41197688}, issn = {1090-2139}, mesh = {*Diet, Ketogenic/methods/psychology ; Pilot Projects ; *Diet, Mediterranean/psychology ; Humans ; Male ; Adult ; Female ; *Obesity/diet therapy/psychology/metabolism/complications ; Middle Aged ; *Depression/diet therapy/metabolism ; *Anxiety/diet therapy/metabolism ; Animals ; Gastrointestinal Microbiome/physiology ; Brain/metabolism ; Mice ; Aged ; Young Adult ; Adolescent ; Impulsive Behavior/physiology ; Brain-Gut Axis/physiology ; }, abstract = {Obesity is associated with depressive symptoms due to biological and psychological factors. Dietary interventions, including the Ketogenic (Keto) and Mediterranean (Med) diets, impact weight loss and mental health differently. While the Keto diet promotes rapid weight loss by increasing ketone body levels, its effects on mental health, particularly in individuals with obesity, remain unclear. This exploratory pilot study explores the impact of both diets on depression and impulsiveness, focusing on the gut-brain axis. Sixty-four participants (Body Mass Index 30-45 kg/m[2], ages 18-65) were randomly assigned to follow one of the two diets for three months. Due to attrition, 37 participants (Med n = 23; Keto n = 14) completed the study. Depression and impulsivity scores were evaluated before and after the intervention. Stool samples were collected for microbiota analysis, and faecal transplants were performed in healthy mice. Brain and serum metabolites in recipient mice were analysed using High-Resolution Magic Angle Spinning (HR-MAS) and Proton Nuclear Magnetic Resonance ([1]H NMR) spectroscopy. The Med diet showed greater improvement in depression scores compared to the Keto diet, while the latter was associated with reductions in impulsivity (urgency subscale). However, faecal transplants from the Keto group induced anxiety-like behaviours in recipient mice, which correlated with significant microbiota and metabolite changes. The Keto group exhibited increased levels of taurine, alanine, and betaine in the brain, and threonine levels were correlated with behavioural changes. These findings suggest that the Med diet offers more consistent short-term benefits related to depressive symptoms, while the Keto diet modulated impulsivity. The animal model findings highlighted the role of diet-induced microbiota changes and metabolite alterations in the gut-brain axis. Long-term studies in a larger population are needed to tailor dietary interventions, essential for optimizing mental and physical health in obesity.}, }
@article {pmid41199348, year = {2025}, author = {Ghozlane, A and Thirion, F and Plaza Oñate, F and Gauthier, F and Le Chatelier, E and Annamalé, A and Almeida, M and Ehrlich, SD and Pons, N}, title = {Accurate profiling of microbial communities for shotgun metagenomic sequencing with Meteor2.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {227}, pmid = {41199348}, issn = {2049-2618}, support = {ANR-11-DPBS-0001//Metagenopolis/ ; }, mesh = {*Metagenomics/methods ; Animals ; Mice ; Humans ; *Microbiota/genetics ; *Bacteria/genetics/classification ; *Metagenome ; *Gastrointestinal Microbiome/genetics ; *Software ; Computational Biology/methods ; }, abstract = {BACKGROUND: The characterization of complex microbial communities is a critical challenge in microbiome research, as it is essential for understanding the intricate relationships between microorganisms and their environments. Metagenomic profiling has advanced into a multifaceted approach, combining taxonomic, functional, and strain-level profiling (TFSP) of microbial communities. Here, we present Meteor2, a tool that leverages compact, environment-specific microbial gene catalogues to deliver comprehensive TFSP insights from metagenomic samples.<br><br>RESULTS: Meteor2 currently supports 10 ecosystems, gathering 63,494,365 microbial genes clustered into 11,653 metagenomic species pangenomes (MSPs). These genes are extensively annotated for KEGG orthology, carbohydrate-active enzymes (CAZymes) and antibiotic-resistant genes (ARGs). In benchmark tests, Meteor2 demonstrated strong performance in TFSP, particularly excelling in detecting low-abundance species. When applied to shallow-sequenced datasets, Meteor2 improved species detection sensitivity by at least 45% for both human and mouse gut microbiota simulations compared to MetaPhlAn4 or sylph. For functional profiling, Meteor2 improved abundance estimation accuracy by at least 35% compared to HUMAnN3 (based on Bray-Curtis dissimilarity). Additionally, Meteor2 tracked more strain pairs than StrainPhlAn, capturing an additional 9.8% on the human dataset and 19.4% on the mouse dataset. Furthermore, in its fast configuration, Meteor2 emerges as one of the fastest available tools for profiling, requiring only 2.3&#xa0;min for taxonomic analysis and 10&#xa0;min for strain-level analysis against the human microbial gene catalogue when processing 10&#xa0;M paired reads - operating within a modest 5&#xa0;GB RAM footprint. We further validated Meteor2 using a published faecal microbiota transplantation (FMT) dataset, demonstrating its ability to deliver an extensive and actionable metagenomic analysis. The unified database design also simplifies the integration of TFSP outputs, making it straightforward for researchers to interpret and compare results.<br><br>CONCLUSIONS: These results highlight Meteor2 as a robust and versatile tool for advancing microbiome research and applications. As an open-source, easy-to-install, and accurate analysis platform, Meteor2 is highly accessible to researchers, facilitating the exploration of complex microbial ecosystems.}, }
@article {pmid41199753, year = {2025}, author = {Zulfatim, HS and Afrina, V and d'Arqom, A and Sutantyo, QE and Amornsupak, K and Nualkaew, T}, title = {Anti-Inflammatory Drugs for Alcoholic Liver Disease: A Systematic Review on Survival and Adverse Events.}, journal = {International journal of hepatology}, volume = {2025}, number = {}, pages = {8535952}, pmid = {41199753}, issn = {2090-3448}, abstract = {AIM: Alcoholic liver disease (ALD) is a major global health burden, with alcoholic hepatitis (AH) and severe alcoholic hepatitis (SAH) contributing significantly to mortality. Inflammation plays a central role in disease progression, and various anti-inflammatory therapies, particularly corticosteroids, have been employed to improve survival. However, clinical outcomes across different treatments vary. This systematic review is aimed at evaluating the effectiveness of anti-inflammatory pharmacological therapies compared to corticosteroids in improving short-term survival at 1, 3, and 6 months and to assess the incidence of adverse events in patients with ALD.<br><br>METHODS: The review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, and Clarivate Web of Science using MeSH terms. Inclusion criteria consisted of full-text, open-access, English articles (2014-2024) that reported survival outcomes and adverse events in patients with ALD treated with corticosteroids versus alternative or adjunctive anti-inflammatory therapies. Studies lacking a corticosteroid comparator were excluded.<br><br>RESULTS: Nine randomized controlled trials (RCTs) involving patients with AH and SAH were included. The interventions compared to corticosteroids included pentoxifylline, anakinra, metadoxine, S-adenosylmethionine (SAMe), granulocyte colony-stimulating factor (G-CSF), rifaximin, and fecal microbiota transplantation (FMT) as monotherapies or combination regimens. Among anti-inflammatory therapies, combination therapy with corticosteroids and metadoxine significantly improves 3- and 6-month survival rates in patients with ALD. Similarly, corticosteroids combined with SAMe demonstrate efficacy in enhancing 1- and 6-month survival rates. Notably, the metadoxine-based combination regimen exhibited a superior safety profile, with fewer adverse events compared to other anti-inflammatory therapies evaluated in this review.<br><br>CONCLUSIONS: Even though corticosteroids remain the current standard of care for severe AH, this review suggests that certain combination therapies, particularly those involving metadoxine or SAMe, may offer some survival benefits. FMT also shows promise by potentially improving survival while maintaining a favorable safety profile. Among these, the metadoxine-based regimen has been explored as a promising therapeutic strategy in some contexts. However, these findings must be interpreted with caution. The evidence is limited by significant study heterogeneity and a lack of high-quality RCTs. These limitations underscore the critical need for well-powered, rigorous RCTs with standardized survival and safety outcomes.}, }
@article {pmid41201220, year = {2025}, author = {Wang, W and Li, J and Mu, L and Bai, Y and Zhu, M and Zhao, Y and Hu, S and Wang, J and Shao, P and Su, X}, title = {Vitamin K2 Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Mitochondrial Dysfunction Modulation via Gut Microbiota.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {5}, pages = {37275}, doi = {10.31083/IJVNR37275}, pmid = {41201220}, issn = {0300-9831}, support = {82103810//National Natural Science Foundation of China/ ; 4457475042JZ2300U0//Outstanding Young Director in Air Force Medical University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects ; Male ; *Vitamin K 2/pharmacology/administration &amp; dosage ; Liver/pathology/drug effects/metabolism ; *Fatty Liver/drug therapy ; *Mitochondria/drug effects ; Disease Models, Animal ; *Non-alcoholic Fatty Liver Disease/drug therapy ; Dysbiosis ; }, abstract = {INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. Meanwhile, the development of MASLD is related to dysbiosis of the gut microbiota (GM). Our previous studies have shown that Vitamin K2 (VK2) has considerable potential to ameliorate mitochondrial dysfunction in mice fed a high-fat diet (HFD); however, the mechanism through which VK2 improves mitochondrial function and mitigates MASLD remains unclear.<br><br>OBJECTIVE: This study aimed to elucidate the mechanism through which VK2 modulates MASLD.<br><br>METHODS: A total of 80 C57BL/6J mice (4-5 weeks old) were fed a HFD for 16 weeks to establish the MASLD animal model. Additionally, VK2 was administered at a dose of 120 mg/kg/day for the last 8 weeks; 30 mice were fed a normal diet for the entire 24-week period. Mice were randomly divided into groups according to different experimental protocols. Hematoxylin and Eosin (H&amp;E) staining, Oil Red O staining, and Cluster of Differentiation 11b (CD11b) immunofluorescence staining were used to detect liver histology and inflammatory cell infiltration in the mouse liver tissues. Moreover, 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation (FMT) were employed to investigate the microbiota-mediated anti-MASLD effects of VK2. Adeno-associated virus 9 (AAV9) was used to elucidate the mechanism through which VK2 regulates MASLD severity.<br><br>RESULTS: VK2 significantly reduced hepatic lipid (triacylglycerol (TG) and total cholesterol (TC)) levels, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HFD-fed mice (p < 0.05). VK2 also significantly suppressed inflammatory responses (p < 0.05), oxidative stress (p < 0.05), and improved mitochondrial dysfunction (p < 0.05) in a GM-dependent manner. Furthermore, VK2 restored the balance in the intestinal microbiota primarily through regulating Lactobacillus spp. abundance, and markedly alleviated MASLD via a GM-dependent manner. VK2 notably upregulated the expression of SIRT3 signaling pathway proteins (p < 0.05), thereby reducing MASLD-associated mitochondrial dysfunction (p < 0.05).<br><br>CONCLUSIONS: VK2 exerts promising therapeutic effects mainly through enhancing intestinal Lactobacillus abundance and ameliorating mitochondrial dysfunction.}, }
@article {pmid41202150, year = {2025}, author = {Champagne-Jorgensen, K and Gommerman, JL}, title = {Two of a kind, one with MS: Gut microbes tip the balance.}, journal = {Science immunology}, volume = {10}, number = {113}, pages = {eaed4910}, doi = {10.1126/sciimmunol.aed4910}, pmid = {41202150}, issn = {2470-9468}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; *Multiple Sclerosis/immunology/microbiology ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {An MS twin study links ileal Lachnospiraceae to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.}, }
@article {pmid41203044, year = {2025}, author = {Jagwani, S and Musumeci, L and Flores, L and Mackenzie, GG and Amiji, MM}, title = {Strategic modulation of the gastrointestinal microbiome to enhance pancreatic cancer immunotherapy.}, journal = {Drug discovery today}, volume = {30}, number = {12}, pages = {104528}, pmid = {41203044}, issn = {1878-5832}, support = {R01 CA269233/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Pancreatic Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Drug Delivery Systems ; }, abstract = {Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome-PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms - including nanoparticles, engineered bacteria, and stimuli-responsive systems - for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.}, }
@article {pmid41204332, year = {2025}, author = {Pala, B and Frank, G and Pennazzi, L and Di Renzo, L and Gualtieri, P and Tocci, G and Rubattu, S}, title = {The role of gut microbiota in hypertension-mediated organ damage (HMOD): a systematic review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1242}, pmid = {41204332}, issn = {1479-5876}, support = {PNRR-MAD-2022-12376295, CUP: F33C22001010006.//Seventh Generation Fund for Indigenous Peoples/ ; }, mesh = {Animals ; Humans ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Hypertension/microbiology/complications/pathology/physiopathology ; }, abstract = {Hypertension (HTN), a multifactorial condition and major modifiable risk factor for cardiovascular disease, has been increasingly linked to gut microbiota (GM) alterations, encouraging investigation into its potential role in the progression of hypertension-mediated organ damage (HMOD). This systematic review aims to evaluate the role of GM in HTN pathophysiology and its contribution to HMOD, with the aim of identifying potential microbiota-related targets for personalized therapeutic strategies. The study, registered in PROSPERO and conducted according to PRISMA guidelines, involved a comprehensive search of five databases up to January 2025, selecting human and complementary animal studies investigating the relationship between GM, HTN, and HMOD. While few studies directly assessed HMOD, emerging evidence suggests a protective role of GM and its metabolites against cardiovascular, cerebral and renal injury. Heterogeneity in design, small sample sizes and a lack of standardized methodologies limited comparability therefore we did not perform a meta-analysis. In conclusion, GM dysbiosis and its metabolites are increasingly recognized as key providers to HMOD, offering encouraging targets for future preventive and therapeutic strategies. A substantial proportion of the available evidence originates from preclinical animal studies. While these findings provide valuable mechanistic insights, further longitudinal and interventional research in human populations is warranted to confirm their translational relevance.}, }
@article {pmid41205107, year = {2026}, author = {Caron, B and Sequier, L and Dignass, A and Ghosh, S and Hart, A and Jairath, V and Kobayashi, T and Kotze, PG and Lakatos, PL and Louis, E and Magro, F and Sebastian, S and Solitano, V and Sidhu, S and Danese, S and Peyrin-Biroulet, L}, title = {Management of Patients with Ulcerative Proctitis: A Global Survey.}, journal = {Digestive diseases and sciences}, volume = {71}, number = {4}, pages = {1416-1424}, pmid = {41205107}, issn = {1573-2568}, mesh = {Humans ; *Proctitis/diagnosis/drug therapy/therapy ; *Colitis, Ulcerative/drug therapy/diagnosis/therapy ; *Practice Patterns, Physicians'/trends/statistics &amp; numerical data ; Male ; Female ; Biological Products/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Surveys and Questionnaires ; Adult ; Middle Aged ; }, abstract = {UNLABELLED: BACKGROUND AND AIM: Ulcerative proctitis affects approximately 30% of patients with ulcerative colitis. Disease control is essential to maintain quality of life and to prevent disability and disease progression. The aim of this study was to investigate current practice on isolated proctitis management across the globe.<br><br>METHODS: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between January and February 2025.<br><br>RESULTS: The survey included 460 physicians from 66 countries. Most participants (87.9%) assessed clinical activity of isolated proctitis within 3&#xa0;months of treatment initiation, 75.9% used fecal calprotectin, and 67.1% used C-reactive protein to measure disease activity. Endoscopic assessment was performed 3 to 6&#xa0;months (34.2%) or 6 to 12&#xa0;months (48.4%) after treatment induction. In this survey, 49% of participants were more reluctant to begin an advanced therapy in patients with isolated proctitis compared to pancolitis or left-sided colitis. About two-thirds of participants were less likely to use biologics in combination with immunosuppressants in isolated proctitis compared to left-sided or pancolitis. Anti-TNF (tumor necrosis factor) was the preferred choice in first-line advanced therapy after failing conventional treatment (48.4%).<br><br>CONCLUSION: This study highlighted differences in management of isolated proctitis compared to left-sided colitis or pancolitis. This is likely explained by the fact that isolated proctitis patients were historically excluded from clinical trials; therefore, management relied on extrapolation of data from studies on more extensive disease.}, }
@article {pmid41206012, year = {2026}, author = {Tan, EK and Wang, JDJ and Pettersson, S and Wang, Q and Takahashi, R and Poewe, W and Jankovic, J and Rascol, O}, title = {Faecal microbiota transplant for Parkinson's disease: promises and future directions.}, journal = {Brain : a journal of neurology}, volume = {149}, number = {1}, pages = {59-70}, doi = {10.1093/brain/awaf419}, pmid = {41206012}, issn = {1460-2156}, support = {//National Medical Research council/ ; }, mesh = {Humans ; *Parkinson Disease/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/trends ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/therapy ; }, abstract = {There is considerable evidence linking alterations in gut microbiome composition with Parkinson's disease, leading to several recent randomized controlled faecal microbiota transplantation (FMT) trials in patients with Parkinson's disease targeting gut dysbiosis with the aim to modulate the gut-brain axis. Some FMT trials have observed motor and non-motor symptoms improvements in patients with Parkinson's disease, possibly through microbiota linked enhanced short-chain fatty acid or other metabolite effects and reduced systemic inflammation. While the findings are exciting and can potentially open a new treatment paradigm, crital questions on donor selection, the optimal screening and selection of the donor microbiome, delivery routes and the timing and frequency of transplantation need to be addressed. We suggest that future FMT trials should incorporate blood, metabolites, urine and functional neuroimaging biological markers and to control for dietary, lifestyle comorbidities, medication intake and/or other potential variables to ensure optimal evaluation of interactions between the gut microbes and brain outcomes prospectively over a longer time frame.}, }
@article {pmid41206121, year = {2026}, author = {Dong, PY and Chen, Y and Li, L and Zhai, CL and Yan, YC and Bai, Y and Li, YY and Dong, Y and Liu, J and Zhang, M and Liu, YH and Zhang, XF}, title = {Deoxynivalenol disrupts male mice reproduction through gut-testis axis dysregulation and metabolic alterations.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {209}, number = {1}, pages = {}, doi = {10.1093/toxsci/kfaf155}, pmid = {41206121}, issn = {1096-0929}, support = {2024LZGC019, 2022LZGC012//Key Research and Development Program of Shandong Province in China/ ; 1120043//High Level Talents Research Fund project of Qingdao Agricultural University in China to X.-F.Z./ ; }, mesh = {Animals ; Male ; *Trichothecenes/toxicity ; *Testis/drug effects/metabolism/pathology ; *Gastrointestinal Microbiome/drug effects ; *Reproduction/drug effects ; Mice ; Mice, Inbred C57BL ; Dysbiosis/chemically induced ; *Blood-Testis Barrier/drug effects/metabolism ; Connexin 43/metabolism/genetics ; Occludin ; }, abstract = {The mycotoxin deoxynivalenol (DON) is a widespread contaminant that threatens male reproductive health, though the systemic mechanisms involving the gut-testis axis remain incompletely understood. We employed a multi-omics approach-integrating transcriptomics, 16S rRNA sequencing, and serum metabolomics-in a mouse model to investigate these mechanisms. Oral exposure to DON (2 mg/kg/day for 2 weeks) induced testicular damage and disrupted the blood-testis barrier, marked by the downregulation of Occludin and GJA1, alongside the suppression of steroidogenesis-related genes and proteins, including StAR and CYP17A1. Concurrently, DON triggered gut microbiota dysbiosis, characterized by an increased abundance of Desulfovibrio and a decline in beneficial bacteria. Serum metabolomics further identified a significant depletion of key fatty acids and the cholesterol precursor 5-Alpha-Cholestanol. Crucially, fecal microbiota transplantation from DON-treated mice reproduced testicular damage and suppressed steroidogenesis in recipient animals, directly establishing the causal role of gut microbiota in DON-induced reproductive toxicity. These findings collectively demonstrate that DON impairs male reproductive function by inducing gut microbiota dysbiosis and associated metabolic alterations. This work advances our understanding of the gut-testis axis in toxicology and provides mechanistic insights for mitigating mycotoxin-induced reproductive dysfunction.}, }
@article {pmid41206275, year = {2026}, author = {Hattoufi, K and Raji, F and Tligui, H and Benlhachemi, S and Heikel, J and Aguenaou, H and Barkat, A}, title = {Association of gut microbiota and type of feeding: Molecular analysis of a cohort of preterm moroccan newborns.}, journal = {Pediatrics and neonatology}, volume = {67}, number = {3}, pages = {282-287}, doi = {10.1016/j.pedneo.2025.04.008}, pmid = {41206275}, issn = {2212-1692}, mesh = {Humans ; Infant, Newborn ; *Gastrointestinal Microbiome ; Prospective Studies ; *Infant, Premature ; Female ; Milk, Human/microbiology ; *Breast Feeding ; Male ; Morocco ; Infant Formula ; Enteral Nutrition ; Feces/microbiology ; }, abstract = {BACKGROUND: We assessed the newborns' intestinal microbiota during the first three weeks of life using molecular biology techniques to understand colonization patterns according to feeding type.<br><br>METHODS: We conducted a prospective, observational descriptive study at the National Reference Centre for Neonatology and Nutrition, in collaboration with the research laboratory of the Children's Hospital at the University Hospital Centre Ibn Sina in Rabat. Stool samples were collected from 29 preterm newborns upon admission to the neonatal unit and subsequently twice weekly over a three-week period. Microbial composition was analyzed using real-time polymerase chain reaction (RT-qPCR), targeting four phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.<br><br>RESULTS: The gestational age of the included preterm infants ranged from 28 to 36 weeks of amenorrhea. Enteral nutrition was initiated between the second and sixth days after birth. None of the infants was nursed immediately after birth or during their hospitalization. However, in 79&#xa0;% of cases, breast milk was collected at home for later use in feeding the newborns, and among these, 21&#xa0;% received more than 50&#xa0;% of the collected breast milk. Over the first two weeks of life, Lactobacillus spp. was only detected in infants nursed by both breast milk and formula milk. Enterococcus spp. was present in all breastfed infants. Clostridium difficile and Clostridium perfringens were found in 83&#xa0;% of formula-fed newborns in the second week of life and in all newborns by the end of the third week.<br><br>CONCLUSION: Promoting breastfeeding whenever possible is crucial for fostering a healthy gut microbiota. When breastfeeding is not feasible, incorporating infant formulas supplemented with probiotics and/or prebiotics can help establish a microbiota similar to that of breastfed infants. Additional preventive strategies, such as vaginal or fecal microbiota transplantation, may be considered, particularly for infants born via caesarean section.}, }
@article {pmid41206510, year = {2025}, author = {Fang, J and Fang, J}, title = {A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {31}, number = {}, pages = {e949286}, pmid = {41206510}, issn = {1643-3750}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Hepatic Encephalopathy/therapy/microbiology ; Gastrointestinal Microbiome/physiology ; Dysbiosis/therapy ; }, abstract = {Hepatic encephalopathy (HE) results from a debilitating complication of liver cirrhosis and acute liver failure, characterized by neuropsychiatric abnormalities ranging broadly from mild cognitive impairment to respiratory failure to coma. The pathogenesis of HE is multifactorial, with gut-derived toxins, particularly ammonia, playing a central role. Recent advances in understanding the gut-liver-brain axis have revealed the importance of gut microbiota and dysbiosis in the development and progression of HE. Fecal microbiota transplantation (FMT), a clinical procedure that is performed to transfer fecal microbiota from a healthy donor to a patient with HE (recipient), has emerged as a promising therapeutic strategy for modulating gut microbiota and ameliorating HE. FMT facilitates the restoration of gut microbiota composition with increased microbial alpha diversity, reestablishment of the balance between beneficial and pathogenic bacteria, reduction in the production of gut-derived toxins, and improvement of intestinal barrier function. It also modulates immune and inflammatory responses, alleviating hepatocyte and biliary injury. FMT has also demonstrated efficacy in improving cognitive function and reducing hospitalizations in HE patients and can maintain a stable donor-like microbiota profile for up to 12 months post-transplantation. FMT is generally well-tolerated, with most adverse events reported to be mild and transient, providing a desirable option for HE treatment. This review provides a comprehensive overview of the current understanding of the role of gut microbiota in the pathogenesis of HE, the mechanisms underlying the therapeutic effects of FMT, and the clinical evidence supporting its use in HE. We will also discuss the limitations, challenges, and future prospects for FMT in the treatment of HE.}, }
@article {pmid41207269, year = {2025}, author = {Xu, M and Fu, Q and Liu, J and Chen, J and Zhai, X and Wang, C and Xu, W and Li, L and Wang, K and Si, H}, title = {Shouhui Tongbian capsule promotes calcium absorption by regulating gut microbiota and protects against osteoporosis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157520}, doi = {10.1016/j.phymed.2025.157520}, pmid = {41207269}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Female ; Mice ; *Calcium/metabolism ; *Osteoporosis, Postmenopausal/prevention &amp; control/drug therapy ; Mice, Inbred C57BL ; Osteogenesis/drug effects ; Ovariectomy ; Fecal Microbiota Transplantation ; Osteoporosis/prevention &amp; control ; Capsules ; }, abstract = {BACKGROUND: Postmenopausal osteoporosis (OP) is a global health problem whose occurrence is strongly associated with intestinal flora dysbiosis. Shouhui Tongbian Capsule (SH) regulates gut microbiota for constipation/obesity, but its role, ability to counter calcium's side effects, and OP-related mechanism remain unclear.<br><br>PURPOSE: This study aimed to investigate the therapeutic effect of SH on OP and elucidate its mechanism in improving bone metabolism via gut microbiota regulation.<br><br>METHODS: Ovariectomized (OVX) mice received SH and/or calcium supplements. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and functional annotations were performed using the Kyoto Encyclopedia of Genes and Genomes database. Gut barrier function was assessed through histology, tight junction protein expression, and serum biomarkers. Micro-CT was used to quantify the bone microstructure. Fecal microbiota transplantation (FMT) validated the microbiota-dependent effects. Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed by calcium deposition staining and western blotting.<br><br>RESULTS: SH restored gut barrier integrity, reduced systemic inflammation, and alleviated constipation. SH reshaped the gut microbiota composition, enriched Lactobacillus, Lachnospiraceae, and Akkermansia, and strengthened metabolic pathways related to mineral absorption. SH synergized with calcium supplementation to significantly enhance bone mass in OVX mice. FMT experiments recapitulated the osteoprotective effects of SH, with calcium supplementation being a necessary factor in this process. SH potentiated the osteogenic capacity of BMSCs while having no effect on osteoclast differentiation.<br><br>CONCLUSION: SH ameliorates OP via the "microbiota-mineral absorption-osteogenesis" network by alleviating calcium-induced intestinal dysbiosis and promoting bone formation. This study is the first to confirm SH's synergistic regulation of gut microbiota and calcium metabolism against OP, offering novel insights for gut-bone axis-based OP therapies and highlighting traditional Chinese medicine's innovative potential in metabolic bone diseases.}, }
@article {pmid41208121, year = {2026}, author = {Calhoun, AC and Shosanya, T and Long, BK and Rehberger, JK and Sadd, BM}, title = {Host-associated beneficial gut microbiota boosts induced immunity and limits immune deployment costs in bumblebees.}, journal = {The Journal of animal ecology}, volume = {95}, number = {1}, pages = {217-229}, pmid = {41208121}, issn = {1365-2656}, support = {F22AP02271//U.S. Fish and Wildlife Service/ ; R15GM12968/NH/NIH HHS/United States ; R15GM12968/NH/NIH HHS/United States ; }, mesh = {Animals ; Bees/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; }, abstract = {Ecological immunology posits that variation in host resistance to infection may be attributed partly to the ecological and evolutionary costs of immunity. While the deployment of immune defence is necessary to combat pathogenic infection, hosts pay energetic and other costs for activation. Host-associated beneficial microbiota have been shown to affect multiple host traits, including immunity, but how interactions with these microbial communities may mitigate the costs of immune activation remains an open question. For apid bees, including eusocial bumblebees, core members of the adult gut microbiota contribute to a variety of fitness-relevant traits and provide a key ecological and evolutionary relationship contributing to ecological success. Here we test the hypothesis that the host-associated microbiota provides benefits to bumblebee immunity, including the mitigation of the costs associated with inducible immune responses. Freshly emerged germ-free adult workers were supplemented with their native microbiota via experimental faecal transplants from nestmates or kept deprived of their native microbiota inoculum. We assessed functional measures of induced immunity and assessed the costs of non-pathogenic immune activation for survival. In support of our hypothesis, we find that microbiota supplementation strengthened functional antibacterial immunity. Moreover, although we observed a cost of immune activation for survival, the cost was much greater for bees deprived of their native gut microbiota compared to those supplemented. Thus, we provide evidence that in addition to other roles, the microbiota mitigates costs of immune deployment. This demonstrates a key role for host-associated microbiota in the realization of induced immune defence, and contributes more broadly to our understanding of microbiota-immune interactions in the context of ecological immunology.}, }
@article {pmid41208872, year = {2025}, author = {Sun, J and Chen, J and Shen, Y and Yao, X and Sun, H and Chen, B and Feng, J}, title = {Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1689522}, pmid = {41208872}, issn = {1663-9812}, abstract = {Diabetes mellitus (DM), a globally prevalent metabolic disorder, poses a significant public health threat due to its systemic complications. Recent studies have increasingly recognized the lung as a target organ in diabetic pathology. However, owing to the respiratory system's complex physiology, the mechanisms underlying DM-associated lung injury remain poorly understood and require further investigation. This review systematically elucidates the multifaceted effects of DM-induced metabolic disturbances on the lung, with a focus on four key pathophysiological axes triggered by hyperglycemic homeostasis, including chronic inflammation, oxidative stress imbalance, endocrine network disruption, and intestinal dysbiosis. Building upon the "metabolism-microbiota-immune" axis framework, this study demonstrates that: persistent hyperglycemia induces pulmonary tissue damage and immune microenvironment disruption through metabolite accumulation and mitochondrial dysfunction; DM-associated intestinal dysbiosis amplifies pulmonary inflammation via the gut-lung axis, mediated by metabolic reprogramming and immune cell trafficking; and metabolic aberration-driven dysregulation of innate/adaptive immunity serves as the pivotal mediator for progressive lung injury. Building on this mechanistic framework, we discuss emerging therapeutic avenues that target metabolic reprogramming, modulation of the gut microbiota, and restoration of immune homeostasis. Promising strategies include repurposed antidiabetic drugs (e.g., SGLT-2 inhibitors, GLP-1 receptor agonists), microbiome-targeted therapies (e.g., fecal microbiota transplantation), and novel immunomodulatory agents. These therapies are offering a new shift towards multi-target treatments for diabetic pulmonary complications.}, }
@article {pmid41211636, year = {2026}, author = {Wu, L and Zhang, Q and Tang, Z and Li, Y and Wu, T and Chen, L and Tan, C and Zhang, L and Ji, X and Zhang, S and Wu, Y and Bozec, A and Zaiss, MM and Luo, Y}, title = {Gut Microbiota-Derived Tryptophan Indole Metabolites Ameliorate Collagen-Induced Arthritis in Mice Via Aryl Hydrocarbon Receptor Activation.}, journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)}, volume = {78}, number = {3}, pages = {613-629}, doi = {10.1002/art.43430}, pmid = {41211636}, issn = {2326-5205}, support = {AB25069068//Guangxi Key Research and Development Program/ ; 2022SCUH0020//Sichuan University from 0 to 1 Innovation Project/ ; 2023YFH0081//Sichuan Province International Cooperative Foundation/ ; 2023NSFSC1702//Science and Technology Department of Sichuan Province/ ; 82271828//National Natural Science Foundation of China/ ; 82302049//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism ; *Tryptophan/metabolism ; *Arthritis, Experimental/metabolism/immunology ; *Gastrointestinal Microbiome/physiology ; Humans ; Mice ; *Arthritis, Rheumatoid/metabolism ; *Indoleacetic Acids/pharmacology/metabolism ; *Indoles/metabolism ; Fecal Microbiota Transplantation ; T-Lymphocytes, Regulatory/metabolism/immunology ; Male ; Female ; Middle Aged ; Mice, Inbred DBA ; Zonula Occludens-1 Protein/metabolism ; }, abstract = {OBJECTIVE: Our study's objective is to investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).<br><br>METHODS: We employed metabolomics to profile metabolites in 53 individuals at high risk for RA (PreRA), 30 patients with established RA, and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluorescence staining, and Western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.<br><br>RESULTS: Dysregulated tryptophan metabolism exists in individuals with RA and PreRA, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator-xenobiotic response element signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.<br><br>CONCLUSION: These findings indicate that tryptophan indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.}, }
@article {pmid41211649, year = {2026}, author = {Zhao, QK and Ning, YX and Xu, TC and Zhao, ZA and Pei, YF and Niu, JY and Li, XD and Chen, HS}, title = {Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke.}, journal = {Journal of the American Heart Association}, volume = {15}, number = {1}, pages = {e045929}, pmid = {41211649}, issn = {2047-9980}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Electroacupuncture/methods ; *Vagus Nerve/physiopathology/metabolism ; Rats ; Male ; Disease Models, Animal ; Rats, Sprague-Dawley ; *Infarction, Middle Cerebral Artery/therapy/microbiology ; *Ischemic Stroke/therapy/microbiology/physiopathology/metabolism ; Brain/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Emerging evidence implicates gut microbiota dysbiosis in exacerbating stroke pathogenesis via the gut-brain axis, suggesting novel therapeutic targets. While electroacupuncture (EA) demonstrates anti-inflammatory effects through vagus nerve activation, its neuroprotective mechanisms via vagus nerve-microbiota crosstalk remain unexplored.<br><br>METHODS: Rats with middle cerebral artery occlusion received daily ST36 (Acupoint Zusanli) EA for 1 to 7&#x2009;days postischemia. Subdiaphragmatic vagotomy and fecal microbiota transplant were implemented to validate pathway specificity. Multimodal assessments included longitudinal neurological scoring, infarct volume, systemic/neuroinflammatory profiling (enzyme-linked immunosorbent assay, immunohistochemistry), intestinal fucosylation dynamics (quantitative polymerase chain reaction, lectin staining), and 16S ribosomal RNA sequencing of gut microbiota.<br><br>RESULTS: EA significantly improved neurological outcomes and reduced infarct volumes at 3 to 7&#x2009;days after middle cerebral artery occlusion (versus controls), which was abolished by vagotomy. Mechanistically, EA restored gut barrier integrity through vagus-dependent upregulation of fucosyltransferase 2 (Fut2)-driven epithelial &#x3b1;1,2-fucosylation, enhancing mucin 2+ goblet cell density and tight junction protein expression (ZO-1/occludin/claudin-1). Concurrent microbiota shifts included Lactobacillales/Bacteroidales enrichment (linear discriminant analysis >4.0) and pathobiont suppression, which was reversed by vagotomy. Crucially, fecal microbiota transplant from EA-treated donors replicated neuroprotection in germ-free recipients, achieving 33% infarct reduction and 30% survival improvement (P=0.012), whereas fecal microbiota transplant from vagotomized donors showed no therapeutic benefits.<br><br>CONCLUSIONS: EA at ST36 produced neuroprotection through activating vagal efferent pathways to orchestrate intestinal mucosal repair via Fut2-mediated fucosylation, which reshape microbial ecosystems and attenuate neuroinflammation. These findings establish a previously unrecognized vagus nerve-gut-brain axis mechanism for stroke recovery, positioning microbiota-directed neuromodulation by EA as a translatable therapeutic strategy.}, }
@article {pmid41212912, year = {2026}, author = {Zhao, C and Ming, S and Zhang, J and Huang, T and Du, Y and Liu, J and Zong, S}, title = {Alleviative Effect of Stropharia rugosoannulata Exopolysaccharide on d-Galactose-Induced Gut Inflammation and Oxidative Stress by Modulating Gut Microbiota.}, journal = {Chemistry &amp; biodiversity}, volume = {23}, number = {1}, pages = {e02918}, doi = {10.1002/cbdv.202502918}, pmid = {41212912}, issn = {1612-1880}, support = {137012023//Yangzhou University/ ; BY20221437//Joint Project of Industry-University-Research of Jiangsu Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Galactose/pharmacology/antagonists &amp; inhibitors ; Mice ; *Oxidative Stress/drug effects ; *Inflammation/drug therapy/chemically induced/metabolism ; Male ; *Polysaccharides/pharmacology/chemistry/isolation &amp; purification ; Cytokines/metabolism ; Mice, Inbred C57BL ; }, abstract = {The exopolysaccharide SREP-1, purified from the fermentation broth of Stropharia rugosoannulata, exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP-1 was investigated using a d-galactose-induced aging mouse model. SREP-1 administration reversed D-galactose-induced body weight loss and colon damage, as evidenced by improved histopathology. SREP-1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH-Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and elevated IL-10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP-1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP-1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium, Akkermansia, Lactobacillus, and Bacteroides), and decreased harmful bacteria (e.g., Escherichia-Shigella and Collinsella). Furthermore, short-chain fatty acids (SCFAs) levels were elevated in the SREP-1 group, which might regulate GPCRs/NF-κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP-1 to alleviate aging-related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.}, }
@article {pmid41214728, year = {2025}, author = {Tang, X and You, X}, title = {Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {86}, pmid = {41214728}, issn = {1757-4749}, abstract = {Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease. Current therapeutic options are limited, with some patients responding poorly to first-line treatment with ursodeoxycholic acid. However, second-line drugs are difficult to develop. There are no drugs available to treat liver dysfunction. Currently, the etiology of PBC is unknown, and the intestinal flora affects the liver through the gut‒liver axis. The hypothesis of intestinal dysbiosis has gradually been accepted and involves mechanisms such as leaky gut, abnormal bile acids metabolism, and dysregulated immune tolerance. We found that gut microbiota-targeted therapy, including antibiotics, dietary regulation, probiotic supplementation, and fecal microbiota transplantation, can effectively improve liver function, remodel the intestinal microbiota, and alleviate symptom. However, this therapy has limitations, such as large individual differences and unknown long-term efficacy and safety. Large-scale and long-term clinical studies are expected to promote the broad application of gut microbiota-targeted therapy in the clinic.}, }
@article {pmid41216880, year = {2025}, author = {Gu, C and Xu, R and Yin, B and Wu, R and Wei, Y and Wang, D and Wei, W}, title = {Sex-Specific Involvement of Gut Microbiota in Behavioral and Endocrine Responses to Chronic Predator Odor in Brandt's Voles.}, journal = {Integrative zoology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1749-4877.13014}, pmid = {41216880}, issn = {1749-4877}, support = {32401290//National Natural Science Foundation of China/ ; 31770422//National Natural Science Foundation of China/ ; //the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Predator cues have profound impacts on the behavior and physiology of prey animals. However, the mechanisms underlying stress responses induced by chronic exposure to predator cues in mammals, particularly the role of the gut microbiota, remain insufficiently understood. This study investigated how gut microbiota contributes to behavioral and physiological responses in Brandt's voles (Lasiopodomys brandtii) under chronic predator odor exposure. Adult voles were repeatedly exposed to cat feces odor (CO) for 18 days (1 h/day), followed by behavioral tests to assess anti-predator and anxiety-like behaviors, hormonal measurements to evaluate basal hypothalamic-pituitary-adrenal (HPA) axis activity, and 16S rRNA sequencing to analyze gut microbiota composition. The results showed that repeated CO exposure increased anxiety-like behaviors and basal HPA axis activity in both sexes. However, anti-predator behaviors exhibited sex-specific responses: Males were habituated to repeated CO exposure by reducing freezing and alerting behaviors, whereas females consistently displayed concealing strategies, reflecting different adaptive strategies to prolonged predator threats. While CO exposure did not alter the α-diversity of gut microbiota, it significantly affected the β-diversity in females, including a reduction in the relative abundance of Treponema and Quinella. Cecal microbiota transplantation from female CO-exposed voles to naive recipients increased anxiety-like behaviors and basal HPA levels but did not alter anti-predator behaviors in the recipients. In contrast, male recipients showed no significant behavioral or physiological changes. These findings suggest that gut microbiota is involved in regulating anxiety-like behavior and HPA axis activity in female voles but has a limited regulating role in male voles.}, }
@article {pmid41217998, year = {2025}, author = {Wei, Q and Rui, M and Wang, Y and Ng, SC and You, JHS}, title = {Cost-Effectiveness Analysis of Fecal Microbiota Transplantation for Patients with Irritable Bowel Syndrome.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-13}, pmid = {41217998}, issn = {1421-9867}, abstract = {INTRODUCTION: Studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) for treatment of irritable bowel syndrome (IBS). This study aimed to evaluate the cost-effectiveness of FMT versus standard drug treatment for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.<br><br>METHODS: Two 1-year Markov models were developed to examine the outcomes of FMT versus standard drug treatment in patients with constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D). The primary model outcomes included direct medical cost and quality-adjusted life-years (QALYs) gained. Model inputs were obtained from literature and public data. Sensitivity analyses were performed to examine the robustness of model results.<br><br>RESULTS: In the base-case analysis, FMT gained higher QALYs (by 0.0159 QALYs for IBS-C and 0.0166 QALYs for IBS-D) with cost savings (USD 7,835 for IBS-C and USD 9,015 for IBS-D) when compared to standard drug treatment. Key influential parameters identified by one-way sensitivity analysis were response probabilities of FMT and first-line treatment, the utility values of therapeutic response and nonresponse, and FMT cost. The probabilities of FMT to be accepted as the preferred strategy at a willingness-to-pay threshold of USD 50,000/QALY were 99.86% and 99.89% for IBS-C and IBS-D, respectively.<br><br>CONCLUSION: FMT appears to be cost-effective for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.}, }
@article {pmid41219653, year = {2025}, author = {Lamba, JK and Tandon, C and Tandon, S}, title = {Gut Microbiota and Chronic Kidney Disease: A Complex Interplay with Implications for Diagnosis and Treatment.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41219653}, issn = {1867-1314}, abstract = {Chronic kidney disease (CKD) progresses over the years with a steady loss of renal function, often culminating in renal failure. While diabetes and hypertension are the major drivers, the exact underlying molecular mechanism for CKD remains only partially understood. Emerging research has revealed a new paradigm, linking microbiota imbalance or dysbiosis with CKD. Dysbiosis leads to the development of uremic toxins, which aggravate kidney damage, inflammation, and metabolic disruptions that accelerate disease progression. This review explores the complex interactions between dysbiosis, uremic toxins, and the major risk factors, namely, diabetes and hypertension. Microbiome-targeted interventions, such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), are discussed with an emphasis on their therapeutic relevance in influencing renal health. Additionally, the potential of genetic engineering, particularly CRISPR-based systems, to develop 'smart bacteria' designed to restore gut health is also examined. Future perspectives highlight the need for personalized therapies targeting the gut-kidney axis. Incorporating microbiome modulation into standard CKD treatments holds the potential to slow disease progression, enhance recovery, and improve the quality of life for patients.}, }
@article {pmid41219783, year = {2025}, author = {Sami, A and Ashraf, R and Nisar, S and Mustehsan, ZH and Javed, MA and Ozsahin, DU and Waheed, Y}, title = {A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence.}, journal = {Journal of health, population, and nutrition}, volume = {44}, number = {1}, pages = {394}, pmid = {41219783}, issn = {2072-1315}, mesh = {Humans ; *Precision Medicine/methods ; *Artificial Intelligence ; *Hypertension/genetics/therapy/microbiology ; *Epigenesis, Genetic ; Epigenomics ; Microbiota ; Gastrointestinal Microbiome ; }, abstract = {Hypertension (HTN) impacts approximately 1.28 billion individuals globally and poses a great burden of disease. The objectives of this study are to explore the role of genetics, epigenetics, microbiome, and artificial intelligence (AI) in the management of HTN. A thorough literature search was conducted across various databases including PubMed, Google Scholar, Web of Science (WoS), and Medline to retrieve articles related to the role of genetics, epigenetics, microbiome, and AI in the precision medicine of HTN. Genes-including ACE, NOS3, ADD1, CYP11B2, NPPA, and NPPB-have a profound impact on blood pressure (BP) regulation in our body and polymorphism in these key genes can lead to HTN. Up or down-regulation of genes by epigenetic factors such as miRNA-155, miRNA-210, and miRNA-122 can significantly contribute to the development of HTN. These genetic and epigenetic factors can also be used as specific targets for gene editing and gene therapy for long-term management of HTN. However, the implementation of these techniques has not been possible in clinical settings due to lack of human studies and safety concerns related to unpredictable DNA alterations, nucleotide deletions, and loss of allele-specific chromosomes. Modulation of gut microbiome through oral supplements, fecal microbiota transplant (FMT), and dietary interventions has emerged as one the most effective and safe techniques for managing HTN in human models. AI-based cutting-edge models have helped curate personalized diet plans based on an individual's unique microbiome, genomic information, and physiological conditions leading to a reduction in BMI, fat, BP, and heart rate while improving overall cardiac health and gut microbial diversity. Despite the significant advantages offered by AI-based medicine, ethical concerns-related to data privacy, bias, and discrimination-and ineffective models have led to limited integration of AI in precision medicine of HTN. The integration of genetics, epigenetics, microbiome, and AI-based models can play a key role in improving the current landscape of precision medicine of HTN. These cutting-edge techniques can lead to a shift from the current one-size-fits all approach to more personalized treatment plan however further research in human models is needed to determine the safety and true efficacy of these techniques. Additionally, new AI-models need to be developed that address ethical concerns and are effective in real-world clinical settings.}, }
@article {pmid41220843, year = {2025}, author = {Kwon, K and Kim, M and Jung, Y and Yoon, MY and Lee, JY and Yoon, SS and Rho, M and Chung, YW and Ryu, JH}, title = {Intestinal Dysbiosis Caused by Epithelial Fabp6 Gene Disruption Exacerbates Gut Inflammatory Disease.}, journal = {Immune network}, volume = {25}, number = {5}, pages = {e35}, pmid = {41220843}, issn = {1598-2629}, abstract = {Ileal lipid binding protein (Ilbp), encoded by Fabp6 gene, plays a critical role in intracellular transport of bile acids (BAs) from apical to basolateral side of ileal enterocytes, maintaining BA homeostasis within enterohepatic circulation. However, pathophysiological consequences of Ilbp deficiency remain largely unexplored. Here, we demonstrate that disruption of BA balance, caused by intestinal epithelial cell (IEC)-specific Fabp6 gene knockout (Fabp6 [ΔIEC]), exacerbates dextran sulfate sodium (DSS)-induced gut inflammation. Fecal microbiota transplantation from Fabp6 [ΔIEC] mice to germ free recipient mice replicated the adverse effects observed in Fabp6 [ΔIEC] mice, which were mitigated when these mice were co-housed with control (Fabp6 [f/f]) mice. Metagenomic analysis identified Ligilactobacillus murinus as a primarily diminished strain in Fabp6 [ΔIEC] mice. Oral administration of L. murinus isolated from feces of Fabp6 [f/f] mice ameliorated DSS-induced colitis in Fabp6 [ΔIEC] mice by restoring epithelial barrier integrity and lowering pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. Furthermore, daily administration of taurodeoxycholic acid-one of the BAs reduced in Fabp6 [ΔIEC] mice and that promotes the growth of L. murinus in an in vitro growth assay-also exhibited a protective effect against DSS-induced colitis through a similar mechanism. These findings suggest that deficiency of specific BAs due to epithelial Fabp6 deletion leads to gut dysbiosis, predisposing the host to inflammatory disease.}, }
@article {pmid41222715, year = {2025}, author = {Almutawif, YA and Khan, NU}, title = {Gut microbiome dysbiosis and antimicrobial resistance in the Middle East: a converging public health crisis in conflict and fragile settings.}, journal = {Archives of microbiology}, volume = {208}, number = {1}, pages = {15}, pmid = {41222715}, issn = {1432-072X}, abstract = {The Middle East is confronting a converging public health crisis as gut microbiome dysbiosis and antimicrobial resistance (AMR) amplify in conflict and fragile settings, driven by war, displacement, and systemic healthcare collapse. This review examines the bidirectional relationship between disrupted gut microbiota and escalating AMR, particularly among vulnerable refugee populations and war-affected communities. Key findings reveal alarming resistance rates in ESKAPE pathogens (e.g., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp), exacerbated by unregulated antibiotic use, malnutrition, and poor sanitation. Dysbiosis fosters AMR through loss of colonization resistance and horizontal gene transfer, while conflict-related healthcare breakdowns—such as empiric antibiotic overuse and absent diagnostics—accelerate resistance spread. Refugee camps, with overcrowding and contaminated water, emerge as critical AMR hotspots. Urgent interventions are needed, including microbiome restoration therapies (e.g., probiotics and faecal microbiota transplantation (FMT), rapid diagnostic tools, and integrated One Health surveillance. Moreover, the increasing trend of AMR is further amplified by the COVID-19 pandemic, which led to widespread antibiotic use and disrupted healthcare services. Review emphasises the importance of regional policy coordination, targeted humanitarian aid focused on microbiome health, and global advocacy to mitigate this crisis, which poses a threat to both local and international health security. Without action, the intersection of dysbiosis and AMR will deepen health inequities in conflict zones, with far-reaching consequences.}, }
@article {pmid41223536, year = {2026}, author = {Toresson, L and Ludvigsson, U and Olmedal, G and Hellgren, J and Toni, M and Giaretta, PR and Blake, AB and Suchodolski, JS}, title = {Repeated fecal microbiota transplantation in dogs with chronic enteropathy can decrease disease activity and corticosteroid usage.}, journal = {Journal of the American Veterinary Medical Association}, volume = {264}, number = {5}, pages = {571-580}, doi = {10.2460/javma.25.08.0563}, pmid = {41223536}, issn = {1943-569X}, mesh = {Animals ; Dogs ; *Dog Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary ; Male ; Female ; Prospective Studies ; *Adrenal Cortex Hormones/therapeutic use ; Longitudinal Studies ; Feces/microbiology/chemistry ; Chronic Disease ; *Inflammatory Bowel Diseases/veterinary/therapy ; *Intestinal Diseases/therapy/veterinary ; }, abstract = {OBJECTIVE: Evaluate clinical and fecal parameters in dogs with refractory chronic enteropathy (CE) treated with repeated fecal microbiota transplantation (FMT) as adjunct treatment.<br><br>METHODS: This was a prospective longitudinal observational study from September 25, 2021, to June 20, 2024. Thirty-nine dogs received 2 to 3 rectal FMTs over 1 month. Canine inflammatory bowel disease activity index (CIBDAI) and fecal samples were assessed for 6 months. Fecal samples were analyzed for dysbiosis index, bile acids, and calprotectin.<br><br>RESULTS: 28 of 39 dogs responded to FMT. Eight dogs had a short-lasting response. Before FMT, baseline CIBDAI was equivalent in responders and nonresponders. Responders had a significantly decreased CIBDAI at 1 month, which remained unaltered at 6 months in long-lasting responders (LLRs). Baseline dysbiosis index (mean [95% CI]) was significantly lower in LLRs (-0.02 [-3.3 to 2.7]) versus nonresponders and short-lasting responders combined (N/SRs; 2.9 [-0.2 to 6.0]). Baseline percentage of secondary unconjugated fecal bile acids was higher in LLRs (65 [41 to 89]) versus N/SRs (30 [6 to 54]). Dysbiosis index decreased significantly at the time point for the third FMT in LLRs (-2.4 [-3.9 to 2.2]) but not in N/SRs (3.3 [-0.4 to 5.7]). Corticosteroid tapering was achieved in 13 responders. Mild adverse events were noted in 4 dogs.<br><br>CONCLUSIONS: This repeated FMT protocol was an effective adjunct treatment in refractory CE dogs, especially in dogs with no or mild dysbiosis. Marked dysbiosis and BA dysmetabolism before and after FMT appeared associated with no clinical response or a short-lasting response to FMT, potentially requiring repeated FMT.<br><br>CLINICAL RELEVANCE: Repeated FMT could reduce disease activity and corticosteroid usage in dogs with refractory CE.}, }
@article {pmid41223655, year = {2026}, author = {Chen, J and Gu, M and Zhang, M and Wang, S and Zhang, X and Zhu, Z and Gan, Q}, title = {Stage-specific gut microbial restructuring drives estrous transition in rabbits.}, journal = {Animal bioscience}, volume = {39}, number = {4}, pages = {250529-250520}, pmid = {41223655}, issn = {2765-0189}, support = {JAT2200220070//Educational and Scientific Research (on Science and Technology) Projects for Young and Middle-aged Teachers/ ; FJXQKFJJ2022-1//Program of Fujian Key Laboratory of Animal Genetics and Breeding/ ; 2023N5004//Fujian Provincial Science and Technology Plan Project-University Industry University Cooperation Project/ ; 2023I1009//Foreign Cooperation Project/ ; }, abstract = {OBJECTIVE: This study aimed to investigate the relationship between colonic microbiota and estrous cycle transition in rabbits by integrating 16S rRNA gene sequencing and metabolomic analyses to identify key microbial taxa and metabolites involved in estrus regulation.<br><br>METHODS: Sixteen female New Zealand white rabbits were divided into diestrus and early estrus groups based on vulvar mucosa color and serum estradiol (E2) concentration. Colonic microbiota dynamics were assessed via 16S rRNA sequencing, while metabolomes of colonic contents were profiled using ultra-high performance liquid chromatography-tandem mass spectrometry. Fecal microbiota transplantation (FMT) was performed by oral administration of colonic contents from diestrus or early estrus rabbits to mice with disrupted estrous cycles to evaluate the regulatory effects of microbiota. Exogenous indole- 3-acetic acid (IAA) was administered to both mice and rabbits to assess its role in estrus onset and cyclicity restoration.<br><br>RESULTS: Colonic microbial composition differed significantly between diestrus and early estrus rabbits. The genera Anaerostipes and Ruminiclostridium were enriched in early estrus, while the genera Oscillospirales UCG_010 and UCG_005 were more abundant in diestrus. FMT from early estrus donors restored cyclicity in mice with disrupted cycles, whereas diestrus FMT did not. Metabolomics identified IAA as a key elevated metabolite in early estrus, and this metabolite accelerated estrus onset and restored cyclicity in both mice and rabbits.<br><br>CONCLUSION: These findings demonstrate that gut microbiota restructuring regulates the estrous transition in rabbits, providing a basis for developing microbiota-targeted strategies to enhance reproductive efficiency in rabbit production and optimize animal reproductive management.}, }
@article {pmid41226824, year = {2025}, author = {de Groen, P and Blok, LCHM and Fuhri Snethlage, CM and Hanssen, NMJ and Rampanelli, E and Nieuwdorp, M}, title = {Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, pmid = {41226824}, issn = {1422-0067}, support = {09150182010020//Personal NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; 2021T055//Senior Clinical Dekker grant by the Dutch Heart Foundation/ ; 09150172210019//ZONMW-VIDI grant 2023/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; *Metabolomics/methods ; *Immunomodulation ; Animals ; Fecal Microbiota Transplantation ; Autoimmunity ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta cells, resulting in insulin deficiency. Both genetic predisposition and environmental factors contribute to T1D development, with growing evidence implicating the gut microbiome as a critical environmental modulator in disease pathogenesis. Gut microbial composition and derived metabolites influence immune homeostasis and autoimmunity. This review summarizes recent advances elucidating immune dysregulations in T1D and novel therapeutic strategies to preserve beta cell function. We discuss approaches such as immune cell engineering, including CAR-Treg therapy, and targeted modulation of immune signaling pathways like JAK-STAT. Furthermore, we explore the role of the gut microbiota and its metabolites in modulating host immunity and describe emerging microbiome-targeting interventions, including fecal microbiota transplantation and metabolite supplementation. These interventions show promise in modulating disease progression in preclinical and early clinical studies. An integrated understanding of immune and microbiome-related mechanisms is critical for developing next-generation therapies. Further research and clinical trials are needed to optimize these approaches and translate them into durable, personalized treatments for individuals with T1D.}, }
@article {pmid41228422, year = {2025}, author = {Diotaiuti, P and Misiti, F and Marotta, G and Falese, L and Calabrò, GE and Mancone, S}, title = {The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review.}, journal = {Nutrients}, volume = {17}, number = {21}, pages = {}, pmid = {41228422}, issn = {2072-6643}, support = {MUR Decree n. 105123.06.2022 PNRR Missione 4 Componente 2 Investimento 1.5-CUP H33C22000420001//Project ECS0000024 "Ecosistema dell'innovazione-Rome Technopole" financed by EU NextGeneration EU plan/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Affect/physiology ; *Decision Making/physiology ; Animals ; Cognition ; Probiotics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut-brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability.}, }
@article {pmid41229548, year = {2025}, author = {Xiao, Y and Wei, L and Yu, J and Liu, Y}, title = {Fecal Microbiota Transplantation for Attention-Deficit/Hyperactivity Disorder: Mechanisms, Evidence, and Future Directions.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {6757-6767}, pmid = {41229548}, issn = {1178-7074}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. While pharmacological and behavioral therapies remain first-line treatments, their limitations in efficacy, tolerability, and long-term adherence underscore the need for innovative interventions. Growing evidence highlights the role of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology, particularly involving immune dysregulation, neurotransmitter imbalance, metabolic disruption, and epigenetic alterations. Fecal microbiota transplantation (FMT), as a microbiota-based intervention, has shown promise in restoring MGBA homeostasis and modulating neural function through multiple mechanisms. This review summarizes current preclinical and clinical research on FMT in ADHD, covering its effects on neuroinflammation, neurotransmitter pathways, vagus nerve and HPA axis signaling, and epigenetic reprogramming. Although preclinical models and early human data indicate potential behavioral benefits and mechanistic plausibility, methodological heterogeneity, limited sample sizes, and incomplete mechanistic validation pose significant challenges. Future research should prioritize protocol standardization, randomized controlled trials, biomarker discovery, and ethical regulation to facilitate the safe and effective clinical translation of FMT in ADHD treatment.}, }
@article {pmid41229686, year = {2025}, author = {Tian, R and Chong, CJ and Bai, YY and Chen, N and Qiao, RR and Wang, K and Wang, YW and Zhao, P and Zhao, CB and Tang, YP and Zhang, L and Zhang, Q}, title = {The role of gut microbiota in diarrhea and its alleviation through microbiota-targeted interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1630823}, pmid = {41229686}, issn = {1664-302X}, abstract = {Diarrhea is a common gastrointestinal disease and closely related to the balance of the gut microbiota (GM). In turn, dysregulation of the GM can affect the onset and progression of diarrhea through regulating the metabolism, intestinal immune function, intestinal barrier function and changes in the brain-gut axis of host. Although increasing evidence suggests that GM is associated with gastrointestinal homeostasis and disease, the underlying mechanisms are not fully understood. GM disorder was often accompanied by diarrhea patients and animals, and the diarrhea caused by GM imbalance mainly involved the effects on short chain fatty acids (SCFAs), bile acids (BAs), intestinal barrier, immune system, and brain-gut microbiota axis (BGMA). In addition, intervening in the GM (probiotics, fecal microbiota transplantation and bacteriophage therapy) has been shown to be an effective way to alleviate diarrhea. In this review, the mechanism of diarrhea occurrence, probiotics, fecal microbiota transplantation and bacteriophage therapy intervene in diarrhea by regulating GM from basic and clinical research were summarized and discussed. We aim to provide the latest reference for studying the mechanism of treating diarrhea from the perspective of GM, and provide data support for clinical treatment of diarrhea.}, }
@article {pmid41229982, year = {2025}, author = {Chen, Z and Li, L and Jin, D and Zhao, Y and Malard, F and Huang, H and Ye, Y and Mohty, M}, title = {Gut microbiota and acute graft-versus-host disease.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {37}, number = {5}, pages = {657-666}, pmid = {41229982}, issn = {1000-9604}, abstract = {Acute graft-versus-host disease (aGVHD) is an important complication which critically impacts the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation. Increasing evidence suggests that dysbiosis of the gut microbiota plays a key role in aGVHD pathogenesis. The biological process involves compromised intestinal barrier integrity, amplified inflammation driven by the translocation of microbial products like lipopolysaccharide, and finally the dysregulated immune response centralized by T cell activation and differentiation. Meanwhile, certain microbial metabolites such as short-chain fatty acids and secondary bile acids exert protective effects. The clinical relevance of these findings is underscored by studies establishing that specific gut microbial signatures, such as low diversity and single pathogen dominance, independently predict aGVHD morbidity and mortality. From a therapeutic perspective, the microbiome has emerged as an important therapeutic target for aGVHD. Fecal microbiota transplantation has shown significant efficacy in clinical trials for prophylaxis and treatment of aGVHD, providing definitive proof-of-concept for ecological restoration. This review synthesizes these foundational mechanistic insights, from metabolic disruption to host-microbe crosstalk at the mucosal barrier, and details the rapidly advancing clinical landscape of microbiome-targeted diagnostics and therapeutics for aGVHD.}, }
@article {pmid41232361, year = {2026}, author = {Bishoyi, AK and Al-Hasnaawei, S and Salem, KH and Ganesan, S and Shankhyan, A and Nanda, A and Sinha, A and Ray, S and Nathiya, D and Hammady, FJ}, title = {Gut microbiome metabolites in lung cancer: The emerging importance of short-chain fatty acids.}, journal = {International immunopharmacology}, volume = {168}, number = {Pt 1}, pages = {115821}, doi = {10.1016/j.intimp.2025.115821}, pmid = {41232361}, issn = {1878-1705}, mesh = {Animals ; Humans ; Dysbiosis/complications ; Epigenesis, Genetic ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Lung/microbiology ; *Lung Neoplasms/metabolism/microbiology/therapy ; Tumor Microenvironment/immunology ; Immunotherapy ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Short-chain fatty acids (SCFAs), which are produced from the fermentation by the gut microbiota of dietary fiber, are now proven to play a vital role in the growth control of lung cancer and drug response. SCFAs have mechanisms of action, including the inhibition of histone deacetylases, activation of G-protein-coupled receptors, and metabolic reprogramming. SCFAs suppress tumor growth, induce apoptosis, suppress angiogenesis, and modulate epithelial-mesenchymal transition. Besides the above direct antitumor effects, SCFAs enhance the therapeutic effect of immune checkpoint inhibitors and reduce the toxicity of radiotherapy and chemotherapy by maintaining the mucosal barrier and restoring systemic immune homeostasis. Butyrate function is highly dualistic; it is usually protective but may confer multidrug resistance under certain therapeuticconditions. To reconcile these opposing effects is akey challenge in the translation of microbiota-based therapeutics and interventions. Therapies such as probiotics, fecal microbiota transplantation, and designed microbial consortia all target SCFAs as central mediators of microbiome-host communication. Overall, SCFAs are candidate metabolic co-adjuvants that can maximize therapeutic efficacy, suppress unacceptable side effects, and redirect therapeutic approaches to lung cancer.}, }
@article {pmid41232540, year = {2026}, author = {Wieringa, JW and Binyamin, D and Jankelowitz, IA and Schweitzer, R and Turjeman, S and Khatib, S and Esser, MJ and van der Woude, CJ and Fuhler, GM and Koren, O}, title = {Intestinal barrier alterations in mice following fecal microbiota transplant from children of IBD-affected mothers.}, journal = {Med (New York, N.Y.)}, volume = {7}, number = {1}, pages = {100915}, doi = {10.1016/j.medj.2025.100915}, pmid = {41232540}, issn = {2666-6340}, mesh = {*Fecal Microbiota Transplantation ; Animals ; Female ; Humans ; Mice ; *Gastrointestinal Microbiome ; Child, Preschool ; *Intestinal Mucosa/microbiology/metabolism ; *Inflammatory Bowel Diseases/microbiology/therapy/genetics ; Child ; Infant ; Male ; Infant, Newborn ; Adult ; Feces/microbiology ; Mothers ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) carries a hereditary risk, which is higher through maternal, rather than paternal, inheritance. Like their mothers, children born to mothers with IBD have an altered microbiome shortly after birth.<br><br>METHODS: To investigate whether this altered microbiome persists later in life and affects the intestinal mucosa, the fecal microbiome was analyzed in samples from 44 infants ranging from 0 to 10 years of age born to 26 women with IBD. Forty-four age-matched children of 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) to germ-free mice was carried out from 4-year-olds born to mothers with IBD and controls. Markers of inflammation, barrier function, and metabolic changes were investigated.<br><br>FINDINGS: Intestinal microbiomes were more similar between women with IBD and their children than between control mothers and their offspring. Microbial changes were noticeable in children from mothers with IBD from the age of 4 years compared to children of controls. No inflammatory response was present in the mucosa of mice receiving FMT from children of mothers with IBD; however, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from these children compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios.<br><br>CONCLUSIONS: Fecal microbiomes of children of mothers with IBD exhibit characteristics that reduce epithelial tight junction barrier genes and tolerogenic tryptophan metabolism. Microbiome-induced gut barrier disruptions may contribute to an enhanced IBD predisposition in infants of mothers with IBD.<br><br>FUNDING: This work was funded by ZonMw.}, }
@article {pmid41234231, year = {2025}, author = {Huang, L and Wang, S and Zhang, H and Feng, S and Zhong, H and Chen, J and Xie, W and Wu, L and Zhang, T and He, X and Yang, J}, title = {Clinical efficacy evaluation of washed microbiota transplantation treatment for metabolic related fatty liver disease and its impact on tongue coating microorganisms.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1684173}, pmid = {41234231}, issn = {1664-2392}, mesh = {Humans ; Female ; Pregnancy ; Middle Aged ; Aged ; Animals ; Tongue/microbiology ; Mice ; *Non-alcoholic Fatty Liver Disease/microbiology/therapy ; RNA ; Fecal Microbiota Transplantation/methods ; Treatment Outcome ; }, abstract = {OBJECTIVE: The present study aims to explore the impact of washed microbiota transplantation (WMT) on the tongue microbiota composition of individuals with metabolic-associated fatty liver disease (MAFLD) and elucidate its biological correlations.<br><br>METHODS: We conducted a comprehensive analysis of hepatic fat deposition and characterized the tongue coating microbiota using 16S rRNA gene sequencing in MAFLD patients before and after undergoing WMT treatment. Furthermore, a MAFLD mouse model was established for additional validation.<br><br>RESULTS: At the genus level, significant differences in tongue coating microbiota structure were observed between MAFLD patients and HC. Specifically, Neisseria positively correlated with the BARD score, Porphyromonas and Rhodococcus positively correlated with fat decay, and Petostreptococcus, a conditionally pathogenic bacterium, exhibited a significantly higher relative abundance in MAFLD patients compared to HC. Conversely, Actinomyces positively correlated with the FIB-4 score, Megasphaera negatively correlated with the APRI score, and Subdoligulum negatively correlated with low-density lipoprotein levels. Notably, following effective WMT treatment, patients exhibited improved symptoms, with a significant reduction in the relative abundance of Petostreptococcus and an increase in potential probiotics such as Lachnospiraceae and Bifidobacterium in their tongue coating microbiota. Additionally, structural differences in the tongue coating microbiota were identified at the genus level between MAFLD model mice and HC mice. After WMT treatment, the relative abundance of conditionally pathogenic bacteria like Enterococcus was significantly decreased in MAFLD model mice.<br><br>CONCLUSIONS: WMT not only significantly ameliorates liver fat deposition in MAFLD patients but also alters the tongue coating microbial structure associated with disease severity, thereby potentially mitigating adverse patient outcomes.}, }
@article {pmid41234596, year = {2025}, author = {Du, Y and Li, Y and Yu, M and Yu, Y and Zhang, Y and Wang, X and He, J and Lin, L and Shen, B and Gong, Y and Zhu, J and Zou, B and Liu, Y and Huang, M and Lu, Y}, title = {Fecal microbiota transplantation plus immune checkpoint inhibitor rechallenges in patients with advanced non-small cell lung cancer: a single-arm exploratory study.}, journal = {Translational lung cancer research}, volume = {14}, number = {10}, pages = {4541-4559}, pmid = {41234596}, issn = {2218-6751}, abstract = {BACKGROUND: The management of advanced non-small cell lung cancer (NSCLC) after progression on initial immunotherapy represents a significant clinical challenge. Immune checkpoint inhibitor (ICI) rechallenge is a considered option, yet its efficacy remains limited. Strategies to enhance the efficacy of ICI rechallenge are urgently needed. There is a pressing need for novel strategies to sensitize tumors to ICI rechallenge. Previous studies have established a correlation between the gut microbiota and the tumor response to immunotherapy, and have explored the application of fecal microbiota transplantation (FMT) in modifying the immune response by restoring the gut microbiota. However, the potential of FMT from healthy donor to reverse immunotherapy resistance in patients with NSCLC has not been previously investigated. This preliminary study aimed to provide initial insights into the safety, tolerability, and potential efficacy of the combined therapy of FMT from healthy donor with immunotherapy rechallenge in NSCLC patients.<br><br>METHODS: In this single-arm exploratory study, patients with advanced NSCLC who progressed after prior immunotherapy were screened and enrolled based on predefined eligibility criteria, including prior response to ICIs and adequate organ function. Eligible patients received oral FMT capsules from healthy donors followed by rechallenge with camrelizumab. The primary endpoint was safety and feasibility [incidence of adverse events (AEs) graded by CTCAE v5.0]. Secondary end points included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Fecal and blood samples were collected for exploratory analyses of microbiota, metabolome, and T cell receptor (TCR) repertoire.<br><br>RESULTS: Seven patients (all male, median age 55 years) were enrolled and constituted the analysis population. The majority (5/7) had received three or more prior lines of therapy. During the follow-up period, none experienced grade 4 or higher AEs. The treatment-related AEs were mainly associated with immunotherapy, and only grade 1 FMT-related AEs (e.g., nausea, diarrhea, bloating, and constipation) were reported. One patient achieved a partial response (PR) and one achieved stable disease (SD) with PFS times of 14.6 and 8.1 months, respectively. The median PFS was 1.5 months [95% confidence interval (CI): 1.24-1.75], and the OS was 12.1 months (95% CI: 0.3-23.9) for all patients. Moreover, the treatment modulated the composition of the intestinal flora in all patients, with alpha diversity increasing in responders and decreasing in non-responders.<br><br>CONCLUSIONS: The results indicated that the combined therapy of FMT and immunotherapy rechallenge was feasible and demonstrated a tolerable safety profile in this small cohort. The observed clinical activity is preliminary. These findings support the need for larger, controlled trials to assess the efficacy of this approach.}, }
@article {pmid41235136, year = {2025}, author = {Wu, Y and Pan, S and Yin, C and Kong, Y and Huo, W and Wang, Q and Wu, J and Li, L and Wei, J and Lu, C and Han, L and Lu, Y}, title = {PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {9993-10010}, pmid = {41235136}, issn = {1177-8881}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Psoriasis/drug therapy/metabolism/pathology ; Mice ; Humans ; *Cell Differentiation/drug effects ; *Sphingolipids/metabolism ; *Epidermis/drug effects/pathology/metabolism ; Keratinocytes/drug effects/metabolism ; }, abstract = {BACKGROUND: Psoriasis is linked to gut dysbiosis and disturbed sphingolipid metabolism. PSORI-CM02 improves epidermal differentiation, yet its impact on the microbiota-sphingolipid axis remains unknown.<br><br>METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.<br><br>RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.<br><br>CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.}, }
@article {pmid41236646, year = {2025}, author = {Ochi, T and Takeda, M and Asahara, T and Kurita, A and Ogata, Y and Suzuki, M and Takei, H and Nittono, H and Miyano, G and Koga, H and Lane, GJ and Okazaki, T and Saiura, A and Mizuta, K and Kasahara, M and Yamataka, A and Yamashiro, Y}, title = {Postoperative gut dysbiosis in biliary atresia patients treated by portoenterostomy or liver transplantation.}, journal = {Pediatric surgery international}, volume = {42}, number = {1}, pages = {9}, pmid = {41236646}, issn = {1437-9813}, support = {22K11861//Japan Society for the Promotion of Science KAKENHI grant/ ; }, mesh = {Humans ; *Biliary Atresia/surgery ; *Dysbiosis/microbiology/etiology ; *Liver Transplantation/adverse effects ; Male ; Female ; *Portoenterostomy, Hepatic/adverse effects ; *Gastrointestinal Microbiome ; *Postoperative Complications/microbiology ; Infant ; Feces/microbiology/chemistry ; Bile Acids and Salts/analysis ; Case-Control Studies ; }, abstract = {PURPOSE: To assess how surgery and management protocols affect gut microbiota in postoperative biliary atresia (BA) patients by comparing survivors with native livers (NL) or transplanted livers (TL) with healthy non-surgical controls (CL).<br><br>METHODS: Subjects were 62 post-portoenterostomy BA patients divided into 2 groups (NL and TL) and CL. All subjects were clinically stable with no dietary restrictions throughout the study period. Stool samples were compared for gut microbiota, organic acids, and fecal bile acids, while blood samples were compared for serum biochemistry and serum bile acids.<br><br>RESULTS: Stool samples from CL (n&#x2009;=&#x2009;30) were normal while NL (n&#x2009;=&#x2009;31) and TL (n&#x2009;=&#x2009;31) showed gut dysbiosis with significantly decreased total bacteria and reduced predominance of obligate anaerobes, and an abundance of Clostridioides difficile, Enterobacteriaceae, and Enterococcus. The latter two were more abundant in TL than NL. Biochemistry was normal in TL. In NL, elevated AST/ALT correlated with increased Clostridioides difficile, decreased Bacteroides fragilis group, and decreased Lactobacilli. Fecal secondary bile acids were lower and serum primary and secondary bile acids were higher in NL and TL compared with CL.<br><br>CONCLUSION: Gut dysbiosis was present in both NL and TL. Pathogenic florae were more abundant in TL despite TL biochemistry being normal.}, }
@article {pmid41237775, year = {2026}, author = {Van Hul, M and Cani, PD}, title = {From microbiome to metabolism: Bridging a two-decade translational gap.}, journal = {Cell metabolism}, volume = {38}, number = {1}, pages = {14-32}, doi = {10.1016/j.cmet.2025.10.011}, pmid = {41237775}, issn = {1932-7420}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome ; *Translational Research, Biomedical ; Prebiotics ; *Microbiota ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.}, }
@article {pmid41237834, year = {2026}, author = {Yang, J and Wang, J and Li, J and Cui, J}, title = {Nanotechnology - Microbiota synergy in cancer immunotherapy.}, journal = {Critical reviews in oncology/hematology}, volume = {217}, number = {}, pages = {105018}, doi = {10.1016/j.critrevonc.2025.105018}, pmid = {41237834}, issn = {1879-0461}, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology/drug effects ; *Nanotechnology/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Tumor Microenvironment/immunology/drug effects ; Animals ; Probiotics/therapeutic use ; }, abstract = {The global burden of cancer continues to escalate, yet the efficacy of current targeted therapies and immune checkpoint inhibitors (ICIs) is often hampered by drug resistance and immune escape. The gut microbiota orchestrates tumor progression and ICI efficacy bidirectionally via the "microbiota-immune-tumor" axis. However, traditional interventions, including fecal microbiota transplantation and antibiotics, are limited by inherent drawbacks such as poor targeting. Nanotechnology can overcome this limitation: it not only enables precise targeting of the gut microbiota and reshapes the tumor immune microenvironment to synergistically enhance ICI efficacy but also reverses drug resistance in tumor chemotherapy, radiotherapy, and targeted therapy through multiple strategies. Additionally, it can synergize with probiotics, extracellular vesicles, and other agents to achieve tumor therapy. This review synthesizes current understanding of gut microbiota-immune crosstalk, the microbiota's role in regulating ICI efficacy, and the central applications of nanotechnology, thereby proposing novel synergistic strategies for cancer treatment.}, }
@article {pmid41238092, year = {2025}, author = {Ye, M and Ju, H and Ren, G and Hu, J}, title = {The role of microbiome in immunotherapy: Insights and perspectives.}, journal = {Seminars in cancer biology}, volume = {117}, number = {}, pages = {131-151}, doi = {10.1016/j.semcancer.2025.11.001}, pmid = {41238092}, issn = {1096-3650}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Fecal Microbiota Transplantation ; *Microbiota/immunology ; Probiotics/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {The intricate interplay between the gut microbiome and the host immune system has been recognized as a pivotal determinant of clinical outcomes in cancer immunotherapy. Mounting evidence suggests that specific microbial communities are associated with both the efficacy and toxicity of immune checkpoint inhibitors in diverse malignancies, underscoring the microbiome's role in modulating systemic and tumour-localized immunity. Mechanistically, the microbiome shapes antitumour immunity by affecting antigen presentation, activation of effector cells, immunosuppression and adverse effects. Key microbial components and metabolites present in distinct anatomical niches have been identified as promoters or inhibitors of therapeutic responsiveness via multiple pathways. Harnessing this knowledge, microbiome-targeted strategies such as antibiotic, probiotic, fecal microbiota transplantation, and dietary modulation are regarded as potential adjuvant therapies to enhance the efficacy of anti-tumour therapies. Although significant progress has been achieved in preclinical studies, challenges persist in translating these findings into standardized clinical applications.}, }
@article {pmid41238277, year = {2025}, author = {Pai, N and Sainath, NN}, title = {Diagnosis and Management of Small Intestinal Bacterial Overgrowth in Pediatric Short Bowel Syndrome.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {4}, pages = {805-821}, doi = {10.1016/j.gtc.2025.07.005}, pmid = {41238277}, issn = {1558-1942}, mesh = {Humans ; *Short Bowel Syndrome/microbiology/complications/therapy ; *Intestine, Small/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Breath Tests ; *Blind Loop Syndrome/diagnosis/therapy ; }, abstract = {This article explores the diagnosis and management of small intestinal bacterial overgrowth in children with short bowel syndrome, a population affected by altered anatomy, dysmotility, and medication-related risk factors. Diagnostic accuracy is limited by the feasibility, and specificity of breath testing and small bowel aspirates. While antibiotics are commonly used, concerns about recurrence and antibiotic resistance remain significant. Emerging nutritional strategies and precision-based, microbiome-targeted therapies offer promising adjunctive treatment options.}, }
@article {pmid41239321, year = {2025}, author = {Alkuwaiti, SH and Skrabulyte-Barbulescu, J and Yassin, LK and Almazrouei, S and Aldhaheri, D and Alderei, M and BaniYas, S and Alshamsi, SH and Alnuaimi, A and Saeed, S and Alawadhi, M and Rutkowska-Gauvry, P and Ismail, FY and Hamad, MIK}, title = {Harnessing the microbiota-gut-brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1286}, pmid = {41239321}, issn = {1479-5876}, abstract = {BACKGROUND: Pediatric neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Rett syndrome (RTT), Tourette syndrome (TS), Down syndrome (DS), Fragile X syndrome (FXS), Prader–Willi syndrome (PWS), fetal alcohol spectrum disorder (FASD), pediatric epilepsy, congenital Zika syndrome (CZS), Wilson’s disease (WD), and cerebral palsy (CP), are associated with long-term impairments and high societal burden. Emerging evidence implicates the microbiota–gut–brain axis (MGBA) in early neurodevelopment with factors, such as maternal microbiota, birth mode, antibiotics, and infant diet shaping microbial colonization and influencing developmental outcomes.<br><br>OBJECTIVE: This review aims to synthesize current translational evidence from animal and human studies to address the following research questions: (1) How do disruptions in the MGBA contribute to the pathophysiology of pediatric neurodevelopmental disorders? (2) What microbiome alterations are consistently associated with these conditions? and (3) What ethical and safety considerations should be addressed in implementing early-life microbiome-based interventions? We also assess emerging microbiota-based interventions, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and traditional therapies, and their potential to modulate disease outcomes.<br><br>CONCLUSION: The MGBA presents a promising, yet currently preliminary, target for early intervention in pediatric neurodevelopmental disorders. There is emerging evidence that therapies targeting the microbiota could have an effect on neurodevelopment and outcomes of health and disease; however, most of the findings are in the initial stages, and the evidence is still inconsistent. Therefore, the findings must be translated into mechanisms of action over extended periods with longitudinal multi-omic studies to identify possible intervention windows, optimize personalized therapies, and evaluate the safety and efficacy of interventions targeting the microbiome. Till that point, these microbiota-targeted approaches should be approached cautiously and treated as experimental in the realm of pediatric interventions, given the present-day state of evidence.}, }
@article {pmid41239968, year = {2025}, author = {Kim, MS and Bisanz, JE}, title = {Design and application of synthetic human gut microbial communities.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2575923}, pmid = {41239968}, issn = {1949-0984}, support = {F31 AI183815/AI/NIAID NIH HHS/United States ; R35 GM151045/GM/NIGMS NIH HHS/United States ; T32 DK120509/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Host Microbial Interactions ; Bacteria/genetics/classification ; Animals ; }, abstract = {The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is associated with a range of infectious and chronic diseases. Owing to the success of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection, FMT has been explored as a therapeutic option for a range of microbiota-associated conditions, including inflammatory bowel disease and obesity. However, the microbial diversity that is the greatest strength of FMT is also its greatest liability. Concerns relating to reliance on human donors, potential for transmission of multidrug-resistant organisms or undesirable phenotypes demonstrate a need for alternate approaches, including the generation of synthetic alternatives to FMT, which can be built in the laboratory from individual strains. Furthermore, these communities are powerful tools for conducting mechanistic research allowing for the generation of 'knockout' communities, which are not possible when working with undefined fecal transplants. This review examines strategies for designing synthetic microbial communities that represent a new generation of microbiome-derived therapies. We highlight how synthetic microbial communities are being used to answer mechanistic questions about host-microbiome interactions relevant to health and disease. Finally, we examine the current clinical translation of these communities as live biotherapeutic products (LBPs). While the regulatory frameworks for LBPs continue to evolve, early clinical successes illuminate the potential for synthetic microbial communities to treat complex human diseases through targeted manipulation and restoration of the gut microbiome.}, }
@article {pmid41239983, year = {2025}, author = {Gabriel-Segard, T and Heberden, C and Mondot, S and Duquesnoy, M and Dicembre, M and Naudon, L and Philippe, C and Maximin, E and Blais, A and Jacota, M and Lapaque, N and Blottière, HM and Paul, S and Doré, J and Rabot, S and Hanachi, M}, title = {Anorexia nervosa symptoms are induced after specific gut microbiota dysbiosis transfer in germ-free mice.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2563701}, pmid = {41239983}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Anorexia Nervosa/microbiology/therapy/physiopathology ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Mice ; Mice, Inbred BALB C ; Female ; Disease Models, Animal ; Humans ; Germ-Free Life ; Feces/microbiology ; Adult ; Male ; }, abstract = {Anorexia nervosa (AN) is the most severe and life-threatening eating disorder. Its pathophysiology remains largely unknown, and no effective treatment currently exists for severe forms of the disease. Gut microbiota (GM) dysbiosis has been consistently reported in AN; however, no study has yet considered the role of the microbiota within the full spectrum of AN symptoms. To investigate the direct involvement of the microbiota in disease symptoms, we developed a murine model of fecal microbiota transplantation (FMT), using germ-free BALB/c mice colonized with fecal samples from well-characterized AN patients and healthy controls. Physiological, organ, and behavioral parameters were systematically monitored. We found that key AN-related features (including food restriction, anxiety-like behavior, physical hyperactivity, and elevated inflammatory responses) were transmitted to germ-free mice following transplantation with AN-derived microbiota. Likewise, organ-specific alterations associated with AN, such as liver dysfunction and disruption of ovarian follicles, were also reproduced. In conclusion, we demonstrate that the transfer of AN microbiota induces behavioral, physiological, and organ-level alterations reminiscent of the human disease. These findings highlight a major role of the gut microbiota in the symptomatology and progression of AN and open new therapeutic perspectives targeting this ecosystem.}, }
@article {pmid41240539, year = {2025}, author = {Ma, J and Li, Y and Yang, Y and Zhao, L and Jiang, Y and Wong, TW and Zhang, D}, title = {Gut-liver axis mechanisms of Hippophae rhamnoides L. in non-alcoholic fatty liver disease prevention.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157517}, doi = {10.1016/j.phymed.2025.157517}, pmid = {41240539}, issn = {1618-095X}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/prevention &amp; control/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Hippophae/chemistry ; Male ; Mice ; *Liver/drug effects/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Phytosterols/pharmacology ; Plant Oils/pharmacology/chemistry ; Seeds/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Phytosterol-rich Hippophae rhamnoides L. can ameliorate abnormal blood lipids in patients with non-alcoholic fatty liver disease (NAFLD). Its gut microbiota modulatory roles along gut-liver axis are not known.<br><br>OBJECTIVE: This study explored the preventive roles of H. rhamnoides L. against NAFLD and the associated gut-liver axis mechanisms.<br><br>METHODS: Sterols were extracted from H. rhamnoides L. seed oil (SHR) and subjected to LC-MS analysis. Their effects on body/liver/epididymal fat mass, intestinal microbiota, metabolites (DAO, D-LA, LPS) and SCFAs secretion, intestinal barrier (claudin-1, ZO-1) and liver lipid composition and molecular biology (AST, ALT, TC, TG, LDL-C, HDL-C, SREBP1c, SCD1, FAS, LXR&#x3b1;, PPAR&#x3b1;) were examined in vivo against normal and high-fat diet mice. The modulatory action of microbiota on liver dysfunction was further verified through SHR-fed fecal transplantation into antibiotic-pretreated mice.<br><br>RESULTS: &#x3b2;-sitosterol, campesterol, stigmasterol, and ergosterol were the primary active constituents of SHR. With reference to high fat diet mice, SHR increased intestinal tight junction functionality, reducing inflammatory LPS migration to liver and hepatic lipid synthesis. SHR raised the relative abundance of Alloprevotella and Lachnospiraceae_NK4A136_group, and Bacteroides/Firmicutes ratio leading to increased SCFA secretion that strengthened intestinal barrier and reduced hepatic hyperlipidemia.<br><br>CONCLUSION: SHR effectively mitigated NAFLD by reducing hepatic lipid expression via regulating intestinal microbiota, its SCFA secretion and intestinal barrier.}, }
@article {pmid41241177, year = {2026}, author = {Rinaldi, M and Gatti, M and Giannella, M}, title = {Avoiding resistance development to newer drugs: open research lines.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {32}, number = {4}, pages = {543-553}, doi = {10.1016/j.cmi.2025.11.009}, pmid = {41241177}, issn = {1469-0691}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use/pharmacokinetics ; *Drug Resistance, Multiple, Bacterial/drug effects ; *Gram-Negative Bacteria/drug effects ; *Gram-Negative Bacterial Infections/drug therapy/microbiology/prevention &amp; control ; beta-Lactamase Inhibitors/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: The spread of multidrug-resistant gram-negative bacteria, particularly those with carbapenem-resistant or difficult-to-treat resistance phenotypes, is a major public health threat. New agents offer potent therapeutic options but carry the challenge of preserving their effectiveness against resistance.<br><br>OBJECTIVES: This narrative review summarizes antimicrobial and non-antimicrobial strategies to prevent or mitigate resistance development to novel agents.<br><br>SOURCES: We searched PubMed-MEDLINE for English-language articles published in the last 5 years.<br><br>CONTENT: Among antimicrobial strategies, we reviewed the role of optimising pharmacokinetic/pharmacodynamic targets for novel &#x3b2;-lactam/&#x3b2;-lactamase inhibitor combinations and the impact of combination vs. monotherapy regimens. Achieving aggressive joint pharmacokinetic/pharmacodynamic targets may help prevent resistance, supported by approaches such as continuous infusion of time-dependent agents and therapeutic drug monitoring. Current evidence does not demonstrate a routine benefit of combination therapy over monotherapy for novel drugs; however, available studies are limited in size and quality, and resistance emergence has rarely been a primary endpoint. Non-antimicrobial strategies reviewed include faecal microbiota transplantation, phage therapy, and active or passive immunisation. These approaches may reduce the burden of multidrug-resistant gram-negative bacteria, particularly in high-risk populations such as immunocompromised patients, those undergoing invasive procedures, or patients with foreign bodies. By lowering pathogen load and transmission, these interventions could enhance the effectiveness of current drugs and limit further resistance development.<br><br>IMPLICATIONS: Prevention of resistance to novel &#x3b2;-lactam/&#x3b2;-lactamase inhibitor combinations currently relies on optimized dosing and infusion strategies. The benefit of combination regimens remains uncertain and warrants further investigation, ideally with resistance emergence as a defined endpoint and addressed with appropriate analysis. Non-antimicrobial interventions show promise as adjunctive tools in high-risk settings and merit integration into broader resistance prevention frameworks.}, }
@article {pmid41241180, year = {2026}, author = {Han, H and Park, J and Zhang, R and Subramaniyam, N and Das, S and Ge, X and Babu Komakula, SS and Wang, C and Desert, R and Chen, W and Song, Z and Athavale, D and Anwar, A and Lantvit, D and Guzman, G and Frutos, MD and Ramos-Molina, B and Nieto, N}, title = {Intestinal Epithelial Cell-derived Osteopontin Protects Against Metabolic Dysfunction-associated Steatohepatitis by Modulating Bile Acid Composition and the Gut Microbiome.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {20}, number = {3}, pages = {101678}, pmid = {41241180}, issn = {2352-345X}, support = {R01 DK134461/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Osteopontin/metabolism/genetics ; *Gastrointestinal Microbiome ; Mice ; *Bile Acids and Salts/metabolism ; *Intestinal Mucosa/metabolism/pathology ; Humans ; Male ; Mice, Knockout ; Disease Models, Animal ; Epithelial Cells/metabolism ; Liver/pathology/metabolism ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology ; }, abstract = {BACKGROUND &amp; AIMS: The gut-liver axis plays a critical role in metabolic dysfunction-associated steatohepatitis (MASH). Osteopontin (OPN, encoded by SPP1) is implicated in chronic liver disease; however, its expression in intestinal epithelial cells (IECs) and role in MASH remain unclear.<br><br>METHODS: We evaluated intestinal OPN expression during MASH progression in patients. To determine the function of IEC-derived OPN, we generated Spp1 knock-in (Spp1[KI IEC]) and knock-out (Spp1[&#x394;IEC]) mice and fed them a high-fat, high-fructose, high-cholesterol diet to induce MASH.<br><br>RESULTS: IEC OPN expression decreased with MASH progression and was inversely associated with liver injury. Loss of Spp1 in IECs exacerbated MASH, whereas overexpression or oral OPN administration was protective. Spp1[&#x394;IEC] mice exhibited increased hepatic inflammation, disrupted IEC morphology, elevated IEC apoptosis, reduced epithelial cell turnover, and heightened intestinal permeability. They also showed hepatic 16s rRNA presence and elevated conjugated bile acids (BAs), particularly taurocholic acid and taurodeoxycholic acid, in portal serum. These BAs promoted hepatocyte injury and activated liver macrophages, enhancing inflammation both in vitro and in vivo. Fecal microbiome analysis revealed reduced abundance of bile salt hydrolase-expressing bacteria. Fecal microbiota transplantation from Spp1[&#x394;IEC] mice or treatment with a bile salt hydrolase inhibitor further worsened MASH.<br><br>CONCLUSIONS: IEC-derived OPN protects against MASH by modulating BA composition and shaping the gut microbiome.}, }
@article {pmid41241335, year = {2025}, author = {Xu, Y and Ni, Y and Zhou, M and Gou, X}, title = {Qushi Huayu decoction alleviates NAFLD in mice by regulating gut microbiota homeostasis in the gut-liver axis via the pregnane X receptor.}, journal = {European journal of pharmacology}, volume = {1008}, number = {}, pages = {178366}, doi = {10.1016/j.ejphar.2025.178366}, pmid = {41241335}, issn = {1879-0712}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome/drug effects ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Mice ; *Liver/drug effects/metabolism/pathology ; Homeostasis/drug effects ; *Pregnane X Receptor/metabolism ; Disease Models, Animal ; Diet, High-Fat/adverse effects ; }, abstract = {BACKGROUND: Qushi Huayu decoction (QHD) is a traditional Chinese medicine formula with clinical experience in the treatment of non-alcoholic fatty liver disease (NAFLD). The gut-liver axis is directly connected via the portal vein, making gut microbiota dysbiosis and endotoxin circulation key drivers in the development and progression of NAFLD. However, the regulation of the gut-liver axis by QHD in NAFLD remains unreported, and its target mechanisms have yet to be elucidated.<br><br>MATERIALS AND METHODS: NAFLD was induced in male C57BL/6J mice via high-fat diet feeding, followed by 4 weeks of QHD administration. Comprehensive evaluation included serum biochemical analysis, liver histopathology examination, and quantification of proinflammatory enzyme activity. Mechanism studies were conducted via 16S rRNA sequencing, transcriptomics analysis, SCFAs analysis, RT-qPCR, Western blotting and ELISA techniques.<br><br>RESULTS: QHD therapy effectively ameliorates hepatic steatosis and lipid accumulation in a mouse model of NAFLD. In addition, QHD significantly increases intestinal tight junction proteins, thereby restoring intestinal barrier integrity and alleviating inflammatory responses. Transcriptomics revealed that QHD regulates multiple biological functions through multiple genes, in which inflammatory responses may play a key role. Simultaneously, QHD exerts beneficial modulation of the gut microbiota, increasing beneficial bacteria, particularly Akkermansia, while decreasing the prevalence of harmful microorganisms, such as Desulfovibrio. Fecal microbiota transplantation experiments demonstrates that gut microbiota remodeling partially mediates pharmacological efficacy of QHD against NAFLD. Notably, subsequent investigations identified that QHD altered the composition of the gut microbiota and the levels of acetic acid, propionic acid, and valeric acid in SCFAs in a PXR-dependent manner.<br><br>CONCLUSIONS: QHD exerts therapeutic effects on NAFLD by regulating the gut-liver axis. The mechanism by which QHD intervention ameliorates gut microbiota dysbiosis in NAFLD mice is associated with its regulation of PXR. This provides further scientific evidence and support for QHD's efficacy in improving NAFLD.}, }
@article {pmid41241915, year = {2025}, author = {Preetham, K and Chatterjee, J}, title = {Research trend on the emerging role of the microbiome in idiopathic male infertility.}, journal = {Antonie van Leeuwenhoek}, volume = {118}, number = {12}, pages = {193}, pmid = {41241915}, issn = {1572-9699}, mesh = {*Biomedical Research/trends ; *Infertility, Male/etiology/microbiology/physiopathology/therapy ; Humans ; Male ; *Reproductive Medicine/trends ; *Bibliometrics ; Multiomics/trends ; Oxidative Stress/physiology ; Gastrointestinal Microbiome/physiology ; *Dysbiosis/diet therapy/microbiology/physiopathology ; Semen/microbiology ; Spermatogenesis/physiology ; *Microbiota/physiology ; Testis/physiology ; Life Style ; Environmental Exposure/adverse effects ; Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation/trends ; }, abstract = {Idiopathic male infertility remains a major challenge in reproductive medicine despite extensive diagnostic workups, prompting research into novel etiologies and interventions. Emerging evidence highlights the microbiome's role in modulating male reproductive health. This study analyzes global research trends on idiopathic male infertility and associated microbial health over the past two decades using a structured bibliometric approach. Data extracted from Scopus were examined through Biblioshiny and VOSviewer. The analysis reveals a clear transition from traditional genetic and oxidative stress-based studies to microbiome-centered and multi-omics investigations. Increased Research output and citation rates in recent years, underscoring the growing relevance of microbiome studies. Key contributors like Agarwal A, Wang X, Zhang H, and Lundy SD advanced understanding from genetic and oxidative causes to gut-testis and semen microbiome interactions. Leading contributors and countries, particularly China and the USA dominate collaborative networks. Key themes link microbial dysbiosis, oxidative stress, inflammation, and hormonal imbalance with impaired spermatogenesis. Environmental and lifestyle factors, including diet, alcohol, antibiotics, endocrine disruptors, and microplastics, were increasingly recognized as influencing microbiome-mediated fertility. Mechanistic insights into the gut-testis axis, endotoxemia, immune modulation, and nutrient metabolism suggest avenues for diagnostics and microbiome-based interventions, including probiotics, nutritional modulation, and fecal microbiota transplantation.}, }
@article {pmid41242566, year = {2026}, author = {Yousefi-Hashemabad, MJ and Hosseini Kakroudi, M and Pourashory, M and Forouzan, K and Yazdanpanah, N and Saleki, K and Rezaei, N}, title = {Intratumoral bacterial microbiota in gastrointestinal adenocarcinoma: From computational insights to clinical practice.}, journal = {Microbial pathogenesis}, volume = {210}, number = {}, pages = {108174}, doi = {10.1016/j.micpath.2025.108174}, pmid = {41242566}, issn = {1096-1208}, mesh = {Humans ; Tumor Microenvironment ; *Adenocarcinoma/microbiology/therapy/pathology ; *Gastrointestinal Neoplasms/microbiology/therapy/pathology ; Bacteria/classification/genetics ; *Gastrointestinal Microbiome ; *Microbiota ; Probiotics/therapeutic use ; Artificial Intelligence ; Fusobacterium nucleatum ; Animals ; }, abstract = {Intratumoral microbiota refers to bacteria and other organisms residing within the tumor microenvironment and are intriguingly found throughout the TME, including in cancer cells, immune cells, and stromal components. Among these microbiota, bacteria have gained attention due to their emerging roles in tumor biology. Recent research has uncovered new pathophysiological and therapeutic roles for targeting intratumoral bacterial microbiota. Emerging evidence pointed out that certain taxa, including Fusobacterium nucleatum and Porphyromonas gingivalis, can drive tumorigenic activity, whereas taxa such as Lactobacillus spp. may act as a protective agent. Overall, bacteria can influence cancer progression through mechanisms including immune modulation, metabolic reprogramming, and genomic instability. Furthermore, advances in artificial intelligence (AI) and microbiome profiling have identified prognostic microbial signatures and markers of treatment response. In addition, the mediation of the tumor microbiota via probiotics, antibiotics, engineered microbes, and fecal transplants exhibits novel approaches in targeted cancer therapy. The present review captures the role of intratumoral bacterial microbiota in adenocarcinomas and their significance in cancer development and progression as evidenced by experimental and clinical research.}, }
@article {pmid41243097, year = {2025}, author = {Hang, WJ and Yin, R and Kang, XW and He, L and Cao, X and Chen, J}, title = {Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {190}, pmid = {41243097}, issn = {1749-8546}, support = {82100402//National Natural Science Foundation of China/ ; 82370837//National Natural Science Foundation of China/ ; 2022CFB201//Bureau of Science and Technology of Hubei Province/ ; 2022YFE0209900//National Key Research and Development Program of China/ ; WZ21A02//Wuhan Municipal Health Commission's Scientific Research/ ; }, abstract = {BACKGROUND: Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.<br><br>METHODS: Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25&#xa0;mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.<br><br>RESULTS: Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 '-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.<br><br>CONCLUSION: Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.}, }
@article {pmid41243436, year = {2025}, author = {Cen, Q and Cui, Y and Jin, J and Feng, J and Xin, Y and Zhang, Z and Li, J and Wang, J and Zhang, A}, title = {Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2576657}, pmid = {41243436}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis/metabolism/microbiology/therapy ; *Lipid Metabolism ; Animals ; }, abstract = {Dysregulation of the structure of the gut microbiota is closely linked to the risk of onset and progression of multiple sclerosis. The intricate interaction between the gut microbiota and lipid metabolism likely serves as a crucial pathway mediating this relationship: the gut microbiota directly or indirectly modifies lipid metabolism (including cholesterol, sphingolipids, phospholipids, and fatty acids) by controlling the production of specific metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, trimethylamine-N-oxide, and lipopolysaccharides), thereby impacting core pathological processes in multiple sclerosis. Therefore, elucidating the specific roles and mechanisms of the gut microbiota in modulating lipid metabolism in multiple sclerosis will accelerate the development of precision therapeutic strategies. In this review, we conduct an in-depth exploration of the interaction between the gut microbiota and lipid metabolism in the context of multiple sclerosis and provide a comprehensive summary of existing strategies targeting the gut microbiota and lipid metabolism for treating multiple sclerosis (including microbiota-based therapies, pharmacotherapy, and lifestyle modifications). Finally, we outline the present challenges in this field and offer an in-depth prospect for future directions.}, }
@article {pmid41244772, year = {2025}, author = {Li, Q and Song, XC and Li, K and Wang, J}, title = {Gut-lung immunometabolic crosstalk in sepsis: from microbiota to respiratory failure.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1685044}, pmid = {41244772}, issn = {2296-858X}, abstract = {Sepsis is a systemic immune-metabolic disorder syndrome caused by infection, in which gut microbiota dysbiosis plays a central role in the occurrence and development of multi-organ dysfunction. This paper systematically elaborates on the bidirectional regulatory mechanism of the "gut-lung axis" in sepsis. Gut microbiota dysregulation damages the gut barrier function, reduces the production of short-chain fatty acids (SCFAs), and increases endotoxin translocation. Subsequently, it activates alveolar macrophage polarization, promotes the formation of neutrophil extracellular traps (NETs), and leads to an imbalance in the Treg/Th17 cell ratio, ultimately exacerbating the pathological process of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Conversely, the pulmonary inflammatory response can also aggravate gut barrier damage through circulating inflammatory mediators, forming a vicious cycle. Mechanistically, HIF-1α, mTOR, and Sirtuins do not act in isolation. Instead, they jointly regulate the metabolic fate of immune cells through spatiotemporally dynamic interactions. During the evolution of sepsis, these signals exhibit opposite regulatory polarities during the hyper-inflammatory phase and the immunosuppressive phase, and mitochondrial dysfunction and oxidative stress further amplify the inflammatory cascade reaction. Preclinical research evidence shows that microbiota-based intervention measures (including probiotic preparations, fecal microbiota transplantation, and SCFA supplementation) and vagus nerve electrical stimulation can effectively alleviate sepsis-related lung injury and improve prognosis, but there is significant individual heterogeneity in their therapeutic effects. Future research should not be restricted to descriptive associations. Instead, it is essential to conduct in-depth analyses of the specific logic of the aforementioned signaling networks in terms of cell types, subcellular compartments, and disease course timings, and clarify their context-dependent controversies to promote the transformation of mechanistic understanding into precision treatment. Meanwhile, research efforts should focus on constructing a multi-omics dynamic biomarker system integrating metagenomics, metabolomics, and immunophenotyping analysis and designing clinical trials through precise patient stratification to facilitate the clinical translation of individualized treatment strategies based on gut-lung axis regulation.}, }
@article {pmid41244880, year = {2025}, author = {Bautista, J and Hidalgo-Tinoco, C and Di Capua Delgado, M and Viteri-Recalde, J and Guerra-Guerrero, A and López-Cortés, A}, title = {The gut-brain-circadian axis in anxiety and depression: a critical review.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1697200}, pmid = {41244880}, issn = {1664-0640}, abstract = {Anxiety and depressive disorders rank among the most prevalent psychiatric conditions worldwide, yet remission rates remain unsatisfactory despite advances in pharmacological and psychotherapeutic interventions. The gut-brain axis has emerged as a transformative framework for understanding these disorders, emphasizing bidirectional communication between the central nervous system, the enteric nervous system, the endocrine and immune systems, and the gut microbiota. Preclinical studies demonstrate that germ-free or dysbiotic states exaggerate hypothalamic-pituitary-adrenal (HPA) reactivity, remodel synaptic plasticity, and induce anxiety- and depression-like behaviors, while fecal microbiota transplantation confirms the causal influence of microbial communities. Mechanistically, neural (e.g., vagal), endocrine (e.g., cortisol), immune (e.g., cytokine), and metabolic (e.g., short-chain fatty acids, tryptophan metabolites, bile acids) pathways converge to regulate mood and stress resilience. An underappreciated yet critical dimension of this model is circadian rhythmicity. Both host endocrine cycles and microbial communities exhibit diurnal oscillations that synchronize metabolism, immune activity, and neural signaling. Disruption of these rhythms, through factors such as sleep disturbance, irregular feeding, or shift work, alters microbial diversity, dampens metabolite oscillations, destabilizes HPA regulation, and enhances neuroinflammation, thereby amplifying vulnerability to psychiatric disorders. Collectively, evidence supports a model in which anxiety and depression are systemic conditions arising from integrated neural, immune, endocrine, metabolic, and circadian dysregulation, rather than isolated brain-based pathologies. This reconceptualization positions microbial taxa and metabolites as candidate biomarkers and therapeutic targets. Precision interventions, ranging from diet and psychobiotics to fecal microbiota transplantation, chrononutrition, and immune-modulatory strategies, offer promising avenues for personalized psychiatry.}, }
@article {pmid41245267, year = {2025}, author = {Makkar, SK and Bishnupuri, KS}, title = {The gut microbiome and gastrointestinal cancers: mechanisms, biomarkers and therapeutic opportunities.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1676796}, pmid = {41245267}, issn = {1664-042X}, abstract = {Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis-characterized by disrupted microbial diversity and function-in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including early diagnosis, prognosis assessment, and therapeutic response prediction. The intricate interactions between microbiota and standard cancer therapies-chemotherapy, immunotherapy, and radiation therapy-are discussed, highlighting microbiome influences on therapeutic efficacy and adverse effect profiles. We also critically assess the impact of modifiable factors such as diet, medications, lifestyle, and environmental exposures on microbiome composition and cancer risk. The review evaluates emerging therapeutic interventions, including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered live biotherapeutics. Despite notable advancements, significant hurdles remain, including clarifying causality, methodological standardization, and equitable global research representation. Addressing these challenges, we propose a strategic research agenda aimed at harnessing microbiome insights to advance precision oncology and improve GI cancer outcomes globally.}, }
@article {pmid41246285, year = {2025}, author = {Ahmed, N and Gaur, V and Kamle, M and Chauhan, A and Chauhan, R and Kumar, P and Singh, NA}, title = {Microbiome-based therapeutics for metabolic disorders: harnessing microbial intrusions for treatment.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1695329}, pmid = {41246285}, issn = {2673-3129}, abstract = {The rising global rates of metabolic disorders, such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, call for new treatment methods beyond traditional drugs. The human gut microbiota, made up of trillions of microorganisms that plays a crucial role in maintaining metabolic balance through complex biochemical processes and interactions between hosts and microbes. Dysbiosis, which involves changes in microbial composition and a decrease in diversity, has become a major factor in metabolic problems. This disruption impacts the production of short-chain fatty acid, increase in permeability of intestine, and causes enduring low-grade inflammation. This review features into the potential of treatments based on microbiome for metabolic syndromes, focusing on probiotics, prebiotics, synbiotics, and postbiotics. It also encompasses innovative methods such as engineered microbial consortium, fecal microbiota transplantation (FMT), and vaginal microbiota transplantation (VMT). Probiotics show significant promise in improving blood sugar control and enhancing lipid levels. Prebiotics help bring about positive changes in microbial composition and the production of beneficial metabolites. Synbiotic combinations provide added benefits by helping good microbes thrive while supplying nutrients they can ferment. Postbiotics have recent research focus because they are safer, more stable, easier to store, and less likely to contribute to antibiotic resistance comparative to live probiotics. Even now there are substantial complications in translating microbiome research into standardized therapeutics despite of promising pre-clinical outcomes and some initial clinical data. These comprises individual variances, strain-specificity, dosage problems, regulation issues, and the necessity for personalised treatment strategies. Future success will depend upon personalized medicine, technological developments, and the incorporation of multi-omics strategy to generate metabolic health therapeutics depending on targeted microbiomes.}, }
@article {pmid41246810, year = {2025}, author = {Tan, H and Chen, M and Yao, H and Li, S and Nie, S}, title = {Dominant Gut Commensals Enriched by Pectin with Low Esterification Degree Orchestrate the Amelioration of Acute Ulcerative Colitis.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {47}, pages = {30275-30288}, doi = {10.1021/acs.jafc.5c09097}, pmid = {41246810}, issn = {1520-5118}, mesh = {*Pectins/chemistry/metabolism/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/microbiology/metabolism/drug therapy/therapy ; Male ; Humans ; Mice ; Esterification ; Mice, Inbred C57BL ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Dietary fiber's health benefits are increasingly recognized as microbiota-dependent, with effects influenced by fiber structure. We previously observed that low-esterified pectin provides superior protection against DSS-induced colitis compared to its high-esterified form, but the mechanism was unknown. This study investigated the microbiota-dependent pathway underlying low-esterified pectin's anticolitic effect using FMT. By evaluating three pectin-induced bacteria (Bifidobacterium longum NSP002, Bacteroides xylanisolvens NSP003, Enterococcus faecium NSP004) individually and in a consortium, we found that the consortium exerted a significantly stronger protective effect, suggesting synergistic interactions and highlighting its potential as an FMT alternative. Mechanistically, this protection may involve three axes: (1) Gut microbiome remodeling (reduced Akkermansia, increased Bacteroides, elevated propionic acid). (2) Intestinal homeostasis modulation (reduced mme/calprotectin expression, activated PI3K/calcium signaling). and (3) Systemic metabolic reprogramming (increased serum phenylethylamine, enriched phenylalanine metabolism). These findings support the clinical potential of pectin for optimizing enteral nutrition and using pectin-enriched microbiota consortia to target IBD pathogenesis.}, }
@article {pmid41247039, year = {2026}, author = {Kelly, CR and Feuerstadt, P}, title = {Diagnosis and Management of Clostridioides difficile.}, journal = {The American journal of gastroenterology}, volume = {121}, number = {3}, pages = {628-634}, doi = {10.14309/ajg.0000000000003844}, pmid = {41247039}, issn = {1572-0241}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Feces/microbiology ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use ; Practice Guidelines as Topic ; }, abstract = {Clostridioides difficile infection (CDI) is challenging to diagnose and treat. Recently published studies and clinical observations have improved our understanding around diagnostic testing and positioning of antibiotics and microbiota-based therapies. This review synthesizes current evidence and guidelines on CDI diagnosis, highlighting the limitations of individual tests and the value of algorithmic approaches. Treatment paradigms are discussed across the spectrum of disease severity, with vancomycin and fidaxomicin as first-line therapies and the diminishing role of metronidazole. For recurrent CDI, newer fecal microbiota-based therapies, including fecal microbiota, live-jslm (Rebyota), and fecal microbiota spores, live-brpk (Vowst), are reviewed. The role of conventional fecal microbiota transplantation, particularly in fulminant CDI, is also addressed, including challenges resulting from US Food and Drug Administration policies around stool bank material. We aim to clarify diagnostic and therapeutic approaches and optimize care for patients with CDI.}, }
@article {pmid41247324, year = {2025}, author = {Weagley, JS and Chica Cárdenas, LA and Romani, A and Sullender, ME and Aggarwal, S and Makimaa, H and Hogarty, MP and Rodgers, R and Kennedy, EA and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Differential microbial community assembly following co-housing versus microbiota transplant.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {41247324}, issn = {1751-7370}, support = {F31 AI167499/AI/NIAID NIH HHS/United States ; R25GM103757/NH/NIH HHS/United States ; DGE-1745038/DGE-2139839//NSF/ ; R01AI139314/NH/NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; U01 AT012998/AT/NCCIH NIH HHS/United States ; R01 AI173360/AI/NIAID NIH HHS/United States ; U01AT012998/NH/NIH HHS/United States ; F31AI167499/NH/NIH HHS/United States ; R25 GM103757/GM/NIGMS NIH HHS/United States ; R01AI173360/NH/NIH HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; T32AI007172/NH/NIH HHS/United States ; #1065897//Crohn's and Colitis Foundation Litwin IBD Pioneers/ ; }, mesh = {Animals ; Mice ; RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology/virology ; Cecum/microbiology ; Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; *Bacteria/classification/genetics ; *Microbiota/drug effects ; Sequence Analysis, DNA ; DNA, Bacterial/genetics/chemistry ; Mice, Inbred C57BL ; DNA, Ribosomal/chemistry/genetics ; *Gastrointestinal Microbiome ; }, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transfer of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of faecal or caecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, faecal transplantation, and caecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR (qPCR), and shotgun sequencing of viral-like particles (VLPs). As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transfer-recipient control mice. Although all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. Overall, faecal and caecal transplant resulted in highly similar colonization processes with some minor variation in enrichment for two specific bacterial families. This study provides valuable insights into microbial ecology, as well as the dynamics underlying experimental microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transfer in mouse models.}, }
@article {pmid41247394, year = {2025}, author = {Wu, Y and Chan, SSM and Leung, PWL and Lo, HHL and Ho, SWS and Mo, FYM and Ho, CSW and Shea, CKS and Su, Q and Leung, TF and Chan, FKL and Ng, SC and Wong, OWH}, title = {The Mediating Role of Eating Behaviors Between Autistic Symptoms and Dietary Issues Among Chinese Children With Autism.}, journal = {Journal of autism and developmental disorders}, volume = {}, number = {}, pages = {}, pmid = {41247394}, issn = {1573-3432}, support = {InnoHK&#x202f;, the Government of Hong Kong, Special Administrative&#x202f;Region of the People's Republic of China//InnoHK&#x202f;, the Government of Hong Kong, Special Administrative&#x202f;Region of the People's Republic of China/ ; InnoHK&#x202f;, the Government of Hong Kong, Special Administrative&#x202f;Region of the People's Republic of China//InnoHK&#x202f;, the Government of Hong Kong, Special Administrative&#x202f;Region of the People's Republic of China/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; PF22-77807//The Hong Kong PhD Fellowship Scheme/ ; }, abstract = {PURPOSE: Eating and dietary challenges are common among children with autism, but their associations with clinical symptoms remain unclear. This study aims to describe dietary issues, including nutritional problems and overexposures to food additives in autistic children, and their associations with clinical symptoms.<br><br>METHODS: This case-control study involved 836 children (469 with autism and 367 without autism; mean age&#x2009;=&#x2009;8.3 years) profiled on autistic symptoms, eating behaviors, and dietary patterns with parent-reported questionnaires. Nutritional insufficiencies, dietary quality and food additives exposures were compared using regression models adjusted for age and sex. Multivariate logistics or linear regression models were used to identify clinical symptoms that predict dietary issues, with mediation analyses examining eating behaviors' roles.<br><br>RESULTS: Autistic children had lower protein intake, more vitamin and mineral insufficiencies, higher exposure to food additives, and poorer diet quality. They consumed fewer fruits/vegetables and more animal-based fats, with 38.2% exceeding 125% of the Estimated Energy Requirement (vs. 22.9% controls), suggesting energy-dense, ultra-processed food preferences. Diminished food enjoyment and increased food fussiness mediated between low social motivation and nutritional insufficiencies, as well as poorer diet quality. Further, difficulties with food responsiveness and emotional eating patterns mediated between more restricted and repetitive behaviors and higher exposures to emulsifiers/thickeners.<br><br>CONCLUSION: Autistic children, especially those with severe core symptoms, are susceptible to multifaceted dietary issues such as preference for low-quality food and nutrient deficiencies. It is crucial to implement personalized treatment strategies that target their specific eating behaviors to effectively address dietary challenges.}, }
@article {pmid41248567, year = {2025}, author = {Huang, F and Zhang, L and Cheng, S and Zhang, Z and Xiang, Q and Xiao, Z}, title = {Banxia Baizhu Tianma Decoction improves posterior circulation ischemia vertigo in rats via gut microbiota and TLR4-NF-κB-MyD88 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157539}, doi = {10.1016/j.phymed.2025.157539}, pmid = {41248567}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Male ; Toll-Like Receptor 4/metabolism ; Rats ; Rats, Sprague-Dawley ; NF-kappa B/metabolism ; Myeloid Differentiation Factor 88/metabolism ; Signal Transduction/drug effects ; Brain Ischemia/drug therapy ; Disease Models, Animal ; }, abstract = {BACKGROUND: Posterior circulation ischemia vertigo (PCIV) frequently presents with vestibular dysfunction in patients suffering from posterior circulation stroke. The conventional approaches often fail to address PCIV's complex pathophysiology, which involves neuroimmune dysregulation, hemodynamic abnormalities, and gut-brain axis disruption. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine, is employed in treating PCIV and vasogenic vertigo, but the mechanisms underlying its efficacy require further elucidation.<br><br>PURPOSE: This study examines the therapeutic mechanisms and efficacy of BBTD for PCIV, particularly focusing on its impacts on neuroinflammation, gut microbiota communities, and gut barrier using a rat model of PCIV.<br><br>METHODS: The chemical and bioactive constituents of BBTD were profiled using ULPLC-Q Exactive-Orbitrap-MS. The PCIV model was employed and treated with BBTD for 7 days. Neurological score was measured with balance beam test; cerebellar pathology was assessed by H&amp;E and Nissl staining. The TTC staining was used to measure cerebral infarct volume. The levels of IL-6, IL-1&#x3b2;, and TNF-&#x3b1; in serum and cerebellar tissue was analyzed by ELISA. Its mechanisms were investigated by 16S rRNA sequencing, antibiotic antagonistic and fecal microbiota transplantation (FMT) experiments. Significant alterations in gut microbiota and their detailed mechanisms were identified. Intestinal barrier integrity was assessed by AB-PAS staining, tight junction proteins (MUC2, occludin, claudin-1, ZO-1), and colonic inflammatory cytokine levels. The levels of short-chain fatty acids in the cecal contents and cerebellar tissues of our experimental rats using gas chromatography-mass spectrometry (GC-MS).<br><br>RESULTS: Our findings demonstrated that BBTD significantly improved neurological function, ameliorates cerebral ischemia, and alleviated neuroinflammation in rats. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, elevating Lactobacillus and Akkermansia, while reducing Clostridiales and Ruminococcaceae. The further antibiotic depletion and FMT experiments confirmed that gut microbiota was essential for BBTD-induced neuroinflammation and gut barrier protection in PCIV. BBTD ameliorated intestinal damage by enhancing acidic mucins and tight junction protein expression. BBTD treatment markedly increased the concentrations of propionic acid in intestinal fecal content and cerebellar tissue. Mechanistically, BBTD ameliorates ischemia-induced neuroinflammation and neuronal injury by modulating the TLR4-NF-&#x3ba;B-MyD88 pathway via the gut-brain axis.<br><br>CONCLUSION: BBTD ameliorates PCIV through gut-brain axis modulation, restoring gut barrier-microbiota balance and suppressing TLR4-NF-&#x3ba;B-MyD88 signaling. BBTD treatment and FMT may serve as an effective therapeutic strategy for mitigating posterior circulation ischemia progression.}, }
@article {pmid41249722, year = {2025}, author = {Xu, N and He, Y and Yang, G and Huang, X}, title = {Exploring the Role of Gut Microbiota in Chronic Spontaneous Urticaria: Mechanisms and Potential Therapeutic Implications.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41249722}, issn = {1867-1314}, support = {no. 82103751//National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota dysbiosis has emerged as a significant factor in the pathogenesis of chronic spontaneous urticaria (CSU), a condition characterized by immune dysregulation and skin inflammation. This review summarizes the current understanding of the role of gut microbiota in CSU pathogenesis, highlighting the alterations in microbial composition and function, the mechanisms by which dysbiosis triggers systemic inflammation and skin mast cell activation, and the impact of microbial metabolites. We critically evaluate the potential of gut microbiota-targeted therapies, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), as novel treatment strategies for CSU. Despite the evident promise of these approaches, significant challenges persist, including the necessity for personalized interventions, the collection of long-term efficacy and safety data, and a more profound understanding of the complex interplay between the gut and skin. Future research endeavors must prioritize the execution of clinical trials that evaluate the efficacy of gut microbiota modulation in CSU patients and the identification of biomarkers that can effectively predict treatment response.}, }
@article {pmid41250124, year = {2025}, author = {Huang, SW and Lin, CR and Chang, YH and Ni, YH and Chen, HL and Liu, HH}, title = {Cross-country multi-modal evidence links Aspergillus to biliary atresia.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {94}, pmid = {41250124}, issn = {1757-4749}, abstract = {BACKGROUND: Biliary atresia (BA) is the leading cause of pediatric liver transplantation. It is characterized by progressive extrahepatic bile duct obstruction in young infants. Inspired by the success of antifungal treatment in a newborn with BA-related obstructive cholangitis, we explored a potential link between BA and fungi, particularly Aspergillus. Fecal DNA was analyzed using 18S ribosomal sequencing and validated with a published fecal metagenomic dataset. Epidemiological data from the UK, Taiwan, and Japan were also examined.<br><br>RESULTS: Gut Aspergillus was exclusively detected in BA cases, suggesting it may be a potential trigger. Independent fecal metagenomic data from China and epidemiological correlations further supported this hypothesis. In the UK, BA presentations strongly correlated (r = 0.98, 95% CI [0.36, 1.0], p = 0.02) with Aspergillosis, but not with Candidiasis, during the COVID-19 lockdown. In Taiwan, a decade of data showed BA incidence was significantly associated (r = 0.78, 95% CI [0.29, 0.94], p = 0.01) with yearly Aspergillus-positive isolates among cancer-adjusted hospital admissions. In Japan, BA cases over 25 years correlated significantly (r = 0.85, 95% CI [0.37, 0.97], p = 0.01) with visceral Aspergillus burdens in autopsied cases, but not with other fungal infections.<br><br>CONCLUSIONS: The resolution of obstructive cholangitis in the antifungal-treated index case, together with multi-modal, cross-country evidence, highlights a potential link between gut Aspergillus and BA. Although limited by small sample size, retrospective design, and lack of mechanistic validation, the study may still be interpreted as hypothesis-generating and underscores the need for prospective studies to validate and extend these observations.}, }
@article {pmid41250648, year = {2025}, author = {Yang, J and Tan, H and Peng, X and Nie, S}, title = {Tamarind Seed-Derived Xyloglucan Attenuates Insulin Resistance in Mice through Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {47}, pages = {30236-30256}, doi = {10.1021/acs.jafc.5c07829}, pmid = {41250648}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Xylans/administration &amp; dosage ; *Glucans/administration &amp; dosage ; Mice ; *Insulin Resistance ; Seeds/chemistry ; Male ; Mice, Inbred C57BL ; *Tamarindus/chemistry ; *Plant Extracts/administration &amp; dosage ; Diet, High-Fat/adverse effects ; Humans ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; }, abstract = {Xyloglucan (XG), a plant polysaccharide abundant in tamarind seeds, is FDA-approved for use as a food additive, stabilizer, thickener, or gelling agent. While its structural properties have been well-studied, its physiological effects remain unclear. This study employed a high-fat diet-induced insulin resistance mouse model to evaluate the effects of XG on metabolic disturbances, combining 16S rRNA sequencing and metabolomics to determine the role of gut microbiota. Results showed that XG intervention in HFD-fed mice improved glucose tolerance and liver function and reduced inflammation and oxidative stress, linked to altered carnitine and tryptophan metabolism. Gut microbiota analysis revealed selective enrichment of Bifidobacterium. Crucially, the benefit of XG was transferable via fecal microbiota transplantation but was abolished by antibiotic-induced microbiota depletion. This study demonstrates that tamarind seed-derived xyloglucan alleviates metabolic disturbances via a gut-microbiota-dependent mechanism, supporting its potential probiotic role in functional foods.}, }
@article {pmid41252206, year = {2026}, author = {Moreau, GB and Tian, J and Natale, NR and Naz, F and Young, MK and Nayak, U and Tanyüksel, M and Rigo, I and Madden, GR and Abhyankar, MM and Hagspiel, N and Brovero, S and Worthington, M and Behm, B and Marie, C and Petri, WA and Ramakrishnan, G}, title = {Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile.}, journal = {JCI insight}, volume = {11}, number = {1}, pages = {}, pmid = {41252206}, issn = {2379-3708}, support = {F31 NS135897/NS/NINDS NIH HHS/United States ; K23 AI163368/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cell Proliferation ; *Clostridioides difficile ; *Clostridium Infections/therapy/immunology/microbiology ; *Colon/immunology/pathology/microbiology ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/immunology ; *Immunity, Mucosal/immunology ; *Intestinal Mucosa/immunology/pathology/microbiology ; Recurrence ; }, abstract = {BACKGROUNDFecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.METHODSWe report the results of a clinical trial of patients undergoing FMT therapy for rCDI (n = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.RESULTSNo patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.CONCLUSIONWe conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.TRIAL REGISTRATIONClinicaltrials.gov NCT02797288.FUNDINGThis work was funded by grants from the NIH.}, }
@article {pmid41252333, year = {2026}, author = {Bahji, A and Brietzke, E and Cooke, NCA and Clement, F and Frey, BN and Hofmeister, M and Kennedy, SH and Lam, R and Milev, R and Moinul, D and Parikh, SV and Patten, S and Ravindran, A and Rosenblat, JD and Samaan, Z and Schaffer, A and Saleem, A and Beaulieu, S and Tourjman, V and Van Ameringen, M and Vigod, S and Yatham, LN and Taylor, V and , }, title = {The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {71}, number = {5}, pages = {346-358}, pmid = {41252333}, issn = {1497-0015}, mesh = {Humans ; *Probiotics/therapeutic use/administration &amp; dosage ; *Fecal Microbiota Transplantation/standards/methods ; *Major Depressive Disorder/therapy/microbiology ; *Synbiotics/administration &amp; dosage ; *Prebiotics/administration &amp; dosage ; Canada ; Adult ; *Gastrointestinal Microbiome ; *Practice Guidelines as Topic/standards ; *Advisory Committees/standards ; }, abstract = {BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.}, }
@article {pmid41253270, year = {2025}, author = {Ding, L and Xu, JY and Zhang, LL and Liu, Y and Gu, KT and Liang, YZ and Hidayat, K and Wan, Z and Chen, GC and Qin, LQ}, title = {Lactoferrin alleviates non-alcoholic steatohepatitis via remodeling gut microbiota to regulate serotonin-related pathways.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.034}, pmid = {41253270}, issn = {2090-1224}, abstract = {INTRODUCTION: Lactoferrin (LF), a multifunctional glycoprotein, has been implicated in the regulation of glucose and lipid metabolism.<br><br>OBJECTIVES AND METHODS: This study employed in vivo and in vitro models to investigate the direct effects of LF on non-alcoholic steatohepatitis (NASH) and to elucidate its underlying mechanisms.<br><br>RESULTS: LF intervention alleviated hepatic lipid metabolic disorders and liver injury in high-fat, high-cholesterol cholate-containing diet (HFCCD)-fed mice by mitigating oxidative stress, suppressing the inflammatory cGAS/STING pathway, and reducing M1 proinflammatory macrophage polarization. These effects were validated in free fatty acid (FFA)-treated HepG2 cells and AML12 cells. Furthermore, LF ameliorated HFCCD-induced gut microbiota dysbiosis and increased short-chain fatty acid levels. The critical role of gut microbiota in mediating the hepatoprotective effects of LF was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation. Mechanistically, LF modulated gut-liver serotonin signaling and promoted fatty acid &#x3b2;-oxidation through the HTR2A-PPAR&#x3b1;-CPT-1A pathway, an effect abolished by the HTR2A agonist DOI. In a co-culture system, LF treatment of the Caco-2/HT29 monolayer alleviated lipid accumulation and regulated the HTR2A-PPAR&#x3b1;-CPT-1A pathway in FFA-treated HepG2 cells.<br><br>CONCLUSIONS: These findings indicate that LF attenuates NASH by remodeling gut microbiota to modulate microbiota-derived serotonin signaling and enhance fatty acid oxidation.}, }
@article {pmid41253445, year = {2025}, author = {Chen, YL and Meng, LL and Wu, JY and Yang, XY and Ouyang, L and Wu, BF and Xu, HX and Gu, JL and Wang, YL and Jing, XY and Lu, SF and Fu, SP}, title = {Electroacupuncture Reprograms Gut Microbiota and Confers Cerebral Protection After Stroke through Enhanced Regulatory T Cell Response.}, journal = {The American journal of Chinese medicine}, volume = {53}, number = {8}, pages = {2307-2330}, doi = {10.1142/S0192415X25500855}, pmid = {41253445}, issn = {1793-6853}, mesh = {*Electroacupuncture ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; *T-Lymphocytes, Regulatory/immunology ; Male ; *Stroke/therapy/immunology ; Mice ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Rats ; Mice, Inbred C57BL ; Brain/immunology/pathology ; Reperfusion Injury/therapy ; *Brain Ischemia/therapy/immunology ; Humans ; }, abstract = {Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.}, }
@article {pmid41254951, year = {2025}, author = {González-Correa, C and Miñano, S and Moleón, J and Toral, M and Robles-Vera, I and Sánchez, M and Jiménez, R and Olivares, M and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Romero, M and Gómez-Guzmán, M and Duarte, J}, title = {The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2586324}, pmid = {41254951}, issn = {1949-0984}, mesh = {Animals ; Rats, Inbred SHR ; *Hydrochlorothiazide/pharmacology/administration &amp; dosage/therapeutic use ; *Probiotics/administration &amp; dosage/pharmacology ; *Hypertension/drug therapy/microbiology/physiopathology ; Gastrointestinal Microbiome/drug effects ; Rats ; *Antihypertensive Agents/pharmacology/administration &amp; dosage/therapeutic use ; Male ; *Limosilactobacillus fermentum/physiology ; Blood Pressure/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {Limosilactobacillus fermentum CECT5716 (LC40) consumption reduces hypertension and improves endothelial dysfunction in spontaneously hypertensive rats (SHRs). The diuretic hydrochlorothiazide (HCTZ) lowers blood pressure in SHR but disrupts the gut microbiota balance. In this study, we investigated whether the LC40 could enhance the antihypertensive effects of HCTZ. Interestingly, we found that coadministration of LC40 with HCTZ potentiated the beneficial effects of HCTZ on endothelial dysfunction and blood pressure without altering plasma HCTZ concentrations or exacerbating electrolyte imbalances. These protective effects were associated with normalization of microbiota alterations, including a reduction in the Firmicutes/Bacteroidota ratio, suppression of lipopolysaccharide biosynthesis, and an increase in acetate-producing bacteria. Additionally, LC40 reduced intestinal pathology and endotoxemia. Furthermore, the HCTZ + LC40-treated rats exhibited reduced neuroinflammation and sympathetic activity, along with an immunoregulatory effect characterized by increased regulatory T cell infiltration and a reduction of vascular oxidative stress in the aorta. The beneficial effects of LC40 in HCTZ-treated rats appeared to be microbiota dependent, as they were replicated through fecal microbiota transplantation in germ-depleted normotensive rats. Our findings identify the gut microbiota as a novel therapeutic target to enhance the antihypertensive effects of diuretics. The coadministration of LC40 with HCTZ modulates immune responses, providing a promising strategy to improve hypertension management.}, }
@article {pmid41255078, year = {2026}, author = {Ghoshal, UC and Ramakrishna, BS and Rathi, PM and Shukla, A and Panigrahi, MK and Jain, S and Saha, I and Chakravartty, K and Singh, M and Mustafa, U and Sahu, S and Ghoshal, U and Chandnani, S and Goenka, MK and Mitra, M}, title = {Probiotic Blend of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. Lactis BB-12 in Non-constipated Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.}, journal = {Journal of gastroenterology and hepatology}, volume = {41}, number = {1}, pages = {140-154}, doi = {10.1111/jgh.70137}, pmid = {41255078}, issn = {1440-1746}, support = {//Zydus Healthcare Limited and Shanti Public Educational and Development Society/ ; }, mesh = {Humans ; *Probiotics/adverse effects/administration &amp; dosage/therapeutic use ; *Irritable Bowel Syndrome/therapy/microbiology ; *Lactobacillus acidophilus ; Double-Blind Method ; Female ; Male ; Adult ; Middle Aged ; Treatment Outcome ; *Bifidobacterium animalis ; Quality of Life ; Gastrointestinal Microbiome ; Feces/microbiology ; Severity of Illness Index ; }, abstract = {BACKGROUND: As dysregulated gut microbiota is known in irritable bowel syndrome (IBS) and probiotics may improve it, we investigated the efficacy and safety of a combination probiotic, Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. lactis BB-12 in non-constipated IBS.<br><br>METHODS: Two hundred non-constipated IBS patients were randomized to the above-mentioned probiotic and placebo for 84&#x2009;days. The outcome measures included IBS-Global Improvement Scale (IBS-GIS), IBS-Quality of Life (IBS-QoL), EAR3Q, IBS-Severity Scoring System (IBS-SSS), and patient-reported improvement. Fecal microbiota was evaluated in a subset.<br><br>RESULTS: Response in IBS-GIS was higher with probiotics than with placebo at days 28 (19.3% vs. 8.9%; p&#x2009;=&#x2009;0.048), 56, and 84. Total and abdominal pain, distension, and QoL scores of IBS-SSS decreased at day 28 with probiotics that persisted till days 56 and 84. The percentage of patients with "severe" symptoms reduced from 20.8% at baseline to 3.9% at day 84, and the median IBS-QoL score decreased significantly at day 28; the beneficial effect on QoL was sustained till days 56 and 84 (p&#x2009;<&#x2009;0.001). Improvement in abdominal pain, distension, urgency of defecation, bowel habit satisfaction, and stool frequency was noted earlier with probiotics than with placebo; 4.0% in the probiotic group and 0.9% in the placebo group had mild/moderate adverse events (p&#x2009;=&#x2009;0.167). Symptom recurrence occurred in 3.0% in the probiotic group and 3.9% in the placebo group during follow-up of 180&#x2009;days (p&#x2009;=&#x2009;0.718). No difference was observed in the fecal microbiota between the two groups, but healthy genera were enriched with probiotics.<br><br>CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults.}, }
@article {pmid41255529, year = {2025}, author = {Horiachok, M and Potapova, K and Ivanykovych, T and Yerokhovych, V and Ilkiv, Y and Sokolova, L}, title = {Integrating gut microbiota into multidisciplinary perspectives on diabetic neuropathy.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1710868}, pmid = {41255529}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetic Neuropathies/microbiology/therapy/metabolism ; *Dysbiosis/microbiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Diabetic neuropathy (DN) is one of the most common and debilitating complications of diabetes mellitus, yet its precise pathogenesis remains incomplete. Emerging evidence highlights the gut microbiome as a key factor linking metabolic dysfunction, immune activation, and neuronal damage. Even minor dysbiosis may interfere with microbial metabolite balance and disrupt intestinal integrity, leading to local and, consequently, systemic inflammation, which in turn drives altered pain response via the gut-brain-immune axis. Recent clinical and preclinical data show that reduced short-chain fatty acid availability, altered bile acid and tryptophan metabolism, let alone expansion of pro-inflammatory species collaboratively contribute to DN onset and progression. Moreover, advances in metagenomics and metabolomics reveal reproducible microbiome-derived biomarkers that could predict neuropathy risk and pain phenotypes independent of glycemic control, supporting the microbiome as both a mechanistic driver and a measurable potential diagnostic tool. In the context of management, microbiota-affected interventions, such as probiotics, synbiotics, omega-3 supplementation, and fecal microbiota transplantation, show early promise in alleviating symptoms and improving nerve function. This mini-review synthesizes current evidence on the microbiome's role in DN, emphasizing its dual potential as a biomarker for early diagnosis and a therapeutic target for precision microbiome-based interventions.}, }
@article {pmid41255657, year = {2025}, author = {Vaou, N and Zavras, N and Fessatou, S and Voidarou, CC and Vrioni, G and Tsakris, A and Vaos, G}, title = {Microbiota decolonization of bacterial pathogens in pediatric surgery-related intestinal disorders: Insights on current strategies and future outlook.}, journal = {World journal of clinical pediatrics}, volume = {14}, number = {4}, pages = {107722}, pmid = {41255657}, issn = {2219-2808}, abstract = {The significance of gut microbiota (GM) in human health is being increasingly researched. An imbalance in GM composition, known as dysbiosis, is linked to various and other health issues. In addition, antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM, which may result in colonization by antimicrobial-resistant (AMR) pathogens. Therefore, alternative antibiotic strategies for combating AMR pathogens are urgently needed. This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies' critical role in pediatric surgical disorders. Strategies such as decontamination of the digestive tract utilizing antibiotics, the use of probiotics, and particularly fecal microbiota transplantation have introduced new options for clinical treatment. These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery, including inflammatory bowel disease, neonatal necrotizing enterocolitis, Hirschsprung-associated enterocolitis, and short bowel syndrome. Despite GM therapeutics, recent strategies are still in their developmental phase and exhibit challenges that need further research. Thus, potential future directions for GM-targeted decolonization therapies are under consideration. Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.}, }
@article {pmid41258493, year = {2025}, author = {Xu, Q and Lin, A and Jiang, A and Chen, L and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Miao, K and Luo, P}, title = {Circadian rhythms as a modulator of gut microbiota-tumor microenvironment crosstalk.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {409}, pmid = {41258493}, issn = {1420-9071}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Circadian Rhythm/physiology ; *Tumor Microenvironment ; Animals ; *Neoplasms/microbiology/pathology/therapy ; Dysbiosis/microbiology ; }, abstract = {Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression. This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME. We examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME. We investigate the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, we evaluate emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation. The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment.}, }
@article {pmid41260222, year = {2025}, author = {Wang, Y and Wu, J and Yao, J and Chen, J and Cheng, KKY and Ho, MY and Lee, CH and Lam, KS and Tse, MA and Panagiotou, G and Xu, A}, title = {Gut microbiome-adipose crosstalk modulates soluble IL-6 receptor influencing exercise responsiveness in glycemic control and insulin sensitivity.}, journal = {Cell metabolism}, volume = {37}, number = {12}, pages = {2323-2341.e6}, doi = {10.1016/j.cmet.2025.10.013}, pmid = {41260222}, issn = {1932-7420}, mesh = {*Receptors, Interleukin-6/metabolism/blood ; *Gastrointestinal Microbiome/physiology ; Animals ; *Insulin Resistance ; Humans ; Mice ; ADAM17 Protein/metabolism ; Male ; Mice, Inbred C57BL ; *Glycemic Control ; *Adipose Tissue/metabolism ; Obesity/metabolism ; *Exercise/physiology ; Physical Conditioning, Animal ; Female ; }, abstract = {Exercise is an effective intervention for the prevention and management of diabetes, but the high interpersonal variability in response to exercise impedes its widespread implementation. Herein, we identify adipocyte-derived soluble interleukin-6 receptor (sIL-6R) as a key exerkine determining exercise efficacy in improving metabolic health. In individuals with obesity who underwent a 12-week exercise intervention, circulating sIL-6R level exhibits dichotomous changes between exercise responders (Rs) and non-responders (NRs), in close association with exercise-mediated alterations in insulin sensitivity and glycemic control. Mechanistically, elevated gut microbiome-mediated leucine in NR acts on white adipocytes to promote disintegrin and metalloproteinase 17 (ADAM17)-mediated sIL-6R production via the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1α (HIF1α) pathway, which in turn impairs the metabolic benefits of exercise through interleukin (IL)-6 trans-signaling-induced adipose inflammation. Adipocyte-selective ablation of ADAM17 prevents the effects of fecal microbiota transplantation from NR on elevation of sIL-6R, thereby restoring the efficacy of exercise-shaped gut microbiome in counteracting glucose intolerance and insulin resistance in obese mice. Thus, therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.}, }
@article {pmid41263038, year = {2025}, author = {Wang, M and Sun, H and Wang, X and Zhang, X and Huang, Y and Cui, R and Sun, Y and Yao, H and Wan, JY}, title = {Tangerine Peel-Based Herbal Formula Ameliorates Metabolic Syndrome via Gut Microbiota-Mediated Bile Acid Remodeling and TGR5 Activation.}, journal = {The American journal of Chinese medicine}, volume = {53}, number = {8}, pages = {2541-2559}, doi = {10.1142/S0192415X25500946}, pmid = {41263038}, issn = {1793-6853}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Metabolic Syndrome/drug therapy/metabolism/microbiology ; *Bile Acids and Salts/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Male ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Mice ; *Phytotherapy ; Humans ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job's tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.}, }
@article {pmid41263392, year = {2025}, author = {Zhao, R and Lu, Y and Xu, Q and Ren, H and Li, H and Gao, J and Cui, H and Yuan, Z and Cao, B and Wei, B}, title = {Gut blautia coccoides-derived 5Z-dodecenoic acid attenuates chronic psychological stress-induced gastric cancer progression.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004080}, pmid = {41263392}, issn = {1743-9159}, abstract = {BACKGROUND: Chronic psychological stress is a critical oncogenic factor of gastric cancer (GC). However, the mechanisms underlying stress-induced malignant progression remain largely unknown. Gut microbiota dysregulation is tightly associated with cancer development and metabolism.<br><br>MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) modeling was used to prepare mice suffering from chronic psychological stress. 16s rRNA sequencing and Q300 targeted metabolite quantification were jointly conducted to depict landscapes of gut microbiome and metabolomics of CUMS mice. Fecal microbiota transplantation was employed to investigate the functions of gut microbial communities in regulating CUMS-mediated GC growth. Drug affinity responsive target stability, surface plasmon resonance and molecular docking assays were performed to screen direct target proteins of 5Z-dodecenoic acid. The interactions between RIOK2 and BYSL were verified with co-immunoprecipitation and GST pull-down and fluorescent co-localization analysis. A series of experiments for malignant behaviors and glycolysis and subcutaneous tumor transplantation were employed to detect alterations of GC cell phenotypes ex vivo and in vivo, respectively.<br><br>RESULTS: Microbiome and metabolomics collectively demonstrated disrupted gut microbial communities and metabolic patterns. Particularly, Blautia coccoides-derived 5Z-dodecenoic acid was predominately declined by CUMS. Supplementation with Blautia coccoides or 5Z-dodecenoic acid effectively mitigated the negative effects of CUMS on glycolysis and malignancy. Mechanistically, 5Z-dodecenoic acid directly inhibits the functions of RIOK2, which maintained ectopic glycolysis and malignant behaviors. RIOK2 further interacted with BYSL and maintained its properties of potentiation of GC progression and metabolism.<br><br>CONCLUSION: Our findings advance the insights of Blautia coccoides-derived 5Z-dodecenoic acid implicated in chronic psychological stress-induced GC progression and provide novel strategies for dampening GC progression.}, }
@article {pmid41263574, year = {2025}, author = {Tang, L and Xie, P and Wang, H and Hong, X and Gong, Z and Zhao, G and Yue, M}, title = {The sex hormone-gut microbiome axis: mechanistic drivers of sex-disparate bacterial infection outcomes and precision clinical interventions.}, journal = {Clinical microbiology reviews}, volume = {38}, number = {4}, pages = {e0023625}, pmid = {41263574}, issn = {1098-6618}, support = {32573359//Chinese National Science Foundation/ ; 2022YFC2604201//National Program on Key Research Project of China/ ; 861917 - SAFFI//EU's Horizon 2020 Research and Innovastion Programme/ ; LZ24C180002, LR19C180001//Zhejiang Provincial Natural Science Foundation of China/ ; 2021JJLH0083//Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City/ ; //Research Funds of Hangzhou Institute for Advanced Study, UCAS/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Gonadal Steroid Hormones/metabolism ; *Bacterial Infections/microbiology/epidemiology/therapy ; Female ; Male ; Sex Factors ; Dysbiosis/microbiology ; }, abstract = {SUMMARYSex disparities in bacterial infections pose significant challenges in clinical microbiology, influencing diagnostic approaches, antimicrobial stewardship, and patient outcomes. Males frequently exhibit heightened severity in conditions like Helicobacter pylori-associated gastritis and Vibrio cholerae outbreaks, whereas females face amplified risks during reproductive phases for pathogens, such as Listeria monocytogenes and Salmonella spp. Beyond genetic and behavioral factors, the bidirectional sex hormone-gut microbiome axis emerges as a key mechanistic driver: estrogens bolster innate immunity and microbial diversity (e.g., enriching short-chain fatty acid-producing taxa like Bifidobacterium), while androgens and progesterone impose immunosuppressive effects, altering colonization resistance and virulence modulation. Microbial contributions-via β-glucuronidase-mediated hormone deconjugation, bile acid biotransformations, and metabolite signaling-further calibrate host responses, as evidenced in Clostridioides difficile recurrence and enterohemorrhagic Escherichia coli virulence upregulation. This review synthesizes epidemiological, preclinical, and emerging clinical data, highlighting the axis's role in pathogen-specific immune evasion and dysbiosis-driven exacerbations. Clinically, these insights advocate for sex-stratified microbiome diagnostics (e.g., 16S rRNA sequencing for risk profiling) and targeted therapies, including hormone-modulated probiotics to restore barrier function, fecal microbiota transplantation to curb antibiotic-associated vulnerabilities, and selective estrogen receptor modulators to enhance clearance in high-risk cohorts. Despite advances, gaps in human longitudinal studies and pathogen-strain interactions limit translation. Future research integrating multi-omics with clinical trials could refine precision interventions, optimizing infection management in diverse populations and aligning with evolving demands for personalized microbiology.}, }
@article {pmid41263913, year = {2025}, author = {Merrick, B and Prossomariti, D and Kertanegara, M and Wyatt, D and Goldenberg, S}, title = {Facilitators and barriers to recruitment and retention in a feasibility trial of encapsulated faecal microbiota transplant to eradicate carriage of antibiotic-resistant bacteria at an academic hospital in central London: a nested qualitative study.}, journal = {BMJ open}, volume = {15}, number = {11}, pages = {e104783}, pmid = {41263913}, issn = {2044-6055}, mesh = {Humans ; London ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Feasibility Studies ; Middle Aged ; Qualitative Research ; Adult ; Focus Groups ; *Patient Selection ; COVID-19/epidemiology ; Aged ; *Carrier State/therapy ; }, abstract = {OBJECTIVES: This nested qualitative study (NQS) aimed to identify facilitators and barriers to the delivery of a substantive randomised controlled trial investigating the eradication of gastrointestinal tract carriage of antibiotic-resistant organisms using encapsulated faecal microbiota transplant (FMT).<br><br>DESIGN: NQS within a participant-blinded, randomised, placebo-controlled, single-centre, feasibility trial (RCT)-Feasibility of ERadicating gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO) (ISRCTN reg. no. 34&#x2009;467&#x2009;677)-with data collected via focus groups and analysed using thematic analysis.<br><br>SETTING: RCT participants were recruited from a large academic tertiary referral hospital in central London. Focus groups were held at the hospital or via videoconferencing for those unable to travel.<br><br>PARTICIPANTS: This study included 13 FERARO study participants across two focus groups. 11 participants were under RCT follow-up and unaware of their treatment allocation, two participants had completed 6-month follow-up and knew whether they had received FMT or matched placebo. Additional data were opportunistically collected on reasons for declining RCT participation.<br><br>RESULTS: Participants found FMT to be an acceptable and holistic management strategy and noted positive impacts from RCT participation including enhanced personal health awareness and valuable support from the research team. The time and travel commitment presented the most substantial barrier to RCT participation. Many participants were motivated by a desire to give something back to the UK National Health Service and/or research. Patients' current health status also influenced the decision-making process, and, while infrequently cited, the COVID-19 pandemic added extra complexity likely impacting individuals' willingness to participate.<br><br>CONCLUSIONS: While FMT is generally acceptable to participants, logistical barriers such as the time and travel commitment associated with RCT participation need consideration. Effective communication, personal connections and participant education on antimicrobial resistance are likely to be crucial for enhancing recruitment and retention in future trials.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN registration number 34&#x2009;467&#x2009;677 and EudraCT number 2019-001618-41.}, }
@article {pmid41265501, year = {2026}, author = {Yan, S and Xie, Y and Xv, J and Wang, K and Wang, J and Cao, Y and Han, X and Chen, F and Zhou, L and Jiang, Y and Liu, Y}, title = {Shengjiang San attenuates sepsis-induced acute intestinal injury via Lactobacillus murinus derived IAAld-mediated macrophage polarization through NF-κB and TGF-β signaling.}, journal = {Journal of ethnopharmacology}, volume = {357}, number = {}, pages = {120910}, doi = {10.1016/j.jep.2025.120910}, pmid = {41265501}, issn = {1872-7573}, mesh = {Animals ; *Sepsis/complications/drug therapy ; NF-kappa B/metabolism ; Male ; Signal Transduction/drug effects ; *Lactobacillus/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects ; *Macrophages/drug effects/metabolism ; Transforming Growth Factor beta/metabolism ; Disease Models, Animal ; Mice ; Fecal Microbiota Transplantation ; Probiotics ; Intestines/drug effects/pathology ; Mice, Inbred C57BL ; }, abstract = {ETHNOPHARMACOLOGY ASSOCIATED: Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, characterized by uncontrolled systemic inflammation and often culminating in multiple organ damage. Shengjiang San (SJS), a classic traditional Chinese medicinal (TCM) formula, has been historically utilized for its efficacy in removing heat, resolving toxicity, and reducing inflammation. Nevertheless, the precise role and mechanisms through which SJS modulates inflammatory responses and protects against sepsis-induced multi-organ injury are not yet fully understood.<br><br>OBJECTIVE: To investigate the protective mechanisms of SJS that improve sepsis-induced acute intestinal injury (SAII) by modulating the abundance and metabolism of the gut microbiota.<br><br>METHODS: A sepsis animal model was established using cecal ligation and puncture. The protective effects of SJS in SAII were evaluated through behavioral assessments, enzyme-linked immunosorbent assay, histological examination, and immunofluorescence analysis. Fecal samples were subjected to 16S rRNA sequencing and non-targeted metabolomics to identify probiotic taxa and metabolites associated with SJS administration. Proteomic analysis integrated with network pharmacology was performed to explore the underlying mechanisms. Fecal microbiota transplantation (FMT) and microbial metabolite analysis were utilized to elucidate the potential mechanism.<br><br>RESULTS: SJS was observed to significantly improve clinical scores, reduce pro-inflammatory cytokines, including IL-6, TNF-&#x3b1; and IL-1&#x3b2;. SJS also restored integrity of the intestinal barrier by upregulating the expression of ZO-1 and Claudin-1. 16S rRNA sequencing analysis demonstrated that SJS induced significant restructuring of the gut microbiota, including a marked increase in Lactobacillus murinus (L.M.) abundance. Proteomic and network pharmacological analyses revealed that SJS was protected against SAII by inhibiting NF-&#x3ba;B-mediated M1 polarization while promoting TGF-&#x3b2;-mediated M2 polarization. In particular, this protective effect was found to depend on the abundance of L.M., which regulated intestinal inflammation through its specific metabolites, indoleacetaldehyde (IAAld).<br><br>CONCLUSION: SJS improves SAII by orchestrating L.M. derived IAAld-mediated macrophage polarization through modulation of NF-&#x3ba;B and TGF-&#x3b2; signaling pathways.}, }
@article {pmid41265661, year = {2026}, author = {Cao, P and Li, Y and Zhang, S and Li, C and Sun, Y and An, B}, title = {Study on the efficacy and mechanism of fecal microbiota transplantation for depression based on circadian rhythm.}, journal = {Brain, behavior, and immunity}, volume = {131}, number = {}, pages = {106186}, doi = {10.1016/j.bbi.2025.106186}, pmid = {41265661}, issn = {1090-2139}, mesh = {*Fecal Microbiota Transplantation/methods ; Animals ; *Circadian Rhythm/physiology ; Mice ; *Depression/therapy/metabolism/microbiology ; Gastrointestinal Microbiome/physiology ; Male ; Mice, Inbred C57BL ; Hippocampus/metabolism ; Disease Models, Animal ; Stress, Psychological ; Tryptophan/metabolism ; Dysbiosis ; Prefrontal Cortex/metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; }, abstract = {BACKGROUND: Depression is closely associated with disruptions in circadian rhythms, and emerging evidence highlights critical roles of gut dysbiosis in its pathogenesis. However, the mechanisms by which FMT chronotherapy influences circadian gene in depression-via gut microbiota-remain poorly understood.<br><br>METHODS: In this study, we established a chronic unpredictable mild stress (CUMS) mouse model and performed fecal microbiota transplantation (FMT) using donor microbiota from healthy mice at two distinct circadian time points-zeitgeber time (ZT) 4 or ZT16 to identify the optimal timing for FMT based on behavioral assessments. Integrating omics dependent mechanisms of antidepressant effects mediated by these key functional bacteria.<br><br>RESULTS: Health-FMT significantly alleviated depressive-like behaviors, with superior efficacy at ZT4. It restored circadian gene expressions and attenuated neuroinflammation expression in the hippocampus and prefrontal cortex. 16S rRNA sequencing revealed that Health-FMT reduced uncultured_bacterium_g_Alistipes abundance, a genus linked to tryptophan availability. Tryptophan supplementation regulated circadian gene expressions, inflammatory factors, brain-derived neurotrophic factors (BDNF), microglial and astrocytic activation, and exerted antidepressant effects via the ERK signaling pathway.<br><br>CONCLUSIONS: These findings suggest that Health-FMT exerts antidepressant effects by restoring gut homeostasis, particularly by reducing Alistipes, thereby rebalancing tryptophan metabolic and circadian gene expressions. These findings offer a new possible mechanism and novel insights into the microbiota-gut-brain axis in depression, and underscore the importance of chronotherapy in FMT-based therapeutic strategies.}, }
@article {pmid41267780, year = {2025}, author = {Sharma, I and Sudarsanan, D and Moonah, S}, title = {The gut microbiome as a major source of drug-resistant infections: emerging strategies to decolonize and target the gut reservoir.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1692582}, pmid = {41267780}, issn = {2235-2988}, support = {R01 DK131313/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Bacterial Infections/microbiology/therapy/prevention &amp; control ; *Drug Resistance, Bacterial ; Phage Therapy ; *Bacteria/drug effects ; Antimicrobial Peptides/therapeutic use ; }, abstract = {Infections caused by antimicrobial-resistant bacteria represent a significant global health crisis that continues to worsen, creating an urgent need for alternative treatment and prevention strategies. A major source of drug-resistant bacteria is the human gut. The gut microbiota consists of bacteria that are frequently exposed to antibiotics, leading to selective pressure that promotes the development of resistant strains such as carbapenem-resistant Enterobacterales (CRE) and vancomycin-resistant enterococci (VRE). These drug-resistant bacteria can spread from the gut to other body sites, leading to hard-to-treat and potentially life-threatening infections such as bacteremia, surgical site infections, and urinary tract infections. Targeting the gut reservoir is essential in the fight against antimicrobial resistance. In this review, we focus on emerging non-antibiotic strategies aimed at eliminating drug resistant bacteria from the gut before they cause invasive infections, with particular emphasis on clinical evidence. Approaches discussed include fecal microbiota transplantation, bacteriophage therapy, antimicrobial peptides, probiotics, and dietary interventions. Optimizing these strategies, while continuing to explore newer approaches, will be essential to combat the growing threat of drug-resistant infections.}, }
@article {pmid41268164, year = {2025}, author = {Zhao, M and Chen, D and Hu, X and Xie, C and Xu, L and Zhou, F}, title = {Gut-ovary axis in polycystic ovary syndrome: mechanistic insights and gut microbiota-targeted therapeutic strategies.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1684492}, pmid = {41268164}, issn = {1664-2392}, mesh = {*Polycystic Ovary Syndrome/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Ovary/microbiology ; Humans ; Female ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that significantly affects women's reproductive health and quality of life. Its pathogenesis involves multiple factors, including genetics, environment, and metabolism. In recent years, with the growing body of research on PCOS, the "gut-ovary axis" hypothesis has become a prominent research focus. This hypothesis suggests that an imbalance in gut bacteria may significantly influence the onset and progression of PCOS through various pathways, such as immune regulation, metabolic disturbances, and hormonal imbalances. This article aims to review the role of the "gut-ovary axis" in PCOS and to explore novel treatment strategies based on gut microbiota modulation, including probiotics, fecal microbiota transplantation, and dietary interventions. These strategies represent promising research avenues for future PCOS treatments, with preliminary studies demonstrating their potential to improve clinical symptoms. However, it is crucial to note that these are not yet established therapies and require substantial further validation. Novelty and Significance of this Review: This review moves beyond a descriptive catalog of associations to provide a critical appraisal of the gut-ovary axis in PCOS. We systematically differentiate well-established mechanisms from speculative hypotheses, explicitly identify persistent knowledge gaps, and evaluate the translational potential of microbiota-targeted therapies, thereby offering a refined framework for future basic and clinical research.}, }
@article {pmid41268538, year = {2025}, author = {Jiao, JM and Liu, CG and Zang, D and Chen, J}, title = {Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1638942}, pmid = {41268538}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology ; *Lung Neoplasms/therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all cases, and is associated with a poor prognosis. Despite significant advancements in treatment modalities, therapeutic efficacy remains suboptimal, underscoring the urgent need for novel strategies. In recent years, increasing attention has been directed toward the pivotal role of gut microbiota-host interactions in the treatment of NSCLC. This review systematically examines the influence of current NSCLC therapies on gut microbiota and metabolism, explores the relationship between the microbiome and therapeutic response, and highlights the critical functions of probiotics, microbial metabolites, fecal microbiota transplantation (FMT), and dietary interventions in NSCLC management. By elucidating the mechanisms through which gut microbiota and their metabolites modulate treatment efficacy, we investigate the potential of exogenous interventions targeting the gut ecosystem to enhance therapeutic outcomes and mitigate adverse effects. Modulating the intestinal microbiota represents a promising clinical avenue and offers a new frontier for the development of future NSCLC treatment strategies.}, }
@article {pmid41269457, year = {2025}, author = {Younis, NK 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 Ali Al-Nuaimi, AM}, title = {Attenuating Neurotoxicity Through Fecal Microbiota Transplant: Mechanisms and Therapeutic Potential.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {128}, pmid = {41269457}, issn = {1559-1182}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Neurotoxicity Syndromes/therapy/microbiology ; }, abstract = {Neurotoxicity, triggered by drugs, environmental pollutants, metabolic disorders, or infections, can cause lasting neurological dysfunction and cognitive impairment. Recent research highlights the gut microbiota's crucial role in regulating brain health and vulnerability to neurotoxic damage, sparking interest in fecal microbiota transplantation (FMT) as a potential treatment. This review examines how FMT may counteract neurotoxicity and assesses its therapeutic potential for neurodegenerative diseases, neuroinflammation, and cognitive decline. The gut-brain axis-a bidirectional communication system between the gut and the central nervous system (CNS)-acts as the primary route through which gut microbes influence brain function. Growing evidence suggests that microbiota imbalances can exacerbate neuroinflammation, oxidative stress, blood-brain barrier disruption, and altered neurotransmitter production, all of which contribute to neurotoxicity. FMT, the transfer of donor fecal microbes to a recipient's gut, has demonstrated promise in restoring microbial equilibrium and reducing neurotoxic effects in both animal studies and human trials. The review also explores microbial profiles tied to neuroprotection versus those linked to neurotoxic conditions, along with the prospects of tailored microbiome therapies. Despite its potential, FMT faces challenges, including protocol standardization, donor selection criteria, and long-term efficacy. More research is needed to unravel the intricacies of gut-brain interactions and optimize FMT for clinical use. If these hurdles are addressed, FMT could become a transformative therapy for neurotoxicity-related disorders.}, }
@article {pmid41269489, year = {2025}, author = {Lapauw, L and Amini, N and Switsers, E and Dupont, J and Vercauteren, L and Derrien, M and Raes, J and Gielen, E}, title = {Effect of host and gut microbiota-altering interventions on sarcopenia or its defining parameters: a systematic review and meta-analysis of nutrition-based intervention studies.}, journal = {Aging clinical and experimental research}, volume = {38}, number = {1}, pages = {17}, pmid = {41269489}, issn = {1720-8319}, mesh = {Humans ; *Sarcopenia/diet therapy/microbiology/physiopathology/therapy ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Middle Aged ; Female ; Prebiotics/administration &amp; dosage ; Muscle Strength ; Synbiotics/administration &amp; dosage ; Male ; Aged ; Diet ; }, abstract = {AIM: To investigate effects of host- and gut microbiota (GM)-altering interventions on sarcopenia (parameters).<br><br>METHODS: Upon PROSPERO registration (CRD42022347363), six databases and one registry were searched until January 5th 2024 and updated on June 10th 2025 for diet, pre-, pro-, or synbiotics mono-interventions in populations with mean age&#x2009;&#x2265;&#x2009;50 years. (Standardized) mean differences (SMD) and 95% confidence intervals (CI) were computed using random-effects models if heterogeneity was >&#x2009;50%. Risk of bias (Rob) &amp; GRADE assessments were carried out to assess the evidence' quality and certainty.<br><br>RESULTS: The qualitative analysis included 38 diet, 13 prebiotics, 11 probiotics and 1 synbiotics studies, totaling 4842 participants (59%&#x2640;), mostly of high RoB. The quantitative analysis included 49 studies. Probiotics improved muscle strength by 1.90&#xa0;kg and gait speed by 0.08&#xa0;m/s. Fiber (whole-food)-enriched diets improved muscle strength with 1.25&#xa0;kg and energy-restricted diets, aimed at weight loss, improved muscle mass if mean age was <&#x2009;60 years and if the intervention lasted no longer than 12 weeks. High-protein diets improved muscle mass in women and if the intervention lasted at least 12 weeks. Studies involving participants with sarcopenia were only included in the qualitative analysis, since none provided sufficient data to allow a quantitative synthesis.<br><br>DISCUSSION: Fiber (whole food)-enriched diets and probiotics improve muscle strength. The latter intervention also improves gait speed. High-protein diets improve muscle mass in women and with intervention durations&#x2009;&#x2265;&#x2009;12 weeks. Future studies should include fecal sampling to assess whether GM modulate the observed effects.<br><br>CONCLUSION: Specific diets and probiotics offer potential to improve sarcopenia parameters.}, }
@article {pmid41270175, year = {2025}, author = {Liu, W and Yang, J and Wei, Z and Kong, W and Dong, Z and Wei, Y and Zhuang, J and Qi, J}, title = {miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease.}, journal = {Science advances}, volume = {11}, number = {47}, pages = {eadw5984}, pmid = {41270175}, issn = {2375-2548}, mesh = {*MicroRNAs/genetics/chemistry/administration &amp; dosage ; *Nanoparticles/chemistry ; Animals ; *Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; Lacticaseibacillus rhamnosus/metabolism/genetics ; Extracellular Vesicles/metabolism ; *Biomimetic Materials/chemistry ; Disease Models, Animal ; Humans ; Colitis/pathology ; Biomimetics ; Probiotics ; }, abstract = {Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli. In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.}, }
@article {pmid41270389, year = {2025}, author = {Zheng, M and Meng, Y and Feng, J and Liang, H and Mu, X and Feng, C}, title = {Shenling Baizhu Powder potentiates immunotherapy response: putative roles of gut microbial remodeling and fatty acid metabolism modulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157559}, doi = {10.1016/j.phymed.2025.157559}, pmid = {41270389}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Drugs, Chinese Herbal/pharmacology ; *Immunotherapy/methods ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Fatty Acids/metabolism ; Tumor Microenvironment/drug effects ; Programmed Cell Death 1 Receptor ; Female ; Lung Neoplasms/drug therapy ; Carcinoma, Lewis Lung/drug therapy ; Cell Line, Tumor ; Male ; }, abstract = {BACKGROUND: Low response rates and immune-related adverse events (irAEs) are major factors affecting the efficacy of PD-1 monoclonal antibody (mAb) immunotherapy in NSCLC. Modulating the gut microbiota-immune-tumor axis is considered a key strategy to overcome these challenges.<br><br>PURPOSE: This study aimed to investigate whether Shenling Baizhu powder (SLBZS), a traditional Chinese medicine formula, could enhance the efficacy of PD-1 mAb immunotherapy and mitigate irAEs by regulating gut microbiota and host metabolism.<br><br>STUDY DESIGN: Two experimental models were employed: (1) a standard Lewis subcutaneous tumor mouse model to evaluate therapeutic effects and irAEs, and (2) a lung metastasis model using bioluminescence imaging to assess tumor progression. Additionally, an antibiotic-cleared mouse model combined with fecal microbiota transplantation (FMT) was used to validate gut microbiota-mediated mechanisms.<br><br>METHODS: Subcutaneous tumor growth, organ toxicity, and metastasis were monitored in vivo. Multi-omics approaches included fecal 16S rDNA sequencing, untargeted/targeted plasma metabolomics, and immune profiling of splenic and tumor microenvironment (TME) lymphocytes. SLBZS/FMT interventions were applied to antibiotic-treated mice to assess microbiota-dependent effects.<br><br>RESULTS: SLBZS synergized with PD-1 mAb to significantly inhibit tumor growth and reduce multi-organ irAEs. In the metastasis model, SLBZS suppressed early tumor implantation and late-stage dissemination. Multi-omics analyses revealed that SLBZS enriched beneficial gut bacteria (e.g., Akkermansia, Lactobacillus, Muribaculum) and microbial metabolites, including short-chain fatty acids (SCFAs), while enhancing anti-tumor T-cell subsets in the spleen and TME. Critically, SLBZS/FMT restored gut microbiota homeostasis and reversed antibiotic-induced immunotherapy resistance.<br><br>CONCLUSION: SLBZS, as a traditional Chinese medicinal formulation, enhances the efficacy of PD-1 mAb through a unique dual-regulatory mechanism. It concurrently remodels the gut microbiota structure and optimizes the metabolic microenvironment, with these synergistic actions collectively amplifying anti-tumor immunity while reducing irAEs. This dual-mode efficacy distinguishes SLBZS from conventional microbial modulators that solely target microbiota without metabolic coordination. Our study provides the first experimental validation of SLBZS as a clinically valuable adjuvant of Chinese medicinal origin for NSCLC immunotherapy. Furthermore, we pioneer a novel research paradigm integrating traditional Chinese medical theory with the "microbiota-metabolism-immune network" axis, thereby offering innovative therapeutic strategies for refining cancer immunotherapies.}, }
@article {pmid41270390, year = {2025}, author = {Chen, L and He, W and Gao, L and Lu, Y and Zhu, L}, title = {Shouhui Tongbian Capsules ameliorate heart failure and atrial fibrillation via gut microbiota regulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157549}, doi = {10.1016/j.phymed.2025.157549}, pmid = {41270390}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Heart Failure/drug therapy ; *Atrial Fibrillation/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Doxorubicin ; Capsules ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Myocardium/pathology ; Transcriptome ; }, abstract = {BACKGROUND: Heart failure (HF) with atrial fibrillation (AF) poses a significant therapeutic challenge due to its complex pathophysiology. Shouhui Tongbian Capsules (SHTB) contain multiple active components that have been proven to affect HF or AF through the intestinal flora. However, the specific therapeutic effects of this drug on HF combined with AF, as well as whether these effects are achieved by regulating the intestinal flora, still require systematic research.<br><br>PURPOSE: This study aimed to elucidate the cardioprotective effects of SHTB in a doxorubicin (DOX)-induced HF/AF rat model, focusing on gut microbiota modulation and myocardial transcriptome regulation.<br><br>METHODS: Rats were randomized into control, model (DOX-induced HF/AF), SHTB treatment (low/medium/high doses), and metoprolol groups. Pharmacodynamically, cardiac function was assessed via echocardiography and electrocardiography. And myocardial fibrosis was quantitatively evaluated using pathomorphology analysis. Mechanistically, microvascular integrity was examined via immunofluorescence, while the neural activity ligand-receptor interaction pathway-related protein expression was analyzed by immunohistochemistry. Additionally, gut microbiota composition was determined via 16S rRNA sequencing, and myocardial transcriptome profiling was performed using RNA sequencing. Furthermore, fecal microbiota transplantation (FMT) experiments were performed to validate the role of gut microbiota in the observed effects.<br><br>RESULTS: The SHTB intervention significantly improved the cardiac function and electrophysiological stability of HF/AF rats, along with enhancing microvascular maturation and reducing myocardial fibrosis. The analysis of the intestinal microbiota showed that SHTB effectively restored the microbial ecological balance, especially regulating the abundance of key genera (such as Turicibacter) closely related to disease progression and treatment efficacy. Transcriptional analysis identified the neural activity ligand-receptor pathway as the key mechanism, and FMT experiments demonstrated that SHTB modulates the Edn1-Agtr1a-Bdkrb2 axis through gut microbiota, ultimately leading to improved cardiac function. The synergistic effect of the composition of the intestinal microbiota and myocardial molecular targets jointly contributed to the improvement of cardiac remodeling in HF/AF.<br><br>CONCLUSION: SHTB ameliorates HF with AF by synergistically modulating the gut-heart axis, involving gut microbiota restoration, myocardial fibrosis suppression, and vascular tension regulation via the Edn1-Agtr1a-Bdkrb2 axis. This multi-target mechanism substantiates SHTB's potential as a promising adjunct therapy for HF/AF.}, }
@article {pmid41270737, year = {2025}, author = {Long, X and Wang, H and Lu, Y and Gao, X and Xiao, Y and Zhang, M and Guo, J and Yang, J and Zhang, R and Li, Q and Zhou, G and Yang, R and Chen, F and Wu, Q and Sun, L and Chu, C and Zhu, X and Wu, Z and Ren, Q and You, C and Liu, Z and Li, Q and Liu, D and Cheng, D and Kang, P and Chen, A and Wu, Q and Fang, Q and Wei, L and Zhang, L and Li, J and Panagiotou, G and Jia, W and Zeng, R and Ni, Y and Chen, L and Li, H}, title = {Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD.}, journal = {Cell metabolism}, volume = {37}, number = {12}, pages = {2342-2361.e9}, doi = {10.1016/j.cmet.2025.10.017}, pmid = {41270737}, issn = {1932-7420}, mesh = {*Gastrointestinal Microbiome ; Humans ; Male ; *Starch/metabolism ; Female ; Middle Aged ; Prebiotics/administration &amp; dosage ; *Resistant Starch ; Fecal Microbiota Transplantation ; Prevotella/metabolism ; Animals ; }, abstract = {Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.}, }
@article {pmid41271774, year = {2025}, author = {Qin, W and Mei, Q and Wang, G and Wang, R and Huang, Z and Fu, Y and Xu, B and Huang, C and Ai, L and Zeng, Y}, title = {Faecalibacterium prausnitzii alleviates experimental recurrent acute pancreatitis by producing oleic acid to regulate MAPK/NF-κB signaling and Th17/Treg balance.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {221}, pmid = {41271774}, issn = {2055-5008}, support = {No.82200714//National Natural Science Foundation--Youth Foundation/ ; No. 82300731//National Natural Science Foundation--Youth Foundation/ ; No.10-21-308-420//USST Medical-engineering Cross-project/ ; No. 32025029//National Science Foundation for Distinguished Young Scholars of China/ ; No. 82270671//Natural Science Foundation of China/ ; CCTR-2022B02//Shanghai General Hospital Characteristic Research Program/ ; }, mesh = {*Pancreatitis/microbiology/therapy ; Animals ; *Faecalibacterium prausnitzii/metabolism/isolation &amp; purification/physiology ; Mice ; Gastrointestinal Microbiome ; *Oleic Acid/metabolism ; Humans ; NF-kappa B/metabolism ; *Th17 Cells/immunology ; Fecal Microbiota Transplantation ; *T-Lymphocytes, Regulatory/immunology ; Disease Models, Animal ; Male ; Signal Transduction ; Feces/microbiology ; Female ; Mice, Inbred C57BL ; }, abstract = {Acute pancreatitis (AP) is a complex gastrointestinal disorder associated with disruptions in the gut microbiome. However, the gut microbial and metabolomic profiles in recurrent acute pancreatitis (RAP), which is a clinically distinct subtype of AP, remain unclear. This study integrated microbiome-metabolome analysis to identify the key gut microbial species and metabolic pathways associated with RAP. The findings reveal that the abundance of Faecalibacterium prausnitzii (Fp) is significantly diminished in RAP patients, exhibiting a strong negative correlation with disease severity. Consistent with this observation, fecal microbiota transplantation enriched with Fp significantly ameliorated pancreatic injury in RAP mice. We further isolated Fp Ai 3-16 strain from the stool of healthy volunteers. Functional validation using experimental AP models demonstrates that Fp Ai 3-16 and its metabolite oleic acid (OA) can effectively attenuate pancreatitis by modulating MAPK/NF-κB signaling pathways and restoring the intestinal Th17/Treg balance. Importantly, these results extend beyond the context of RAP, as they highlight the broader significance of the gut-pancreas axis in the pathogenesis of AP. Thus, the elucidation of the underlying molecular mechanisms offers novel therapeutic avenues for RAP management and provides a foundation for further investigations into the intricate interplay between the gut microbiome and the pancreas.}, }
@article {pmid41273871, year = {2025}, author = {Jie, L and Liu, J and Liu, Y and Zhang, K and Shen, X and Xu, B and Ji, W and Shi, X}, title = {Sclareol alleviates synovial inflammation in knee osteoarthritis by regulating sphingolipid metabolism along the gut-bone axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157563}, doi = {10.1016/j.phymed.2025.157563}, pmid = {41273871}, issn = {1618-095X}, mesh = {Animals ; Gastrointestinal Microbiome/drug effects ; Male ; Rats ; *Sphingolipids/metabolism ; Rats, Sprague-Dawley ; *Diterpenes/pharmacology ; *Osteoarthritis, Knee/drug therapy/metabolism/microbiology ; *Anti-Inflammatory Agents/pharmacology ; Synovial Membrane/drug effects ; Metabolomics ; Inflammation/drug therapy ; }, abstract = {OBJECTIVE: Sclareol(SCL) is a diterpene alcohol compound with anti-inflammatory, antibacterial, and antioxidant properties, and it has high oral bioavailability. However, its pharmacological effects in the field of knee osteoarthritis(KOA) remain unclear.<br><br>METHODS: The pharmacological effects of SCL intervention on synovial inflammation in KOA rats were observed using methods such as histopathology and molecular biology. Subsequently, further in vivo and in vitro experiments were conducted to explore the effects of SCL. By combining metabolomics and 16S rRNA sequencing, the impact of SCL on the gut microbiota and metabolic levels was investigated. Based on the results of the omics analyses, the mechanism by which SCL alleviates synovial inflammation in KOA was verified.<br><br>RESULTS: Histopathology and molecular biology showed that SCL can significantly improve synovial inflammation and pathological progression in KOA. However, SCL did not exhibit anti-inflammatory effects in vitro experiments or in rats treated with antibiotics. Combined analysis of untargeted metabolomics and 16S RNA-seq indicated that SCL may exert its effects by altering the abundance of bacterial groups like Prevotellaceae ga6a1 group and Corynebacterium and regulating the levels of lipid metabolites such as ceramides. Finally, our combined in vivo and in vitro experiments confirmed that fecal microbiota transplantation (FMT) from SCL-treated rats could modulate gut microbiota composition, reduce sphingolipid metabolism, lower necroptosis levels of synovial macrophages, and decrease inflammation in KOA rats.<br><br>CONCLUSION: SCL reduces the abundance of Prevotellaceae ga6a1 group and Corynebacterium decreased levels of ceramides, sphingomyelin, and sphingosine, which in turn lower synovial macrophage necroptosis and synovial inflammation.}, }
@article {pmid41274019, year = {2025}, author = {Chen, R and Qian, J and Wang, Q and Li, Y and Xu, Z and Zhang, M and Wang, M and Nie, H and Yang, W and Tong, X and Yan, F}, title = {Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity.}, journal = {EBioMedicine}, volume = {122}, number = {}, pages = {106037}, pmid = {41274019}, issn = {2352-3964}, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; *Tryptophan/metabolism ; *Gastrointestinal Microbiome ; Mice ; *Periodontitis/metabolism/complications/microbiology ; Humans ; *Obesity/metabolism/complications/etiology ; Male ; Disease Models, Animal ; Diet, High-Fat/adverse effects ; Mice, Knockout ; Metabolomics/methods ; *Fatty Liver/metabolism/etiology/pathology ; *Basic Helix-Loop-Helix Proteins/metabolism/genetics ; Dysbiosis ; }, abstract = {BACKGROUND: Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear.<br><br>METHODS: Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography-tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout (Ahr[-/-]) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro.<br><br>FINDINGS: Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr[-/-] mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the liver. Conditioned medium from endotoxin-stimulated THP-1 cells promoted mitochondrial fission in HepG2 cells by upregulating Drp1 expression.<br><br>INTERPRETATION: Periodontitis exacerbates MASLD by disrupting the gut microbiota-tryptophan metabolism-AHR axis, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin translocation. Endotoxin plays a pivotal role in promoting hepatic mitochondrial fission during the exacerbation of MASLD by periodontitis. AHR agonists offer a novel intervention strategy for patients with comorbid MASLD and periodontitis.<br><br>FUNDING: This work was supported by the Jiangsu Province Key Research and Development Program [No. BE2022670]; National Natural Science Foundation of China [No. 82270979]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [No. JSDW202246]; and High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University [No. 0224C001].}, }
@article {pmid41275982, year = {2026}, author = {Huang, Y and Hu, J and Xu, H and Zhu, R and Liu, L and Chen, X and Sun, Y and Zhao, Y and Zhong, Y and Cheng, B and Huang, X and Lu, H and Xu, ZZ}, title = {Propylparaben induces immunotoxicity in zebrafish via oxidative stress and gut microbiota-immune axis dysregulation.}, journal = {Fish &amp; shellfish immunology}, volume = {169}, number = {}, pages = {111024}, doi = {10.1016/j.fsi.2025.111024}, pmid = {41275982}, issn = {1095-9947}, mesh = {Animals ; *Zebrafish/immunology ; *Gastrointestinal Microbiome/drug effects ; *Oxidative Stress/drug effects ; *Parabens/toxicity ; Embryo, Nonmammalian/drug effects/immunology ; *Food Preservatives/toxicity ; Dose-Response Relationship, Drug ; *Immunity, Innate/drug effects ; }, abstract = {Propylparaben (PP), a widely used preservative, has an unclear immunotoxicity profile. In this study, zebrafish embryos were exposed to 2.5, 5, and 10 μM PP to investigate its developmental and immunological effects. PP induced dose-dependent developmental abnormalities and immunotoxicity. Specifically, it significantly reduced the populations of neutrophils, macrophages, and hematopoietic stem cells (HSCs) in zebrafish embryos. Mechanistically, PP suppressed the TLR4/MyD88/NF-κB pathway and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in embryos, whereas adult zebrafish exhibited marked upregulation of this pathway and these cytokines in intestinal and splenic tissues. PP exposure also elevated reactive oxygen species (ROS) and lipid peroxidation. Co-treatment with the antioxidant astaxanthin (AST) attenuated PP-induced immunotoxicity by reducing ROS level and restoring HSCs, neutrophil, and macrophage populations, confirming oxidative stress as a key mechanism. Furthermore, PP induced gut microbiota dysbiosis and intestinal developmental defects. Exposing germ-free (GF) zebrafish embryos to PP resulted in no significant changes in neutrophils and HSCs, indicating that its immunotoxicity is microbiota-dependent. This was confirmed by fecal microbiota transplantation (FMT), where embryos receiving microbiota from PP-treated donors showed concentration-dependent decreases in neutrophils and HSCs. Our study elucidates the ecological and health risks of PP, advocating for reevaluation of preservative safety and microbiota-targeted mitigation strategies.}, }
@article {pmid41276052, year = {2026}, author = {Huan, P and Wang, W and Qi, Y and Sun, J and Zhou, R and Liu, L and Pan, S and Xu, Y and Wang, Z and Zhu, Z and Han, C}, title = {Cynomorium songaricum polysaccharide attenuates high-fat diet-induced testicular dysfunction by modulating the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {335}, number = {Pt 1}, pages = {149114}, doi = {10.1016/j.ijbiomac.2025.149114}, pmid = {41276052}, issn = {1879-0003}, mesh = {Animals ; Male ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Polysaccharides/pharmacology/chemistry ; Mice ; *Testis/drug effects/pathology/metabolism/physiopathology ; *Cynomorium/chemistry ; Obesity/drug therapy ; Mice, Inbred C57BL ; }, abstract = {Obesity disrupts gut microbiota homeostasis and impairs spermatogenesis; however, microbiota-targeted therapies remain insufficiently explored. In this study, a water-soluble polysaccharide(CSP1) was purified from the medicinal plant Cynomorium songaricum. Structural characterization identified CSP1 as a homogeneous α-glucan (Mw 5776 Da) with a backbone of →4)-α-D-Glcp-(1 → residues and C-6 branching. In high-fat diet (HFD)-induced obese mice, CSP1 administration alleviated testicular dysfunction by enhancing sperm count and motility, restoring serum testosterone levels, and ameliorating histopathological damage and germ cell apoptosis. Mechanistically, CSP1 remodeled the gut microbiota composition by suppressing LPS-producing taxa while enriching beneficial populations including SCFA-producing Lachnospiraceae and Bacteroidota. This reshaping reinforced intestinal barrier integrity, as evidenced by the upregulation of ZO-1, occludin, and MUC2. Consequently, CSP1 treatment led to a favorable shift in gut microbiota-derived metabolites, significantly reducing systemic LPS translocation while increasing beneficial short-chain fatty acids (SCFAs) such as acetate and propionate. These changes collectively inhibited testicular TLR4/MyD88/NF-κB activation and downstream pro-inflammatory cytokines (TNF-α, IL-1β). Fecal microbiota transplantation confirmed the causal role of the gut microbiota in mediating CSP1's protective effects. Our findings establish CSP1 as a gut-microbiota-targeting polysaccharide that alleviates obesity-associated male infertility by orchestrating a beneficial remodeling of the gut microbial ecosystem and its metabolic output, offering a novel therapeutic strategy for metabolic reproductive disorders.}, }
@article {pmid41276714, year = {2025}, author = {Mustafa, MA and Vadia, N and Varma, P and Al-Shaker, H and Mohanty, B and Dhyani, A and Kaur, I and Chauhan, AS and Garg, G}, title = {The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {151}, pmid = {41276714}, issn = {1559-1182}, mesh = {*Alzheimer Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism/pathology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.}, }
@article {pmid41277357, year = {2026}, author = {Zheng, X and Jiang, Y and Wang, W and Sun, K and Zhou, L and Zhang, Y and Cui, J and Yu, H and Dong, W and Yan, B}, title = {Asiatic Acid Alleviates Ulcerative Colitis Through a Gut Microbiota-Driven cAMP/PKA/NF-κB Pathway: γ-Glutamyltyrosine Is a Crucial Player.}, journal = {Phytotherapy research : PTR}, volume = {40}, number = {1}, pages = {267-285}, doi = {10.1002/ptr.70132}, pmid = {41277357}, issn = {1099-1573}, support = {82304807//National Natural Science Foundation of China/ ; BK20220299//Natural Science Foundation of Jiangsu Province/ ; Syhky202307//Clinical Pharmaceutical Research Foundation of Jiangsu Hengrui Medicine/ ; JLY2021052//Clinical Medical Science and Technology Development Foundation of Jiangsu University/ ; KS2203//Science and Technology Project of Kunshan/ ; KSF202139//Science and Technology Project of Kunshan/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/microbiology/chemically induced/metabolism ; NF-kappa B/metabolism ; *Pentacyclic Triterpenes/pharmacology ; Mice ; Male ; Signal Transduction/drug effects ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Disease Models, Animal ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Tyrosine/analogs &amp; derivatives/metabolism ; Colon/drug effects ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica, has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.}, }
@article {pmid41277418, year = {2025}, author = {Guggeis, MA and Andreani, NA and López-Agudelo, VA and Tran, F and Kadibalban, AS and Moors, KA and Marinos, G and Saboukh, A and Harris, D and Falk-Paulsen, M and Weber-Stiehl, S and Järke, L and Sommer, F and Welz, L and Bang, C and Franke, A and Chung, CJ and Bronowski, C and Schuchardt, S and Künzel, S and Aden, K and Schreiber, S and Kaleta, C and Baines, JF and Rosenstiel, P}, title = {Cross-species engraftment biases and metabolic divergence in gnotobiotic mice humanized with ulcerative colitis microbiota.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2581445}, pmid = {41277418}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Mice ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Disease Models, Animal ; Male ; Female ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Fungi/classification/genetics/isolation &amp; purification ; Middle Aged ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.}, }
@article {pmid41277959, year = {2025}, author = {Zhang, S and Li, J and Li, L and Yuan, X}, title = {Gut microbiota on cardiovascular diseases-a mini review on current evidence.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1690411}, pmid = {41277959}, issn = {1664-302X}, abstract = {The gut microbiome has emerged as a critical modulator of cardiovascular disease (CVD) risk, offering a novel frontier for therapeutic intervention. This mini-review synthesizes current evidence on how probiotic-like bacteria and their metabolites mediate protective physiological mechanisms against CVD. Drawing from both animal models and human clinical trials, we elucidate the biological pathways, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acid metabolism, through which the gut microbiota influences hypertension, atherosclerosis, and heart failure. Furthermore, we examine microbiota-based strategies such as dietary modification, fecal microbiota transplantation (FMT), and pharmacological agents aimed at restoring microbial homeostasis. Despite promising mechanistic insights, human trials have yet to consistently demonstrate significant clinical benefits in reversing CVD outcomes via gut microbiota modulation. This review underscores the necessity of moving from correlation to causation, highlighting current limitations and future prospects for leveraging gut microbiome research in the development of personalized, effective therapeutic strategies for cardiovascular diseases.}, }
@article {pmid41277972, year = {2025}, author = {Ye, N and Song, X and Yu, J and Bao, X and Ye, M and Jiang, L}, title = {Effects of gut microbiota interventions on patients with schizophrenia: a systematic review and meta-analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1681559}, pmid = {41277972}, issn = {1664-302X}, abstract = {INTRODUCTION: Schizophrenia (SCH) is a chronic psychiatric disorder characterized by disturbances in thought, emotion, perception, and behavior. Although gut microbiota interventions (e.g., probiotics, prebiotics, synbiotics, dietary modifications and fecal microbiota transplantation) have been widely applied in the treatment of SCH, the most effective intervention strategy remains uncertain.<br><br>METHODS: By searching four databases, only randomized controlled trials (RCTs) were included to examine the impacts of gut microbiota interventions on SCH. The Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was employed to assess the methodological quality of the included studies, RevMan5.4 was used for the meta-analysis, Stata 18 was used for sensitivity analysis, Engauge Digitizer was used to convert pictures to numbers and GRADEPro3.6 was used to grade the evidence quality.<br><br>RESULTS: This study incorporated RCTs published from the earliest records up to December 2024. A total of 10 RCTs, encompassing 585 participants, were analyzed. The meta-analysis demonstrated that interventions primarily utilizing probiotics to modulate gut microbiota significantly lowered the total Positive and Negative Syndrome Scale (PANSS) scores among patients (p&#x2009;=&#x2009;0.001). Furthermore, substantial improvements were observed across multiple metabolic parameters: fasting blood sugar, triglycerides, total cholesterol, homeostasis model assessment of insulin resistance, and quantitative insulin sensitivity check index (all p&#x2009;<&#x2009;0.05). While no significant effects were observed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, and insulin.<br><br>CONCLUSION: This meta-analysis suggests that auxiliary probiotic interventions hold promise as an adjunctive therapy for schizophrenia, potentially yielding benefits in psychopathological, metabolic, and physiological domains. However, the current evidence remains inconclusive due to the limited number of studies, small sample sizes, and methodological variations. Firm therapeutic recommendations cannot be made at this time. The findings underscore the need for more robust, large-scale, and rigorously designed randomized controlled trials to definitively establish the efficacy and optimal protocols of auxiliary probiotic supplementation for SCH.<br><br>https://www.crd.york.ac.uk/PROSPERO, CRD 420250652507.}, }
@article {pmid41278045, year = {2025}, author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A}, title = {Retraction: Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {r206}, doi = {10.7759/cureus.r206}, pmid = {41278045}, issn = {2168-8184}, abstract = {[This retracts the article DOI: 10.7759/cureus.85054.].}, }
@article {pmid41278154, year = {2025}, author = {Zheng, L and Duan, SL and Wang, K}, title = {Research progress concerning the involvement of the intestinal microbiota in the occurrence and development of inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {42}, pages = {113170}, pmid = {41278154}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/genetics ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/immunology/pathology ; *Crohn Disease/microbiology/therapy/immunology ; *Colitis, Ulcerative/microbiology/therapy/immunology ; Genetic Predisposition to Disease ; Dysbiosis/microbiology/immunology/therapy ; *Inflammatory Bowel Diseases/microbiology/therapy ; Metagenomics ; Animals ; Metabolomics ; Immunity, Mucosal ; }, abstract = {Inflammatory bowel disease (IBD), a chronic disorder characterized by intestinal inflammation and mucosal damage, includes mainly Crohn's disease and ulcerative colitis. However, the cause of its onset remains unclear. The pathogenesis of IBD is closely related to host genetic susceptibility, disorders of the intestinal flora, damage to the intestinal mucosal barrier, and abnormal intestinal mucosal immunity. On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD, the influence of genetics on the intestinal barrier and intestinal microbiota; the metagenomics, metatranscriptomics, and metabolomics of the intestinal microbiota involved in IBD; and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.}, }
@article {pmid41278477, year = {2025}, author = {Chang, L and Liu, Y and Li, H and Yan, J and Wu, W and Chen, N and Ma, C and Zhao, X and Chen, J and Zhang, J}, title = {Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1717696}, pmid = {41278477}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Cirrhosis/microbiology/metabolism/pathology ; Dysbiosis/microbiology ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; }, abstract = {Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)-producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40-70%, accompanied by a two- to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions-including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators-restore community balance in 70-85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome-metabolome models achieve areas under the curve (AUCs) of 0.82-0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome-metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.}, }
@article {pmid41278627, year = {2025}, author = {Pandey, S and Abu, YF and Singh, P and Roy, S}, title = {Cross-Fostering with control dams rescues Gut Dysbiosis and Chromatin-associated Transcriptional Changes in Offspring of Opioid-Exposed Dams.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.11.07.687278}, pmid = {41278627}, issn = {2692-8205}, abstract = {Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naïve dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal injury, indicating a microbiome-driven mechanism. These findings reveal a novel gut-microbiome-epigenome axis underlying opioid-induced injury and highlight early microbial intervention as a potential strategy to mitigate developmental harm.}, }
@article {pmid41280275, year = {2026}, author = {Qi, X and Zhang, Y and Sun, Z and Wang, G and Ling, F}, title = {A simplified synthetic microbial community enhances resistance of crucian carp (Carassius auratus) to Aeromonas hydrophila infection through host immune activation.}, journal = {Synthetic and systems biotechnology}, volume = {11}, number = {}, pages = {407-418}, pmid = {41280275}, issn = {2405-805X}, abstract = {Bacterial diseases represent a major bottleneck in the sustainable development of aquaculture. The gut microbiota plays a vital role in host growth and health, including the enhancement of disease resistance. Although substantial progress has been made in elucidating the mechanisms of disease resistance in fish, the precise role of the gut microbiota in enhancing pathogen resistance in aquatic animals remains poorly understood. In this study, crucian carp (Carassius auratus) were used as a model to investigate the role of intestinal microbiota in modulating resistance to Aeromonas hydrophila. Individual crucian carp exhibited distinct clinical phenotypes following A. hydrophila infection. Specifically, significant differences were observed in the composition of the intestinal microbiota between fish displaying mild symptoms and those exhibiting severe phenotypic manifestations (α diversity: p < 0.01; β diversity: p = 0.001). Fecal microbiota transplantation (FMT) experiments demonstrated that fish with mild symptoms conferred enhanced resistance to A. hydrophila when their intestinal contents were transplanted into other individuals (p = 0.006). Further microbial analysis identified Cetobacterium (p = 0.013), Paraclostridium (p < 0.01), and Pseudomonas (p < 0.01) as key differential taxa. A simplified microbial community comprising these three strains was subsequently constructed. Feeding experiments confirmed that administration of this community significantly improved host resistance to A. hydrophila (p < 0.05) by activating intestinal immune responses and reinforcing the gut barrier. Overall, our findings underscore the potential of the microbial community as a novel strategy for disease prevention and control in aquaculture, providing a theoretical foundation for the development of microbiome-based therapies in fish health management.}, }
@article {pmid41280320, year = {2025}, author = {Shackelford, BB and Kedir, K and Babiker, A and Sintayehu, B and Negash, AA and Abdissa, A and Taye, WA and Beyene, E and Woodworth, MH and Hennink, MM}, title = {Knowledge and Acceptability of Fecal Microbiota Transplantation Among Patients, Caregivers, and Health Care Providers in Ethiopia.}, journal = {Open forum infectious diseases}, volume = {12}, number = {11}, pages = {ofaf676}, pmid = {41280320}, issn = {2328-8957}, abstract = {BACKGROUND: Malnutrition and antimicrobial-resistant infections are major causes of morbidity and mortality in low-income countries. These conditions have been associated with the gut microbiome, although little is known about the acceptability of microbiota therapies such as fecal microbiota transplantation (FMT). We explored the acceptability of FMT among health care providers (HCPs) and patients in Addis Ababa, Ethiopia.<br><br>METHODS: In this qualitative study, we purposively sampled patients with bacterial infections and acute malnutrition, caregivers, and HCPs at two hospitals. Eight focus group discussions were held. Amharic and English discussion guides covered knowledge of FMT and perceived barriers or facilitators for uptake. Data were transcribed and translated into English when necessary. MAXQDA software was used for a thematic analysis, with trained researchers closely reading transcripts to identify issues, develop a codebook, iteratively code data, and assess intercoder agreement. Description, comparison, and categorization were conducted to discern core themes, and validity checks ensured that findings were grounded in the data.<br><br>RESULTS: HCPs indicated a general willingness to prescribe FMT, provided that there was sufficient evidence supporting its efficacy and safety and they were confident on patient adherence. Patient acceptability of FMT was categorized along a continuum from those who were unconvinced, persuadable, amenable, and accepting of salvage treatment.<br><br>CONCLUSIONS: FMT may be acceptable for HCPs and patients in Addis Ababa, although interventions are needed to enhance acceptance among some groups, such as marketing it as standard medication, obtaining endorsement by religious leaders, providing multiple formulations, and/or providing thoughtful health communication.}, }
@article {pmid41280921, year = {2025}, author = {Li, X and Yuan, Q and Huang, H and Wang, L}, title = {Gut microbiota in irritable bowel syndrome: a narrative review of mechanisms and microbiome-based therapies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1695321}, pmid = {41280921}, issn = {1664-3224}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Animals ; Prebiotics/administration &amp; dosage ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and its pathogenesis remains unclear. Dysbiosis of the gut microbiota is associated with IBS. The gut microbiota may modulate IBS symptoms via the epithelial barrier, mucosal immunity, microbial metabolites (e.g., short-chain fatty acids and bile acids), and gut-brain signaling. Currently, dietary approaches, probiotics, prebiotics, rifaximin, and fecal microbiota transplantation show variable benefit; effects are strain-/context-dependent and evidence certainty varies, with adverse-event reporting inconsistent. This narrative review takes a subtype-aware, mechanism-first perspective to summarize microbiota functions, symptom links, and intervention evidence with safety considerations. This review offers new perspectives and insights for precision treatment and microbiome research in IBS.}, }
@article {pmid41280983, year = {2025}, author = {Nadeem, O and Imran, MS and Siddique, N}, title = {Recurrent Clostridium difficile Infections in a Patient With Ulcerative Colitis: A Case Report.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e95130}, pmid = {41280983}, issn = {2168-8184}, abstract = {Clostridium difficile infection (CDI) poses a substantial clinical challenge, especially in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). Patients with UC are at greater risk of CDI and tend to experience a more severe disease course and higher rates of recurrence than the general population. We report a case of an elderly man in his early 90s with a long-standing history of UC treated with mesalazine, who had a prior hospitalization for hyponatremia and a history of CDI. During his most recent four-month hospitalization, he developed three separate episodes of CDI, confirmed by stool PCR and toxin assays. Despite treatment with vancomycin, metronidazole, and fidaxomicin in succession, he experienced recurrent episodes of CDI that ultimately progressed to septic shock and death. This case highlights the nature of recurrent CDI in this patient population and the complexity and increased morbidity associated with its management in elderly patients with UC. It underscores the importance of careful evaluation of underlying risk factors, judicious antibiotic use, and consideration of alternative treatment modalities, such as faecal microbiota transplantation (FMT), for the prevention of recurrent CDI.}, }
@article {pmid41281468, year = {2025}, author = {Rijkers, GT and Langcauon, Y and van Leersum, P and Popović, L and van Overveld, FJ}, title = {Role of microbiota in the outcome of immune checkpoint inhibition therapy of cancer.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002348}, pmid = {41281468}, issn = {2692-3114}, abstract = {The realization that the composition and functionality of gut microbiota have an impact on the outcome of immune checkpoint inhibition (ICI) therapy of cancer has initiated research into the potential of microbiota management as adjunctive therapy. Fecal microbiota transplantation can improve the outcome of ICI, but for optimal donor selection, safety, and large-scale implementation, there remain bottlenecks. Alternative strategies, such as the use of selected bacterial species, require fundamental knowledge of the underlying mechanisms governing the interaction between (intestinal) microbiota and the immune system. Gut microbiota also appears to be able to colonize the tumor microenvironment. Some bacterial species directly or indirectly promote tumor growth. Other defined species have tumoricidal properties. These findings and insights are now being used to further optimize the functionality of the immune system and shape the tumor microenvironment in order to improve the outcome of ICI.}, }
@article {pmid41281485, year = {2025}, author = {Demirli Atici, S}, title = {Innovative insights into gut microbiota modulation in colorectal cancer: From microbial dysbiosis to therapeutic strategies.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {11}, pages = {108747}, pmid = {41281485}, issn = {1948-5204}, abstract = {Colorectal cancer (CRC) is increasingly recognized as a multifactorial disease influenced by hereditary, environmental, and microbial factors. This article explores recent insights into the role of gut microbiota dysbiosis in CRC pathogenesis and progression. Key differences in microbial composition, characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii, have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids. We discuss immune system modulation by the microbiota, formation of bacterial biofilms, and the activation of host pathways such as the urea cycle during tumorigenesis. Special attention is given to therapeutic innovations, including microbiota-informed precision modelling, synthetic biology-based engineered probiotics, and evolving alternatives to fecal microbiota transplantation. These integrative strategies represent promising tools in the era of personalized oncology for CRC.}, }
@article {pmid41282140, year = {2025}, author = {Gascoigne, N and Wojciech, L and Prasad, M and Brzostek, J and Rybakin, V and Hoerter, J and Hou, B and Tung, D and Chua, YL and Ampudia, J and Rai, A and Chodaczek, G and Fu, G and Pettersson, S}, title = {The role of Themis in development of type 2 diabetes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41282140}, issn = {2693-5015}, support = {R21 DK094173/DK/NIDDK NIH HHS/United States ; }, abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder driven by chronic inflammation and immune dysregulation, particularly within adipose tissue. This study investigates the role of the T cell-specific protein Themis in modulating immune-metabolic interactions that contribute to T2D pathogenesis. Using high-fat diet (HFD)-induced obesity models, we demonstrate that Themis-deficient (KO) mice exhibit accelerated weight gain, glucose intolerance, and insulin resistance compared to wild-type (WT) controls. These metabolic abnormalities are linked to functional alterations in the CD8[+] T cell compartment, including site-specific clonal expansion and reshaping of the T cell receptor (TCR) repertoire within adipose tissue, suggesting antigen-driven activation. Additionally, Themis deficiency leads to significant shifts in gut microbiome composition, characterized by reduced diversity and increased abundance of Firmicutes, particularly Clostridium species. However, fecal microbiota transplantation from Themis KO mice into germ-free WT hosts failed to recapitulate the full T2D phenotype, underscoring the dominant role of intrinsic immune dysfunction over microbial dysbiosis. These findings highlight a synergistic interplay between adaptive immunity and the microbiome in shaping metabolic outcomes and suggest that T cells play a central role in responses that influence T2D progression. Our data advocate for a more integrated approach to T2D research, incorporating genetic, immunological, and microbial factors.}, }
@article {pmid41282164, year = {2025}, author = {Gavini, C and Raux, L and Labouèbe, G and Gornick, E and Hugh, SM and Elshareif, N and Calcutt, N and Summa, PD and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V}, title = {Dietary Fiber Improves Somatosensory Function in Western Diet-Fed Mice by Remodeling Adipose Immune Cells via FFAR2 Signaling.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41282164}, issn = {2693-5015}, support = {U24 DK076169/DK/NIDDK NIH HHS/United States ; U24 DK115255/DK/NIDDK NIH HHS/United States ; }, abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that short-chain fatty acids (SCFAs) generated by fermentation remodel adipose tissue depots and act via the SCFA receptor FFAR2 (GPR43) to ameliorate sensory deficits. These findings identify a microbiota-SCFA-FFAR2 axis that couples dietary fiber to PNS function and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.}, }
@article {pmid41282240, year = {2025}, author = {Gancz, AS and Zhang, G and McMillan, AS and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Successful Fecal Microbiota Transplants in Post-antibiotic Treated Recurrent Clostridioides difficile Patients Induce Acylcarnitine and Sphingolipid Lipidomic Shifts.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41282240}, issn = {2693-5015}, support = {P42 ES027704/ES/NIEHS NIH HHS/United States ; R01 GM141277/GM/NIGMS NIH HHS/United States ; RM1 GM145416/GM/NIGMS NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) is an urgent public health threat in the United States, resulting on an annual basis in over half a million cases, more than 29,000 deaths, and $4.8 billion in healthcare costs. While fecal microbiota transplants (FMTs) have proven more effective than standard-of-care antibiotics in resolving recurrent CDI (rCDI), their inherent risks underscore the need for advancements in regulated alternative therapies such as live biotherapeutic products (LBPs). The development of effective LBPs, however, is contingent upon better understanding the biological mechanisms underlying FMT efficacy. Building on our previously published untargeted metabolomic study which identified lipids as major explanatory factors associated with successful FMTs, we assessed additional lipid species using an instrumental platform coupling liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) techniques. This platform and data analysis workflow enable the evaluation of >850 unique lipid species across 26 classes. Here, we confidently identified 397 lipids in the stools of 15 rCDI patients at pre- and post-FMT (2 week, 2 month, and 6 month) time points. Statistical evaluations of the lipidomic data illustrated that FMT-administration drastically reshapes the lipidome (adonis test, R[2]=0.11999, Pr(>F) <0.001), including 96 specific lipid species across 18 lipid classes (mixed effects modeling, BH correction, p < 0.05). In particular, we noted that medium and long-chain acylcarnitines decreased following FMT administration, while very long-chain acylcarnitines were elevated in post-FMT samples. Additionally, we observed assayed sphingolipids to be elevated pre-FMT with the exception of trihydroxy ceramides, which were highly upregulated post-FMT. These lipidomic alterations suggest that FMT administration may influence intestinal barrier integrity, inflammatory signaling, or apoptosis pathways. Interestingly, there was a strong co-occurrence of medium and long-chain acylcarnitines with Enterobacteriaceae, a bacterial family that has been demonstrated to utilize carnitine for growth. These findings highlight the critical role of the lipidome in patient susceptibility to rCDI and suggest the interactions between microbiota and lipids pre- and post-FMT as targets for developing next-generation LBPs.}, }
@article {pmid41284175, year = {2025}, author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Erikstrup, C and Olsen, K and Dahlerup, JF and Kjaer, TK and Krogh, CB and Ehlers, LH and Hvas, CL}, title = {Increasing patient access to faecal microbiota transplantation with remote delivery: a cost analysis of outpatient versus home-based treatment.}, journal = {Health economics review}, volume = {15}, number = {1}, pages = {108}, pmid = {41284175}, issn = {2191-1991}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) is used in less than 10% of the patients in Europe who meet the indication. Encapsulated FMT allows increased use for CDI because capsules can be safely shipped to local healthcare facilities and administered orally to patients without use of e.g. colonoscopy. The aim of this study was to calculate and compare the costs of alternative ways of delivering encapsulated FMT to patients with CDI in Denmark, including outpatient treatment at a specialised FMT centre, outpatient treatment at local hospitals including remote delivery to the Faroe Islands, and home-based care.<br><br>METHODS: Applying a healthcare perspective, we used an activity-based costing approach, combining data from a pragmatic clinical randomised trial with the best available literature and expert input. Only relevant costs were included. The main outcome was the average cost of delivering outpatient, encapsulated FMT treatment at an FMT centre, at a local hospital, or in the patient's home, only including additional costs related to delivery. An 8-week time horizon was applied for the analysis. Probabilistic and deterministic sensitivity analyses were applied to evaluate decision uncertainty and the robustness of the results.<br><br>RESULTS: In a pragmatic randomised trial including 217 patients with CDI, 135 patients received FMT. Analysing relevant costs in a base case analysis, local outpatient treatment (&#x20ac;145) was cost-saving compared with both treatment at the FMT centre (&#x20ac;209) and home-based treatment (&#x20ac;353). These differences remained robust across sensitivity analyses, including those accounting for patients' time costs. In the Faroe Islands case, shipment to remote locations added an average cost of &#x20ac;54 per FMT to the cost for the local outpatient treatment.<br><br>CONCLUSION: Capsule-based FMT treatment has made it clinically and economically feasible to administer FMT in contextual settings outside of specialised hospitals. Our findings highlight the importance of local hospital-based treatment for increasing patient access to FMT, the ability to ship FMT to remote locations lacking a FMT centre, and the option of home-based treatment for a selected group of patients who may not tolerate transport to hospital.}, }
@article {pmid41285255, year = {2026}, author = {Wang, S and Ma, G and Qi, C and Cheng, S and Lai, H and Zhou, L and Wu, G and Chen, Z and Mao, X and Jing, T and He, Y and Zhou, H}, title = {Trimethylamine-N-oxide disrupts spermatogenesis by inducing mitochondrial oxidative stress injury through Hippo signaling.}, journal = {Free radical biology &amp; medicine}, volume = {243}, number = {}, pages = {452-465}, doi = {10.1016/j.freeradbiomed.2025.11.052}, pmid = {41285255}, issn = {1873-4596}, mesh = {Male ; Animals ; *Mitochondria/metabolism/drug effects/pathology ; *Oxidative Stress/drug effects ; Humans ; Mice ; *Methylamines/metabolism/blood ; *Spermatogenesis/drug effects ; Hippo Signaling Pathway ; Signal Transduction/drug effects ; Testis/metabolism/drug effects/pathology ; Leydig Cells/metabolism/drug effects ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Adult ; Spermatozoa/drug effects/metabolism/pathology ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: The gut-testis axis is increasingly recognized as a regulator of male reproductive health; however, the key microbial contributors, metabolites, and underlying mechanisms remain unclear.<br><br>METHODS: We performed fecal metagenomic sequencing in 107 participants to identify microbial taxa associated with abnormal semen parameters. Serum trimethylamine-N-oxide (TMAO) levels were measured and correlated with semen quality. In mouse models, including fecal microbiota transplantation, dietary choline supplementation, mono-colonization, and direct TMAO administration, we assessed sperm morphology, testicular androgen synthesis, and testicular histology. Testicular transcriptomics, in vitro Leydig cell assays, and mitochondrial function analyses were conducted to investigate the effects of TMAO on Hippo signaling, oxidative phosphorylation, mitochondrial membrane damage, and steroidogenesis.<br><br>RESULTS: Choline-to-trimethylamine converting bacteria, including Phocaeicola massiliensis, Veillonella spp., and Klebsiella pneumoniae, were enriched in men with abnormal semen parameters. Circulating TMAO levels were inversely associated with semen volume, total sperm count, and motile sperm count. In mouse models, elevated TMAO induced testicular dysfunction characterized by impaired sperm morphology, reduced testicular androgen synthesis, and histological abnormalities. Consistently, gene set enrichment analysis (GSEA) of testicular transcriptomes revealed significant suppression of mitochondrial translation, membrane integrity, oxidative phosphorylation, and adenosine triphosphate (ATP) metabolism. TMAO also suppressed steroidogenesis by reducing the expression of steroidogenic acute regulatory protein (StAR). Mechanistic studies in TM3 Leydig cells further demonstrated that TMAO, by promoting Yap phosphorylation, disrupted mitochondrial structure and morphology, decreased mitochondrial membrane potential, increased mitochondrial reactive oxygen species (ROS) levels, impaired ATP synthesis, and promoted mitochondrial fragmentation with upregulation of the mitochondrial fission molecule (Fis1).<br><br>CONCLUSIONS: Our findings demonstrate that TMAO activates Hippo signaling to induce mitochondrial dysfunction and suppress testosterone synthesis, thereby impairing spermatogenesis. These results highlight TMAO biosynthesis and its downstream signaling as potential therapeutic targets for improving male fertility.}, }
@article {pmid41287633, year = {2025}, author = {Marques, I and Marcos, P}, title = {Acute hepatic porphyrias.}, journal = {Porto biomedical journal}, volume = {10}, number = {6}, pages = {e308}, pmid = {41287633}, issn = {2444-8672}, abstract = {INTRODUCTION: Porphyrias are rare genetic disorders caused by heme biosynthesis pathway enzyme mutations, leading to porphyrin precursors build up in various tissues and diverse symptoms. This review centers on acute hepatic porphyrias (AHP).<br><br>METHODS: A MEDLINE through PubMed database literature review was conducted. Systematic reviews, clinical trials, cohort studies, case-control studies, expert reviews, and guidelines were preferred for analysis.<br><br>RESULTS: There are 4 types of AHP: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and &#x3b4;-aminolevulinic acid dehydratase deficiency porphyria. These conditions primarily present as neurovisceral attacks, characterized by severe abdominal pain, neuropsychiatric symptoms, or skin lesions, predominantly affecting women aged 15 to 50 years. The diagnostic methods include biochemical tests that assess urinary levels of aminolevulinic acid and porphobilinogen. In addition, measuring porphyrin levels in urine or feces can provide more insights into the type of AHP; however, a definitive diagnosis of the specific type is made through genetic testing. Treatment involves high-glucose diets, intravenous hemin for acute attacks, and givosiran for the prophylaxis of frequent attacks. Liver transplantation remains the only curative option. It is crucial to monitor chronic complications associated with hepatic porphyrias, particularly hepatocellular carcinoma, kidney disease, and arterial hypertension.<br><br>CONCLUSION: AHP continues to be an underrecognized condition, warranting consideration in individuals experiencing unexplained abdominal pain, neuropathy, psychiatric symptoms, or skin lesions. There is a need for improved diagnostic techniques and treatment options.}, }
@article {pmid41287858, year = {2025}, author = {Liu, N and Wang, DX and Hao, JX and Yan, XF and Lv, CL and Yan, JG and Liu, GF}, title = {Fecal Microbiota Transplantation Combined with Lifestyle Modification in the Management of Metabolic Dysfunction-Associated Fatty Liver Disease: Two Case Reports and Literature Review.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {18}, number = {}, pages = {4299-4307}, pmid = {41287858}, issn = {1178-7007}, abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent condition, with gut microbiota dysbiosis playing a contributory role in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach for MAFLD. This report describes two patients diagnosed with MAFLD who underwent FMT in combination with lifestyle intervention. Post treatment findings demonstrated notable improvements in body mass index (decreased by 20.7% and 3%, respectively), serum transaminases levels (decreased by 51% and 27.2%, respectively), lipid profiles, uric acid concentrations, and liver stiffness measurements (decreased by 22.2% and 24.2%, respectively). Additionally, microbiome analysis showed increased diversity, improved anti-inflammatory and colonization resistance capacity, reduced pathogens, and enriched probiotics. A review of seven Chinese and international randomized controlled trials (RCTs) investigating the application of FMT in MAFLD was conducted. Among these, four trials reported improvement in liver function post-treatment. Two trials reported reductions in small intestinal or gastric permeability, one trial demonstrated a decrease in homeostasis model assessment of insulin resistance (HOMA-IR), one trial noted a reduction in blood lipid levels, and one trial documented a decrease in fat attenuation index (FAI). Only one trial included histological evaluation of liver tissue before and after FMT, which did not demonstrate significant pathological improvement. The combination of FMT and lifestyle intervention has achieved quite satisfactory therapeutic effects in the treatment of MAFLD, providing new ideas and potential therapeutic targets for the management of MAFLD. This approach holds broad application prospects. However, further confirmation through large-scale RCTs is still needed.}, }
@article {pmid41288714, year = {2025}, author = {Quiroga-Centeno, AC and Atanasova, K and Ebert, MP and Thomann, AK and Reindl, W}, title = {Emerging microbiome-directed therapies in inflammatory bowel disease: beyond diet modification and FMT.}, journal = {Seminars in immunopathology}, volume = {47}, number = {1}, pages = {42}, pmid = {41288714}, issn = {1863-2300}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/etiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Animals ; Dysbiosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a multifactorial and heterogeneous disorder that remains challenging to manage. Growing evidence implicates the gut microbiome as a key player in IBD pathogenesis, with many patients displaying intestinal dysbiosis that can drive aberrant immune responses. Traditional microbiome-targeted interventions, such as dietary modifications, probiotics, and fecal microbiota transplantation (FMT), have yielded mixed and often temporary benefits in IBD. This shortcoming of broad-spectrum approaches underscores the need for more precise, personalized strategies that account for each patient's unique microbiota and disease phenotype. Recent advances in omics and bioengineering have catalyzed the development of emerging microbiome-directed therapies that move beyond these broad approaches. This narrative review highlights emerging microbiome-directed therapies that aim to restore gut homeostasis and mitigate inflammation in IBD. We critically evaluate the rationale and therapeutic potential of rationally designed bacterial consortia and genetically engineered bacteria, which represent next-generation probiotics tailored to complement deficient microbial functions or deliver anti-inflammatory agents in situ. We also expand the discussion to underexplored microbiome constituents - archaea, protists, bacteriophages, and fungi - highlighting their roles in IBD and potential as therapeutic targets. Finally, we discuss the key advances and ongoing challenges of these innovative approaches, from ecological stability and engraftment to safety and regulatory considerations.}, }
@article {pmid41290520, year = {2025}, author = {Kumari, A and Priya, S and Barman, I and Dhasmana, A and Rustagi, S and Thapliyal, S and Deshwal, RK and Malik, S and Bora, J}, title = {Gut Microbiota Dynamics and Their Role in Pathogenesis and Management of Diabetes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {133}, number = {11}, pages = {e70090}, doi = {10.1111/apm.70090}, pmid = {41290520}, issn = {1600-0463}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/microbiology/therapy ; Dysbiosis/microbiology ; *Diabetes Mellitus, Type 1/microbiology/therapy ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The gut microbiota (GM) has emerged as an important element in the management of host metabolism, immune functions, and overall metabolic well-being. This review consolidates contemporary research regarding the intricate relationship between GM and diabetes mellitus, focusing on the mechanisms by which microbial composition and activity affect the development of both Type 1 (T1D) and Type 2 diabetes (T2D). Dysbiosis-characterized by diminished microbial diversity, a modified Firmicutes/Bacteroidetes ratio, and a reduction in advantageous SCFA-producing bacteria-has been significantly associated with disrupted glucose metabolism, insulin resistance, and persistent inflammation. Additionally, the review discusses the potential for microbial signatures and metabolites, such as SCFAs, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), to serve as novel biomarkers for early detection and risk evaluation. Moreover, it investigates therapeutic approaches designed to reestablish microbial balance through the use of probiotics, prebiotics, dietary changes, fecal microbiota transplantation (FMT), and microbiome engineering. By integrating findings from recent research, this paper emphasizes the groundbreaking possibilities of microbiome-centric diagnostics and treatments in individualized diabetes care.}, }
@article {pmid41291207, year = {2025}, author = {Li, C and Wang, H and Lin, X and Zeng, G and Li, X and Chen, W and Lu, H and Pan, J and Zhang, X and Rong, X and He, L and Peng, Y}, title = {Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1847}, pmid = {41291207}, issn = {2399-3642}, mesh = {Animals ; *Blood-Brain Barrier/drug effects/metabolism ; Male ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Alcoholism/microbiology/metabolism ; Female ; Adult ; Middle Aged ; Mice, Inbred C57BL ; *Alcohol Drinking/adverse effects ; *Brain-Gut Axis ; Hippocampus/metabolism ; }, abstract = {Chronic alcohol consumption can lead to disruption of the blood-brain barrier. The gut-brain axis may be involved in this pathological process. We investigated the gut microbiota of 30 healthy individuals and 30 alcohol use disorder (AUD) patients and found that at the genus level, AUD patients had decreased Faecalibacterium and increased Streptococcus. Liquid chromatography mass spectrometer (LC-MS/MS) revealed that 604 metabolites were upregulated and 606 were downregulated in AUD patients with cognitive impairment, compared to healthy controls. Chronic alcohol consumption led to cognitive decline in mice, with increased 20 kDa FITC-dextran leakage in the prefrontal cortex (PFC) and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5. Transplantation of feces from AUD patients into germ-free mice resulted in increased 20 kDa FITC-dextran leakage in PFC and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5, compared to mice receiving feces from healthy individuals. Administration of Faecalibacterium prausnitzii to chronically alcohol-fed mice improved cognitive function, reduced 20 kDa FITC-dextran leakage in PFC and hippocampus, and increased the expression of ZO-1, occludin, and claudin-5. Chronic alcohol consumption can disrupt the blood-brain barrier through the gut-brain axis. Faecalibacterium prausnitzii can improve alcohol-induced blood-brain barrier disruption and cognitive impairment.}, }
@article {pmid41292332, year = {2025}, author = {Bø, S and Wiig, H and Juul, FE and Garborg, KK and Johnsen, PH and Bretthauer, M}, title = {Faecal microbiota transplantation for primary Clostridioides difficile infection.}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {145}, number = {14}, pages = {}, doi = {10.4045/tidsskr.25.0276}, pmid = {41292332}, issn = {0807-7096}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Female ; Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use/adverse effects ; Middle Aged ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile (C. difficile) infection. The recommended treatment for primary C. difficile infection is antibiotics. We present a patient who requested FMT for primary C. difficile infection.<br><br>CASE PRESENTATION: A patient in her sixties developed primary C. difficile infection following antibiotic therapy atter surgery for small bowel volvulus. The patient refused antibiotic treatment and contacted a research group that had just concluded a randomised phase III trial assessing FMT for primary C. difficile infection. The trial had not yet been published, and FMT was not included in guideline recommendations for this indication. After joint decision-making involving the patient, her general practitioner, gastroenterologists and the research group, the patient received FMT and experienced complete remission of C. difficile symptoms within two days of treatment.<br><br>INTERPRETATION: This case illustrates how to evaluate experimental versus established treatments in light of new evidence and patient preferences that do not align with guideline recommendations.}, }
@article {pmid41292506, year = {2026}, author = {Arawker, MH and Habibullah, F and Baral, S and Fu, L and Sun, N and Li, H and Ji, F and Qiu, X}, title = {Microbiome Mediated Immune Crosstalk on the Gut-Thyroid Axis in Autoimmune Thyroid Disease.}, journal = {Immunological investigations}, volume = {55}, number = {2}, pages = {448-468}, doi = {10.1080/08820139.2025.2593335}, pmid = {41292506}, issn = {1532-4311}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Dysbiosis/immunology ; *Thyroiditis, Autoimmune/immunology/microbiology ; *Thyroid Gland/immunology ; Autoimmunity ; }, abstract = {BACKGROUND: The gut microbiota plays an important role in systemic immune homeostasis and is increasingly implicated in autoimmune thyroid disease (AITD). Evidence suggests that gut dysbiosis, impaired intestinal barrier function, and altered microbial metabolites particularly short-chain fatty acids contribute to immune imbalance along the gut-thyroid axis. Although molecular mimicry between microbial and thyroid antigens has been proposed, current human evidence remains associative rather than causal.<br><br>METHODS: This review synthesized current observational, translational, and preclinical studies evaluating microbial composition, barrier integrity, microbial metabolites, and immune pathways relevant to AITD. Mechanistic insights into T-lymphocyte regulation and microbial-host interactions were integrated with emerging interventional data.<br><br>RESULTS: Gut dysbiosis in AITD is linked to reduced regulatory T-lymphocytes, expansion of Th17 cells, increased intestinal permeability, and the loss of short-chain-fatty-acid-producing taxa. Observational studies consistently report disease-associated taxonomic alterations, while preclinical models support causal pathways through barrier disruption and microbiota-driven immune activation. Early interventional approaches such as high-fiber dietary patterns, probiotics, prebiotics, and experimental fecal microbiota transplantation show modest reductions in thyroid autoantibodies in small trials, though effects are strain-specific, short-term, and not disease-modifying.<br><br>CONCLUSION: Despite largely associative human evidence, converging mechanistic findings highlight the gut microbiota as a modifiable contributor to thyroid autoimmunity. Future priorities include clarifying causality, identifying keystone microbial taxa and metabolites, and establishing standardized interventional frameworks to facilitate translation into endocrine practice.}, }
@article {pmid41293177, year = {2025}, author = {Li, P and Wang, Y and Dong, Y and Zhang, X}, title = {Unveiling the gut-liver axis: the behind-the-scenes "manipulator" of human immune function.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1638197}, pmid = {41293177}, issn = {1664-3224}, mesh = {Humans ; *Liver/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; Animals ; Bile Acids and Salts/metabolism ; }, abstract = {The "gut-liver axis" enables bidirectional immunoregulation between the intestine and the liver through the portal venous circulation, bile acid metabolism, and the neuro-lymphatic network. This paper reviews its physiological pathways (vascular, biliary, neural, and lymphatic), immunomodulatory mechanisms (interaction of innate/adaptive immune cells, balance between inflammation and tolerance), and associations with diseases such as PSC, MAFLD, and IBD. Metabolites of gut microbiota activate immune cell receptors to regulate the differentiation of Tregs, while cytokines (such as IL-6) and chemokines (such as CCR9) drive the synergy of gut-liver immunity. In pathological conditions, dysbiosis, endotoxin translocation, and bile acid metabolic disorders trigger immunological dysregulation through this axis. Strategies such as targeted fecal microbiota transplantation and bile acid receptor (FXR) agonists show clinical potential. This paper systematically elaborates on the physiological and immunoregulatory mechanisms of the "gut-liver axis", explores the associations between its abnormalities and immune diseases, as well as the prospects of translational medicine. It is proposed that future research should deepen the analysis of single-cell interactions, conduct personalized interventions, and establish a new paradigm of "gut-liver axis medicine" to provide cross-organ solutions for the precise prevention and control of immune-related diseases.}, }
@article {pmid41294832, year = {2025}, author = {Susiriwatananont, T and Eiamprapaporn, P and Vazquez Roque, M and Farraye, FA and Perlman, A and Chumsri, S}, title = {The Gut Microbiome as a Biomarker and Therapeutic Target of Immune Checkpoint Inhibitors: A Review for Oncologists.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, pmid = {41294832}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Oncologists ; *Neoplasms/drug therapy/immunology/microbiology ; Biomarkers/metabolism ; Immunotherapy/methods ; Biomarkers, Tumor/metabolism ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their benefits remain limited to a subset of patients, underscoring the need for more reliable biomarkers and novel therapeutic strategies. The gut microbiome has emerged as a critical modulator of systemic immunity and a promising determinant of ICI response. Evidence links specific microbial features, taxa, and bioactive metabolites to enhanced antitumor immunity, whereas disruptions, such as antibiotic exposure, are associated with poorer outcomes. Advances in sequencing and multi-omics technologies have provided more profound insights into microbiome-immune crosstalk, though methodological heterogeneity continues to challenge reproducibility. Translational studies demonstrate that microbiome-based intervention, including fecal microbiota transplantation (FMT), biotics supplementation, and engineered microbial strains, can enhance ICI efficacy or mitigate immune-related toxicities. Despite encouraging early clinical signals, broader implementation requires methodological rigor, standardized protocols, and innovative trial designs that account for host and environmental factors. For clinicians, the most immediate strategies involve prudent antibiotic stewardship and patient enrollment in microbiome-focused clinical trials. Overall, the gut microbiome is a promising biomarker and a therapeutic target, representing a new frontier for personalizing immunotherapy and improving patient outcomes in oncology.}, }
@article {pmid41296090, year = {2025}, author = {Wang, M and Zeng, Y and Jin, Y and Wu, J and Li, J}, title = {Progress and Perspectives on the Estrogen-Microbiota-Brain Axis in Alzheimer's Disease.}, journal = {Neurochemical research}, volume = {51}, number = {1}, pages = {3}, pmid = {41296090}, issn = {1573-6903}, support = {No. QKHJC-ZK[2022]-260//Guizhou Provincial Science and Technology Projects/ ; NO.gzwjrs2023-005//Guizhou Provincial High level Innovative Talent Fund/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/microbiology ; *Estrogens/metabolism ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/drug effects ; Animals ; Dysbiosis/metabolism ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder shaped by genetic, metabolic, environmental, and sex-specific factors. Emerging evidence highlights the estrogen-gut microbiota-brain (EGMB) axis as a critical framework linking endocrine regulation, microbial activity, and cognitive outcomes. Estrogen exerts neuroprotective effects by modulating synaptic plasticity, oxidative stress, amyloid and tau pathology, and neuroinflammation, while its decline during menopause increases AD vulnerability. Parallel to this, gut dysbiosis and altered microbial metabolites, particularly short-chain fatty acids (SCFAs) and secondary bile acids (sBAs), contribute to barrier dysfunction, chronic inflammation, and synaptic impairment. Importantly, estrogen remodels microbial composition and metabolite profiles, whereas microbial β-glucuronidase (β-GUS) activity sustains estrogen bioavailability, establishing a reciprocal regulatory loop. Preclinical studies demonstrate that depletion of gut microbiota diminishes estrogen's protective effects, underscoring the central role of microbial metabolites as signaling bridges.Therapeutically, these insights support the integration of hormone replacement therapy with microbiota-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Such combined strategies may synergistically enhance neuroprotection, though their efficacy depends on timing, dosage, and individual variability. Future precision approaches integrating multi-omics profiling and sex-specific stratification hold promise for identifying predictive biomarkers and optimizing treatment windows. In summary, the EGMB axis offers a mechanistic foundation for understanding sex differences in AD and a translational framework for developing individualized, multidimensional strategies for early diagnosis, prevention, and therapy.}, }
@article {pmid41297113, year = {2025}, author = {Lyu, L and Ma, Y and Sun, X and Luo, M and Wang, Z and Fang, L and Li, W and Chen, Y and Liu, S and Jia, X}, title = {Human cord blood mononuclear cells alleviate intestinal inflammation and barrier dysfunction by regulating gut metabolites and Th17/Treg balance.}, journal = {Molecular immunology}, volume = {188}, number = {}, pages = {179-191}, doi = {10.1016/j.molimm.2025.11.004}, pmid = {41297113}, issn = {1872-9142}, mesh = {Animals ; *Th17 Cells/immunology ; *T-Lymphocytes, Regulatory/immunology ; Humans ; Mice, Inbred C57BL ; Male ; Mice ; *Colitis/immunology/therapy/chemically induced/metabolism ; *Fetal Blood/cytology ; *Leukocytes, Mononuclear/immunology/transplantation ; Dextran Sulfate ; *Inflammation/immunology ; *Intestinal Mucosa/metabolism/immunology ; Inflammatory Bowel Diseases/immunology/therapy ; }, abstract = {BACKGROUND: Cord blood mononuclear cells (CB-MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB-MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear.<br><br>METHODS: In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6&#x202f;J mice, followed by treatment with CB-MNCs, umbilical cord-derived mesenchymal stem cells (UC-MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study.<br><br>RESULTS: Our findings demonstrated that compared with UC-MSCs and mesalazine, CB-MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC-MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB-MNCs were also more effective than UC-MSCs and mesalazine at maintaining Th17/Treg balance than UC-MSC and mesalazine in colitis mice.<br><br>CONCLUSIONS: The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.}, }
@article {pmid41297775, year = {2025}, author = {Ferrini, A and He, M and Mont, MA and Goodman, SB and Parvizi, J}, title = {Osteonecrosis of the Femoral Head: A Dysbiotic Condition?.}, journal = {The Journal of arthroplasty}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arth.2025.11.044}, pmid = {41297775}, issn = {1532-8406}, abstract = {Osteonecrosis of the femoral head (ONFH) is a progressive and disabling condition of the hip joint that primarily affects young and active individuals, leading to progressive collapse of subchondral bone and often secondary arthritis. Despite extensive investigation, the precise etiology often remains unclear. While high-dose corticosteroids, chronic alcohol ingestion, and smoking are known associated risk factors, approximately 20 to 30% of ONFH cases are classified as idiopathic. Recently, the concept of gut dysbiosis, i.e., disruption of the normal intestinal microbial balance, has gained increasing attention due to its systemic immunologic and metabolic implications. Dysbiosis is associated with an increase in gut permeability, leading to the translocation of bacteria and their metabolic products, including lipopolysaccharides and short-chain fatty acids, into the systemic circulation. This may stimulate proinflammatory cascades throughout the body, including the joints, initiating a bone remodeling process. Emerging evidence from preclinical and human research suggests that specific gut microbiota taxa may influence key mechanisms involved in the pathogenesis of ONFH. In addition, early findings support the therapeutic potential of microbiota-targeted therapies such as probiotics, short-chain fatty acids-enriched diets, and fecal microbiota transplantation. Although a growing number of descriptive studies support this link, the current evidence remains associative rather than causal, as no longitudinal cohort studies have confirmed this relationship. Future investigations are needed to establish causality between gut dysbiosis and ONFH. To our knowledge, this review offers the first comprehensive synthesis of the literature aiming to explore current evidence and the potential link between gut dysbiosis and ONFH, highlighting future directions for microbiome-based therapeutic interventions.}, }
@article {pmid41298101, year = {2025}, author = {Liu, CS and Merrick, B and Taboun, ZS and Mullish, BH and Goldenberg, SD and Terveer, EM and Porcari, S and Bradbury, RS and Ianiro, G and Ng, SC and ,  and Kao, D and Kuijper, E}, title = {Towards optimising and standardising donor screening for faecal microbiota transplantion.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336532}, pmid = {41298101}, issn = {1468-3288}, abstract = {Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.}, }
@article {pmid41299728, year = {2025}, author = {Vaziri, Y and Olia, JBH and Avci, CB and Nourazarian, A}, title = {Molecular mechanisms of gut microbiota dysbiosis and metabolites in Alzheimer's disease pathogenesis: implications for precision therapeutics.}, journal = {Molecular brain}, volume = {18}, number = {1}, pages = {92}, pmid = {41299728}, issn = {1756-6606}, mesh = {Humans ; *Alzheimer Disease/therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome ; *Dysbiosis/metabolism/microbiology/complications/therapy ; Animals ; *Precision Medicine ; }, abstract = {Alzheimer's disease (AD) originates from both central and peripheral pathways. The gut microbiota is a clear risk factor. In AD, microbiota imbalances drive immune system activation, disrupt protective barriers, and alter neuromodulatory signaling. Additionally, gut microbiota dysbiosis has been identified as a risk factor for AD. Recent research indicates that dysbiosis of the microbiota in AD is linked to immune activation, barrier dysfunction, and neuromodulatory signaling. Studies of AD pathology reveal that short-chain fatty acids, indole derivatives, and bile acids can have both protective and harmful effects. New strategies, such as probiotics, dietary changes, and fecal microbiota transplantation, may influence disease progression in AD. However, conflicting methods, unaccountable motives, and ethical concerns surrounding microbiome interventions pose significant hurdles. To translate findings related to the gut-brain axis into effective solutions, we need standardized multi-omics approaches, personalized therapies, and oversight from regulatory authorities. Ultimately, leveraging insights from the gut microbiome holds great promise for transforming how we diagnose, prevent, and treat AD.}, }
@article {pmid41299731, year = {2025}, author = {Zhao, Y and Li, H and Xu, J and Li, H and Bao, L and Wu, K and Qiu, M and Yu, H and Shang, S and He, Y and Yuan, C and Zhang, N and Hu, X and Fu, Y and Li, W and Zhao, C and Wang, J}, title = {Phytosphingosine contributes gut microbiota metabolism to alleviate low-grade endotoxemia-induced mastitis.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {2}, pmid = {41299731}, issn = {2049-2618}, support = {32330105//National Natural Science Foundation of China/ ; 2023M741348//China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; *Endotoxemia/complications/microbiology ; Mice ; Dysbiosis/microbiology ; Cattle ; *Sphingosine/analogs &amp; derivatives/administration &amp; dosage/metabolism/pharmacology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Metabolomics ; Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Mammary Glands, Animal/pathology ; Fatty Acids, Volatile/metabolism ; *Mastitis/microbiology/etiology ; }, abstract = {BACKGROUND: Recently, evidence has indicated that mastitis is closely associated with the ruminal dysbiosis caused by subacute ruminal acidosis (SARA) and subsequent low-grade endotoxemia (LGE). However, whether and how ruminal metabolic dysbiosis influences SARA-associated mastitis is still unclear.<br><br>RESULTS: Using untargeted metabolomics, we found that cows with SARA-associated mastitis exhibited altered ruminal metabolic profiles, particularly a reduced level of phytosphingosine (PS), compared to healthy cows. Oral administration of PS to mice alleviated LGE-induced mastitis, as evidenced by attenuated mammary injury and improved function of mammary tight junctions (TJs). Furthermore, we demonstrated that LGE induced significant gut dysbiosis, characterized by increased abundances of opportunistic pathogens such as Enterococcus, which was mitigated by PS treatment. Interestingly, transplantation of both fecal microbiota (FMT) and matched sterile supernatant (FST) from PS-treated mice alleviated LGE-induced mastitis, restored the blood-milk barrier, and modulated the gut microbiota in recipient mice following LGE exposure. Additionally, PS and PS-FMT treatments increased the abundances of fecal short-chain fatty acid (SCFA) producers, accompanied by elevated fecal SCFA levels, particularly butyric acid, in PS- and PS-FMT-treated mice. Butyric acid was negatively correlated with mammary inflammatory markers, and butyrate administration attenuated LGE-induced mastitis in mice. Mechanistically, butyrate promotes M2 macrophage polarization and inhibits NF-&#x3ba;B and NLRP3 inflammasome activation via G-protein-coupled receptor 41 (GPR41).<br><br>CONCLUSIONS: Collectively, our results demonstrate that gut microbiota from PS-dosed mice alleviate LGE-induced mastitis in mice by promoting SCFA production and regulating macrophage polarization. Our findings provide deeper insights into gut dysbiosis-associated mastitis and highlight the potential of modulating gut microbiota and its metabolism as a strategy for managing mastitis and other related diseases. Video Abstract.}, }
@article {pmid41300676, year = {2025}, author = {Marano, G and Sfratta, G and Marzo, EM and Cozzo, G and Abate, F and Traversi, G and Mazza, O and Capristo, E and Gaetani, E and Mazza, M}, title = {The Pediatric Microbiota-Gut-Brain Axis: Implications for Neuropsychiatric Development and Intervention.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {41300676}, issn = {2227-9067}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota-gut-brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota-gut-brain axis, increasing risk and/or severity of neuropsychiatric outcomes, and that microbiota-targeted strategies may mitigate this risk.<br><br>METHODS: We conducted a narrative review by searching PubMed, Scopus, and Web of Science up to January 2025 for studies addressing pediatric microbiota, neuropsychiatric development, and interventions. Human and animal studies were included if they provided mechanistic or clinical insights.<br><br>RESULTS: Key determinants of microbiota development in childhood include mode of delivery, feeding practices, antibiotic exposure, diet, and environment. Altered microbial composition has been associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorders, anxiety, and anorexia nervosa. Mechanistic pathways involve immune modulation, neural signaling (including the vagus nerve and enteric nervous system), and microbial metabolites such as short-chain fatty acids. Interventions targeting the microbiota-ranging from dietary strategies and probiotics to psychobiotics and fecal microbiota transplantation-show promise but require further pediatric-focused trials.<br><br>CONCLUSIONS: The pediatric microbiota-gut-brain axis represents a critical window for neuropsychiatric vulnerability and intervention. Early-life strategies to support a healthy microbiota may help reduce the risk or severity of psychiatric disorders. Future research should prioritize longitudinal pediatric cohorts and clinical trials to translate mechanistic insights into precision interventions.}, }
@article {pmid41300985, year = {2025}, author = {De Lucia, SS and Nista, EC and Candelli, M and Archilei, S and Deutschbein, F and Capuano, E and Gasbarrini, A and Franceschi, F and Pignataro, G}, title = {Microbiota and Pancreatic Cancer: New Therapeutic Frontiers Between Engineered Microbes, Metabolites and Non-Bacterial Components.}, journal = {Cancers}, volume = {17}, number = {22}, pages = {}, pmid = {41300985}, issn = {2072-6694}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal human malignancies, with five-year survival rates showing only marginal improvement despite decades of intensive research. Its dismal prognosis reflects a combination of intrinsic biological aggressiveness, late clinical presentation, and marked resistance to standard therapies, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Growing evidence indicates that the microbiome is a modifiable factor influencing the onset, progression, and treatment response of PDAC. Microbial communities originating from the gut, oral cavity, and even the tumor microenvironment can shape carcinogenic pathways, modulate immune activity, and alter the efficacy of chemotherapy and immunotherapy. In addition to bacteria, fungal and viral populations are emerging as relevant contributors within this complex ecosystem. This review provides a comprehensive overview of the current mechanistic and translational evidence linking the microbiome to PDAC biology and therapy. It further explores microbiota-targeted interventions-such as probiotics, postbiotics, engineered bacterial strains, bacteriophages, oncolytic viruses, and fecal microbiota transplantation-as promising adjuncts to conventional treatments. A deeper understanding of host-microbiome interactions could yield novel biomarkers and open innovative avenues for precision medicine in PDAC, ultimately improving patient outcomes and reshaping therapeutic paradigms. Integrating microbiome-based strategies into PDAC management may thus represent a crucial step toward more effective and personalized oncologic care.}, }
@article {pmid41301443, year = {2025}, author = {Papavassiliou, KA and Sofianidi, AA and Spiliopoulos, FG and Margoni, A and Papavassiliou, AG}, title = {Emerging Issues Regarding the Effects of the Microbiome on Lung Cancer Immunotherapy.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, pmid = {41301443}, issn = {2218-273X}, mesh = {Humans ; *Lung Neoplasms/therapy/microbiology/immunology ; *Immunotherapy/methods ; *Microbiota/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Lung cancer remains the deadliest malignancy, with limited effective and long-term therapeutic options. Immunotherapy has revolutionized the therapeutic landscape of lung cancer. However, not everyone with lung cancer responds to immunotherapy, while, inpatients who temporarily derive clinical benefit, resistance eventually develops. The host microbiome has emerged as a pivotal player in cancer growth and progression. It has been implicated in the intricate connections between immune cells and tumor cells, ultimately augmenting immunotherapy efficacy in solid tumors, while simultaneously mitigating the immune-related adverse events associated with this type of treatment. Notably, lung cancer patients who obtain benefit from immunotherapy have been found to be colonized with specific bacterial populations, and it is this observation that the scientific community is trying to exploit, aspiring to improve lung cancer immunotherapy response rates. Delving deeper into the molecular mechanisms underpinning the effects of the microbiome on immunotherapy is an area that we should pay attention to if we want to utilize microbiome modulation in everyday clinical practice. Fecal microbiota transplantation, probiotics, targeted antibiotic interventions, and dietary modifications are among the strategies that are under investigation in clinical trials, with the ultimate endpoint of lengthening the life expectancy of lung cancer patients.}, }
@article {pmid41301795, year = {2025}, author = {Seguiti, C and Tettoni, E and Pezzuto, E and Gerardi, V and Quadarella, A and Cesaro, P and Colombini, P}, title = {Clostridioides difficile Infection in Special Populations: Focus on Inflammatory Bowel Disease-A Narrative Review from Pathogenesis to Management.}, journal = {Biomedicines}, volume = {13}, number = {11}, pages = {}, pmid = {41301795}, issn = {2227-9059}, abstract = {Clostridioides difficile infection (CDI) is a major complication in inflammatory bowel disease (IBD), due to coexistence of altered microbiota, chronic inflammation, and immune dysregulation. This narrative review summarizes recent evidence on the epidemiology, pathogenesis, risk factors, diagnosis, and management of CDI in IBD. Overall, IBD patients have a four- to five-fold higher risk of CDI than the general population and face more severe courses, higher rates of hospitalization, colectomy, recurrence, and mortality. Pathogenesis involves profound dysbiosis with loss of butyrate-producing Firmicutes and Bacteroidetes, bile acid imbalance that promotes spore germination, and enhanced toxin effects on an already inflamed mucosa. Major risk factors include active colonic disease, broad-spectrum antibiotic exposure, prolonged hospitalization, and corticosteroid or combined immunosuppressive therapy. Diagnosis requires careful integration of stool assays with clinical evaluation, supported by endoscopy or imaging when needed, to distinguish infection from IBD flares. Recommended first-line treatments are fidaxomicin or oral vancomycin, reserving fecal microbiota transplantation for recurrent or high-risk cases. Optimal IBD control is essential to reduce both primary and recurrent infection. CDI and IBD share a mutual pathogenic interplay in which microbial, immune, and therapeutic factors from each condition drive and magnify the other. Early recognition, guideline-based antibiotic therapy, judicious use of immunosuppression, and microbiota-based preventive strategies are crucial to improve patient outcomes and limit recurrence, thus reducing healthcare costs.}, }
@article {pmid41303703, year = {2025}, author = {Qassadi, FI and Johnson, C and Robinson, K and Griffin, R and Polytarchou, C and Kao, D and Kim, DH and Griffiths, RL and Zhu, Z and Monaghan, TM}, title = {Untargeted Metabolomics Identifies Faecal Filtrate-Derived Metabolites That Disrupt Clostridioides difficile Metabolism and Confer Gut Barrier Cytoprotection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303703}, issn = {1422-0067}, support = {1074742634//Saudi Ministry of Higher Education/ ; }, mesh = {*Clostridioides difficile/metabolism ; *Metabolomics/methods ; Humans ; *Feces/microbiology/chemistry ; *Clostridium Infections/metabolism/therapy/microbiology ; Fecal Microbiota Transplantation ; *Cytoprotection ; Metabolome ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism/microbiology ; Female ; Male ; }, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major therapeutic challenge. Although faecal microbiota transplantation (FMT) is highly effective and thought to restore microbial composition and metabolic function, the mechanisms underlying its success are not fully understood. In particular, the contribution of non-bacterial components such as soluble metabolites remains unclear. Therefore, further investigation is needed to identify the mechanistic drivers of FMT efficacy and clarify how non-bacterial factors contribute to therapeutic outcomes. Here, we applied untargeted three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) to profile faecal metabolic reprogramming in rCDI patients pre- and post-FMT, alongside C. difficile cultures exposed to sterile faecal filtrates. FMT induced extensive metabolic shifts, restoring glyoxylate/dicarboxylate and glycerophosphoinositol pathways and normalising disrupted bile acid and amino acid profiles. Faecal filtrate exposure caused strain-specific metabolic disruption in C. difficile, depleting proline, fumarate and succinate while enriching tryptophan. While multiple metabolite classes were profiled, the most significant functional changes were observed in lipids. Lipidomics identified >3.8-fold enrichment of phosphatidylinositol (PI) species, which localised to bacterial membranes and conferred cytoprotection against C. difficile toxins and other epithelial insults. Spatial metabolomics imaging revealed, for the first time, metabolite compartmentalisation within C. difficile, with proline and succinate broadly distributed across the cell surface and fumarate confined to distinct microdomains, highlighting functional heterogeneity in pathogen metabolism. Collectively, these findings demonstrate that soluble metabolites within faecal filtrates mediate pathogen suppression and epithelial barrier protection, establishing metabolite-driven mechanisms underlying FMT efficacy and identifying PI lipids as candidate post-biotic therapeutics for rCDI.}, }
@article {pmid41304131, year = {2025}, author = {Lv, D and Han, N and Liu, H and Tang, H}, title = {Hepatitis B Virus-Related Liver Disease and Gut Microbiota: An Updated Review.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304131}, issn = {2076-2607}, abstract = {Although gut microbiota plays a pivotal role in numerous biological functions (e.g., energy, nutrients, metabolism, and immunological processes), growing evidence demonstrates that the gut microbiota is involved in the progression of liver diseases. The liver can be greatly influenced by alterations in intestinal microbiota due to increased gut permeability, allowing for the entry of bacterial products into the liver through the gut-liver axis. Recently, clinical and experimental research findings have demonstrated that microbiota dysbiosis plays an important role in the pathogenesis and progression of HBV-related liver diseases. In this review, we provide an overview of the gut microbiota and the microbiota-gut-liver axis in health; review HBV infection interactions with microbiota; discuss the role of microbiota dysbiosis in the pathogenesis of HBV-related liver disease, such as chronic HBV infection, liver cirrhosis, and hepatocellular carcinoma; and, finally, assess the potential for microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation. This review will provide novel insights into individualized therapy for CHB patients based on gut microbiota alteration.}, }
@article {pmid41304151, year = {2025}, author = {Reveles, KR and Meehan, J and Tillotson, G}, title = {Fecal Microbiota Transplantation in Animals: Therapeutics, Conservation, and Farming.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304151}, issn = {2076-2607}, support = {UM1 TR004538/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly used in both human and veterinary settings to restore gut microbiota and promote health. Advances in sequencing technologies and microbiome analysis have expanded our understanding of microbial communities and enabled broader FMT applications. As insights grow into what constitutes a healthy microbiome, interest in using FMT across a range of animal contexts has also increased. This narrative review highlights recent progress in the use of FMT to improve the welfare of farm animals, manage infectious and chronic conditions in companion animals, and support the health of wildlife in conservation and reintroduction programs. Representative examples from each domain are discussed.}, }
@article {pmid41304202, year = {2025}, author = {Feng, JJ and Maddirala, NR and Saint Fleur, A and Zhou, F and Yu, D and Wei, F and Zhang, Y}, title = {Gut Microbiome and Immune System Crosstalk in Chronic Inflammatory Diseases: A Narrative Review of Mechanisms and Therapeutic Opportunities.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304202}, issn = {2076-2607}, support = {R01 AI148270/AI/NIAID NIH HHS/United States ; R01 AI190438/AI/NIAID NIH HHS/United States ; R21 AI183094/AI/NIAID NIH HHS/United States ; }, abstract = {The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment.}, }
@article {pmid41304215, year = {2025}, author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV}, title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, pmid = {41304215}, issn = {2076-2607}, support = {DPI/BCE n&#xba; 01/2025//University of Brasilia/ ; FAPDF n&#xba; 09/2023//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; }, abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.}, }
@article {pmid41304963, year = {2025}, author = {Golčić, M and Radoš, L and Skočilić, I and Badovinac, I and Hauser, G and Krznarić Zrnić, I and Šantić, M and Fučkar Čupić, D and Francetić, S and Lisica, K and Juras, L and Škrtić, M and Bešvir Džubur, A and Šeparović, R and Tomašić, V and Tečić Vuger, A and Mikolašević, I}, title = {Fecal Microbiota Transplantation in Refractory Immune-Mediated Colitis: Case Series and Review of the Literature.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {11}, pages = {}, pmid = {41304963}, issn = {1424-8247}, abstract = {Background/Objectives: Immune checkpoint inhibitors (ICI) represent a significant breakthrough in cancer management, but they can cause adverse effects such as immune-mediated colitis (IMC). The standard first-line treatment is corticosteroids, and second-line treatment is infliximab or vedolizumab. However, a proportion of immune-mediated colitis (IMC) cases are refractory to immunosuppressive treatment, which has led to the exploration of novel approaches such as fecal microbiota transplantation. Methods: We present two patients who both developed grade III IMC following application of durvalumab and pembrolizumab, respectively. Both patients were refractory to corticosteroid therapy, while the first one also showed no improvement to infliximab. We performed two separate applications of FMT on both patients, from different donors, as a rescue treatment. Results: After unsuccessful immunosuppressive treatment and following rescue FMT, both patients demonstrated a rapid and sustained improvement in inflammatory markers, clinical symptoms, quality-of-life scores, and colonoscopy findings, without additional immunosuppressive treatment. Conclusions: FMT appears to be safe and a potentially effective treatment option for patients with refractory IMC both as second- and third-line therapy options. Continued efforts toward rigorous donor screening, use of standardized biobanks, and standardizing FMT protocols will further enhance safety and reproducibility.}, }
@article {pmid41305382, year = {2025}, author = {Zhang, Z and Kang, W and Mi, Y and Zhong, X and He, Y}, title = {The Microbiota-Gut-Brain Axis in Autism: Associations, Causal Inference, and Interventions-A Narrative Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {41305382}, issn = {2076-0817}, support = {Grant No. LCYSSQ20220823091203008//the Shenzhen Clinical Research Center for Gastroenterology/ ; Grant No. A2402008//the Shenzhen Medical Research Fund/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain ; Probiotics/therapeutic use ; *Autism Spectrum Disorder/microbiology/therapy ; *Autistic Disorder/microbiology/therapy ; *Brain-Gut Axis ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {Autism spectrum disorder is markedly heterogeneous and frequently accompanied by gastrointestinal symptoms that often correlate with behavioral phenotypes. Emerging evidence suggests that the microbiota-gut-brain axis may contribute to these associations through multiple bidirectional communication routes-including neural, immune, and endocrine pathways, as well as microbial metabolites such as short-chain fatty acids and tryptophan-kynurenine intermediates. This narrative review synthesizes clinical, mechanistic, and interventional evidence published between January 2010 and July 2025, clarifies the extent to which current data support association versus causation, evaluates key confounding factors, summarizes evidence for interventions such as probiotics, prebiotics, and fecal microbiota transplantation, and outlines future directions for precision research and targeted interventions based on functional pathways and stratified subgroups.}, }
@article {pmid41305918, year = {2025}, author = {Shao-Yu, Y and Niu, D and Chen, J and Li, WY and Wang, X and Meng, QW and Song, WJ and Yang, YG and Wang, H and Li, RR and Li, BY and Zhang, LG and Hu, CJ and Xu, LF and Wang, HH and Zhang, L and Liang, CZ and Du, HX}, title = {Antibiotic cocktail-induced changes in gut microbiota drive alteration of bile acid metabolism to restrain Th17 differentiation through the FXR-NLRP3 axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2582944}, pmid = {41305918}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Th17 Cells/drug effects/immunology/cytology ; Male ; *Bile Acids and Salts/metabolism ; *Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Inbred C57BL ; Cell Differentiation/drug effects ; Fecal Microbiota Transplantation ; *Prostatitis/immunology/microbiology/drug therapy ; Disease Models, Animal ; Interleukin-17 ; RNA, Ribosomal, 16S/genetics ; Receptor, Farnesoid X-Activated ; }, abstract = {Antibiotics influence both gut microbial composition and immune regulation, but the detailed mechanisms are still undefined. Shifts in the microbiome caused by antibiotic exposure can modulate immune activity through various pathways. Therefore, we aimed to explore how antibiotics affect immune-inflammation by regulating Th17 cells through the gut microbiota of mice with experimental autoimmune prostatitis (EAP). Antibiotic-driven shifts in gut microbial communities and metabolite profiling in EAP mice were performed by integrating 16S rRNA sequencing with mass spectrometry-driven metabolomic analysis. Antibiotic cocktail (ABX) therapy mitigated EAP, modified the gut microbiome composition, and influenced bile acid metabolism. Fecal microbiota transplantation (FMT) using microbiota from ABX-treated feces into EAP mice effectively altered gut microbiome composition and alleviated disease symptoms, indicating that microbiome intervention reduces autoimmune inflammation and decreases deoxycholic acid (DCA) in mice. Subsequent experiments demonstrated that DCA suppresses farnesol X receptor (FXR) expression which can inhibit the NLRP3‒ IL17A axis, thus promoting Th17 cell development and exacerbating inflammatory cell infiltration of the prostate. Our initial clinical examination of patients with prostatitis and antibiotic treatment indicated that bile acid metabolism and Th17 cell development are affected by antibiotic therapy. This work revealed that antibiotic-induced gut microbiota dysbiosis decreases the bile acid metabolite DCA, further restraining Th17 cell differentiation via the FXR‒NLRP3 axis to alleviate autoimmune prostatitis. Our results reveal new perspectives regarding the interconnected dynamics of antibiotics, gut microbiota, bile acid metabolism, and immune regulation, with potential relevance for therapies targeting immune-mediated diseases.}, }
@article {pmid41306279, year = {2025}, author = {Feng, S and Wang, J and Si, X and Lu, S and Lu, C and Gao, Z and Yang, J and Wu, J and He, X and Wu, L}, title = {Washed microbiota transplantation: candidates for a novel strategy for ameliorating autism spectrum disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1688325}, pmid = {41306279}, issn = {1664-302X}, abstract = {Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder with an increasing global incidence, imposing substantial burdens on both society and affected families. The pathogenesis of ASD is complex, involving genetic, environmental, and other factors. Notably, children with ASD often exhibit gut microbiota dysbiosis, and the relationship between gut microbiota and ASD has garnered growing attention. Current treatments for ASD remain limited and unsatisfactory. As an emerging therapeutic approach, Washed Microbiota Transplantation (WMT) reduces undigested food residues, fungi, parasite eggs, and pro-inflammatory metabolites, thereby lowering the incidence of adverse clinical events. WMT also addresses ethical and aesthetic concerns associated with Fecal Microbiota Transplantation (FMT), enhances treatment safety, and offers new hope for ASD management. This review integrates global literature to analyze the latest findings on ASD epidemiology, societal impacts, existing therapies, and clinical research on WMT, aiming to provide scientific evidence for the clinical application of WMT in ASD treatment.}, }
@article {pmid41306971, year = {2025}, author = {Han, T and Zhang, Y and Zheng, G and Guo, Y}, title = {From pathogenic mechanisms to therapeutic perspectives: a review of gut microbiota and intestinal mucosal immunity in inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1704651}, pmid = {41306971}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunity, Mucosal ; *Intestinal Mucosa/immunology/microbiology ; *Inflammatory Bowel Diseases/therapy/immunology/microbiology/etiology ; Animals ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel diseases (IBDs), which comprises Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial disorder with an as-yet undetermined etiology, with its global incidence rising rapidly, particularly in developing and Western countries. Although the exact etiology remains unclear, recent research implicates genetic predisposition, environmental factors, gut microbiota, and immune responses in the pathogenesis of IBD. Notably, dysbiosis of the gut microbiota-characterized by a reduction in the abundance and diversity of specific bacterial genera-has been suggested as a potential trigger for the onset of IBD, accompanying with dysregulated intestinal mucosal immunity involving in immune cells and nonimmune cells. Understanding and restoring the imbalanced gut microbiota, as well as identifying key bacterial species involved in IBD, are critical for elucidating disease mechanisms and developing therapeutic strategies. In this review, we explore the role of gut microbiota and intestinal mucosal immunity in the pathogenesis of IBD and offers insights into microbiota-centered therapeutic interventions, including probiotics, fecal microbiota transplantation, and microbial metabolites, that aim to modulate the gut microbiota for the treatment of IBD.}, }
@article {pmid41308055, year = {2025}, author = {Oprea, A and Steinman, J and Huang, G and Soyinka, O and Brookbank, M and Abesteh, J and Hartman, M and McEvoy, A and Dionne, JC and Milev, R and Samaan, Z}, title = {Oral Methods of Microbiota Manipulation for Depression Symptoms: A Systematic Review: Méthodes orales de manipulation du microbiote pour traiter les symptômes de dépression : Une revue systématique.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251394369}, pmid = {41308055}, issn = {1497-0015}, abstract = {ObjectiveThe effectiveness of current treatment options for depressive symptoms has been widely investigated with acknowledgment that some patients were either not adequately responding to treatment, finding the existing treatment intolerable, or otherwise prefer alternative options. There is increasing interest in microbiota modulation as an alternate form of depression treatment, with a growing number of trials and reviews on the subject published in the last five years. This systematic review aimed to analyze all completed randomized control trials (RCTs) that assessed depression symptoms in adults not using antidepressants, before and after oral methods of microbiota manipulation.MethodAll completed parallel-arm RCTs that assessed depression symptoms in adult participants before and after oral methods of microbiota manipulation were retrieved from four databases, MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Data on study and intervention characteristics as well as RCT conclusions were collected independently and in duplicate, and each study's findings were summarized individually. Risk of bias was completed.ResultsWe included 66 RCTs in our review, 34 of which concluded significant differences between the intervention and control group in depressive symptom using different interventions and measures. Of the 66 trials, 54 used probiotic interventions, seven used prebiotic, eight used synbiotic and two used oral fecal microbiota transplantation. Wide variation was observed in studies' design, intervention composition and consumption methods across all 66 RCTs. No statistical synthesis or meta-analyses were possible due to the wide variety of interventions, measures and outcomes.ConclusionsThe heterogeneity of the existing RCTs did not allow for concrete conclusions on whether oral microbiota manipulation interventions are viable alternative treatment options for adults experiencing depression symptoms. We encourage the development of standardized guidelines for the design and reporting of microbiota studies in depression for the possibility of future intervention efficacy testing.}, }
@article {pmid41308390, year = {2025}, author = {Fan, Q and Tao, X and Huang, H and Jiang, S and Ren, H and Liu, Y and Yang, C and Wang, Y and Yan, K and Li, J and Zhao, C and Li, X}, title = {Evodiamine relieves ulcerative colitis through reinventing the communication of "host-gut microbiota-macrophages".}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157541}, doi = {10.1016/j.phymed.2025.157541}, pmid = {41308390}, issn = {1618-095X}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Zebrafish ; *Macrophages/drug effects ; Mice, Inbred C57BL ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Male ; *Anti-Inflammatory Agents/pharmacology ; Colon/drug effects ; NF-kappa B/metabolism ; Trinitrobenzenesulfonic Acid ; Dextran Sulfate ; STAT3 Transcription Factor/metabolism ; Quinazolines ; }, abstract = {BACKGROUND AND PURPOSE: Accumulating evidence suggests that Evodiamine (EVO) exerts anti-inflammatory properties in ulcerative colitis (UC). Macrophages serve as driving factors of inflammation and the crosstalk within the "host-gut microbiota-macrophages" is considered essential in the pathogenesis of UC, however the underlying connections and mechanisms involved remained unclear. This study aimed to investigate how EVO modulates macrophages polarization balance in UC model through remodeling of host-microbiota interactions.<br><br>METHODS: UC models were induced in zebrafish and C57BL/6J mice through trinitro-benzene-sulfonic acid (TNBS) and dextran sulfate sodium salt (DSS), respectively. The key indicators of intestinal inflammation, macrophage polarization ratio in colon, colon transcriptomics and fecal microbiota were detected. Additionally, fecal microbiota transplantation (FMT) experiment was conducted to determine whether EVO ameliorates UC symptoms by regulating the intestinal microbiota and subsequently influencing M1/M2 macrophage polarization balance.<br><br>RESULTS: We found that EVO administration significantly alleviated intestinal tissue damage in both zebrafish and murine models of UC. Additionally, EVO treatment restored the M1/M2 macrophage polarization balance in the intestinal tissue of UC mice, and 16S rRNA analysis indicated that EVO alleviated the intestinal inflammation by modulating the composition of the intestinal microbiota. Furthermore, antibiotics and FMT experiments confirmed that modulation of M1/M2 macrophages polarization balance by EVO was mediated by the intestinal microbiota, potentially through NF-&#x3ba;B/STAT3 and interferon regulatory factor 5 (IRF5) pathway.<br><br>CONCLUSIONS: EVO remodeled the communication of "host-gut microbiota-macrophages" by regulating the NF-&#x3ba;B/STAT3 and IRF5 pathway, thereby providing novel perspectives into underling mechanism of EVO in the therapeutic effects against UC.}, }
@article {pmid41308392, year = {2025}, author = {Lv, Y and Yang, L and Li, W and Hu, Y and Zhu, B and Zhou, M and Ye, Y and Ding, Z and Zhou, F}, title = {Tetrastigma hemsleyanum polysaccharides alleviate inflammatory bowel disease via the gut microbiota-SCFA-GPR43 signaling axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157523}, doi = {10.1016/j.phymed.2025.157523}, pmid = {41308392}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Humans ; *Polysaccharides/pharmacology ; *Receptors, G-Protein-Coupled/metabolism ; *Inflammatory Bowel Diseases/drug therapy/microbiology/metabolism ; Mice ; Signal Transduction/drug effects ; Fatty Acids, Volatile/metabolism ; Mice, Inbred C57BL ; Caco-2 Cells ; HT29 Cells ; Male ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Dextran Sulfate ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {INTRODUCTION: This study investigates the protective mechanism of Tetrastigma hemsleyanum polysaccharides (THP) against inflammatory bowel disease (IBD) by focusing on its interactions with gut microbiota and metabolites.<br><br>OBJECTIVES: The study aims to elucidate how THP exerts anti-inflammatory effects on IBD through modulating gut microbiota and activating relevant signaling pathways.<br><br>METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was used. Antibiotic-treated mice showed that THP's protective effect is microbiota-dependent. Fecal microbiota transplantation (FMT) from THP-treated donors replicated the therapeutic benefits in recipient mice. In vivo studies with GPR43 agonists/inhibitors and in vitro experiments in GPR43-knockdown HT-29 cells explored the signaling pathways. A Caco-2/HT-29 co-culture model assessed the direct protection of intestinal epithelial cells by THP-derived metabolites. 16S rRNA sequencing and metabolomics analyzed microbiota and metabolic changes.<br><br>RESULTS: THP's protective effect was abolished in microbiota-depleted mice. FMT confirmed the microbiota-mediated effect. THP suppressed intestinal inflammation via the GPR43/&#x3b2;-arrestin2-JNK pathway. THP-derived metabolites directly protected intestinal epithelial cells. THP modulated gut microbiota, increased short-chain fatty acid (SCFA) production, and stimulated Resolvin E1 biosynthesis, which were associated with inflammation resolution and epithelial repair.<br><br>CONCLUSION: THP exerts anti-colitic effects by modulating gut microbiota, activating GPR43-mediated signaling, and enhancing pro-resolving lipid mediators, showing potential for IBD treatment.}, }
@article {pmid41308739, year = {2025}, author = {Zhang, Y and Liu, J and Zhang, X and Cheng, S and Liu, S and Huang, A and Yu, Y and Liu, J and Chen, H and Shang, D and Yin, P and Ma, S}, title = {Rhein alleviates acute pancreatitis by inhibiting TMAO-mediated inflammatory signaling pathways and reducing acinar cell injury.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.056}, pmid = {41308739}, issn = {2090-1224}, abstract = {INTRODUCTION: Acute pancreatitis (AP) represents a significant global health challenge. Despite recent advances in medical treatment, the development of novel therapeutic strategies remains crucial.<br><br>OBJECTIVES: Rhein, a natural compound of the Chinese herb Rheum, shows promise in the treatment of AP. However, the exact mechanism underlying its therapeutic effect is still not fully understood.<br><br>METHODS: To investigate the association between the rhein-related gut microbiota and AP, we conducted antibiotic-mediated microbiota depletion experiments, fecal microbiota transplantation (FMT), and in vitro bacterial culture experiments. Concurrently, we performed 16S rRNA gene sequencing, metagenomic sequencing, and liquid chromatography&#x2012;mass spectrometry (LC&#x2012;MS) analyses on mouse fecal samples to characterize alterations in the microbiota and metabolome. Transcriptomic studies were also performed to elucidate the mechanisms underlying acinar cell inflammation.<br><br>RESULTS: Rhein alleviated AP by modulating the gut microbiota, as demonstrated by changes in the gut microbiota composition and improvements in AP after FMT in rhein-treated mice compared with those in cerulein-induced AP mice. Specifically, rhein is concentrated mainly in the stomach and intestines, where it exerts anti-inflammatory effects on acinar cells by antagonizing the TLR4/NF-&#x3ba;B/NLRP3 signaling pathway activated by trimethylamine-N-oxide (TMAO). This mechanism is associated with lipid peroxidation and necrosis mediated by oxidative stress. Clinically, disease severity in patients with AP is positively correlated with serum TMAO concentration.<br><br>CONCLUSION: Rhein alleviates AP by modulating the intestinal microbiota to reduce TMAO production, thereby suppressing TMAO-induced activation of the TLR4/NF-&#x3ba;B/NLRP3 signaling pathway and inhibiting acinar cell inflammation.}, }
@article {pmid41309372, year = {2025}, author = {Xu, S and Su, W and Qin, Z and Xuan, Z and Wang, J and Wang, J and Tang, R and Yin, J and Liang, J and Jia, X}, title = {Er Miao San Attenuates Collagen-Induced Arthritis Mice by Regulating Gut Microbiota and Its Metabolites.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2507054}, pmid = {41309372}, issn = {1738-8872}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Arthritis, Experimental/drug therapy/microbiology ; Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/drug therapy ; Fatty Acids, Volatile/metabolism ; *Arthritis, Rheumatoid/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred DBA ; Butyrates/metabolism ; Bacteria/classification/genetics/metabolism/drug effects ; Disease Models, Animal ; Bacteroidetes/drug effects ; }, abstract = {Dysbiosis of the gut microbiota plays a key role in the pathogenesis of rheumatoid arthritis (RA). However, it is still unclear whether the classic prescription Er Miao San (EMS) can exert therapeutic effects on RA by regulating the gut microbiota. In this study, we investigated whether EMS alleviates collagen-induced arthritis (CIA) by modulating the gut microbiota and its metabolites. We demonstrated that EMS significantly reduced arthritis severity, paw swelling, and systemic inflammation in CIA mice. In addition, 16S rRNA sequencing analysis revealed that EMS restored gut microbiota homeostasis, as evidenced by an increased abundance of Bacteroidetes, and a decreased Bacteroidetes/Firmicutes ratio. Crucially, antibiotic depletion of the gut microbiota abolished the protective effects of EMS, whereas fecal microbiota transplantation (FMT) from EMS-treated donors replicated its anti-arthritic efficacy, confirming the indispensable role of the microbiota. Measurement of short-chain fatty acids (SCFAs) further revealed a significant increase in the microbial metabolite butyrate following EMS treatment. Subsequent supplementation with sodium butyrate mimicked the therapeutic effects of EMS, ameliorating joint inflammation and cartilage damage. Mechanistically, butyrate enhanced the expression of intestinal tight junction proteins (ZO-1 and occludin), thereby restoring intestinal barrier integrity. Collectively, our results demonstrate that EMS exerts its anti-arthritic effects by modulating the gut microbiota-butyrate-intestinal barrier axis, highlighting the critical value of microbial metabolites in RA treatment. This study provides novel insights into the mechanism of EMS and suggests the therapeutic potential of butyrate for RA.}, }
@article {pmid41310268, year = {2025}, author = {Fazeli, SA and Soleimani Samarkhazan, H}, title = {Metabolic Memory Following Metabolic Bariatric Surgery: Mechanisms, Clinical Implications, and Strategies for Long-Term Success.}, journal = {Obesity surgery}, volume = {35}, number = {12}, pages = {5606-5624}, pmid = {41310268}, issn = {1708-0428}, mesh = {Humans ; *Bariatric Surgery ; *Obesity, Morbid/surgery/metabolism ; Gastrointestinal Microbiome ; Epigenesis, Genetic ; Weight Loss ; Diabetes Mellitus, Type 2/metabolism ; }, abstract = {Metabolic bariatric surgery (MBS) treats severe obesity, but long-term benefits are often lost to weight regain and metabolic relapse driven by persistent molecular imprints. This narrative review synthesizes recent evidence and examines epigenetic, inflammatory, mitochondrial, and microbiota mechanisms underlying metabolic memory after MBS. Key imprints include altered adipose transcriptomes (e.g., lower IGF1 and GPX3), persistent NLRP3 inflammasome activation, and gut dysbiosis with variable, individual patterns. We highlight how these mechanisms drive clinical outcomes such as type 2 diabetes recurrence and residual cardiovascular risk, with tissue-specific epigenetic retention slowing renal and cardiac recovery. We evaluate evidence-based strategies to counteract or modulate metabolic memory. These include the strategic selection of bariatric procedure, preoperative metabolic optimization, Mediterranean diets rich in polyphenols, GLP-1/GIP co-agonists, senolytics (e.g., dasatinib + quercetin), and autologous fecal microbiome transplantation. Emerging preclinical approaches like CRISPR-dCas9 epigenetic editing and exploratory strategies like vagal neuromodulation show theoretical promise in targeting obesogenic memory pathways but remain far from clinical application. The review underscores the need for longitudinal multi-omics cohorts and metabolic memory biomarkers (e.g., PPARGC1A methylation, CCL25) to enable personalized interventions. By targeting metabolic memory proactively, MBS can evolve from weight-loss procedure to a durable reset of metabolic set points. However, it is crucial to acknowledge that many proposed strategies are derived from preliminary studies with limited sample sizes and follow-up, necessitating further validation in large-scale trials.}, }
@article {pmid41312383, year = {2025}, author = {Miao, Z and Long, J and Huang, B and Yan, D and Wang, A}, title = {Roseburia hominis enriched by baicalin reverses the non-response to metformin via upregulating linolenic acid metabolism.}, journal = {iScience}, volume = {28}, number = {11}, pages = {113892}, pmid = {41312383}, issn = {2589-0042}, abstract = {Metformin is the most commonly used hypoglycemic drug for patients with type 2 diabetes (T2D), but about 30% of patients show non-response potentially linked to gut microbiota imbalance. Although baicalin exhibits potent gut microbiota-modulating activity, its role in reversing metformin non-response remains unclear. Here, we recruited patients with T2D who were non-responders to metformin treatment and collected their fecal samples to construct a humanized mouse model via fecal microbial transplantation. We found that baicalin combined with metformin improved the abnormal glucose tolerance in non-response mice, in which Roseburia hominis was considerably enriched. Mechanically, baicalin combined with metformin activated the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/carnitine palmitoyl transferase 1 (CPT1) pathway, and its enriched R. hominis promoted linolenic acid metabolism, thus reversing the non-response to metformin. Besides, the efficacy of R. hominis in reversing the non-response of metformin was dependent on phospholipase A2 (linolenic acid metabolism key enzyme). Our findings provide feasibility strategies for the metformin treatment of non-responsive patients.}, }
@article {pmid41312988, year = {2026}, author = {Schluter, J and Jogia, W and Matheis, F and Ebina, W and Sullivan, AP and Gordon, K and Cruz, EFdl and Victory-Hays, ME and Heinly, MJ and Diefenbach, CS and Kang, UJ and Peled, JU and Foster, KR and Levitt, A and McLaughlin, E}, title = {A retrospectively registered pilot randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health-associated taxa.}, journal = {Infection and immunity}, volume = {94}, number = {1}, pages = {e0039025}, pmid = {41312988}, issn = {1098-5522}, support = {//Helen Hay Whitney Fellowship/ ; R01CA269617/NH/NIH HHS/United States ; R01 CA269617/CA/NCI NIH HHS/United States ; DP2 AI164318/AI/NIAID NIH HHS/United States ; DP2 AI164318-01/NH/NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08HL143189/NH/NIH HHS/United States ; }, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/adverse effects/administration &amp; dosage ; Male ; Female ; Middle Aged ; Pilot Projects ; Feces/microbiology ; *Probiotics/administration &amp; dosage ; Adult ; Retrospective Studies ; *Microbiota/drug effects ; *Gastrointestinal Microbiome/drug effects ; Aged ; Bacteria/classification/drug effects ; }, abstract = {Antibiotic-induced microbiome injury, defined as a reduction of ecological diversity and obligate anaerobe taxa, is associated with negative health outcomes in hospitalized patients, and healthy individuals who received antibiotics in the past are at higher risk for autoimmune diseases. Postbiotics contain mixtures of bacterial fermentation metabolites and bacterial cell wall components that have the potential to modulate microbial communities. Yet, it is unknown if a fermentation-derived postbiotic can reduce antibiotic-induced microbiome injury. Here, we present the results from a single-center, randomized placebo-controlled trial involving 32 patients who received an oral, fermentation-derived postbiotic alongside oral antibiotic and probiotic therapy for non-gastrointestinal (GI) infections. At the end of the antibiotic course, patients receiving the postbiotic (n = 16) had significantly higher fecal bacterial alpha diversity (+40%, inverse Simpson index) compared to the placebo group (n = 16), and the treatment was well-tolerated. Analysis of 157 longitudinal fecal samples revealed that this increased diversity was driven by enrichment of health-associated taxa, notably obligate anaerobic Firmicutes, particularly Lachnospiraceae. In contrast, Escherichia/Shigella species, often linked to pathogenicity and antibiotic resistance, were reduced in postbiotic-treated patients at the end of antibiotic treatment and remained lower up to 10 days later. Our findings suggest that postbiotic co-administration during antibiotic therapy may augment health-associated gut microbiome composition and mitigate antibiotic-induced microbiome injury.Trial registration ISRCTN30327931 retrospectively registered.}, }
@article {pmid41313537, year = {2025}, author = {Vishwakarma, RK and Gautam, P and Sahu, M and Nath, G and Yadav, BS}, title = {Gut Microbiome in Obesity: A Narrative Review of Mechanisms, Interventions, and Future Directions.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41313537}, issn = {1867-1314}, abstract = {Obesity has reached pandemic levels worldwide and is increasingly recognized as a multifactorial condition beyond excess caloric intake and sedentary lifestyle. Accumulating evidence emphasizes that the gut microbiota (GM), primarily composed of Firmicutes and Bacteroidetes, plays a crucial role in regulating energy balance, immune response, and host metabolism. Gut dysbiosis, characterized by reduced microbial diversity and altered phylum-level composition and shifts toward commonly observed higher Firmicutes-to-Bacteroidetes ratios (although this finding is inconsistent across studies), contributes to enhanced energy harvest, systemic inflammation, and metabolic dysfunction. Key mechanisms involve GM production of short-chain fatty acids (SCFAs) and modulation of hormonal signals, including leptin, ghrelin, insulin, GLP-1, and PYY, alongside interactions via the gut-brain axis. These pathways link microbial composition to appetite regulation, fat storage, and energy balance. Emerging microbiome-targeted therapies, such as probiotics, prebiotics, dietary modulation (e.g., fiber-rich diets), fecal microbiota transplantation, and bacteriophage therapy, show promise in restoring GM balance, promoting weight loss, and improving metabolic health, though results vary and require further validation. Despite advances in metagenomics and metabolomics, gaps persist in establishing causality and long-term efficacy. The integration of GM data with host genetics, diet, and environmental factors through systems biology has the potential to facilitate personalized management of obesity. This review synthesizes the GM's role in obesity pathogenesis and hormonal regulation, highlighting therapeutic potential and research directions for microbiota-based prevention and treatment.}, }
@article {pmid41313610, year = {2025}, author = {Butcher, J and Gosse, JT and Gobin, J and Ravel-Chapuis, A and Jasmin, BJ and Stintzi, A}, title = {Dystrophic Skeletal Muscle Phenotypes Can Be Horizontally Transferred via Fecal Microbiome Transplantations.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {23}, pages = {e71281}, pmid = {41313610}, issn = {1530-6860}, support = {OGI-149//Genome Canada (GC)/ ; Project 13440//MDECEC | Ontario Ministry of Research and Innovation (MRI)/ ; //Defeat Duchenne Canada (Vaincre Duchenne Canada)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; Mice, Inbred mdx ; *Muscle, Skeletal/pathology/microbiology/metabolism ; *Muscular Dystrophy, Duchenne/therapy/microbiology/pathology ; Mice, Inbred C57BL ; Phenotype ; *Muscular Dystrophy, Animal/microbiology/therapy ; *Gastrointestinal Microbiome ; Male ; }, abstract = {Duchenne muscular dystrophy (DMD) has no cure and accounts for > 80% of muscular dystrophy cases around the world. DMD patients experience severe muscle degeneration that continues until death and also suffer from gastrointestinal complications that undoubtedly impact their microbiotas. It is unclear whether dystrophic microbiotas simply reflect the disease or whether microbes are directly involved in muscle phenotypes. Here, we sought to determine the microbiota's causal role in promoting dystrophic muscles by performing intra/inter-genotype fecal microbiota transplantations (FMT) between wildtype and mdx mice; assessing FMT's impact on muscles and microbiotas over 9 weeks. Transplanting mdx microbiotas into wildtype mice induced an mdx-like muscle phenotype while the inverse improved muscle features. We identified several taxa differentially abundant between wildtype mice receiving either wildtype or mdx FMT, highlighting their potential role in muscle health. Our results highlight the active role microbes have in impacting muscle health through both beneficial and detrimental mechanisms. Accordingly, microbes represent unexploited therapeutic targets for improving health outcomes in muscular dystrophies.}, }
@article {pmid41315900, year = {2025}, author = {Ardis, CK and Bui, TPN and Nieuwdorp, M}, title = {Gut microbiota in cancer cachexia: a new frontier for research and therapy.}, journal = {Genes &amp; nutrition}, volume = {20}, number = {1}, pages = {28}, pmid = {41315900}, issn = {1555-8932}, support = {09150182010020//European Union's Horizon Training Mobility Actions- Consortium Grant agreement MiCCrobioTAckle/ ; 09150182010020//NWO VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; }, abstract = {Cancer cachexia is a multifactorial syndrome characterized by systemic inflammation, progressive weight loss, muscle wasting, and metabolic alterations, which negatively affect quality of life, treatment response, and survival in cancer patients. Despite its prevalence and impact, effective treatments remain limited, in part due to the complex and poorly understood pathophysiology of the syndrome. Recent studies have revealed that gut microbiota alterations may contribute to the development and progression of cachexia through mechanisms involving immune activation, impaired gut barrier function, and disrupted metabolic signaling. This review explores the interplay between the altered gut microbiome and cancer cachexia, focusing on microbial metabolites such as short-chain fatty acids, gut barrier dysfunction and the impact of cancer therapies on microbial homeostasis. We evaluate emerging microbiota-targeted strategies, including traditional and next-generation probiotics and fecal microbiota transplantation, as novel therapeutic avenues. A deeper understanding of host–microbiome interactions may lead to the development of more effective, personalized interventions to improve cancer cachexia patient care.}, }
@article {pmid41316344, year = {2025}, author = {Ren, Y and Liang, J and Xie, J and Hu, W and Lai, M and Li, X and Zhang, J and Zheng, Y and Wu, Q and Zhou, H and Yin, J}, title = {Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {6}, pmid = {41316344}, issn = {2049-2618}, support = {82171317//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Female ; Male ; Mice ; Bacteria/metabolism ; *Brain-Gut Axis/drug effects ; *Butyrates/metabolism ; Cell Line ; *Cognitive Dysfunction/drug therapy/microbiology ; Gastrointestinal Microbiome ; Glucuronates/metabolism ; *Infarction, Middle Cerebral Artery/complications/microbiology ; *Mannose/analogs &amp; derivatives/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Neurogenesis/drug effects ; *Oligosaccharides/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {BACKGROUND: Post-stroke cognitive impairment (PSCI) affects up to half of stroke survivors, severely impacting their quality of life. Despite its prevalence, the pathogenesis of PSCI remains poorly understood, and no specific pharmacological treatments are currently available.<br><br>RESULTS: In PSCI patients, fecal butyrate levels were significantly reduced and correlated with cognitive scores. A machine learning model incorporating butyrate levels, butyrate-producing bacteria, and clinical factors (education, smoking, body mass index [BMI], hemoglobin) demonstrates strong predictive performance (area under the curve [AUC]: 0.793 internal, 0.795 external validation). In a transient middle cerebral artery occlusion (tMCAO) mouse model, both sexes displayed sustained gut microbiota dysbiosis featuring decreased butyrate-producing bacteria and fecal butyrate concentrations, concomitant with hippocampal neuronal loss and microglial activation.&#xa0;Sodium oligomannate (GV-971) treatment ameliorated cognitive impairment in a sex-independent manner and restored butyrate-producing gut bacteria. Metagenomic analysis revealed that GV-971 enhanced butyrate production by promoting D-glucuronate degradation and upregulating butyrate synthesis pathway abundance. The elevated butyrate promoted acetylation of histone H3 at lysines 9 and 14 (Ac-H3K9/K14) in colonic and hippocampal neurons, stimulating neurogenesis, while concurrently reducing gut-derived lipopolysaccharide (LPS) and microglial inflammation. Antibiotic treatment and fecal microbiota transplantation established the essential role of butyrate-producing microbiota in mediating GV-971's effects.&#xa0;In vitro, butyrate supplementation significantly inhibited HDAC3 enzymatic activity in HT22 cells and alleviated LPS-induced inflammatory responses in BV2 microglia.<br><br>CONCLUSIONS: Intestinal butyrate levels are significantly associated with PSCI. GV-971 mitigates post-stroke cognitive decline by modulating the gut microbiota to increase butyrate production, highlighting its potential as a therapeutic agent for PSCI.}, }
@article {pmid41316345, year = {2025}, author = {Li, M and Zhang, X and Lu, J and Xiang, J and Wu, J and Zheng, M and Yang, S and He, L and Shao, X}, title = {Isoliquiritigenin ameliorates Parkinson's disease via gut microbiota remodeling: potential mediating role of Parabacteroides distasonis.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1363}, pmid = {41316345}, issn = {1479-5876}, support = {2024ZF031//Zhejiang Traditional Chinese Medicine Administration/ ; 2024ZF165//Zhejiang Traditional Chinese Medicine Administration/ ; 2023RC287//Medical Science and Technology Project of Zhejiang Province/ ; 2023KY345//Medical Science and Technology Project of Zhejiang Province/ ; 2022KY001//Shaoxing Bureau of Science and Technology/ ; 2023SKY015//Shaoxing Bureau of Science and Technology/ ; 2023A14011//Shaoxing Bureau of Science and Technology/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Chalcones/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy/microbiology ; Fecal Microbiota Transplantation ; *Bacteroidetes/drug effects/physiology ; Male ; Mice, Inbred C57BL ; Dopaminergic Neurons/drug effects/pathology/metabolism ; Mice ; Neuroprotective Agents/pharmacology/therapeutic use ; Behavior, Animal/drug effects ; }, abstract = {BACKGROUND: Increasing evidence implicates the gut microbiota in the pathogenesis of Parkinson's disease (PD). Microbiota-targeted interventions may be a promising therapeutic approach. Isoliquiritigenin (ISL), a natural flavonoid and primary pharmacological constituent of licorice (Glycyrrhiza), has neuroprotective effects. Whether this neuroprotection involves modulation of the gut microbiota is unclear.<br><br>PURPOSE: The study assessed whether ISL mediates neuroprotective in PD by modulating the gut microbiota, and investigated the functional involvement of Parabacteroides distasonis (P. distasonis) in this process.<br><br>METHODS: Mice with chemically-induced PD were first treated with ISL via oral gavage to assess its therapeutic effects. To investigate the microbiota-mediated mechanisms, fecal microbiota transplantation (FMT) from ISL-treated donors and direct gavage of live or heat-killed P. distasonis were performed in separate cohorts. Behavioral performance, dopaminergic neuron integrity, intestinal barrier function, neuroinflammation, gut microbiota composition, and serum metabolomic profiles were systematically evaluated.<br><br>RESULTS: ISL and FMT significantly improved motor deficits and protected dopaminergic neurons in the substantia nigra. ISL treatment compositionally reshaped the gut microbiota by suppressing pro-inflammatory genera and enriching beneficial bacteria, such as Parabacteroides. Oral administration of live P. distasonis fully reproduced the neuroprotective effects of ISL, including improved motor function, reduced neuroinflammation, restoration of blood-brain barrier integrity, and attenuation of intestinal mucosal damage. Heat-killed P. distasonis had no significant effects. Metabolomic analysis revealed that ISL and live P. distasonis jointly regulate neuroprotective pathways and metabolites related to the gut-brain axis.<br><br>CONCLUSION: ISL alleviates PD-related pathology partly through gut microbiota remodeling, with P. distasonis as a potential mediator.}, }
@article {pmid41317234, year = {2025}, author = {Hetta, HF and Alanazi, FE and Alqifari, SF and Ali, MAS and Albalwi, MA and Albalawi, AA and Ramadan, YN}, title = {The Gut-Brain Axis in Autism: Inflammatory Mechanisms, Molecular Insights, and Emerging Microbiome-Based Therapies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {211}, pmid = {41317234}, issn = {1559-1182}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/pathology ; Animals ; *Inflammation/microbiology ; Fecal Microbiota Transplantation ; *Autism Spectrum Disorder/therapy/microbiology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; *Autistic Disorder/therapy/microbiology ; }, abstract = {Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiology, including genetic, environmental, and microbial influences. Recent studies have highlighted the gut-brain axis as a crucial mediator in ASD pathophysiology, linking alterations in gut microbiota to neurodevelopmental and behavioral abnormalities. Individuals with ASD frequently exhibit dysbiosis, characterized by an imbalance in gut microbial composition, reduced microbial diversity, and increased intestinal permeability. These changes contribute to systemic inflammation, altered neurotransmitter synthesis, and metabolic dysfunctions, ultimately impacting brain function. Emerging therapeutic approaches targeting gut microbiome, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), have shown potential in alleviating both gastrointestinal (GI) and ASD-related symptoms. This review explores the latest evidence on microbiome alterations in ASD, the mechanisms by which gut dysbiosis influences neurodevelopment, and the therapeutic potential of microbiome-based interventions. Understanding these connections may open new avenues for targeted treatments in ASD management.}, }
@article {pmid41317323, year = {2025}, author = {Phelps, CM and Rodriguez J, DM and Meisel, M}, title = {Protocol for preparing murine fecal microbiota transplant and fecal microbiota metabolites for in vivo and in vitro use.}, journal = {STAR protocols}, volume = {6}, number = {4}, pages = {104240}, pmid = {41317323}, issn = {2666-1667}, support = {T32 CA082084/CA/NCI NIH HHS/United States ; P50 CA254865/CA/NCI NIH HHS/United States ; R21 CA259636/CA/NCI NIH HHS/United States ; R01 CA293654/CA/NCI NIH HHS/United States ; R01 DK130897/DK/NIDDK NIH HHS/United States ; F31 CA290756/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome/physiology ; Microbiota ; }, abstract = {Accumulating evidence demonstrates that microbiota-derived metabolites can modulate host immune responses and influence complex pathologies. Despite their therapeutic potential, the isolation of fecal microbial metabolites and their scalable ex vivo production remain challenging. Here, we present a protocol for preparing murine fecal microbiota transplant (FMT) and fecal microbiota metabolites for in vivo and in vitro use. We describe steps for collecting and preparing donor feces, isolating fecal microbial metabolites, and producing fecal microbial metabolites ex vivo with a broth expansion culture. For complete details on the use and execution of this protocol, please refer to Phelps et al.[1].}, }
@article {pmid41317866, year = {2026}, author = {Davido, B and Corcione, S}, title = {Re: Faecal microbiota transplantation for urinary tract infections.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {32}, number = {4}, pages = {676-677}, doi = {10.1016/j.cmi.2025.11.028}, pmid = {41317866}, issn = {1469-0691}, }
@article {pmid41317880, year = {2026}, author = {Colica, C and Vecchio, I}, title = {Gut microbiota: origin or panacea for all ills? Immune and metabolic diseases, nutrition, and microbiota-based interventions.}, journal = {Microbial pathogenesis}, volume = {212}, number = {}, pages = {108213}, doi = {10.1016/j.micpath.2025.108213}, pmid = {41317880}, issn = {1096-1208}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Metabolic Diseases/microbiology/therapy ; Dysbiosis/microbiology ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; *Noncommunicable Diseases ; Animals ; *Immune System Diseases/microbiology ; Diet ; Synbiotics/administration &amp; dosage ; }, abstract = {Chronic non-communicable diseases (CNCDs), including obesity, type 2 diabetes, allergies, and autoimmune conditions, represent a significant global health burden, exacerbated by the interplay between genetic and environmental factors, such as diet, and the gut microbiota. The gut microbiota is a complex and dynamic microbial community that influences host immune and metabolic systems from birth through adulthood. Dysbiosis - an imbalance in gut microbial composition - has been implicated in the development of low-grade inflammation, insulin resistance, and metabolic and immune disorders. This paper reviews the critical role of gut microbiota in CNCDs, emphasizing its interactions with the immune system, including regulatory T cell induction and the Th1/Th2 balance. Furthermore, it explores the influence of birth mode, diet, and xenobiotics on microbiota composition and function. Finally, the study highlights the potential of microbiota-targeted interventions - such as prebiotics, probiotics, synbiotics, and fecal microbiota transplantation - to modulate gut ecology and mitigate disease risk. From literature revision emerges the need for integrative approaches in disease prevention and management, considering microbiota as a key player in health and disease.}, }
@article {pmid41318842, year = {2026}, author = {Malard, F and Holler, E and Peric, Z and Mehra, V and Duarte, R and Sanz, J and Spyridonidis, A and Poiré, X and Morsink, L and Clausen, J and Bazarbachi, A and Nagler, A and Ciceri, F and Ruggeri, A and Mohty, M}, title = {Microbiotherapy and fecal microbiota transplantation in hematology-oncology: a European clinical perspective to navigate the evolving regulatory framework and the emergence of a new therapeutic class.}, journal = {Bone marrow transplantation}, volume = {61}, number = {2}, pages = {125-127}, pmid = {41318842}, issn = {1476-5365}, }
@article {pmid41320323, year = {2026}, author = {Wu, X and Wu, M and Li, H and Yang, Y and Shen, H and Huang, S and Pan, Y and Tao, L and Guo, S and Chen, J and Wu, Y and Zhong, X and Li, S and Liu, B and Zhang, W and Zhu, R and Fan, L and Wang, W}, title = {Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis.}, journal = {Gut}, volume = {75}, number = {6}, pages = {1110-1122}, doi = {10.1136/gutjnl-2025-336185}, pmid = {41320323}, issn = {1468-3288}, mesh = {*Endometriosis/microbiology/immunology ; Female ; Animals ; *Gastrointestinal Microbiome/physiology ; *Extracellular Traps/metabolism/immunology ; Mice ; Humans ; *Neutrophils/immunology ; *Bacterial Translocation ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Pseudomonas aeruginosa ; Dysbiosis ; Peritoneum/microbiology ; }, abstract = {BACKGROUND: Endometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.<br><br>OBJECTIVE: This study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.<br><br>DESIGN: We combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.<br><br>RESULTS: We identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.<br><br>CONCLUSION: Our findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.}, }
@article {pmid41321404, year = {2025}, author = {Shalbaf, N and Sadeghi, S and Homaee, S and Saberian, F}, title = {Probiotics, prebiotics, synbiotics, and FMT for glycemic control: A systematic review of clinical efficacy and mechanistic readouts in type 2 diabetes and related dysglycemia.}, journal = {Metabolism open}, volume = {28}, number = {}, pages = {100419}, pmid = {41321404}, issn = {2589-9368}, abstract = {OBJECTIVE: To systematically evaluate the clinical efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on glycemic control in adults with type 2 diabetes (T2D) and related dysglycemia, and to synthesize associated mechanistic changes in microbial metabolites and composition.<br><br>METHODS: A systematic review was conducted following PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 2025 for randomized controlled trials (RCTs) in adults with T2D, prediabetes, or metabolic syndrome. Interventions included probiotics, prebiotics, synbiotics, or FMT compared to control. Outcomes were glycemic indices (e.g., HbA1c, HOMA-IR) and mechanistic biomarkers (e.g., SCFAs, bile acids). Risk of bias was assessed using the Cochrane RoB 2 tool. A narrative synthesis was performed.<br><br>RESULTS: Thirty studies were included. Multi-strain probiotics, prebiotics, and synbiotics yielded modest but significant improvements in HbA1c (&#x2248;-0.2 to -0.4&#xa0;%), fasting glucose, and HOMA-IR, particularly with durations &#x2265;12 weeks. These benefits were linked to mechanistic shifts, including increased circulating butyrate and ursodeoxycholate, enrichment of SCFA-producing taxa, and reduced endotoxemia. Efficacy was moderated by concomitant medications: metformin use was synergistic, while sulfonylureas attenuated effects. FMT consistently improved clamp-measured insulin sensitivity in insulin-resistant phenotypes, but its effects on HbA1c were less consistent and donor-dependent.<br><br>CONCLUSION: Microbiome-targeted interventions, especially multi-strain probiotics and substrate-matched synbiotics, are effective adjuncts for improving glycemic control, with effects mediated through microbial metabolite production. FMT primarily modulates insulin sensitivity. Clinical outcomes are context-dependent, influenced by intervention design, duration, and pharmacomicrobiomic interactions.}, }
@article {pmid41321593, year = {2025}, author = {Zhao, N and Wang, K and Jiang, Y and Huang, R}, title = {Clinical Treatment and Clinical Application Research Progress of Psoriasis and Intestinal Microbiota Dysbiosis.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {18}, number = {}, pages = {3155-3164}, pmid = {41321593}, issn = {1178-7015}, abstract = {Psoriasis is a prevalent chronic inflammatory dermatosis. Recent evidence indicates a significant association between gut microbiota dysbiosis and its pathogenesis, potentially mediated through immunoinflammatory modulation and skin barrier integrity. This article systematically reviews the mechanisms linking gut microbiota to psoriasis, with emphasis on clinical treatment strategies targeting microbiota modulation-including probiotics, fecal microbiota transplantation (FMT), dietary interventions, and antibiotic therapies. However, current research exhibits notable limitations: most evidence derives from small-scale studies or animal models, lacking validation via large-scale clinical trials; microbiota-targeted interventions are poorly standardized, and the impact of individual variability on therapeutic outcomes remains unclear; the long-term safety of antibiotics and FMT requires further assessment. While summarizing existing advances, this review presents an evaluative overview to highlight research gaps and proposes future directions, such as integrated multi-omics studies, development of standardized therapeutic protocols, and exploration of personalized microbiota-based strategies, to innovate clinical management of psoriasis.}, }
@article {pmid41321823, year = {2025}, author = {Zheng, Z and Xie, D and Han, Y and Li, G and Wang, S and Zhang, X and Huang, T and Xu, W and Wu, G}, title = {Deciphering the urinary microbiome and urological cancers: from correlation to mechanisms and treatment.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699308}, pmid = {41321823}, issn = {1664-302X}, abstract = {Given that the sterility of urine and the urinary tract has been questioned by research, urinary microbiome dysbiosis has been recognized as one of the potential cancer-promoting factors. The composition of the urinary microbial community in healthy individuals has a relatively high similarity at the phylum level, with factors like age and gender influencing the expression and distribution. In contrast, the urinary microbiome of patients with urologic cancers shows significant variability and diversity depending on the type of cancer. Most of the early studies focused on the distribution, aggregation, and expression of microbiota in urologic cancers, warranting advanced studies on the causal relationship between microbes and urologic cancers. Bladder and prostate cancer tumorigenesis and progression can be influenced by microbes through chronic inflammatory or immunomodulatory pathways making them cancer models strongly associated with the urinary microbiome. Here, we summarize the expression characteristics of the microbiomes associated with these cancers and analyze the pathophysiological mechanisms and signaling pathways of the microbiome in the tumor promotion or suppression. By examining the role played by the urinary microbiome in the pathogenesis of urologic cancers, we assess the potential of specific microbial groups as biomarkers for diagnosis and surveillance. Additionally, involving the microbiome or using adjunctive participation in tumor therapy is becoming an emerging cancer treatment option. Improving urinary microbial homeostasis in urinary cancers by direct treatment with microbial products, microbial co-immunotherapy, probiotic-assisted therapy, and fecal microbial transplantation may broaden the scope of therapy and enhance the efficacy of conventional medicines.}, }
@article {pmid41322104, year = {2025}, author = {Khawaja, TW and Zhao, L and Siddiq, R and Ahmad, MU and Burns, CP and Parker, JM and Wakefield, MR and Fang, Y}, title = {Unmasking the microbiome: the hidden role of gut bacteria in the pathogenesis of colorectal cancer and its prevention strategies.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002351}, pmid = {41322104}, issn = {2692-3114}, abstract = {Colorectal cancer (CRC) is a significant global health problem, ranking as the third most common cancer and the second leading cause of cancer deaths in the world. The highest incidence of CRC is found in developed regions, thus underlining its characterization as a Western disease. Major risk factors for CRC include an unhealthy diet, lack of physical exercise, and cigarette smoking. The gut microbiota refers to the complex community of microorganisms inhabiting the digestive tract and plays a crucial role in the maintenance of host health and modulation of immune responses. Gut dysbiosis can be caused by poor diet and alcohol consumption, increasing CRC risk. Specific bacteria, such as Fusobacterium nucleatum and Escherichia coli, may have a close relationship with CRC development, while the beneficial bacteria are frequently depleted in CRC patients. This paper will discuss the mechanisms of colorectal carcinogenesis, focusing on the effects of bacterial genotoxins, immune evasion, inflammation, and diet. Additionally, it reviews preventative strategies including short-chain fatty acids (SCFAs), prebiotics, probiotics, synbiotic supplements, and the method of fecal microbiota transplantation (FMT), showing their potential to improve overall gut health and reduce the risk for CRC. Understanding these mechanisms and implementing specific preventative strategies could significantly enhance clinical interventions and reduce the global burden of CRC.}, }
@article {pmid41323559, year = {2025}, author = {Tian, S and Liu, Y and Yang, H and Chen, K and Li, J and Chen, L and Wu, T and Zhang, L}, title = {Multi-Omics Reveal That Gut Microbial Dysbiosis Drives Lipid Metabolic Disturbances and Inflammation in Gestational Hypertension.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {16411-16425}, pmid = {41323559}, issn = {1178-7031}, abstract = {BACKGROUND: Gestational hypertension (GH) is a common complication during pregnancy that poses serious health risks to both mother and fetus. Recent studies have underscored the potential roles of gut microbiota, lipid metabolism, and inflammatory response in GH's development and progression. However, the exact mechanisms behind these interactions are still unclear. Understanding how gut microbial composition impacts lipid metabolism and inflammation could offer valuable insights into GH's pathogenesis and may lead to new prevention and treatment methods.<br><br>METHODS: In this study, we conducted ELISA experiments to detect inflammatory cytokines in the serum of GH patients. Additionally, we performed 16S-rDNA sequencing analysis on the feces of GH patients to investigate the characteristics of their intestinal microbial communities; GH mouse model was constructed to assess the impact of intestinal flora on offspring. Furthermore, we utilized non-targeted lipid metabolomics to analyze lipid metabolic characteristics in the feces and blood of GH patients and established connections between the microbiome and lipidome through correlation analysis.<br><br>RESULTS: ELISA tests suggested the levels of inflammatory factors in the serum of GH patients increased significantly, including IL-6, IL-8, IL-17, IL-18, and IFN-&#x3b3;. In comparison to the normal group, the GH group exhibited a marked reduction in microbial richness. LEfSe analysis found 16 distinct bacterial communities between the two groups. Animal models suggested that fecal microbiota transplantation from the GH group's intestinal flora resulted in a significant decrease in the birth weight of the offspring. Furthermore, comparative analysis of fecal and blood metabolic profiles suggested that TG (54:5/FA22:5) may serve as a key metabolite. Correlation analysis demonstrated that f-Oxalobacteraceae exhibited a significant negative correlation with the inflammatory factor IL-17 and TG (54:5/FA22:5) in the blood, while showing a significant positive correlation with g-Oxalobacter and s-formigenes.<br><br>CONCLUSION: Our results establish a connection between gut microbiota, lipid metabolism, and the inflammatory response in patients with GH. This understanding may enhance our comprehension of the underlying mechanisms associated with GH.}, }
@article {pmid41327482, year = {2025}, author = {Wu, J and Guo, P and Wang, M and Men, Z and Lin, Z and Wang, J and Zhang, S and Zhou, M and Zhao, J and Liu, H and Ma, X}, title = {Butyrate-producing commensal bacteria confers colon immune defense function via enhancing H4K31 Crotonylation of macrophages.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {8}, pmid = {41327482}, issn = {2049-2618}, support = {32302758//National Natural Science Foundation of China/ ; 32402706//National Natural Science Foundation of China/ ; 31829004//National Natural Science Foundation of China/ ; 2022M723422//China Postdoctoral Science Foundation/ ; GZB20230848//Postdoctoral Fellowship Program of CPSF/ ; 2022YFD1300404//National Key Research and Development Program of China/ ; 1041-00109019//2115 Talent Development Program of China Agricultural University/ ; }, mesh = {Animals ; Mice ; *Macrophages/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; Muramidase/metabolism/genetics ; *Colon/immunology/microbiology ; Swine ; *Butyrates/metabolism ; Fecal Microbiota Transplantation ; *Histones/metabolism ; *Clostridium butyricum/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The mechanisms by which microbiota from disease-resistant populations or animals improve intestinal immune defense remain incompletely elucidated. Tibetan pig, a renowned disease-resistant breed, serve as a valuable research subject for the health of humans and economic animals.<br><br>RESULTS: In this study, fecal microbiota transplantation from Tibetan piglets into mice conferred enhanced resistance to C. rodentium DBS100. Further microbiota profiling and metabolomics analysis showed this protection may be partly ascribed to C. butyricum SLZX19-05 in recipients' colon. Administration of C. butyricum SLZX19-05 to germ-free mice resulted in the significantly increased lysozyme expression within colonic macrophages, subsequently bolstering the resistance to C. rodentium infection. In mice and piglets, this C. butyricum similarly elevated the lysozyme level in colon and decreased diarrhea incidence. Conversely, lyz1-knockout heightened mice's susceptibility to C. rodentium, highlighting lysozyme's critical role in immune defense. Mechanistically, this study systematically revealed that C. butyricum enhanced lysozyme expression by inhibiting mTORC1-HDAC3/8 pathway, leading to the increased H4K31 Crotonylation (H4K31Cr) and openness of an upstream region of lyz1 promoter via butyrate in macrophages. Additionally, H4K31-mutant mice showed the leukopenia, further validating the significance of H4K31Cr in immune regulation.<br><br>CONCLUSIONS: Collectively, mTORC1-HDAC3/8-H4K31Cr pathway is a key mechanism by which butyrate-producing commensal bacteria enhance immune defense in gut. This discovery provides a novel foundation for the screening and application of the next generation of butyrate-producing probiotics. Video Abstract.}, }
@article {pmid41329062, year = {2025}, author = {Yun, Y and Xu, GQ and Jiang, XJ and Ren, XY and Lu, MF and Chen, JW and Zhang, SX}, title = {Gut Microbiota in Rheumatoid Arthritis: Unraveling Pathogenic Mechanisms and Therapeutic Opportunities.}, journal = {Comprehensive Physiology}, volume = {15}, number = {6}, pages = {e70078}, doi = {10.1002/cph4.70078}, pmid = {41329062}, issn = {2040-4603}, support = {202203021221269//Natural Science Foundation of Shanxi Province/ ; 82001740//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Arthritis, Rheumatoid/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Dysbiosis/immunology ; Antirheumatic Agents/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Rheumatoid arthritis (RA), a chronic autoimmune disorder driven by genetic-environmental interplay, manifests as progressive synovitis and irreversible joint damage. Despite mechanistic advances in disease-modifying antirheumatic drugs (DMARDs) and biologics, upstream mucosal triggers of autoimmunity remain elusive. Mounting evidence implicates gut microbiota dysbiosis as a pivotal environmental factor in RA pathogenesis through multifaceted mechanisms: (1) compromising intestinal barrier integrity, (2) facilitating molecular mimicry via cross-reactive microbial antigens, (3) skewing mucosal immunity toward pro-inflammatory T helper 17 (Th17)/T follicular helper (Tfh) cell responses, and (4) generating bioactive metabolites with dual roles in regulating osteoclastogenesis and synovial inflammation. This review synthesizes recent advances in gut microbiome profiling, mechanistic studies, and preclinical models, elucidating microbial-host crosstalk in autoimmune cascades. Furthermore, we critically evaluate microbiota-directed strategies, including dietary and probiotic modulation, microbiome-informed optimization of conventional DMARDs and biologics, and investigational approaches like fecal microbiota transplantation and Chinese herbal medicine, that may offer promising adjunctive approaches to complement conventional RA management.}, }
@article {pmid41329233, year = {2026}, author = {Guarino, M and Di Ciaula, A and Portincasa, P and De Giorgio, R}, title = {Narrative review on microbiota and sepsis: the host's betrayal?.}, journal = {Internal and emergency medicine}, volume = {21}, number = {2}, pages = {607-619}, pmid = {41329233}, issn = {1970-9366}, mesh = {Humans ; *Sepsis/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/physiopathology ; *Microbiota/physiology ; }, abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide. Increasing evidence suggests that the gut microbiota, long considered a "less relevant" to human body health, it plays a crucial role in the pathophysiology of sepsis. Disruption of the host-microbe balance contributes to impaired barrier integrity, microbial translocation, and dysregulated immune responses. This perspective raises the possibility that dysbiosis is not merely a consequence of critical illness, rather an active driver of septic progression. This narrative review explores the relationship between sepsis and gut microbiome. PubMed, Scopus, and EMBASE were searched from inception to September 2025. Recent studies have highlighted the triangular interplay between the intestinal barrier, gut microbiota, and immune system. Altered microbial composition and increased permeability foster systemic inflammation and immune dysfunction. Biomarkers such as diamine oxidase and intestinal fatty acid-binding protein are emerging as promising indicators of gut injury. Experimental therapies (i.e., faecal microbiota transplantation, targeted probiotics, prebiotics, postbiotics, and personalized antibiotic regimens guided by microbial profiling) provide potential to modulate host-microbe interactions. Integration of microbiome analysis with multi-omics and advanced bioinformatics may enable stratification of septic patients by microbial signatures, paving the way for precision medicine approaches. Modulation of gut microbiota represents a novel therapeutic frontier in sepsis. Conceptualizing sepsis as a disease of disrupted host-microbe symbiosis may unravel new diagnostic and therapeutic strategies. Future research should aim at prioritizing high-quality trials, innovative designs, and equitable implementation to target microbiota to improve survival and recovery in patients with sepsis.}, }
@article {pmid41331614, year = {2025}, author = {Yu, H and Zhang, Y and Yang, D and Luo, H and Zhou, Y}, title = {Advances in capsule-based fecal microbiota transplantation: clinical applications and innovations.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1370}, pmid = {41331614}, issn = {1479-5876}, support = {LTGD23C040008//Zhejiang Provincial Natural Science Foundation of China/ ; LBY23H200006//Natural Science Foundation of Hebei Province/ ; 2023020612//Ningbo Top Medical and Health Research Program/ ; 2023-S013//Ningbo Public Welfare Project/ ; 06-445-1211//Talent Initiation Program of the High-Level University Development Project at Guangzhou Medical University/ ; }, abstract = {Capsule-based fecal microbiota transplantation (cFMT) has emerged as a vital tool for modulating gut dysbiosis for therapeutic intervention. This noninvasive alternative to traditional FMT avoids procedural invasiveness while offering logistical advantages in terms of storage, administration, and patient compliance. This review evaluates cFMT as a transformative approach across diverse diseases. Notably, cFMT demonstrates robust efficacy in restoring the microbial balance in Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and multidrug-resistant infections, with outcomes comparable to those of conventional methods. It also alleviates symptoms and enhances microbiota diversity in small intestinal bacterial overgrowth (SIBO). However, the clinical benefits remain inconsistent for individuals with in irritable bowel syndrome (IBS) and functional constipation (FC), despite alterations in gut microbial diversity. Emerging applications highlight the potential of cFMT metabolic disorders (e.g., obesity and hypertension) via the modulation of gut-derived metabolites and neuropsychiatric conditions (e.g., depression and autism) through gut–brain axis signaling, in addition to chronic kidney disease and hepatic encephalopathy. Challenges such as donor variability, standardization gaps, and transient adverse effects hinder widespread adoption. Further advancements, including targeted colon-release formulations, synthetic microbial consortia, and single-cell delivery systems, could improve precision and scalability. Despite its transformative potential, the clinical adoption of cFMT hinges on rigorous quality control, mechanistic insights, and long-term safety data. In recent years, the United States Food and Drug Administration (FDA) has officially approved the oral microbiome therapy Vowst for marketing. This marked the gradual transition of fecal microbiota transplantation (FMT)-related therapies from clinical research to standardized clinical application, and at the same time, Vowst has become the world’s first oral fecal microbiome therapy approved by the FDA. This review highlights the role of cFMT in microbiota-targeted therapies while advocating for innovation to address current limitations and expand its therapeutic scope.}, }
@article {pmid41332430, year = {2025}, author = {Li, L and Zhou, N and Wang, Z and Wang, T and Wang, Y and Qiao, F and Du, ZY and Zhang, ML}, title = {Intestinal microbiota contributes to the heterogeneity of fat deposition by promoting mitochondrial fatty acid β-oxidation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2593076}, pmid = {41332430}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Fatty Acids/metabolism ; Carnitine/biosynthesis/metabolism ; Oxidation-Reduction ; *Mitochondria/metabolism ; Zebrafish ; Lipid Metabolism ; *Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Male ; Humans ; Feces/microbiology ; }, abstract = {The gut microbiota plays a crucial role in lipid metabolism in both humans and animals. However, the specific contributions of gut microbiota and their associated metabolites to fat deposition, as well as the underlying mechanisms, remain largely unexplored. In this study, we demonstrated that the intestinal microbiota mediated the heterogeneity of mesenteric fat index (MFI), as evidenced by fecal microbiota transplantation (FMT) experiments. Notably, analysis of the 16S rRNA gene amplicon sequencing of 44 samples revealed a significantly higher abundance of Cetobacterium somerae in the Low MFI group, with a positive correlation to reduced MFI. Serum metabolomics analysis confirmed that L-Carnitine emerged as the most differentially abundant metabolite in the Low MFI group and exhibited a strong positive correlation with C. somerae abundance. Metagenomic analysis showed that microbial genes related to L-Carnitine biosynthesis were significantly enriched in the Low MFI group. Further, C. somerae was isolated and cultured, and its subsequent monocolonization in germ-free zebrafish and tilapia demonstrated its lipid-lowering effects by enhancing mitochondrial fatty acid β-oxidation. Whole genome sequencing demonstrated C. somerae could encode the [EC:1.2.1.3] gene, which promotes the production of 4-trimethylammoniobutanoate, a precursor of L-Carnitine, thereby enhancing L-Carnitine biosynthesis by the host and gut microbiota, leading to the reduced fat deposition in Nile tilapia. In conclusion, C. somerae, a core gut microbe with high abundance in aquatic teleost intestines, plays an important role in host lipid metabolism. This study advances our understanding of how core gut microbes shape host phenotypes and provides novel insights into manipulating core gut colonizers to reduce fat deposition.}, }
@article {pmid41332712, year = {2025}, author = {Romo, R and Ricks, E and Ogden, R and Bonnette, PE and Olson, SC and Pearman, K and Call, GB and Chaston, JM}, title = {Whole-body homogenates restore disrupted microbiota composition in a model insect better than feces or no restoration treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41332712}, issn = {2692-8205}, support = {R15 GM140388/GM/NIGMS NIH HHS/United States ; }, abstract = {Antibiotic treatment can disrupt gut microbiota and pose challenges and opportunities for the establishment or restoration of healthy microbial communities. Using the fruit fly, Drosophila melanogaster, as an experimental model, we evaluated the impact of two types of microbial transplants-fly feces and whole-body fly homogenates-on host microbiota composition, following, or independent of, tetracycline-induced community disruption. Using 16S rRNA sequencing, we compared community beta diversity between treatments. We show that antibiotic treatment significantly altered microbiota composition and community structure relative to untreated controls. Flies inoculated with whole body homogenates of age-matched, antibiotic-free flies had a more similar microbial community composition to the untreated communities than flies exposed to fly feces or to flies that received no restoration treatment. We also found that the presence of Wolbachia was associated with variation in microbiota composition and specific locomotor functions. These findings show that whole-body homogenates are a superior method for microbiota restoration in Drosophila melanogaster and contribute to a growing body of research on microbial community restoration following disturbance.}, }
@article {pmid41334445, year = {2025}, author = {Jing, M and Jiang, Y}, title = {Microbiome-mediated crosstalk between T2DM and MASLD: a translational review focused on function.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1677175}, pmid = {41334445}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism ; *Fatty Liver/microbiology/metabolism ; }, abstract = {Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently co-occur and aggravate one another through shared pathways of insulin resistance, low-grade inflammation and disordered lipid handling. Framing their interaction through the gut-liver-pancreas axis, this review synthesizes recent progress with a function-first emphasis, moving beyond taxonomic lists to the microbial outputs most consistently linked to dual metabolic-hepatic endpoints. We summarize how short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharide (LPS) and other microbe-associated molecular patterns, branched-chain amino-acid (BCAA) catabolites, trimethylamine N-oxide (TMAO) and endogenous ethanol reach the liver via portal inflow or the enterohepatic BA cycle and act on epithelial, immune and endocrine interfaces, including the farnesoid X receptor (FXR), G-protein-coupled BA receptor 1 (TGR5) and fibroblast growth factor 19/15 signaling. Mechanistic routes-barrier dysfunction and endotoxaemia; SCFA signaling with effects on enteroendocrine tone and substrate flux; BA remodeling that resets hepatic and pancreatic set-points; and nitrogen/choline and ethanol pathways that promote lipotoxic injury-offer biologically coherent explanations for parallel trajectories of hyperglycemia and steatosis/inflammation. We appraise therapeutic modulation spanning diet and fermentable substrates, live biotherapeutics/postbiotics, BA-targeting drugs, fecal microbiota transplantation and metabolic/bariatric surgery, and we outline clinically actionable biomarker opportunities using function-based panels (fermentative capacity, BA transformation, inflammatory ligands, nitrogen/methyl flux) integrated with host metabolites and genetics for diagnosis, risk stratification and response prediction. By advocating standardized reporting, careful control of diet/medications and composite metabolic-hepatic endpoints in prospective trials, this review provides a practical framework to accelerate translation from association to targeted prevention and therapy that improves glycemic control and MASLD activity in parallel.}, }
@article {pmid41334562, year = {2025}, author = {Yurtseven, B and Aydemir, E and Ayaz, F}, title = {The Role of Intestinal Microbiota and Immune System Interactions in Autoimmune Diseases.}, journal = {ImmunoTargets and therapy}, volume = {14}, number = {}, pages = {1347-1372}, pmid = {41334562}, issn = {2253-1556}, abstract = {BACKGROUND: The intricate interplay between the intestinal microbiota and the immune system has emerged as a central theme in understanding autoimmune disease pathogenesis. This review comprehensively explores the role of gut microbiota in shaping immune development, establishing immune tolerance, and contributing to both local and systemic immune regulation.<br><br>METHODS: This review synthesizes the modulatory effects of microbial metabolites (eg, short-chain fatty acids and indole derivatives) on regulatory T cells (Tregs) and inflammatory pathways. The concept of "dysbiosis" is examined from functional and compositional perspectives, linking microbial imbalances to autoimmune disorders (IBD, MS, RA, and T1D). Microbiota-targeted therapeutic interventions (probiotics, prebiotics, FMT) are also evaluated.<br><br>KEY FINDINGS: The synthesis of the literature confirms that microbial metabolites have a direct impact on Treg differentiation and inflammatory pathways. Dysbiosis, through functional and compositional disruptions, is strongly associated with the pathogenesis of various autoimmune disorders, including Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, and Type 1 Diabetes. Therapeutic interventions such as probiotics, prebiotics, and Fecal Microbiota Transplantation show promising potential in restoring microbial and immune homeostasis.<br><br>CONCLUSION: This review highlights the role of the gut-immune axis in autoimmune diseases. Despite current challenges, such as individual variability and determining causality, future directions toward precision microbiota and immune modulation are promising. This study provides a robust foundation for researchers and clinicians seeking to understand and therapeutically target the gut-immune axis.}, }
@article {pmid41335362, year = {2025}, author = {Jia, Y and Shi, Y and Wang, J and Liu, H and Wang, H and Huang, Y and Liu, Y and Chen, P and Peng, J}, title = {Astragalin attenuates caerulein-induced acute pancreatitis by targeting the NLRP3 signaling pathway and gut microbiota.}, journal = {Bioresources and bioprocessing}, volume = {12}, number = {1}, pages = {139}, pmid = {41335362}, issn = {2197-4365}, support = {82170661//National Natural Science Foundation of China/ ; 2023DK2002//Key Project of Research and Development Plan of Hunan Province/ ; 2025JJ60669//Hunan Provincial Natural Science Foundation of China/ ; 2024M763719//China Postdoctoral Science Foundation/ ; GZC20242045//Postdoctoral Fellowship Program of CPSF/ ; }, abstract = {BACKGROUND: Acute pancreatitis (AP) has caused great concern worldwide due to its serious threat to human health. Astragalin is a bioactive natural flavonoid compound with several pharmacological activities, but it remains unclear about its effect on AP. The objective of this experiment was to explore the mitigating efficacy of astragalin on caerulein-induced AP model and examine the underlying mechanisms.<br><br>METHODS: Following the assessment of astragalin's direct effects on pancreatic acinar cells using an in vitro AP model, an in vivo mouse model was established to further validate its efficacy and elucidate the underlying mechanisms. Pancreatic histopathology, amylase, and lipase levels of mice were observed to determine the optimal therapeutic dose of astragalin. The network pharmacology and RNA sequencing technology were used to reveal the possible targets and pathways. Subsequent molecular docking and western blot were conducted to validate the association between astragalin and key target molecules, as well as the NLRP3 signaling pathway. Combined with metagenomics and metabolomics analysis, the astragalin effective gut microbiota-metabolite-gene network was constructed. Moreover, fecal microbiota transplantation experiments were performed to clarify the importance of gut microbiota in astragalin-mediated alleviation of AP.<br><br>RESULTS: The results showed that astragalin attenuated caerulein-induced injury in AR42J cells in vitro. Consistent with these findings, in vivo experiments revealed that astragalin treatment significantly improved pancreatic pathological injury, cell apoptosis, and systemic inflammatory response in AP mice, particularly at high doses. The integrated analysis of network pharmacology and transcriptomics revealed that the NLRP3 signaling pathway was a key molecular pathway, which was further validated using western blot. Docking analysis showed that 12 target genes had good docking activity with astragalin. More intriguingly, it was found that astragalin could reverse gut microbiota dysbiosis by restoring microbial diversity, altering bacterial community composition, and modulating key metabolic pathways. Specifically, astragalin-effective correlation networks were constructed with Lachnoclostridium sp. YL32, Roseburia intestinalis, Ruminococcus gnavus, Lachnospiraceae bacterium Choco86, Anaerobutyricum hallii, etc. as the core strains, 22 metabolites, including 5-Methoxytryptophan, D-Serine, L-Tryptophan, L-Methionine, etc. as core metabolites, and NLRP3 pathway-related genes as the main regulatory targets. Furthermore, fecal microbiota transplantation experiments confirmed the involvement of gut microbiota in AP remission.<br><br>CONCLUSION: Collectively, these findings identify astragalin as a promising therapeutic agent for AP, targeting both the NLRP3 signaling cascade and gut microbial homeostasis.}, }
@article {pmid41337660, year = {2025}, author = {Silva, IB and Puig-Domingo, M}, title = {The impact of thyroid disorders on the gut microbiome: emerging mechanisms and clinical relevance.}, journal = {Archives of endocrinology and metabolism}, volume = {70}, number = {Spe1}, pages = {e250075}, pmid = {41337660}, issn = {2359-4292}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Thyroid Diseases/microbiology/immunology/metabolism ; Dysbiosis/microbiology/immunology ; Thyroid Gland/metabolism/immunology ; Animals ; Clinical Relevance ; }, abstract = {The thyroid-gut axis represents a dynamic interaction between the intestinal microbiota and thyroid function, with growing evidence linking gut dysbiosis to thyroid diseases. The gut microbiome, comprising over 100 trillion microorganisms, influences immune modulation, iodine metabolism, and thyroid hormone regulation. Short-chain fatty acids, produced by beneficial gut bacteria, support immune homeostasis and thyroid function, while pathogenic bacteria and lipopolysaccharides trigger inflammatory pathways that impair thyroid activity. Alterations in gut microbiota composition have been associated with autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves' disease. Dysbiosis increases intestinal permeability, antigen exposure, and immune activation, exacerbating thyroid autoimmunity. A reduction in short-chain fatty acids-producing bacteria weakens immune tolerance, promoting inflammatory cytokine release and autoantibody production. Recent studies highlight microbial metabolites such as tryptophan derivatives and their role in immune regulation. Gut dysbiosis is also implicated in thyroid nodules and cancer. Decreased butyrate-producing bacteria and increased inflammatory bacterial taxa have been observed in thyroid malignancies. Microbiota influence iodine and selenium bioavailability, essential for thyroid hormone synthesis, and modulate sodium-iodide symporter expression, affecting thyroid cancer response to radioactive iodine therapy. Microbiome-targeted interventions, including probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation, may restore microbial balance, enhance immune regulation, and improve thyroid treatments. This review synthesizes our current understanding of the thyroid-gut axis, indicating that the intestinal microbiota and its metabolites may act directly or indirectly on the thyroid gland, highlighting potential clinical implications and paving the way for therapeutic strategies targeting the intestinal microbiota.}, }
@article {pmid41337940, year = {2026}, author = {Han, M and Dong, X and Zhao, R and Hu, X and Li, D and Yan, X and Liu, Y and Du, Q and Li, M}, title = {Fecal metabolomics in Crohn's disease reveal N-Acetylglutamine as a Th17/Treg modulator.}, journal = {Molecular immunology}, volume = {189}, number = {}, pages = {82-97}, doi = {10.1016/j.molimm.2025.11.012}, pmid = {41337940}, issn = {1872-9142}, mesh = {Humans ; *Th17 Cells/immunology ; *Crohn Disease/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology ; *Metabolomics/methods ; Female ; Male ; *Feces/chemistry ; Adult ; Cell Differentiation/immunology ; Middle Aged ; Glutamine ; Gastrointestinal Microbiome/immunology ; }, abstract = {The gut microbiota is widely recognized as a key component in the pathogenesis of inflammatory bowel disease (IBD), and one of its primary modes of interaction with the host occurs via metabolites. Studies have confirmed that gut microbiota dysbiosis affects immune maturation, immune homeostasis, host energy metabolism, and the maintenance of mucosal integrity. However, the specific metabolites that influence the differentiation of mucosal CD4[+] T cells remain insufficiently elucidated. This study aimed to identify and validate unknown metabolites capable of affecting the differentiation of CD4[+] T cell subsets by characterizing changes in fecal metabolites between IBD patients and non-IBD controls. Using untargeted metabolomics, we quantitatively detected a total of 1480 metabolites in positive ion mode and 1178 metabolites in negative ion mode. Regression analysis results showed that N-Acetylglutamine was significantly downregulated in IBD patients and was identified as a key differential metabolite. Further in vitro functional experiments confirmed that this metabolite could directly regulate the differentiation balance of CD4[+] T cells, specifically inhibiting the differentiation of pathogenic Th17 (pTh17) cells while promoting the generation of Treg. This study verifies the critical role of the metabolite N-Acetylglutamine in regulating the Treg/pTh17 cell balance, providing a theoretical basis for its potential as a therapeutic target for IBD.}, }
@article {pmid41338112, year = {2026}, author = {Hu, L and Zhang, Z and Xu, T and Ma, P and Wang, Z and Zhang, L and Chen, J and He, P and Yang, X and Du, G and Lian, F and Li, X and Qiang, G}, title = {Jiangtang Tiaozhi Formula alleviates obesity by enhancing adipose thermogenesis via TGR5-mediated gut-liver-adipose axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157608}, doi = {10.1016/j.phymed.2025.157608}, pmid = {41338112}, issn = {1618-095X}, mesh = {Animals ; *Obesity/drug therapy/metabolism ; *Thermogenesis/drug effects ; Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; *Drugs, Chinese Herbal/pharmacology ; Liver/drug effects/metabolism ; *Anti-Obesity Agents/pharmacology ; Hep G2 Cells ; *Receptors, G-Protein-Coupled/metabolism ; *Adipose Tissue/drug effects/metabolism ; Lipid Metabolism/drug effects ; Fecal Microbiota Transplantation ; Insulin Resistance ; Diet, High-Fat ; }, abstract = {BACKGROUND: Development of safe and effective anti-obesity drugs has emerged as an urgently needed issue. Jiangtang Tiaozhi Formula (JTTZF), a traditional Chinese medicine formulation, has demonstrated potential antidiabetic and hypolipidemic properties. However, the anti-obesity efficacy of JTTZF and its mechanisms remain insufficiently understood.<br><br>METHODS: We assessed the pharmacodynamic effects of JTTZF in diet-induced obese (DIO) mice, as well as in HepG2 cells and adipocytes, focusing on body weight and glucose/lipid metabolism in vivo and in vitro, respectively. 16S rDNA sequencing profiling and fecal microbiota transplantation (FMT) were applied to validate the contribution of gut microbiota in anti-obesogenic effects of JTTZF. Untargeted fecal metabolomics was utilized to explore the potential metabolic pathways mediating gut-liver-adipose axis leading to anti-obesity effect of JTTZF via thermogenesis, which were subsequently confirmed by qPCR detection.<br><br>RESULTS: JTTZF exhibited a significant effect of anti-obesity and metabolic benefit, including inhibiting weight gain and adiposity, reducing blood glycolipid, ameliorating glucose intolerance and insulin resistance, together with protecting against hepatic steatosis, compared with orlistat. Mechanistically, JTTZF boosted white fat browning and brown fat thermogenesis. More importantly, JTTZF remodeled gut microbiota by enhancing the colonization of beneficial bacteria. Further JTTZF-FMT induced weight loss and metabolic benefits in DIO mice, verifying that gut microbiota played a crucial role in the anti-obesity effect of JTTZF. Additionally, enrichment analysis of differential metabolites revealed that JTTZF obviously upregulated bile acid metabolism pathway, which promoted TGR5-mediated thermogenesis and energy expenditure in adipose tissue.<br><br>CONCLUSION: JTTZF exerted significant anti-obesity effect and metabolic benefits via gut-liver-adipose axis, indicating that JTTZF hold a promising potential at the preclinical stage for obesity treatment.}, }
@article {pmid41338385, year = {2025}, author = {Zhang, X and Qi, J and Dong, C and Zhang, L and Chen, J and Liu, J and Jiang, T and Song, J}, title = {Intratumoral microbiota in colorectal cancer: roles, therapeutic potential, and challenges.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.067}, pmid = {41338385}, issn = {2090-1224}, abstract = {BACKGROUND: Colorectal cancer (CRC) is a multifactorial disease characterized by disruptions in cellular and immune functions, influenced by genetic mutations, environmental factors, and infections. Recent studies have highlighted the intratumoral microbiota as a critical component of the tumor microenvironment (TME), with a significant role in CRC initiation, progression, and therapeutic response. While the gut microbiota's influence on CRC is well-established, the specific contribution of intratumoral microbiota remains inadequately explored. Emerging evidence suggests that intratumoral microbiota may promote cancer progression through inflammatory pathways, metabolic alterations, and resistance to chemotherapy. Conversely, certain microbial communities exhibit tumor-suppressive properties by modulating immune responses and inducing apoptosis in tumor cells.<br><br>AIM OF REVIEW: This review aims to highlight the dual role of the intratumoral microbiota in CRC and explore the potential of microbial interventions such as probiotics, phage therapy, and fecal microbiota transplantation (FMT) in enhancing therapeutic outcomes. Furthermore, the review examines the potential of microbiota-targeted therapies to optimize cancer treatment strategies and stresses the need for personalized approaches based on microbial biomarkers.<br><br>Intratumoral microbiota, as emerging tumor components, has been identified in various solid tumors. The review emphasizes the mechanisms by which intratumoral microbiota mediate inflammation, metabolic alterations, and immune modulation in CRC. It highlights how certain intratumoral microbiota are associated with resistance or sensitivity to treatments, and how manipulating the microbiota could enhance immunotherapy efficacy. By integrating advancements in multi-omics and clinical research, targeting the intratumoral microbiota represents a promising avenue for improving CRC therapies and overcoming treatment resistance. The clinical application of the intratumoral microbiota has the potential to revolutionize the treatment of CRC, paving the way for novel therapeutic strategies in oncology.}, }
@article {pmid41338419, year = {2026}, author = {Wei, MX and Wu, XY and Lin, JW and Huang, JY and Cheng, J and Huang, WF and Xu, GH and Yi, LT}, title = {Astaxanthin alleviates DSS-induced ulcerative colitis in mice associated with Nrf2-mediated ferroptosis independently of gut microbiota modulation.}, journal = {The Journal of nutritional biochemistry}, volume = {149}, number = {}, pages = {110212}, doi = {10.1016/j.jnutbio.2025.110212}, pmid = {41338419}, issn = {1873-4847}, mesh = {Animals ; *NF-E2-Related Factor 2/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism/pathology ; Xanthophylls/pharmacology/therapeutic use ; Mice ; *Ferroptosis/drug effects ; Male ; Mice, Inbred C57BL ; Colon/pathology/drug effects/metabolism ; Fecal Microbiota Transplantation ; Kelch-Like ECH-Associated Protein 1/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Cytokines/metabolism ; Heme Oxygenase-1/metabolism ; }, abstract = {Astaxanthin, a natural carotenoid predominantly synthesized by marine microorganisms, has shown promise in attenuating inflammatory diseases, yet its role in colitis remains unclear. Here, we evaluated the therapeutic effects of astaxanthin in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Our findings revealed that astaxanthin significantly ameliorated colitis symptoms, notably at the dose of 100 mg/kg, demonstrated by reduced Disease Activity Index (DAI), increased colon length, diminished colon histopathological damage, and enhanced goblet cell population. Mechanistically, astaxanthin decreased proinflammatory cytokines and malondialdehyde (MDA) levels, suppressed Keap1 expression, activated phosphorylated Nuclear factor erythroid 2-related factor two (Nrf2), and increased downstream protein expression of HO-1 and GPX4, ultimately inhibiting ferroptosis. Although astaxanthin altered gut microbiota composition, antibiotic treatment and fecal microbiota transplantation confirmed that its anti-colitis effects were independent of microbiota changes. These findings suggest that astaxanthin alleviates colitis associated with Nrf2 pathway mediated ferroptosis, rather than through gut microbiota modulation.}, }
@article {pmid41339918, year = {2025}, author = {Liu, H and Xiong, X and Zhu, W and Wang, S and Huang, W and Zhu, G and Xu, H and Yang, L}, title = {Gut microbial metabolites in cancer immunomodulation.}, journal = {Molecular cancer}, volume = {25}, number = {1}, pages = {8}, pmid = {41339918}, issn = {1476-4598}, support = {2022YFC3602900//National Key Research and Development Program of China/ ; 82372831//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunomodulation ; *Neoplasms/metabolism/immunology/etiology/pathology ; Tumor Microenvironment/immunology ; Animals ; *Metabolome ; }, abstract = {Gut microbiota-derived metabolites are emerging as systemic "remote immunoregulators" that shape tumor immunity across tissues. Integrating evidence across short-chain fatty acids, tryptophan derivatives, secondary bile acids, polyamines and other metabolites, we advance a metabolite-immune pathway-cancer framework that links receptor-mediated signaling, epigenetic remodeling and metabolic reprogramming to context-dependent, bidirectional immune effects. Importantly, in addition to the g protein-coupled receptor / aryl hydrocarbon receptor pathway, the selected microbial small molecule metabolites are the true T-cell receptor ligands of unconventional T cells, directly shaping the tissue resident immune and tumor microenvironment, supplementing the receptor signaling and epigenetic programs in our framework. We synthesize how these metabolites recalibrate the tumor immune microenvironment-modulating antigen presentation, T-cell effector fitness and exhaustion, regulatory T-cell activity, and myeloid polarization-and why the same metabolite can either potentiate immune surveillance or entrench immunosuppression depending on ligand-receptor pairing, dose and tissue niche. We compare tumor-type specific patterns (e.g., colorectal, liver, lung, breast and prostate cancers) to highlight common circuits and organ-restricted idiosyncrasies. Methodologically, we outline how single-cell and spatial multi-omics, imaging mass spectrometry and functional biosensors now enable co-registration of metabolite exposure with immune-cell states in human tumors, providing an actionable basis for biomarker discovery. Given ongoing debate about signals attributed to intratumoral microbiota in low-biomass tumor tissues, we foreground quantifiable, spatially mappable and pharmacologically tractable metabolite-receptor pathways, using microbe-associated molecular patterns / translocation as comparators to judge when chemical signals should be prioritized as intervention targets. Finally, we evaluate precision intervention avenues-including fecal microbiota transplantation, rational bacterial consortia, engineered microbes and nanoparticle-enabled metabolite delivery-and propose stratification rules that pair metabolite/receptor signatures with fit-for-purpose delivery. Together, mapping tissue-specific metabolite-immune circuits and embedding them in robust biomarker frameworks may convert microbial metabolites from correlative markers into therapeutic targets and tools, improving the efficacy and durability of cancer immunotherapy.}, }
@article {pmid41339929, year = {2025}, author = {Yang, Y and Chen, H and Lu, J and Yang, N and Liu, L and Zhang, Q and Tang, M and Li, X and Meng, B and Li, Y and Yu, L and Gao, L and Zhang, H and Wu, T and Zheng, Y and Liu, Y and Shen, Y and Li, J}, title = {Modulating the gut-bladder axis: fecal transplantation protects antibiotic-treated mice from E. coli cystitis via the Ahr/Prg4 pathway.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {15}, pmid = {41339929}, issn = {2049-2618}, support = {U24A20643, 82270015, 82400132, 82100017&#xff0c;82302577&#xff0c;82304209, 82370016//National Natural Science Foundation of China/ ; 2023B700,2024C875//Anhui Province Postdoctoral Research Funding Project/ ; 2208085QH236, 2208085MH264, 2308085QH284, 2308085MH243//Anhui Provincial Natural Science Foundation/ ; 202304295107020032, 202304295107020043//Anhui Province Clinical Medical Research Transformation Special Project/ ; 2023AH01008, 2023AH053282//Anhui Province Scientific Research Planning Project/ ; 2023AH010083, 2024AH010114, 2024AH050826//Anhui University Natural Science Research Project/ ; gxbjZD08//Top Talents Academic Funding Key Programs in Universities/ ; 2021xkjT021//Basic and Clinical Cooperative Research Program of Anhui Medical University/ ; MTP2022A015//China Primary Health Care Foundation/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Cystitis/microbiology/prevention &amp; control/therapy ; *Urinary Bladder/microbiology/metabolism ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; Escherichia coli/drug effects ; *Escherichia coli Infections/microbiology/therapy ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Female ; *Basic Helix-Loop-Helix Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Signal Transduction ; Mice, Knockout ; Disease Models, Animal ; }, abstract = {BACKGROUND: Bacterial cystitis, caused by Escherichia coli (E. coli), is a common urinary tract infection that frequently recurs and seriously affects patient health. Although it is known that gut dysbiosis increases susceptibility to recurrent urinary tract infections, its impact on non-complicated bacterial cystitis-the most common and primary form of urinary tract infection-remains uncertain.<br><br>RESULTS: This study found that bacterial infection can cause long-term alterations in gut microbiota structure and affect the production of metabolites. Depletion of the gut microbiota worsens the inflammatory response to bacterial infection, disrupts the epithelial barrier of the bladder, and increases E. coli retention in the bladder and bloodstream. Fecal microbiota transplantation was found to significantly alleviate these excessive inflammatory responses. The study also identified that several tryptophan derivatives derived from the gut microbiota were significantly altered during bacterial microbiota depletion and bacterial infection, with indole-3-propionic acid (IPA) exhibiting the most significant alleviating effect on the excessive inflammatory response during infection. Additionally, the study demonstrated that transcriptional activation of the immune-inhibitory protein Prg4 is regulated by the IPA receptor AhR, which is expressed in bladder urothelial cells. Knockout of AhR in bladder urothelial reduced Prg4 expression and overactivated NF-&#x3ba;B signaling, resulting in the loss of the IPA-alleviating effect. This study suggests that the normal gut microbiota can activate AhR in bladder urothelial cells through its metabolite IPA, regulating the transcription of Prg4 and subsequently modulating the inflammatory response to bacterial cystitis caused by E. coli infection.<br><br>CONCLUSIONS: These findings provide a theoretical foundation for the clinical diagnosis and treatment of bacterial cystitis by leveraging the gut microbiota and their metabolites as promising therapeutic targets. Video Abstract.}, }
@article {pmid41340133, year = {2025}, author = {Abavisani, M and Sajjadi, SM and Ebadpour, N and Karav, S and Sahebkar, A}, title = {Gut microbiota-cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation.}, journal = {Nutrition &amp; metabolism}, volume = {23}, number = {1}, pages = {4}, pmid = {41340133}, issn = {1743-7075}, abstract = {Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Genetic factors, and various environmental factors, including nutrition and the composition of the gut microbiota, have been identified as important factors in the initiation of CVD. Among them, the pivotal role of the gut microbiota in modulating cholesterol metabolism and influencing cardiovascular outcomes has recently been highlighted. Extensive research has confirmed that the gut microbiota has direct and indirect regulatory effects on host cholesterol homeostasis. Recent studies have shown that the microbiota can influence blood cholesterol levels and thus the risk of CVD through various pathways, such as the production of certain metabolites such as bile acids (BAs), SCFAs, and TMAO, the activation of nuclear and membrane-bound receptors such as farnesoid X receptor (FXR), the regulation of gene expression involved in lipid metabolism and inflammatory responses, as well as microbial enzymatic pathways. These complex regulatory mechanisms make the gut microbiota a potential therapeutic target in cholesterol-related diseases and CVD. Microbiota-modulating strategies, including the use of probiotics, prebiotics, fecal microbiota transplantation (FMT), and selective antibiotics, have shown beneficial effects in previous studies. In this regard, in this study, we conducted an in-depth investigation of the regulatory effect of intestinal microbiota on cholesterol metabolism and their impact on the development and progression of atherosclerosis and CVD, and described potential therapeutic pathways based on the regulation of intestinal microbiota in CVD.}, }
@article {pmid41341415, year = {2025}, author = {Memariani, M and Memariani, H}, title = {Dysbiosis and Therapeutic Modulation of the Gut Microbiota in Multiple Sclerosis: A Narrative Review.}, journal = {Health science reports}, volume = {8}, number = {12}, pages = {e71564}, pmid = {41341415}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Multiple sclerosis (MS) is a persistent autoimmune disease that affects the central nervous system. The etiology of MS is complex, involving a variety of genetic and environmental factors. Mounting evidence suggests that dysbiosis significantly impacts the progression of MS mainly through its direct effects upon the immune system. Given the vital connection between the gut microbiota and immune health, particularly in the context of autoimmune diseases, this review aims to summarize the existing knowledge regarding alterations in the gut microbiota among MS patients, with a focus on microbiota-based therapeutic approaches.<br><br>METHODS: A detailed literature review was carried out to gather contemporary evidence on dysbiosis of the gut microbiota in MS patients. Furthermore, studies dealing with the modification of gut microbiota for therapeutic applications in MS have been included.<br><br>RESULTS: A distinct variation in specific bacterial phyla, orders, families, and genera, as well as metabolites, was found in MS patients. Exploring therapeutic options such as antibiotics, probiotics, dietary interventions, fecal microbiota transplantation, phage therapy, and helminth therapy may present valuable opportunities for gut microbiota modification in MS treatment.<br><br>CONCLUSION: Altering the gut microbiota in patients with MS may serve as a potentially effective treatment strategy. Nevertheless, future research should prioritize the standardization of these therapies. Finally, it is imperative that researchers concentrate on large-scale studies or trials to scrutinize the practical relevance of these therapeutic options.}, }
@article {pmid41342899, year = {2026}, author = {Wang, LJ and Mo, YK and Cheng, Y}, title = {The role of intratumoral microbiota in the occurrence and progression of tumors and its implications for guiding tumor treatment.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {73}, number = {1}, pages = {1-12}, doi = {10.1556/030.2025.02747}, pmid = {41342899}, issn = {1588-2640}, mesh = {Humans ; Animals ; *Neoplasms/microbiology/therapy/pathology ; *Microbiota ; Disease Progression ; Mice ; }, abstract = {In recent years, the presence of microbiota in tumors has been discovered through extensive research, overturning the longstanding belief that "tumors are sterile." Advanced techniques such as 16S rRNA gene sequencing, fecal microbiota transplantation, and the construction of mouse models specific to different tumor types have been utilized to validate the existence of microbiota within various tumors. The intratumoral microbiota significantly influences tumor development by modulating immune responses, mediating inflammatory reactions, and interfering with or enhancing immunotherapy or chemotherapy. For instance, Aspergillus sydowii in lung adenocarcinoma promotes immunosuppression via the Dectin-1/CARD9 pathway, while colibactin-producing Escherichia coli in colorectal cancer facilitates tumor progression through lipid metabolism dysregulation. Moreover, intratumoral microbiota can predict patient prognosis and guide personalized cancer treatment strategies, highlighting their potential as therapeutic targets. This review synthesizes current evidence on the roles of intratumoral microbiota across multiple cancer types and discusses their clinical implications.}, }
@article {pmid41343181, year = {2026}, author = {Roth, TD and Russo-Savage, L and Bahojb Habibyan, Y and Keenan, CM and Wallace, LE and Nasser, Y and Mawe, GM and Lavoie, B and Sharkey, KA}, title = {Microbial dysbiosis alters serotonin signaling in a postinflammatory murine model of visceral pain.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {330}, number = {1}, pages = {G29-G44}, pmid = {41343181}, issn = {1522-1547}, support = {R21 AT011203/AT/NCCIH NIH HHS/United States ; FDN148380//Canadian Institutes of Health Research (CIHR)/ ; DK113800//HHS | National Institutes of Health (NIH)/ ; R01 DK113800/DK/NIDDK NIH HHS/United States ; AT011203//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Serotonin/metabolism ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/metabolism/microbiology ; Mice ; *Visceral Pain/metabolism/microbiology ; Signal Transduction ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; Enterochromaffin Cells/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Hydroxyindoleacetic Acid/metabolism ; Dextran Sulfate ; *Colitis/chemically induced/metabolism/microbiology ; Colon/metabolism ; Tryptophan Hydroxylase/metabolism/genetics ; }, abstract = {Serotonin (5-HT) is a multifunctional signaling molecule in the gastrointestinal (GI) tract. 5-HT synthesis is regulated by the gut microbiota. Microbial dysbiosis has been implicated in visceral pain and persistent alterations in gut function that occur following inflammation. Here, we tested the hypothesis that alterations in gut microbiota in a postinflammatory model of visceral pain contribute to dysregulated 5-HT signaling. We used mice treated with dextran sodium sulfate (DSS) 42 days earlier (postcolitis) or untreated mice as donors for fecal microbiota transplants (FMTs) into germ-free mice to explore changes in enterochromaffin (EC) cell populations, expression of 5-HT synthesis, transport, and degradation genes, levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT release. Significant differences were observed in EC cells, Tph1, Slc6a4, and Maoa gene expression, 5-HT and 5-HIAA levels, and 5-HT release between germ-free mice and mice receiving an FMT from either control or postcolitis donor mice. We observed no differences in the total number of EC cells, Tph1, or Slc6a4 gene expression of mice after FMT from postcolitis or control mice. However, there was a significant increase in Maoa gene expression in the terminal ileum, an increased 5-HIAA/5-HT ratio in the proximal colon, and reduced 5-HT release to mechanical and chemical stimulation in the proximal and distal colon after FMT from postcolitis mice. Collectively, these findings provide additional evidence that the gut microbiota regulates 5-HT signaling. Moreover, they reveal functional changes in EC cell sensitivity in the presence of an altered microbiota after recovery from inflammation. NEW &amp; NOTEWORTHY The gut microbiota regulates serotonin biosynthesis in enterochromaffin cells. Here, we show that a dysbiotic gut microbiota that occurs after recovery from inflammation alters serotonin signaling and produces functional changes in enterochromaffin cell sensitivity.}, }
@article {pmid41344523, year = {2026}, author = {Yang, Y and Gan, D and Liang, B and Qian, S and Yang, H and Han, C and Wang, Z}, title = {Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice.}, journal = {Journal of ethnopharmacology}, volume = {358}, number = {}, pages = {120992}, doi = {10.1016/j.jep.2025.120992}, pmid = {41344523}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology/pathology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Dextran Sulfate ; Mice ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; *Intestinal Mucosa/drug effects/metabolism/microbiology/pathology ; Mice, Inbred C57BL ; Colon/drug effects/pathology/microbiology ; }, abstract = {The Quyushengxin formula (QYSXF), a clinically validated traditional Chinese medicine (TCM) formula, has been demonstrated to be safe and effective for the treatment of ulcerative colitis (UC), but its mechanism of action in UC treatment is still unclear.<br><br>AIMS OF THE STUDY: The aim of this study was to investigate the effects of QYSXF on gut microbiota modulation in DSS-induced colitis mice and to explore its role in regulating intestinal barrier function and inflammation.<br><br>MATERIALS AND METHODS: First, the chemical constituents of QYSXF and mouse plasma were identified using high-performance liquid chromatography coupled with mass spectrometry. An active UC mouse model was established by treating the mice with 3&#xa0;% DSS. The efficacy of QYSXF was evaluated by colonoscopy, body weight, disease activity index (DAI), colon length and histological examinations. Faecal microbiota transplantation (FMT) was performed by transferring the faecal from QYSXF-treated donor mice to DSS-induced UC recipient mice. Intestinal barrier integrity and inflammation were assessed through immunofluorescence, ELISA, and western blotting. Additionally, 16S rDNA sequencing was used to elucidate the composition of the QYSXF-regulated microbiota.<br><br>RESULTS: QYSXF effectively ameliorated local ulcer surface, reduced weight loss, decreased the DAI, restored colon length, and improved histopathological scores in UC model mice. QYSXF restored the integrity of the mechanical barrier by increasing the expression of tight junction proteins and restored the integrity of the chemical barrier through increased secretion of Mucin 2 (MUC2). FMT with faecal from QYSXF-treated mice ameliorated inflammation and restored both the mechanical barrier and the chemical barrier. Moreover, both QYSXF and FMT reduced the release of proinflammatory cytokines by inhibiting the NF-&#x3ba;B signalling pathway and increasing the release of anti-inflammatory cytokines. 16S rDNA sequencing demonstrated that QYSXF modulated the composition of the gut microbiota by increasing the abundance of beneficial bacterial, specifically Dubosiella and Ligilactobacillus, while concurrently reducing the prevalence of the pathogenic Escherichia-Shigella.<br><br>CONCLUSIONS: The mechanism underlying the efficacy of QYSXF involves restoring the composition of the gut microbiota to improve intestinal barrier, reducing the release of proinflammatory cytokines, and ultimately alleviating UC. This research not only confirms the therapeutic potential of QYSXF in UC treatment but also, more importantly, highlights the critical role of gut microbiota regulation in restoring barrier dysfunction and mitigating inflammatory responses involved in the pathogenesis of UC.}, }
@article {pmid41344924, year = {2026}, author = {Raso, T and D'Arcangelo, G and Renzo, S and Strisciuglio, C and Colucci, A and Saccomani, MD and Bramuzzo, M and Bravin, F and Sansotta, N and Russo, G and Lionetti, P and Zullo, A and Oliva, S}, title = {Diagnostic accuracy of non-invasive tests for helicobacter pylori infection in children: A multicenter retrospective study by SIGENP.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {58}, number = {1}, pages = {82-87}, doi = {10.1016/j.dld.2025.11.013}, pmid = {41344924}, issn = {1878-3562}, mesh = {Humans ; *Helicobacter Infections/diagnosis ; Retrospective Studies ; Female ; Male ; *Helicobacter pylori/isolation &amp; purification ; Child ; Breath Tests ; Child, Preschool ; Sensitivity and Specificity ; Adolescent ; Italy ; *Feces/chemistry/microbiology ; *Antigens, Bacterial/analysis ; Predictive Value of Tests ; Urea/analysis ; Infant ; }, abstract = {BACKGROUND: Helicobacter pylori (H. pylori) infection remains prevalent in children, with significant clinical implications. While endoscopy with biopsy is the gold standard for diagnosis, non-invasive tests such as the stool antigen test (SAT) and urea breath test (UBT) may offer alternatives.<br><br>OBJECTIVES: To assess the diagnostic accuracy of SAT and UBT in children with suspected H. pylori infection and identify clinical predictors of infection.<br><br>METHODS: This retrospective multicenter study included pediatric patients undergoing endoscopy for suspected H. pylori across six Italian centers. Histological analysis served as the reference standard. Diagnostic metrics of SAT and UBT were calculated. Demographic and clinical factors were analyzed to identify independent predictors.<br><br>RESULTS: Of 256 patients, 150 (58.6 %) had confirmed infection. SAT showed higher sensitivity [94 % (95 % CI: 0.87-0.97)] than UBT [87 % (CI: 0.64-0.98)] but lower specificity [55 % vs 67 %], with lower PPV (64 % vs 78 %) and higher NPV (91 % vs 80 %). Independent predictors for H. pylori infection included family history [OR 4.4], positive SAT [OR 16.29], and non-Caucasian ethnicity [OR 4.3].<br><br>CONCLUSIONS: SAT demonstrates high sensitivity and NPV, supporting its role as a screening tool. In children without alarm symptoms, a negative SAT may safely exclude infection and help avoid unnecessary endoscopy.}, }
@article {pmid41344956, year = {2026}, author = {Jia, D and Wang, L}, title = {Opportunities and challenges in applying microbiota to clinical cancer immunotherapy.}, journal = {Trends in microbiology}, volume = {34}, number = {4}, pages = {367-377}, doi = {10.1016/j.tim.2025.11.011}, pmid = {41344956}, issn = {1878-4380}, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; Clinical Trials as Topic ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive '4D' framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation. It is hoped that this opinion will help researchers and clinicians aiming to harness microbiome-based strategies to improve cancer immunotherapy outcomes.}, }
@article {pmid41345102, year = {2025}, author = {Pope, R and Visconti, A and Zhang, X and Louca, P and Baleanu, AF and Lin, Y and Asnicar, F and Bermingham, K and Wong, KE and Michelotti, GA and Wolf, J and Segata, N and Berry, SE and Spector, TD and Leeming, ER and Gibson, R and Menni, C and Falchi, M}, title = {Faecal metabolites as a readout of habitual diet capture dietary interactions with the gut microbiome.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10051}, pmid = {41345102}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 27/2023//Chronic Disease Research Foundation (CDRF)/ ; }, mesh = {Humans ; *Feces/chemistry/microbiology ; *Gastrointestinal Microbiome/physiology ; *Diet ; Male ; Female ; Metabolome ; Middle Aged ; Metabolomics/methods ; Aged ; Metagenomics ; Adult ; Machine Learning ; }, abstract = {The interplay between diet and gut microbiome composition is complex. Faecal metabolites, the end products of human and microbial metabolism, provide insights into these interactions. Here, we integrate faecal metabolomics, metagenomics, and habitual dietary data from 1810 individuals from the TwinsUK and 837 from the ZOE PREDICT1 cohorts. Using machine learning models, we find that faecal metabolites accurately predict reported intakes of 20 food groups (area under the curve (AUC) > 0.80 for meat, nuts and seeds, wholegrains, tea and coffee, and alcohol) and adherence to seven dietary patterns (AUC from 0.71 for the Plant-based Diet Index to 0.83 for the Dietary Approaches to Stop Hypertension score). Notably, the faecal metabolome is a stronger predictor of atherosclerotic cardiovascular disease risk (AUC = 0.86) than the Dietary Approaches to Stop Hypertension score (AUC = 0.66). We identify 414 associations between 19 food groups and 211 metabolites, that significantly correlate with microbial α-diversity and 217 species. Our findings reveal that faecal metabolites capture mediations between diet and the gut microbiome, advancing our understanding of diet-related disease risk and informing metabolite-based interventions.}, }
@article {pmid41346294, year = {2025}, author = {Salinas-Velarde, ID and Donaciano-Domínguez, JM and Oros-Pantoja, R and Aguirre-Garrido, JF and González-Cervantes, RM and Munguía-Cervantes, JE and López, MG and Bustos-Martínez, J and Soto-Piña, AE}, title = {Narrative Review: Gut Microbiota and Its Impact on α-syn Function in Parkinson's Disease.}, journal = {MicrobiologyOpen}, volume = {14}, number = {6}, pages = {e70173}, pmid = {41346294}, issn = {2045-8827}, support = {P01 AT002024/AT/NCCIH NIH HHS/United States ; //This review was funded by the "Consorcios Proyectos de Colaboraci&#xf3;n Interinstitucional UAM-IPN -UAEMEX" (grant number 7152/2024ECON) and publication grant 34503067 (UAM-Xochimilco). Additionally, I.D.S.V. received a grant from the Consejo Mexiquense de Ciencia y Tecnolog&#xed;a (COMECYT, grant number CAT2024-0080)./ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Parkinson Disease/microbiology/therapy/metabolism ; Humans ; *alpha-Synuclein/metabolism ; Fecal Microbiota Transplantation ; Animals ; Bacteria/metabolism/classification ; }, abstract = {Gut microbiota (GM) plays a pivotal role in human health and disease, and its alterations have been implicated in various neurological disorders, including Parkinson's disease (PD). Growing evidence reveals correlations between the abundance of specific bacterial taxa and the severity of motor symptoms and intestinal dysfunction in PD. Moreover, bacterial metabolites have been shown to influence α-synuclein (α-syn) aggregation and neurodegeneration. This narrative review aims to explore the current understanding of the gut-brain axis in PD, specifically the connection between GM and α-syn function in PD experimental models and patients. Several therapeutic strategies aimed at modulating gut microbiota, such as dietary interventions, fecal microbiota transplantation, and targeted bacterial therapies with the goal of alleviating or preventing PD symptoms, are examined. Understanding the mechanisms through which GM influence neurodegeneration, including inflammation, immune modulation, and microbial metabolite production, offers promising avenues for the development of novel therapeutic strategies targeting the microbiome.}, }
@article {pmid41346377, year = {2025}, author = {Ishikawa, D and Zhang, X and Nomura, K and Nagahara, A}, title = {Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Where We Stand and What Is Next.}, journal = {Inflammatory intestinal diseases}, volume = {10}, number = {1}, pages = {371-386}, pmid = {41346377}, issn = {2296-9365}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy for inflammatory bowel disease (IBD). Every step of the FMT process, from donor recruitment and patient selection to pretreatment protocols, administration techniques, and post-FMT interventions, can significantly influence treatment outcomes. These components are interrelated, and even subtle differences in methodology may affect the overall efficacy of FMT for IBD. This review aimed to outline the current clinical experience and findings regarding FMT for IBD during the application process.<br><br>SUMMARY: Donor screening has traditionally focused on safety. In recent years, although safety remains essential, increasing attention has been paid to the donor selection efficacy. Particularly, identifying patients who are most likely to benefit from FMT is crucial because timely and appropriate patient selection can prevent delays in effective treatment. Pretreatment strategies and FMT procedures remain hot topics of current research. Approaches, such as antibiotic pretreatment, may enhance microbial engraftment; however, the optimal antibiotic combination remains unclear. Bowel lavage is commonly used to reduce the microbial burden and facilitate donor microbiota colonization, whereas corticosteroid pretreatment has shown conflicting results. There are various routes of administration, and oral capsules are gaining popularity owing to their safety and patient acceptability. Stool preparation factors, including the use of single versus pooled donors, anaerobic processing, and storage form (fresh, frozen, or freeze-dried), can significantly influence microbial viability and clinical outcomes. Repeated FMTs tend to be more effective than single infusions; nonetheless, the optimal frequency remains unclear. Post-FMT interventions, such as dietary modifications and supplementation with prebiotics, such as pectin and alginic acid, are also promising strategies.<br><br>KEY MESSAGES: Despite encouraging results, variations in treatment protocols, donor characteristics, and host factors continue to obscure the definitive predictors of FMT success. Further randomized controlled trials and mechanistic studies are required to standardize these procedures and optimize their long-term efficacy.}, }
@article {pmid41348832, year = {2025}, author = {Cervantes-Echeverría, M and Jimenez-Rico, MA and Manzo, R and Hernández-Reyna, A and Cornejo-Granados, F and Bikel, S and González, V and Hurtado Ramírez, JM and Sánchez-López, F and Salazar-León, J and Pedraza-Alva, G and Perez-Martinez, L and Ochoa-Leyva, A}, title = {Human-derived fecal virome transplantation (FVT) reshapes the murine gut microbiota and virome, enhancing glucose regulation.}, journal = {PloS one}, volume = {20}, number = {12}, pages = {e0337760}, pmid = {41348832}, issn = {1932-6203}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Fecal Microbiota Transplantation/methods ; *Virome ; Male ; Diet, High-Fat/adverse effects ; Obesity/therapy/microbiology ; *Feces/virology ; Mice, Inbred C57BL ; *Glucose/metabolism ; Metabolic Syndrome/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; }, abstract = {The gut microbiome, comprising bacteria, viruses, archaea, fungi, and protists, plays a crucial role in regulating host metabolism and health. This study explored the effects of fecal virome transplantation (FVT) from healthy human donors on metabolic syndrome (MetS) in a diet-induced obesity (DIO) mouse model, without diet change. Mice received a single oral dose of human-derived virus-like particles (VLPs) and continued on a high-fat diet (HFD) for 17 weeks. Despite persistent dietary stress, FVT significantly improved glucose tolerance. Longitudinal profiling by virome shotgun metagenomics and bacterial 16S rRNA sequencing revealed marked, durable shifts in both viral and bacterial community composition. Notable bacterial changes included a decrease in Akkermansia muciniphila and Peptococcaceae and increases in Allobaculum and Coprococcus; A. muciniphila positively correlated with glucose levels and negatively correlated with body weight. Together, these results suggests that human-derived virome can durably reshape gut microbial ecology and improve glucose metabolism in mice with obesity, even without dietary modification, offering a novel avenue for developing phage-based therapies. This proof-of-concept study provides foundational observations for using human-derived VLPs for FVT in standard laboratory mouse models, and provides a foundation for elucidating bacteria-phage interactions and their role in host metabolic health.}, }
@article {pmid41349548, year = {2026}, author = {Zarour, HM and Trinchieri, G}, title = {Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.}, journal = {Annual review of immunology}, volume = {44}, number = {1}, pages = {41-70}, pmid = {41349548}, issn = {1545-3278}, support = {P50 CA254865/CA/NCI NIH HHS/United States ; R01 CA257265/CA/NCI NIH HHS/United States ; R01 CA222203/CA/NCI NIH HHS/United States ; ZIA BC010793/ImNIH/Intramural NIH HHS/United States ; ZIA BC011152/ImNIH/Intramural NIH HHS/United States ; U01 CA268806/CA/NCI NIH HHS/United States ; ZIA BC011153/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology/etiology ; *Immunotherapy/methods ; *Microbiota/immunology ; Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {Humans are metaorganisms, composed of both host (human) cells and a roughly equal number of commensal microorganisms-collectively known as the microbiome-residing primarily at epithelial barrier surfaces. This review considers human cancer as a disease of the metaorganism, to which the microbiome contributes by influencing genome stability, tissue organization, inflammation, immunity, tumor initiation and promotion, metastasis formation, and therapeutic response. We summarize evidence demonstrating that machine learning models trained on patients' microbiome features moderately predict clinical response to immunotherapy and the development of immune-related adverse events. We review results from single-arm and randomized clinical trials wherein fecal microbiome transplantation from therapy-responsive patients or healthy donors, when combined with therapy targeting programmed cell death 1 (PD-1), improved outcomes in PD-1-refractory patients or served as an effective first-line intervention. We conclude by highlighting the emerging opportunities and ongoing challenges in leveraging the microbiome to enhance the efficacy and safety of cancer immunotherapy.}, }
@article {pmid41350095, year = {2025}, author = {Deleu, S and Sabino, J}, title = {Cutting edge developments and novel targets in IBD: Microbiome in IBD.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {78}, number = {}, pages = {102060}, doi = {10.1016/j.bpg.2025.102060}, pmid = {41350095}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Inflammatory Bowel Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; *Crohn Disease/microbiology/therapy ; *Colitis, Ulcerative/microbiology/therapy ; Synbiotics/administration &amp; dosage ; }, abstract = {Inflammatory bowel disease (IBD), a non-communicable disease encompassing Crohn's disease and ulcerative colitis, is a chronic disorder with increasing prevalence and complex etiology. Emerging evidence highlights the gut microbiome's pivotal role in IBD pathogenesis, driving interest in microbiome-targeted therapeutic strategies. This narrative review explores the latest advancements in microbiome modulation for IBD management, encompassing antibiotics, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Additionally, dietary interventions, physical activity, as well as non-bacterial microbiota components such as fungi, archaea, and bacteriophages are examined for their potential roles in restoring microbial equilibrium and mitigating intestinal inflammation. As research progresses, a multimodal approach integrating microbiota-targeted therapies with lifestyle modifications and conventional pharmacologic treatments may offer a personalized and effective strategy for IBD management.}, }
@article {pmid41351413, year = {2025}, author = {Xu, Y and Tao, Y and Pan, H and Wang, Z and Wang, H and Luo, Q}, title = {Microbiome Modulation in Lung Cancer Immunotherapy: Unveiling the Role of Respiratory and Gut Microbiota in the PD-1/PD-L1 Response.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {11}, pages = {41531}, doi = {10.31083/FBL41531}, pmid = {41351413}, issn = {2768-6698}, support = {24ZR1464400//Shanghai Municipal Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lung Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; *B7-H1 Antigen/antagonists &amp; inhibitors/immunology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Dysbiosis/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Lung cancer, the leading cause of cancer-related mortality worldwide, poses considerable therapeutic challenges due to the varied responses to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Emerging highlight the pivotal role of host-microbiome interactions in modulating antitumor immunity and influencing clinical outcomes. This review examines how the respiratory and gut microbiota contribute to the immunosuppressive tumor microenvironment through dysbiosis-induced T-cell exhaustion and regulatory cell activation, while certain commensals facilitate dendritic cell-mediated recruitment of cytotoxic T lymphocytes. Additionally, this review explores the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids, influence myeloid-derived suppressor cells. Therapeutically, microbiota-modulation strategies-such as tailored probiotic formulations and precision fecal microbiota transplantation-offer potential to enhance immunotherapy efficacy. This review provides a foundation for microbiome-guided immunotherapy, advocating for biomarker-driven patient stratification and the use of engineered microbial consortia to counteract therapeutic resistance. These findings pave the way for the integration of microbiome science into next-generation precision oncology.}, }
@article {pmid41351660, year = {2025}, author = {A, AP and Daksh, R and Dinil, A and B, AC and Nampoothiri, M and Nampoothiri, KM}, title = {Investigations on the Prospects of Using Lactiplantibacillus plantarum to Combat Depression through Gut Microbiota-Brain Axis.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {259}, pmid = {41351660}, issn = {1559-1182}, support = {DBT/2021-22/NIIST/1743//DBT/ ; IF230068//INSPIRE, New Delhi/ ; }, mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; Humans ; *Depression/therapy/microbiology ; *Brain/metabolism ; *Probiotics/therapeutic use/pharmacology ; Animals ; *Lactiplantibacillus plantarum ; }, abstract = {Depression is a common neurological disorder that causes a substantial burden of disease due to higher mortality and prevalence rates. The gut microbiota plays a major role in mood regulation and offers novel insights into the etiology and management of depression. However, gut dysbiosis has a negative impact on mood, cognition, behavior, and brain development. Therefore, approaches to restore the normal gut composition, such as probiotics, prebiotics, and fecal microbiota transplant, may offer novel tactics to improve therapy for depression, among which probiotics have drawn significant attention as a therapeutic intervention. Although there is no consensus on the most effective probiotic strain for treating depression, Lactiplantibacillus plantarum (L. plantarum) has gained considerable prominence due to its therapeutic potential in managing depression. The mechanisms by which L. plantarum regulates depression involve modulating the gut-brain axis through the production of various compounds, including gamma-aminobutyric acid (GABA), tryptophan, lactate, short-chain fatty acids (SCFAs), acetylcholine, and vitamins. This review highlights the antidepressant potential of L. plantarum through modulation of the gut microbiota and explores the possible mechanism of action of L. plantarum and its metabolites, as well as the genetic and epigenetic regulation of host responses and potential microRNA interactions that modulate the gut microbiota. Furthermore, metabolic engineering techniques for the L. plantarum strain, as well as promising strategies for delivering L. plantarum to the brain, have been discussed. A deeper insight into the mechanisms and gut microbiota interventions may provide effective treatment approaches for depression.}, }
@article {pmid41351979, year = {2026}, author = {Yang, Q and Huo, J and Peng, R and Qiu, S and Li, P and Wei, W and Zhou, J and Tang, Q and Wang, W}, title = {Glycitein in Zhi-Zi-Chi decoction alleviates anxiety via inosine enrichment mediated by Akkermansia muciniphila to regulate MT3-Sema7a interaction.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157622}, doi = {10.1016/j.phymed.2025.157622}, pmid = {41351979}, issn = {1618-095X}, mesh = {Animals ; *Anxiety/drug therapy ; Male ; Gastrointestinal Microbiome/drug effects ; *Anti-Anxiety Agents/pharmacology ; *Drugs, Chinese Herbal/pharmacology/chemistry ; Mice ; *Akkermansia ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Zhi-Zi-Chi Decoction (ZZCD) is used for treating emotional disturbances and insomnia. Its potential anti-anxiety efficacy has been proposed, yet the bioactive constituents and underlying mechanisms remain poorly defined.<br><br>OBJECTIVE: This study aimed to investigate the anxiolytic effects of ZZCD, identify its active components, and elucidate the mechanisms involved, with particular emphasis on the gut-microbiota-brain axis.<br><br>METHODS: The anxiety model was established using the chronic restraint stress (CRS) method. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) were employed to investigate the role of gut microbiota in the development and treatment of anxiety. N500-targeted metabolomics and RT-qPCR identified key microbial taxa and their functionally relevant metabolites. Key bioactive components of ZZCD were screened through in vitro bacterial co-culture and confirmed by in vivo pharmacological experiments. Molecular mechanisms were further explored via transcriptomics, western blotting, and co-immunoprecipitation.<br><br>RESULTS: ZZCD alleviated CRS-induced anxiety behaviors, restored brain neurotransmitter homeostasis, and reduced pro-inflammatory cytokine expression. Mechanistically, its anxiolytic effect was associated with Akkermansia muciniphila (A. muciniphila). A. muciniphila supplementation improved anxiety symptoms and promoted neurotransmitter balance. Targeted metabolomics identified inosine as a key microbial metabolite. Inosine enhanced neuronal activity, restored intestinal barrier integrity, and suppressed hippocampal NLRP3/Caspase-1/IL-18 signaling. Further, -a major isoflavone in ZZCD-was confirmed as a key anxiolytic compound, acting by promoting inosine production from A. muciniphila and regulating Metallothionein3-Sema7a protein interaction in the hippocampus.<br><br>CONCLUSION: Glycitein in ZZCD exerts anxiolytic effects by facilitating A. muciniphila -derived inosine production and modulating hippocampal MT3-Sema7a signaling, highlighting a novel microbiota-mediated therapeutic strategy for anxiety.}, }
@article {pmid41352125, year = {2026}, author = {Taki, AG and Shareef, A and Arora, V and Oweis, R and Jyothi, SR and Singh, U and Sahoo, S and Chauhan, AS and Alimova, F and Sameer, HN and Yaseen, A and Athab, ZH and Adil, M}, title = {Unraveling the microbiome's role in breast cancer progression and treatment response.}, journal = {Current problems in cancer}, volume = {60}, number = {}, pages = {101264}, doi = {10.1016/j.currproblcancer.2025.101264}, pmid = {41352125}, issn = {1535-6345}, mesh = {Humans ; *Breast Neoplasms/microbiology/pathology/therapy ; Female ; Disease Progression ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Tumor Microenvironment ; *Microbiota ; }, abstract = {The human microbiome, encompassing microbial communities in the gut and breast tissue, has emerged as a critical modulator of breast cancer (BC) initiation, progression, and treatment response. This review synthesizes current evidence on the microbiome's role in BC, highlighting its influence on tumorigenesis, tumor microenvironment (TME), and therapeutic outcomes. Breast cancer, the most prevalent malignancy among women globally, exhibits significant heterogeneity across its molecular subtype's hormone receptor-positive, HER2-enriched, and triple-negative-each with distinct clinical challenges. Recent studies reveal that microbial dysbiosis in the gut and breast tissue can drive oncogenesis through mechanisms such as immune modulation, estrogen metabolism, and inflammation. Gut microbes, via the "estrobolome," regulate circulating estrogen levels, impacting hormone-driven BC, while breast tissue microbiota contributes to local inflammation and DNA damage, promoting tumor progression. Specific microbial taxa, including Bacillus, Staphylococcus, and Escherichia coli, are enriched in BC patients, whereas beneficial species like Lactobacillus and Bifidobacterium are diminished. The microbiome also influences treatment efficacy, with gut microbial diversity linked to enhanced chemotherapy and immunotherapy responses, while antibiotic-induced dysbiosis may impair outcomes. Emerging research suggests microbiome signatures as potential biomarkers for predicting therapeutic success, with Akkermansia muciniphila and short-chain fatty acids showing promise in enhancing anti-tumor immunity. Probiotics, prebiotics, and fecal microbiota transplantation offerel therapeutic avenues, though challenges such as standardization, interindividual variability, and safety concerns remain. Integrating multi-omics and machine learning could elucidate microbiome-host interactions, paving the way for precision oncology. This review underscores the transformative potential of microbiome-based diagnostics and interventions in improving BC management, emphasizing the need for large-scale, longitudinal studies to validate these findings and address existing research gaps.}, }
@article {pmid41352744, year = {2026}, author = {Wei, D and Sun, Y and Han, J and Liu, J}, title = {Microbiota and cancer immunotherapy: Mechanisms, clinical implications, and precision therapeutics.}, journal = {Seminars in cancer biology}, volume = {118}, number = {}, pages = {62-73}, doi = {10.1016/j.semcancer.2025.12.002}, pmid = {41352744}, issn = {1096-3650}, mesh = {Humans ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods/adverse effects ; *Precision Medicine/methods ; *Microbiota/immunology ; Animals ; Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/immunology ; Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; Dysbiosis/immunology ; }, abstract = {The microbiota has emerged as a pivotal modulator of cancer immunotherapy, offering novel insights into the efficacy and toxicity of immune checkpoint inhibitors (ICIs). Recent evidence highlights that microbial communities and their metabolites dynamically regulate host immunity by priming dendritic cells, enhancing T-cell infiltration, and reprogramming the tumor microenvironment. Microbiome dysbiosis is implicated in immune-related adverse events (irAEs), underscoring its dual role in therapeutic outcomes. Leveraging these findings, precision microbiome interventions, including fecal microbiota transplantation, engineered probiotics, and dietary modulation, which demonstrate potential to enhance ICIs responsiveness and mitigate irAEs in preclinical and early-phase clinical studies. However, translating these strategies into clinical practice requires rigorous validation through multicenter trials to establish safety, efficacy, and standardized protocols. This review synthesizes current knowledge on the microbiome-immune-oncology axis, with a focus on mechanistic underpinnings, translational challenges, and innovative therapeutic strategies. By integrating microbiome profiling with patient-specific factors, proposing a roadmap for personalized immunotherapy, aligning with the emerging paradigm of precision oncology.}, }
@article {pmid41355913, year = {2025}, author = {Roganovic, J and Radosevic, M and Dordevic, A}, title = {Role of the gut microbiome in the development and prognosis of pediatric leukemia.}, journal = {World journal of clinical oncology}, volume = {16}, number = {11}, pages = {111419}, pmid = {41355913}, issn = {2218-4333}, abstract = {The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation, both of which are critically involved in the pathogenesis and progression of pediatric leukemias. Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis, marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus. This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation. Chemotherapy significantly alters the gut microbiome, inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts. Specific microbial signatures, such as the enrichment of Bacteroides, correlate with reduced inflammation and improved prognosis, underscoring the gut microbiome's prognostic value. Emerging therapies, including dietary adjustments, probiotics, and fecal gut microbiome transplantation, aim to restore microbial balance and reduce treatment-related complications. Moreover, gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition, paving the way for early diagnosis and tailored preventive strategies. This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias, emphasizing its role as both a therapeutic target and a prognostic biomarker. Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.}, }
@article {pmid41356485, year = {2025}, author = {Bai, B and Ma, J and Xu, W and Chen, X and Chen, X and Lv, C and Su, W and Li, Y and Sun, H and Zhang, B and Xiang, D and Li, Z and Wu, Y and Sun, J and Yin, M}, title = {Gut microbiota and colorectal cancer: mechanistic insights, diagnostic advances, and microbiome-based therapeutic strategies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699893}, pmid = {41356485}, issn = {1664-302X}, abstract = {Colorectal cancer (CRC) is closely linked to gut microbiota dysbiosis. We synthesize evidence that carcinogenic microbes promote CRC through chronic inflammation, bacterial genotoxins, and metabolic imbalance, highlighting key pathways involving Fusobacterium nucleatum, pks [+] Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF). Building on these mechanisms, we propose a minimal diagnostic signature that integrates multi-omics with targeted qPCR, and a pathway-therapy-microbiome matching framework to guide individualized treatment. Probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy show promise as adjunctive strategies; however, standardization, safety monitoring, and regulatory readiness remain central hurdles. We advocate a three-step path to clinical implementation-stratified diagnosis, therapy matching, and longitudinal monitoring-supported by spatial multi-omics and AI-driven analytics. This approach aims to operationalize microbiome biology into deployable tools for risk stratification, treatment selection, and surveillance, advancing toward microbiome-informed precision oncology in CRC.}, }
@article {pmid41356558, year = {2025}, author = {Wang, H and Yang, F and Gao, Z and Cheng, Z and Liang, X}, title = {The gut-brain axis in Alzheimer's disease: how gut microbiota modulate microglial function.}, journal = {Frontiers in aging}, volume = {6}, number = {}, pages = {1704047}, pmid = {41356558}, issn = {2673-6217}, abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder that can be caused by multiple factors, such as abnormal amyloid-beta (Aβ) deposition, pathological changes in Tau protein, lipid metabolism disorders, and oxidative stress. Recent studies have revealed the potential link between gut microbiota and AD, particularly the impact of gut microbiota and its derivatives on microglia. As immune cells in the central nervous system (CNS), microglia are involved in neuroinflammation and the regulation of cognitive function. Research indicates that the dysregulation of gut microbiota may affect the phenotype and function of microglia through various mechanisms, including direct metabolite action and indirect immune and neurotransmitter regulation. This article reviews the direct and indirect effects of gut microbiota and its derivatives on microglia, explores their role in the pathogenesis of AD, and discusses therapeutic strategies based on gut microbiota, such as dietary regulation, probiotics, fecal microbiota transplantation, and traditional Chinese medicine. Although existing studies have shown the potential of these interventions, further research is needed to completely understand their application in the treatment of AD.}, }
@article {pmid41357831, year = {2025}, author = {Xiao, J and Xia, J and Chen, Z and Zha, W and Xu, T and Chen, X and Yin, X}, title = {Gut microbiota dysbiosis drives stroke-associated pneumonia: mechanisms and targeted therapeutic strategies.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1677744}, pmid = {41357831}, issn = {1662-4548}, abstract = {The gut microbiota has been increasingly recognized as a central regulator of immune function, with growing research highlighting its association with the development of stroke-associated pneumonia (SAP). This review provides an overview of current research on the correlation between SAP and alterations in gut microbial composition and metabolism, with a focus on microbial imbalance, changes in key metabolites, and relevant biological mechanisms. Clinical and preclinical studies consistently report a decline in short-chain fatty acids (SCFAs)-producing bacteria, an increase in potentially harmful microbial species, reduced SCFAs levels, and elevated lipopolysaccharide (LPS) concentrations. These disturbances appear to be associated with SAP progression through the microbiota-gut-brain and microbiota-gut-lung axes by affecting immune regulation and inflammatory responses. The review also examines microbiota-targeted treatment approaches, including dietary modification, antibiotic therapy, probiotics, microbiota-regulating compounds, fecal microbiota transplantation (FMT), and respiratory microbiota transfer. A deeper understanding of how microbial disturbances are correlated with SAP may help explain the increased vulnerability to pulmonary infections following stroke and support the design of more effective, microbiota-based therapeutic strategies.}, }
@article {pmid41357887, year = {2025}, author = {Peng, Q and Hao, L and Li, S and Yu, F and Li, N and Hu, X}, title = {A critical review of natural products driven correction of bile acid dysregulation: a therapeutic strategy for nonalcoholic fatty liver disease.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1640873}, pmid = {41357887}, issn = {1663-9812}, abstract = {Nonalcoholic fatty liver disease (NAFLD) represents a significant global health challenge. While two drugs (semaglutide, resmetirom) have recently been approved for nonalcoholic steatohepatitis (NASH), their clinical utility is constrained by gastrointestinal side effects, insufficient efficacy against fibrosis, and dose-related adverse events. Similarly, obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with antifibrotic potential, is associated with significant side effects, including severe pruritus. Dysregulation of bile acid (BA) metabolism is a central driver of NAFLD progression, characterized by imbalances in synthesis, impaired enterohepatic circulation, and aberrant nuclear receptor signaling. Certain hydrophobic BAs contribute to hepatocyte apoptosis, oxidative stress, and inflammation, thereby exacerbating liver injury. Targeting BA homeostasis is thus a promising therapeutic strategy, with natural products emerging as attractive candidates due to their multi-target actions and favorable safety profiles. This review summarizes 10 major classes of natural products, including traditional Chinese medicine (TCM) formulas, flavonoids, saccharides, saponins, alkaloids, curcuminoids, lignans, iridoid glycosides, sterols/terpenoids, and phenolic acids/other phenolics, that alleviate NAFLD by regulating BA metabolism. These agents modulate BA-sensing receptors, reshape the gut microbiota to optimize BA conversion, and regulate key BA transporters and enzymes. Compared with synthetic drugs, natural products offer broader efficacy, lower toxicity, and greater adaptability to the heterogeneity of NAFLD. However, significant limitations persist. Preclinical studies rely heavily on single-sex rodent models, while clinical evidence remains inconsistent. Crucially, mechanistic causality, such as the interplay between the gut microbiota and BAs, lacks rigorous validation through methods like fecal microbiota transplantation (FMT) or gene knockout studies. Furthermore, challenges in metabolite standardization and dose rationality hinder clinical translation. Future research must prioritize human-relevant models, large-scale randomized controlled trials (RCTs) with histological endpoints, and robust causal validation. By addressing these gaps, natural products targeting BA metabolism hold great promise to complement or replace existing therapies, offering safer and more effective personalized treatments for NAFLD.}, }
@article {pmid41358173, year = {2025}, author = {Othman, AAA}, title = {From rescue to recovery: Reframing severe alcoholic hepatitis management through 90-day survival.}, journal = {World journal of gastroenterology}, volume = {31}, number = {43}, pages = {113141}, pmid = {41358173}, issn = {2219-2840}, mesh = {Humans ; Adrenal Cortex Hormones/therapeutic use ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; *Hepatitis, Alcoholic/mortality/therapy/diagnosis ; Randomized Controlled Trials as Topic ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; Systematic Reviews as Topic ; }, abstract = {Severe alcoholic hepatitis remains one of hepatology's most urgent challenges, with rapid clinical deterioration and high early mortality. This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al, which redirects attention from short-term endpoints toward 90-day survival, integrating evidence from associated clinical studies. For decades, corticosteroids have been the mainstay of treatment, reducing 28-day mortality but offering limited benefit for three months. The review emphasizes that the most critical threats to recovery, late infections, renal decline, and relapse, often emerge after the first month. By synthesizing recent studies, it highlights promising interventions such as fecal microbiota transplantation (FMT), which improved 90-day survival in a small randomized trial, and granulocyte colony-stimulating factor (G-CSF), which showed a robust survival benefit in a large retrospective cohort, alongside emerging strategies like plasma exchange and targeted biologics. These findings support a shift toward a two-phase care model: Early stabilization followed by recovery consolidation. For clinicians, such a model may help guide treatment decisions, with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders, pending further validation in larger randomized controlled trials. Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission, providing a more realistic measure of therapeutic success in one of hepatology's most unforgiving conditions.}, }
@article {pmid41361135, year = {2025}, author = {Konturek, PC and Ghopreal, T and Dieterich, W and Zopf, Y}, title = {[Gut-lung axis from a gastroenterological perspective].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {Suppl 6}, pages = {22-26}, doi = {10.1007/s15006-025-5477-3}, pmid = {41361135}, issn = {1613-3560}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Dysbiosis/immunology/therapy ; *Lung/microbiology/immunology ; Fecal Microbiota Transplantation ; *Lung Diseases/microbiology/immunology ; Lung Neoplasms/immunology ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: The microbiome is unique to each individual. It plays a key role in numerous physiological processes in the body. Intestinal dysbiosis is associated with various diseases.<br><br>METHOD: This work provides an overview of the current state of knowledge regarding the role of microbiota in the lungs and the gut-lung axis.<br><br>RESULTS AND CONCLUSIONS: Numerous studies have demonstrated a link between respiratory diseases and an altered lung microbiome. Dysbiosis of the gut microbiota influences the lung's immune response via gut-lung axis. Changes in the lung microbiome due to various environmental factors, such as smoking, particulate matter, or air pollution, contribute to lung cancer development. The composition of the gut microbiome influences the response to therapy with immune checkpoint inhibitors. Modulation of the gut microbiota through fecal microbiota transplantation (FMT), diet, prebiotics, probiotics, and synbiotics can positively influence the response to immunotherapy.}, }
@article {pmid41361755, year = {2025}, author = {Dong, R and Meng, X and Hu, H and Pan, J and Wang, W}, title = {Integrating gut microbiota and metabolomics in pediatric inflammatory bowel disease: insights into pathogenesis and potential role of precision medicine.}, journal = {European journal of medical research}, volume = {31}, number = {1}, pages = {63}, pmid = {41361755}, issn = {2047-783X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Precision Medicine/methods ; *Metabolomics/methods ; Child ; *Inflammatory Bowel Diseases/therapy/microbiology/metabolism ; Dysbiosis ; Probiotics/therapeutic use ; }, abstract = {Pediatric inflammatory bowel disease (IBD) is a chronic and relapsing disorder with rising global incidence. Gut microbiota dysbiosis and metabolic alterations have been implicated in disease pathogenesis, yet their precise roles in pediatric IBD remain incompletely understood. This review synthesizes current evidence on the interplay between the gut microbiota and metabolomics in pediatric IBD, highlighting their contributions to disease onset, progression, and therapeutic response. We examine changes in microbial composition, alterations in short-chain fatty acid, bile acid, and amino acid metabolism, and their effects on intestinal immunity and barrier function. In addition, we discuss microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, along with the potential of metabolomic profiles for diagnostic and prognostic use. Finally, we emphasize integrating multi-omics approaches to uncover novel therapeutic targets and advance precision medicine strategies in pediatric IBD. A deeper understanding of microbiota-metabolite interactions may pave the way for personalized interventions to improve clinical outcomes in pediatric patients with IBD.}, }
@article {pmid41361827, year = {2025}, author = {Tao, M and Wu, T and Li, S and Tan, Y and Zhou, X and Chen, Y and Huang, L and Wang, W and Li, S and Wang, L and Luo, Z and Wang, Y and Ling, K and Liang, Z}, title = {Intratumoral Collinsella aerofaciens exhibits antitumor activity in endometrial carcinoma through activation of the p53 signaling pathway.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {54}, pmid = {41361827}, issn = {1479-5876}, support = {2019YFC1005202//National Key Research and Development Program of China/ ; }, mesh = {Female ; Humans ; *Signal Transduction ; *Tumor Suppressor Protein p53/metabolism ; *Endometrial Neoplasms/microbiology/pathology/metabolism/therapy ; Animals ; Cell Line, Tumor ; Mice ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Microbiota ; In Situ Hybridization, Fluorescence ; }, abstract = {BACKGROUND: The intratumoral microbiota plays dual roles in cancer progression and suppression, but its composition and functional mechanisms in endometrial carcinoma (EC) remain incompletely defined. This study aimed to characterize the EC intratumoral microbiome, elucidate microbial spatial localization, and identify bacteria with tumor-suppressive properties.<br><br>METHODS: Tumor and adjacent normal tissues from patients with EC were analyzed using 5R 16S rRNA sequencing to profile microbial communities, with fluorescence in situ hybridization (FISH) validating bacterial localization. Spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), and FISH were integrated to map microbiota-niche cell interactions. RNA sequencing was performed on EC cells treated with bacterial supernatant. Fecal microbiota transplantation (FMT) from EC patients to mice was used to assess gut-tumor microbial crosstalk.<br><br>RESULTS: Collinsella aerofaciens (C. aerofaciens), Haloamaerobium gallinarum, and Massilia oculi were enriched in adjacent normal tissues, while Bacteroides vulgatus (B. vulgatus) and Delfia tsuruhatensis dominated tumor tissues. Tumors exhibited reduced microbial richness versus normal tissues. C. aerofaciens localized predominantly to smooth muscle cells and modulated the tumor microenvironment, as revealed by FISH and ST-scRNA-seq integration. RNA sequencing suggested that C. aerofaciens suppressed EC progression by activating the p53 signaling pathway. FMT experiments demonstrated gut microbiota-driven remodeling of the tumor microbiome.<br><br>CONCLUSIONS: This study identifies C. aerofaciens as a novel tumor-suppressive bacterium in EC, with mechanistic evidence linking its activity to p53 pathway activation. Gut microbiota modulates intratumoral microbial composition, suggesting potential dual-target therapeutic strategies for EC.}, }
@article {pmid41367416, year = {2025}, author = {Liu, SH and Yang, XF and Liang, L and Song, BB and Song, XM and Yang, YJ and Alhoot, MA}, title = {Regulatory mechanisms of the gut microbiota-short chain fatty acids signaling axis in slow transit constipation and progress in multi-target interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1689597}, pmid = {41367416}, issn = {1664-302X}, abstract = {Slow-transit constipation (STC) is an increasingly prevalent disorder that imposes a substantial health and economic burden. Mounting evidence highlights the "gut microbiota-short-chain fatty acid (SCFA)-motility" axis as a central pathophysiological link between dysbiosis and impaired colonic transit. This review synthesizes current knowledge of how SCFAs, especially acetate, propionate and butyrate, shape motility through serotonergic signaling, enteric nervous system modulation, epithelial barrier integrity and immune regulation. Particular attention is devoted to the biased-signaling properties of the SCFA receptors FFAR2 and FFAR3 (free fatty acid receptors 2 and 3, respectively), including emerging data on their heterodimerization. The article then appraises recent randomized controlled trials and meta-analyses of multi-target interventions (dietary fibers, synbiotics, postbiotics, fecal microbiota transplantation, phytochemicals, and small-molecule FFAR agonists) highlighting their efficacy, safety, and translational hurdles. Finally, the authors propose a precision-medicine framework that integrates multi-omics microbiome profiling, metabolomics, and host genetics to enable phenotype-stratified therapy. Key research gaps include limited long-term safety data, heterogeneous human cohorts and the need for large multicenter trials and machine-learning-guided responder prediction. Collectively, the review provides a roadmap for shifting STC management from symptom control to mechanism-based, personalized care.}, }
@article {pmid41368309, year = {2025}, author = {Liu, L and Yang, L and Zhang, H and Li, H and Shang, T and Liu, L}, title = {Lung cancer and the Gut-microbiota-lung Axis: emerging evidence and potential clinical implications.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1655780}, pmid = {41368309}, issn = {2296-858X}, abstract = {Lung cancer remains the leading cause of cancer-related deaths globally, with a 5-years survival rate of only around 20%. Merging cohort and Mendelian-randomization studies indicate that gut dysbiosis is associated with-though not yet proven to cause-an elevated risk and worse prognosis of non-small-cell lung cancer. Lower fecal abundance of butyrate producers such as Faecalibacterium prausnitzii and expansion of Enterobacteriaceae correlate with reduced systemic CD8 + T-cell infiltration and shorter progression-free survival during immune-checkpoint blockade. Antibiotic exposure within 30 days before anti-PD-1 initiation is consistently linked to diminished objective response and overall survival in retrospective cohorts, whereas supplementation with butyrogenic probiotics or fecal microbiota transplantation from responders restores therapeutic efficacy in pre-clinical models. This review integrates epidemiological, mechanistic and clinical data to clarify the current evidence, identify gaps and outline the steps needed to translate gut-lung-axis research into safe, effective adjunctive therapies for patients with lung cancer.}, }
@article {pmid41368634, year = {2025}, author = {Shen, X and Li, Y and Wang, D and Sun, K}, title = {The gut microbiota and its metabolites: novel therapeutic targets for inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1690279}, pmid = {41368634}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/therapy/microbiology/metabolism/immunology ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; Fatty Acids, Volatile/metabolism ; Tryptophan/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) pathogenesis is critically influenced by gut microbiota dysbiosis and perturbations in associated metabolites. This review outlines current IBD diagnostic and therapeutic paradigms, highlighting the persistent focus on the management of inflammatory symptoms and the absence of curative interventions. We elucidate the mechanistic links between gut microbiota dysregulation and IBD progression, with an emphasis on the immunomodulatory functions of microbial metabolites-specifically short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) metabolism-in maintaining intestinal barrier integrity and attenuating inflammation. Furthermore, we evaluate microbiota-targeted therapeutic strategies, including probiotics, fecal microbiota transplantation (FMT), and metabolite-based interventions, as novel approaches for IBD management. This synthesis aims to inform future therapeutic development and accelerate the clinical translation of microbiota-modulating regimens.}, }
@article {pmid41368686, year = {2025}, author = {Wu, J and Zheng, W and Ding, X and Jin, Q and Ding, M}, title = {Obesity-induced gut microbiota transplantation promotes the occurrence and development of hepatocellular carcinoma.}, journal = {Future science OA}, volume = {11}, number = {1}, pages = {2599729}, pmid = {41368686}, issn = {2056-5623}, abstract = {OBJECTIVE: Obesity is a recognized risk factor for hepatocellular carcinoma (HCC), yet the causal role of obesity-remodeled gut microbiota remains poorly defined. This study aims to investigate the direct impact of obesity-related gut microbiota on the development of hepatocellular carcinoma.<br><br>METHODS: C57BL/6J mice were fed a high-fat diet (HFD) to establish obesity. Fecal microbiota from HFD or normal-chow diet (NCD) mice was transplanted into DEN-initiated recipients. Tumor burden was assessed by incidence, multiplicity, and size. Histomorphology and biochemical methods were employed to assess liver injury, inflammation, fibrosis, lipid metabolism, and the potential signaling pathways involved in these events.<br><br>RESULTS: The gut microbiota of obese mice significantly promoted the incidence of HCC, and increased tumor number, and size spectrum. Specifically, obesity-related gut microbiota significantly aggravated hepatocarcinogenesis (increasing GPC3, GP73, AFP, and N-cadherin, and decreasing E-cadherin), pro-inflammatory cytokine surge (increasing IL-6, IL-1&#x3b2;, IL-17, and TNF-&#x3b1;), and fibrotic activation (increasing &#x3b1;-SMA, TGF-&#x3b2;, and Col1a1) were observed. Mechanistically, obesity-FMT dysregulated lipid metabolism (increasing free fatty acids, total cholesterol, and triglycerides) and activated TLR4-NF-&#x3ba;B and mTOR pathways.<br><br>CONCLUSION: Our findings suggest that gut microbiota from obese donors directly promotes HCC progression via TLR4-NF-&#x3ba;B/mTOR-driven inflammation, fibrosis, and metabolic dysregulation, offering novel targets for microbiota-based interventions in obesity-associated liver cancer.}, }
@article {pmid41369516, year = {2026}, author = {Yang, J and Yu, J and Chen, Y and Xu, A and Yang, C and Li, J and Wu, F and Li, X and Bi, J and Xiang, B and Jiang, K}, title = {Hyperoside, a dietary flavonoid, protects against endometritis via gut microbiota-dependent production of hydroxyphenyllactic acid and the gut-uterus axis.}, journal = {Food &amp; function}, volume = {17}, number = {1}, pages = {408-425}, doi = {10.1039/d5fo04275e}, pmid = {41369516}, issn = {2042-650X}, mesh = {Female ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Endometritis/microbiology/prevention &amp; control/drug therapy/metabolism ; *Quercetin/analogs &amp; derivatives/pharmacology/administration &amp; dosage ; *Uterus/metabolism/drug effects ; Escherichia coli ; Mice, Inbred C57BL ; Escherichia coli Infections ; }, abstract = {Endometritis, primarily caused by Escherichia coli (E. coli) infection, poses significant therapeutic challenges due to rising antibiotic resistance. The associated pro-inflammatory cytokines cause persistent endometrial damage, thereby leading to infertility, pregnancy loss, and other gynecological complications, which impose substantial long-term medical and socioeconomic burdens. Hyperoside, a flavonol glycoside abundant in various common fruits (e.g., hawthorn) and vegetables, exhibits significant anti-inflammatory activity, highlighting its potential as a functional food or nutraceutical. Our present study firstly demonstrated that hyperoside could alleviate E. coli-induced endometritis in mice through a gut-uterus axis mechanism. Specifically, hyperoside remodeled the gut microbiota by enriching beneficial genera, such as Lactobacillus and Prevotella, which subsequently elevated the production of the metabolite hydroxyphenyllactic acid (HPLA). Crucially, antibiotic treatment and fecal microbiota transplantation (FMT) experiments further confirmed that gut microbiota restructuring was essential for the anti-endometritic effect of hyperoside. Mechanistically, HPLA enters systemic circulation and targets uterine tissue, where it is directly bound to TLR4 to suppress the activation of the TLR4/NF-κB pathway and then the release of inflammatory cytokines. The present study provides the first systematic evidence of the gut-uterus axis, establishing microbiota-derived HPLA as a key effector against E. coli-induced endometritis, offering a novel nutritional intervention strategy for inflammatory reproductive disorders.}, }
@article {pmid41370004, year = {2026}, author = {Syed, S and Moayyedi, P and Kao, D and Patel, J and Marshall, JK and Surette, M and Narula, N}, title = {Combination Therapy With Fecal Microbiota Transplantation and Vedolizumab for Induction of Remission in Ulcerative Colitis: An Open-Label Pilot Study.}, journal = {Inflammatory bowel diseases}, volume = {32}, number = {2}, pages = {394-398}, pmid = {41370004}, issn = {1536-4844}, support = {//Takeda Canada/ ; }, }
@article {pmid41370178, year = {2025}, author = {Peto, L and Fawcett, N and Kamfose, MM and Scarborough, C and Peniket, A and Danby, R and Peto, TEA and Crook, DW and Llewelyn, MJ and Walker, AS}, title = {The impact of different antimicrobial exposures on the gut microbiome in the ARMORD observational study.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {41370178}, issn = {2050-084X}, support = {NIHR200915//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; Adult ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Anti-Bacterial Agents/pharmacology ; *Anti-Infective Agents/pharmacology ; Feces/microbiology ; Metagenomics ; United Kingdom ; *Bacteria/drug effects/classification/genetics ; Young Adult ; }, abstract = {Better metrics to compare the impact of different antimicrobials on the gut microbiome would aid efforts to control antimicrobial resistance (AMR). The Antibiotic Resistance in the Microbiome - Oxford (ARMORD) study recruited inpatients, outpatients, and healthy volunteers in Oxfordshire, UK, who provided stool samples for metagenomic sequencing. Data on previous antimicrobial use and potential confounders were recorded. Exposures to each antimicrobial were considered as factors in a multivariable linear regression, also adjusted for demographics, with separate analyses for those contributing samples cross-sectionally or longitudinally. Outcomes were Shannon diversity and relative abundance of specific bacterial taxa (Enterobacteriaceae, Enterococcus, and major anaerobic groups) and antimicrobial resistance genes (targeting beta-lactams, tetracyclines, aminoglycosides, macrolides, and glycopeptides). 225 adults were included in the cross-sectional analysis, and a subset of 79 patients undergoing haematopoietic cell transplant provided serial samples for longitudinal analysis. Results were largely consistent between the two sampling frames. Recent use of piperacillin-tazobactam, meropenem, intravenous co-amoxiclav, and clindamycin was associated with large reductions in microbiome diversity and reduced abundance of anaerobes. Exposure to piperacillin-tazobactam and meropenem was associated with a decreased abundance of Enterobacteriaceae and an increased abundance of Enterococcus and major AMR genes, but there was no evidence that these antibiotics had a greater impact on microbiome diversity than iv co-amoxiclav or oral clindamycin. In contrast, co-trimoxazole, doxycycline, antifungals, and antivirals had less impact on microbiome diversity and selection of AMR genes. Simultaneous estimation of the impact of over 20 antimicrobials on the gut microbiome and AMR gene abundance highlighted important differences between individual drugs. Some drugs in the WHO Access group (co-amoxiclav, clindamycin) had similar magnitude impact on microbiome diversity to those in the Watch group (meropenem, piperacillin-tazobactam) with potential implications for acquisition of resistant organisms. Metagenomic sequencing can be used to compare the impact of different antimicrobial agents and treatment strategies on the commensal flora.}, }
@article {pmid41371856, year = {2026}, author = {Na, C and Shi, X and Fu, J and Li, J and Jiang, H and Guo, Z and Lai, H and Zhang, Z and Zhao, L and Yuan, Q and Zhang, B}, title = {Pectic polysaccharides from Mongolian medicinal Hypecoum leptocarpum: Structure and ulcerative colitis amelioration via gut microbiota and intestinal inflammation regulation.}, journal = {Carbohydrate polymers}, volume = {374}, number = {}, pages = {124717}, doi = {10.1016/j.carbpol.2025.124717}, pmid = {41371856}, issn = {1879-1344}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology/pathology ; Mice ; *Pectins/chemistry/pharmacology/isolation &amp; purification ; Male ; *Polysaccharides/chemistry/pharmacology ; Inflammation/drug therapy ; Mice, Inbred C57BL ; Dextran Sulfate ; Fatty Acids, Volatile/metabolism ; }, abstract = {Ulcerative colitis (UC) poses a global health burden due to its refractoriness. Our previous study demonstrated that Hypecoum leptocarpum (H. leptocarpum) crude polysaccharides mitigate UC-related intestinal inflammation. In this study, we extracted, purified, and characterized a pectic polysaccharide (HLP-4-2, 19.7 kDa) from H. leptocarpum, which contained homogalacturonan (HG) and rhamnogalacturonan-I (RG-I). Specifically, RG-I comprises a repeating disaccharide unit of 1,4-α-GalpA and 1,2-α-Rhap (with arabinogalactan branches), whereas HG has partially methyl-esterified GalA residues. In DSS-induced UC mice, HLP-4-2 alleviated disease symptoms in a dose-dependent manner, as evidenced by a reduced disease activity index (DAI), restored colon length, and decreased spleen index. Mechanistically, HLP-4-2 modulated gut microbiota by promoting growth of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella) and reducing abundance of pathogenic bacteria (e.g., Klebsiella). This microbial shift elevated SCFA levels (particularly propionic and isobutyric acids) and reduced isocaproic acid levels. These changes may, in turn, strengthen the intestinal barrier by enhancing mucin secretion, preserving goblet cells, and reducing inflammation via downregulating proinflammatory cytokines. Fecal microbiota transplantation (FMT) experiments confirmed that these microbial changes contributed to HLP-4-2's therapeutic effects. These findings endorse the traditional use of H. leptocarpum for inflammation and indicate HLP-4-2 as a potential treatment for ulcerative colitis.}, }
@article {pmid41372103, year = {2026}, author = {Lee, YT and Akan, A and Önel, DB and Medawar, E and Jensen, DEA and Villringer, A and Witte, AV}, title = {Impacts of Lifestyle and Microbiota-Targeted Interventions for Overweight and Obesity on the Human Gut Microbiome: A Systematic Review.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {27}, number = {3}, pages = {e70037}, pmid = {41372103}, issn = {1467-789X}, support = {209933838//German Research Foundation (DFG)/ ; WI 3342/3-1//German Research Foundation (DFG)/ ; //Max Planck Society/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Obesity/microbiology/therapy ; *Overweight/microbiology/therapy ; Probiotics/therapeutic use ; *Life Style ; Prebiotics ; Fecal Microbiota Transplantation ; Exercise ; Adult ; Randomized Controlled Trials as Topic ; Middle Aged ; Aged ; }, abstract = {Obesity is intricately associated with the gut microbiome, and emerging research suggests that lifestyle interventions, such as dietary changes and active lifestyle, can significantly affect the composition and function of the gut microbiome. However, evidence demonstrating a causal link between these changes and long-term weight loss or metabolic improvements remains limited. This systematic review investigates how overweight- and obesity-targeted interventions, such as dietary modifications, physical activity, supplementation with prebiotics and probiotics, and fecal microbiota transplantation (FMT), manipulate gut microbiome diversity and composition, major metabolites, and weight status. We conducted a systematic literature search and included 87 out of 255 randomized clinical trials with 6086 adults aged 18-84 with a BMI ≥ 25 kg/m[2]. The quality of the included RCTs ranged from very low to moderate risk of bias. Most interventions did not cause any significant changes in microbial alpha or beta diversity, however, positive associations between prebiotic consumption and abundance of Actinobacteria and Bifidobacterium were observed, and intake of probiotics was related to increased levels of Lactobacillus and reduced body weight and body fat. We did not observe strong evidence for associations between SCFA levels, gut microbiome, and obesity. Overall, diversity and heterogeneity in reported outcomes, both in methods and results, were large. Taken together, our findings suggest that overweight- and obesity-targeted dietary interventions of at least 4 weeks, particularly those involving prebiotics and probiotics, have the potential to beneficially alter the gut microbiome, although standardized protocols and harmonized reporting are needed to confirm this through meta-analysis.}, }
@article {pmid41373016, year = {2025}, author = {Qian, J and Tao, Q and Shen, Y and Wang, L and Wang, M and Wang, N and Liang, Q and Lu, J and Huang, Y and Liao, W and Chen, R and Ge, R and Yuan, Z and Li, Y and Shen, H and Gao, Q and Yan, F}, title = {Periodontitis salivary microbiota exacerbates colitis by CXCL3 derived from gut microbiota-induced macrophages.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {255}, pmid = {41373016}, issn = {2049-2618}, support = {No. 0224C030//High-Level Hospital Construction Project of Nanjing Stomatological Hospital/ ; No. 82270979, 81970939//The National Natural Science Foundation of China/ ; JSDW202246//Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit/ ; No. 2019060009//Nanjing Clinical Research Center for Oral Diseases/ ; }, mesh = {*Gastrointestinal Microbiome ; *Periodontitis/complications/microbiology ; *Saliva/microbiology ; *Colitis/microbiology/therapy ; Probiotics/therapeutic use ; Case-Control Studies ; Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; RAW 264.7 Cells ; Lacticaseibacillus rhamnosus ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Increasing research has focused on the role of the oral-gut axis in the development of colitis. Saliva contains a large number of oral bacteria that influence gut microbiota and colitis, but the underlying mechanisms remain unclear. In this study, we investigated the role and mechanisms of gut microbiota in salivary microbiota-affected colitis.<br><br>RESULTS: We confirmed that periodontitis salivary microbiota (PSM) exacerbated colitis compared to healthy salivary microbiota (HSM). Antibiotics could reverse the effect of PSM in exacerbating colitis, suggesting that the altered gut microbiota was pathogenic. PSM resulted in the enrichment of pathogens, such as Escherichia coli, and lipopolysaccharide in the gut microbiota, and this gut microbiota was shown to be detrimental to colitis by C-X-C motif chemokine ligand 3(CXCL3) in our study. Mechanistically, PSM-derived gut microbiota significantly upregulated CXCL3 in the macrophages, and these Cxcl3&#x2009;+&#x2009;macrophages contributed to colitis pathology by secreting CXCL3. The macrophages-derived CXCL3 exacerbated colitis via neutrophil chemotaxis and macrophage polarization. CXCL3 induced M2b-like polarization in macrophages, with functions related to immunomodulation and lipid catabolism. These macrophages exacerbated colitis in a gut microbiota-dependent manner. In terms of treatment, administration of Lactobacillus rhamnosus GG, a well-known probiotic, improved gut microbiota and CXCL3, and ameliorated the PSM-exacerbated colitis.<br><br>CONCLUSIONS: Gut microbiota was a key factor in PSM-exacerbated colitis, which was by activating macrophage to secrete CXCL3. Our study provides new insights into the role of gut microbiota with macrophages and chemokines in colitis, and the mechanism of oral disease affecting the distal organs systemically.}, }
@article {pmid41373570, year = {2025}, author = {Mashal, R and Al-Muhanna, A and Khader, S and Khudair, A and Khudair, A and Butler, AE}, title = {The Role of the Gut Microbiome in Type 2 Diabetes Mellitus.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373570}, issn = {1422-0067}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Animals ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {The gastrointestinal tract in humans hosts trillions of microorganisms, collectively termed the gut microbiota, which perform essential physiological processes and roles, including nutrient metabolism and immunomodulation. Influenced by genetics, age, diet, medication, and the environment, the disruption of this system leads to dysbiosis, which has been linked to a range of diseases, notably type 2 diabetes mellitus (T2DM). As the global prevalence of T2DM continues to trend upwards, research investigating and highlighting the influence the gut microbiome exerts on this disease is warranted. The literature was examined regarding microbial metabolites and metabolic signaling pathways, as well as interventions relating to diet, prebiotics, probiotics, pharmacological agents, and fecal microbiota transplantation (FMT). The gut microbiome, through its effects on insulin resistance, inflammation, bile acid signaling, and glucose-lipid metabolism, impacts the development and progression of T2DM. Furthermore, patients with T2DM have demonstrated reduced microbial diversity, depletion of butyrate-producing bacteria, and an increase in pathogenic species. Interventions including high-fiber diets, metformin, probiotics, and FMT were shown to enrich beneficial microbes and improve metabolic outcomes. Targeted modulation of the microbiome, such as through next-generation probiotics and CRISPR-based therapies, may enhance metabolic control in the context of the future of personalized medicine. This review investigates the intricate relationship between the gut microbiome and T2DM, emphasizing its role in disease pathogenesis, the factors that may impact the microbiome in these patients, as well as therapeutic approaches toward its management.}, }
@article {pmid41374078, year = {2025}, author = {Biscaglia, G and Gentile, A and Parente, P and Calvo, A and Fontana, R and Continisio, A and Di Brina, ALP and Ciardiello, D and McIlwain, G and Latiano, A and Perri, F and Palmieri, O}, title = {Inflammatory Bowel Disease, Gastrointestinal Graft-Versus-Host Disease and Immune Checkpoint Inhibitors Induced Colitis: Similar Diseases to Treat with Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {17}, number = {23}, pages = {}, pmid = {41374078}, issn = {2072-6643}, support = {n/a//This research was funded by the Italian Ministry of Health (Ricerca Corrente) and 5 per mille/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/adverse effects ; *Graft vs Host Disease/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis/therapy/chemically induced ; Gastrointestinal Microbiome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic strategy designed to modify and enrich the recipient's gut microbiota by administering processed donor stool, with the goal of treating dysbiosis and related conditions. In 2013, the United States Food and Drug Administration (FDA) approved FMT for recurrent Clostridioides difficile infection (rCDI). Since then, its use has been proposed and investigated in several other disorders characterized by gut microbiota imbalance and altered host-microbiota interactions, including inflammatory bowel disease (IBD), immune checkpoint inhibitor-induced colitis (ICI-iC), and gastrointestinal graft-versus-host disease (GI-GVHD). This review aims to highlight the commonalities among these conditions, the pathophysiological mechanisms that support the rationale for FMT, and emerging evidence from clinical studies. Although available studies are heterogeneous, FMT is a rapidly evolving field of research with promising potential to treat IBD and improve outcomes following oncological immunotherapy and allogenic stem cell transplantation. With further validation, FMT could become an important approach in managing immune-mediated gastrointestinal diseases.}, }
@article {pmid41375540, year = {2025}, author = {Schank, N and Cottone, A and Wulf, M and Seiter, K and Thomas, B and Miller, LMJ and Anderson, SL and Sahyoun, A and Abidi, AH and Kassan, M and Verma, A}, title = {The Role of Short-Chain Fatty Acids (SCFAs) in Colic and Anti-Inflammatory Pathways in Horses.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {23}, pages = {}, pmid = {41375540}, issn = {2076-2615}, abstract = {Equine colic remains a prevalent and potentially life-threatening condition with multifactorial origins, including dietary imbalances, stress, and microbial dysbiosis. Central to equine gut health is the production of short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, generated through microbial fermentation of dietary fibers in the hindgut. These metabolites not only serve as vital energy sources but also play crucial roles in maintaining intestinal barrier integrity, modulating motility, and suppressing inflammation. This review explores the role of SCFAs in equine gastrointestinal health, with particular emphasis on their anti-inflammatory effects and potential to prevent or mitigate colic. We examine how SCFAs interact with immune pathways, via G-protein-coupled receptors and regulatory T-cell promotion, to reduce pro-inflammatory cytokines such as TNF-α and IL-6. Evidence suggests that dietary shifts toward high-starch or low-fiber intake can reduce SCFA production, contributing to microbial imbalance, increased gut permeability, and systemic inflammation, all hallmarks of colic pathophysiology. Strategies to enhance SCFA levels, including high-forage diets, targeted prebiotic and probiotic supplementation, and emerging approaches like fecal microbiota transplantation, are discussed. Despite promising findings, significant gaps remain in equine-specific research, highlighting the need for longitudinal and mechanistic studies. Understanding and harnessing the therapeutic potential of SCFAs could pave the way for novel, microbiome-based interventions in colic prevention and treatment.}, }
@article {pmid41375654, year = {2025}, author = {Soares Ferreira Junior, A and Amanda Niz Alvarez, D and da Silva Souza, L and Linares Silva, N and Dias Machado, L and Yoshio Hirai, W and Mesquita Ciconelli, R and Piccolo Feliciano, JV and Colturato, I and Maurício Navarro Barros, G and Scheinberg, P and Chao, NJA and Lelis Vilela de Oliveira, G}, title = {A Distinct Intestinal Domination Fingerprint in Patients Undergoing Allo-HSCT: Dynamics, Predictors and Implications on Clinical Outcomes.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, pmid = {41375654}, issn = {2077-0383}, support = {#2022/12989-6//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #2023/08142-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #2024/02936-8//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #2023/12271-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; }, abstract = {Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and clinical implications of intestinal domination in Brazilian patients undergoing allo-HSCT. Methods: In a prospective study of four Brazilian centers, fecal specimens were collected longitudinally prior to allo-HSCT until six months post-transplantation. To identify intestinal domination, we performed 16S rRNA gene sequencing using the Illumina platform. We then evaluated the impact of intestinal domination on overall survival and acute Graft-versus-Host-Disease (aGvHD) incidence. Finally, to identify predictors of intestinal domination, we performed a logistic regression model. Results: A total of 192 fecal specimens were collected from 69 patients. No significant changes in alpha or beta diversity were observed over the course of allo-HSCT. Among the 192 specimens, 131 (68%) presented intestinal domination. The top four dominant genera were Bacteroides, Akkermansia, Phascolarctobacterium, and Escherichia-Shigella. No significant associations were found between domination by these genera and either overall survival or aGvHD incidence. Furthermore, no patient-level characteristics, including age, sex, underlying disease, conditioning regimen, or stem cell source, reliably predicted intestinal domination. Conclusions: Our findings reveal a unique intestinal domination fingerprint in Brazilian patients and highlight the importance of geographic context in interpreting microbiota-outcome associations in allo-HSCT settings.}, }
@article {pmid41377246, year = {2025}, author = {Singh, PK and Rathi, D and Shweliya, MA and Farooq, A and Anfaal, Z and Saleem, NUA and Hamza, M and Qadri, M and Rath, S and Hemida, MF and Rani, H and Mahgoub, AMA and Wazir, HU}, title = {The interplay of the microbiome and breast cancer: beyond the gut: a narrative review.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {12}, pages = {8496-8507}, pmid = {41377246}, issn = {2049-0801}, abstract = {Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with emerging evidence underscoring the microbiota's pivotal role in its etiology, progression, and therapeutic response. This narrative review synthesizes the intricate interplay between the breast tissue, skin, and lung microbiomes in breast cancer pathogenesis, with particular emphasis on inflammatory breast cancer (IBC) and metastatic dissemination. The healthy breast microbiome, dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, maintains tissue homeostasis through pH regulation, metabolite production, and immune modulation. Dysbiosis disrupts this equilibrium, fostering carcinogenesis via chronic inflammation, estrogen deconjugation, and DNA damage-induced genomic instability, with subtype-specific microbial signatures influencing tumor growth and therapy resistance. In IBC, skin microbiome alterations characterized by overgrowth of pathogens like Pseudomonas aeruginosa and Staphylococcus aureus exacerbate inflammation, epithelial-mesenchymal transition (EMT), and lymphatic invasion, while promoting a pro-tumorigenic microenvironment enriched in regulatory T cells and M2 macrophages. Concurrently, lung microbiota dysbiosis impairs immune surveillance, remodels the extracellular matrix, and facilitates metastatic seeding through neutrophil extracellular traps and cytokine storms. Cross-talk among these microbiomes amplifies systemic effects, highlighting their synergistic contributions to disease aggressiveness. Advanced analytical techniques, including 16S rRNA sequencing, metagenomics, and metabolomics, offer promising microbial biomarkers for early detection and risk stratification. By elucidating these host-microbe dynamics, this review advocates for microbiome-centric interventionssuch as probiotics, fecal microbiota transplantation, and targeted antimicrobials to enhance precision diagnostics and therapies, ultimately improving outcomes in breast cancer management.}, }
@article {pmid41377546, year = {2025}, author = {Wang, JDJ and Suan, E and Li, SS and Shelat, VG}, title = {Sepsis and the diverse organ-gastrointestinal tract axis.}, journal = {World journal of critical care medicine}, volume = {14}, number = {4}, pages = {105547}, pmid = {41377546}, issn = {2220-3141}, abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide, driven by a dysregulated host immune response to infection that culminates in multi-organ dysfunction. Recent advances highlight the gut microbiota's pivotal role in modulating immune responses and influencing the pathophysiology of sepsis through the organ-gastrointestinal tract axis. This review synthesizes current evidence on the bidirectional interplay between gut dysbiosis and the dysfunction of major organ systems-liver, lungs, kidneys, brain, and heart-during sepsis. We explore how gut-derived factors such as microbial translocation, endotoxins, and altered metabolite production exacerbate systemic inflammation and organ injury. In particular, we emphasize the roles of short-chain fatty acids, uremic toxins, bile acids, and trimethylamine-N-oxide in mediating immune dysfunction across the gut-organ axes. Therapeutic strategies targeting the gut microbiota- including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation- show promise in preclinical and early clinical settings. However, challenges related to patient heterogeneity, safety, and the lack of precise biomarkers persist. This review consolidates disparate findings to underscore the gut as a central modulator in sepsis and advocates for microbiota-based interventions as adjunctive therapies in sepsis management.}, }
@article {pmid41377642, year = {2025}, author = {Edpuganti, S and Subhash, S and Subrahmaniyan, SL and Latheef, S and Albarari, SS}, title = {Gut Microbiome and Cardiovascular Health: Mechanisms, Therapeutic Potential and Future Directions.}, journal = {Heart international}, volume = {19}, number = {2}, pages = {12-20}, pmid = {41377642}, issn = {2036-2579}, abstract = {BACKGROUND: The gut microbiome has a crucial role in host metabolism and immune regulation, and there is growing evidence that dysbiosis may be associated with the pathogenesis of cardiovascular disease (CVD). This narrative review provides an overview of the recent literature on mechanistic connections between the gut and heart, as well as on the therapeutic strategies and research gaps in the gut-heart axis.<br><br>METHODS: We conducted a systematic literature search on PubMed and Embase databases with MeSH and keyword terms: 'gut microbiome', 'cardiovascular disease', 'TMAO', 'short-chain fatty acids', 'probiotics' and 'faecal microbiota transplantation'. We considered human and relevant animal studies focusing on mechanistic pathways or microbiome treatments and excluded editorials, small (less than 10 subjects) case series and articles not published in the English language.<br><br>RESULTS: Key microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), contribute to atherogenesis, blood pressure and myocardial inflammation. Dysbiosis-induced barrier dysfunction and disturbed bile acid signalling also serve as the mediators of cardiac remodelling. Dietary fibre, probiotics/prebiotics, postbiotics and faecal microbiota transplantation are emerging interventions for the modulation of CVD risk. Nevertheless, most result from observational studies, whilst such are heterogeneous in sequencing platforms and too small to draw any definitive conclusions.<br><br>CONCLUSION: The modulation of gut microbiome might be a new target for CVD prevention and treatment. Large-scale, standardized randomized trials with hard cardiovascular endpoints, as well as integrated multi-omics profiling, will be required to validate microbial biomarkers and to optimize microbiome-based interventions.}, }
@article {pmid41378067, year = {2025}, author = {Vargas-Beltran, AM and Mialma-Omana, SJ and Vivanco-Tellez, DO}, title = {Targeting gut microbiota in liver disease: A pharmacological approach for hepatic encephalopathy and beyond.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {4}, pages = {110271}, pmid = {41378067}, issn = {2150-5349}, abstract = {The gut microbiota plays a pivotal role in the pathogenesis of liver diseases, particularly hepatic encephalopathy (HE), in which dysbiosis contributes to ammonia production, systemic inflammation, and neurocognitive dysfunction. Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity. This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease, focusing on traditional approaches such as non-absorbable disaccharides (lactulose, lactitol), antibiotics (rifaximin), and probiotics as well as novel interventions, including postbiotics, synbiotics, and fecal microbiota transplantation. Additionally, bile acid modulators, short-chain fatty acid derivatives, and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis. We also discussed the implications of gut microbiota modulation in conditions beyond HE, such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. By integrating gut microbiota-targeted therapies into liver disease management, we may develop more effective, personalized approaches to improve patient outcomes and reduce complications.}, }
@article {pmid41378072, year = {2025}, author = {Wang, SY and Zhang, MZ and Chen, ZM and Li, ZM and Xie, CY and Yang, GH and Xu, B and Xu, TC}, title = {Intestinal-related substances in obesity regulation: A comprehensive review.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {4}, pages = {111082}, pmid = {41378072}, issn = {2150-5349}, abstract = {With the rising global obesity rates, particularly in industrialized nations, obesity has become an increasingly significant public health concern. This review analyzes 132 relevant studies published between 2020 and 2025, with a focus on the role of gut-derived substances in regulating obesity. These include gut hormones [such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY, cholecystokinin, and ghrelin], microbial metabolites [such as short-chain fatty acids (SCFA) and indole-3-propionic acid (IPA)], and neurotransmitters (such as serotonin and dopamine).The findings suggest that gut hormones play a crucial role in regulating appetite, glucose metabolism, and energy expenditure, and their dysregulation is closely linked to the development of obesity. Moreover, microbial metabolites like SCFA and IPA are strongly associated with metabolic health and significantly influence obesity-related mechanisms. This review also explores emerging therapeutic strategies, including GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, modulation of the gut microbiota, and fecal microbiota transplantation, all of which demonstrate promising potential in obesity management. However, challenges remain in optimizing these interventions, mitigating adverse effects, and establishing regulatory standards for microbiota-based therapies. Future research should aim to develop personalized, multi-targeted approaches to more effectively combat obesity and its associated metabolic disorders.}, }
@article {pmid41378248, year = {2025}, author = {Abdulaal, R and Afara, I and Harajli, A and Al Mashtoub, E and Tarchichi, A and Hassan, K and Afara, A and Abou Fakher, J and Salhab, S and Fassih, I and Tlais, M}, title = {Gut microbiome and chemotherapy-induced cardiotoxicity: A systematic review of evidence and emerging therapies.}, journal = {World journal of biological chemistry}, volume = {16}, number = {4}, pages = {112221}, pmid = {41378248}, issn = {1949-8454}, abstract = {BACKGROUND: Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy, limiting treatment efficacy and worsening patient outcomes. Recent studies have implicated the gut microbiome and its key metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), in mediating inflammation, oxidative stress, and cardiac damage. The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.<br><br>AIM: To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.<br><br>METHODS: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2013 and December 2024. Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition, microbial metabolites (e.g., SCFAs, TMAO), or microbiome-targeted interventions. Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction focused on microbiota alterations, mechanistic pathways, cardiac outcomes, and quality assessments using standardized risk-of-bias tools.<br><br>RESULTS: Eighteen studies met the inclusion criteria. Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains. This imbalance contributed to gut barrier disruption, systemic inflammation, and oxidative stress, all of which promote myocardial damage. SCFA depletion weakened anti-inflammatory responses, while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction. Preclinical studies showed promising cardioprotective effects from probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, though human data remain limited.<br><br>CONCLUSION: Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity. Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury. Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology, warranting further clinical validation through well-designed trials.}, }
@article {pmid41378445, year = {2025}, author = {Behling, AH and Portlock, T and Ho, D and Wilson, BC and Paramsothy, S and Kamm, MA and Cutfield, WS and Kaakoush, NO and O'Sullivan, JM and Vatanen, T}, title = {Cohort-specific determinants of donor strain engraftment following multi-donor faecal microbiota transplantation in two randomised clinical trials.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2597628}, pmid = {41378445}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/therapy/microbiology ; Tissue Donors ; Feces/microbiology ; *Obesity/therapy/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Randomized Controlled Trials as Topic ; Male ; Female ; Adult ; Middle Aged ; Cohort Studies ; }, abstract = {Disrupted human gut microbiota have been associated with the development of certain disease states, including obesity and ulcerative colitis (UC). Faecal microbiota transplantation (FMT) from healthy donors is a promising avenue to shift the microbiome profile of the recipient towards that of the donor, potentially ameliorating related symptoms. Several recent meta-analyses have investigated the clinical and microbial determinants that influence the retention of transplanted donor microbial strains within the recipient gut microbiome following FMT (i.e. engraftment). However, the specific factors that affect donor strain engraftment in different disease states require further exploration. Here, we perform a strain engraftment analysis on data from two multi-donor FMT clinical trials: the Gut Bugs Trial for obesity and the FOCUS Trial for UC. Using donor strain matching, the donor-recipient pairings of the FOCUS Trial were first predicted in a blinded manner. The subsequent, unblinded, strain engraftment analysis of both datasets highlighted a differential effect of donor-recipient microbiome complementarity on engraftment across the two disease cohorts; greater engraftment efficiency was associated with increased donor-recipient microbial similarity in the FOCUS Trial, and decreased similarity in the Gut Bugs Trial, suggesting that the factors influencing engraftment may differ across disease cohorts.}, }
@article {pmid41381864, year = {2026}, author = {Tang, A and Chen, Y and Si, K and Lai, J and Gong, W and Hu, S}, title = {Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.}, journal = {Molecular psychiatry}, volume = {31}, number = {5}, pages = {2589-2604}, pmid = {41381864}, issn = {1476-5578}, support = {LR20F050002//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LR22F050007//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 82201676//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82471542//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Ventral Tegmental Area/metabolism ; *Bipolar Disorder/metabolism/physiopathology/microbiology ; *Neuronal Plasticity/physiology ; Mice ; Prefrontal Cortex/metabolism ; Dopamine/metabolism ; Male ; Synaptic Transmission/physiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Neural Pathways/metabolism ; Fecal Microbiota Transplantation/methods ; Neurons/metabolism ; Dendritic Spines/metabolism ; Dysbiosis ; Depression ; }, abstract = {Adequate evidence has shown that gut microbial dysbiosis is an emerging disease phenotype of bipolar disorder (BD), and is closely related to clinical symptoms of this intractable disease. However, how gut microbiota affects the nervous system in BD remains largely unclear. In this study, we constructed a BD depression-like mouse model via fecal microbiota transplantation, and explored the changes of synaptic plasticity and connectivity in the medial prefrontal cortex (mPFC) of BD mice. We found that bipolar depression-like mice presented with a decrease in the density of dendritic spines in medial prefrontal neurons, and "Translation at postsynapse" as a key contributor to the changes in synaptic plasticity. In addition, analysis of synaptic connectivity in the mPFC revealed that compared to control mice, less connections were observed between ventral tegmental area and mPFC glutamate neurons and dopamine response was decreased in BD mice. These findings suggest that gut microbiota from BD depression patients induces the development of bipolar depression possibly by modulating aberrant synaptic connectivity and dopamine transmission in the VTA-mPFC pathway, which sheds light on the microbiota-gut-brain mechanisms underlying BD.}, }
@article {pmid41382117, year = {2025}, author = {Wang, Y and Bai, Z and Sun, J and Gong, Q and Miao, W and Niu, Z and Li, X and Xu, J and Lai, Z}, title = {Intestinal congestion-driven gut dysbiosis: a cross-disease hemodynamic mechanism in liver cirrhosis and heart failure.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {79}, pmid = {41382117}, issn = {1479-5876}, support = {SYYYRC-2022006//First Hospital of Shanxi Medical University/ ; 202103021224408//Natural Science Foundation of Shanxi Province/ ; 202203021221248//Natural Science Foundation of Shanxi Province/ ; 202204010931008//Shanxi Provincial Science and Technology Department/ ; YDZJSX2021B012//Shanxi Provincial Science and Technology Department/ ; 82470693//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2023065//Health Commission of Shanxi Province/ ; }, abstract = {BACKGROUND: Intestinal congestion is a common pathophysiological feature of both liver cirrhosis and heart failure (HF). This study aimed to investigate whether intestinal congestion induces similar gut microbiota and metabolite alterations under both conditions, and to identify key microbial and metabolic signatures.<br><br>METHODS: We analyzed 117 cirrhosis patients (uncomplicated cirrhosis, cirrhosis with hepatocellular carcinoma, transjugular intrahepatic portosystemic shunt, and liver transplantation), 75 HF patients, and 31 healthy controls (CG). We performed 16S rRNA sequencing on all samples to assess gut microbial diversity, and subjected six representative samples per group to metagenomic sequencing. We conducted untargeted metabolomics on 30 fecal samples each from the uncomplicated cirrhosis, HF with reduced ejection fraction (HFrEF), and CG groups to profile intestinal metabolites, followed by correlation analyses among representative taxa, clinical characteristics, and key metabolites.<br><br>RESULTS: Intestinal congestion of different etiologies exhibits similar alterations in the gut microbiota, particularly in patients with uncomplicated cirrhosis and HFrEF. Alterations in Bacteroides were closely associated with the severity of congestion. Veillonella and Lactobacillales were enriched in cirrhotic patients, whereas Coprococcus was uniquely abundant in HFs. Metabolomic analysis revealed significant reductions in tripeptides, anti-inflammatory compounds, and prostaglandin analogs in patients with intestinal congestion. Musacin D and neopterin may serve as potential noninvasive biomarkers for HF and cirrhosis, respectively.<br><br>CONCLUSION: Intestinal congestion is associated with gut microbiota dysbiosis and metabolic disturbances in cirrhosis and HFs, with specific microbes and metabolites showing potential predictive value for distinguishing underlying diseases.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07547-3.}, }
@article {pmid41383587, year = {2025}, author = {Bibbò, S and De Maio, F and Capone, F and Quaranta, G and Rondinella, D and Rosato, R and Minelli, M and De Lorenzis, D and Sanguinetti, M and Cammarota, G and Di Lazzaro, V and Masucci, L}, title = {Case Report: Fecal microbiota transplantation via capsules ameliorated clinical outcomes in a patient with multiple sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1678759}, pmid = {41383587}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Female ; Adult ; *Gastrointestinal Microbiome ; *Multiple Sclerosis/therapy/microbiology ; Treatment Outcome ; Capsules ; Dysbiosis/therapy ; }, abstract = {Multiple Sclerosis (MS) has long been recognized as a multifactorial disease, associated with both genetic and enviromental factors. Its link to inflammatory processes has led to significant advances in understanding the immunological and neurobiological mechanisms underlying the disease. The presumed autoimmune etiology is currently guiding the development of therapeutic protocols in this direction. The intestinal bacteria population, known as Gut Microbiota (GM), plays a well-documented role in autoimmune and inflammatory diseases. Gut microbiota dysbiosis is associated in patients affected by MS. Fecal Microbiota Transplantation (FMT) is emerging as a potential strategy to restore eubiosis and modulate systemic inflammation. We treated a 42-year-old woman with severe MS disability by FMT via colonoscopic infusion followed by a 3-month treatment of daily oral capsules, containing frozen microbiota, in order to resolve gastrointestinal symptoms. Clinical follow-up was conducted at 30, 60, and 90 days. Microbiota profiling (16S rRNA sequencing) and intestinal permeability testing were performed at several time points before and post infusion. Post-FMT, gastrointestinal symptoms improved significantly, as well as in limb spasticity, trunk stability, and fine motor skills. Microbiota analysis revealed a marked reduction in the abundance of Akkermansia muciniphila (22.5% vs 6.6%). At phylum level, Actinomycetota remained elevated (22%), while Bacteroidota consistently showed low abundance (14%). The most favorable microbiota profile was observed at 90 days, which coincided with the peak of clinical improvement. Intestinal permeability also improved over time, despite the patient's microbiota profile remaining distinct from the donor. This is the first report about combined FMT in MS. The procedure was safe, well tolerated, and associated with both gastrointestinal and neurological improvements. These findings support further exploration of FMT as a therapeutic adjunct in MS through controlled clinical trials.}, }
@article {pmid41383731, year = {2025}, author = {Zhang, M and Liu, L and Lian, J and Zhang, M and Yang, X and Wang, H}, title = {Changes in gut microbiota in Gynura segetum-induced liver injury.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1684570}, pmid = {41383731}, issn = {1664-302X}, abstract = {INTRODUCTION: Gynura segetum (GS) has been shown to induce hepatotoxicity. Growing evidence suggests that the response to herbal medicines may be linked to shifts in the gut microbiota. This study aims to investigate the association between gut microbiota and liver injury induced by GS.<br><br>METHODS: The mice model of liver injury was established by oral gavage of GS decoction for 4 weeks, with or without the broad-spectrum antibiotics (Abx) or fecal microbiota transplantation (FMT). Liver function was assessed through the hematoxylin and eosin (H&amp;E) staining and biochemical indices. The microbiota in the intestinal tract and peritoneal cavity were determined by 16S rRNA gene sequencing. Senecionine, seneciphylline, ferulic acid, beta-sitosterol, vanillic acid, vanillin, isorhamnetin, quercetin, kaempferol, and luteolin were isolated from GS plants, and the effects of these chemical compounds on the intestinal flora were analyzed.<br><br>RESULTS AND DISCUSSION: Compared to controls, mice treated with the GS decoction exhibited decreased body weight and increased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and aspartate aminotransferase, regardless of whether they were given Abx or FMT. The abundance of Akkermansia (phylum Verrucomicrobia) persistently increased in the GS group. In contrast, other bacterial groups showed different trends under Abx or FMT conditions. Additionally, compared with the GS group, the linear discriminant analysis (LDA) score revealed the increase in abundance of Bifidobacterium, Bacteroides, Ruminococcaceae_UCG-007, and Coriobacteriaceae_UCG-002 in the Abx group, and Blautia and Bifidobacterium in the FMT group. 16S sequencing of ascitic fluid detected multiple bacterial phyla. Moreover, the administration of chemical compounds isolated from the GS plant by gavage did not increase the abundance of Akkermansia in the intestine.<br><br>CONCLUSION: GS increased the relative abundance of the Akkermansia genus in the intestinal tract. None of the above chemical compounds had this effect. This suggests that some components of GS may promote the growth of beneficial bacteria such as Akkermansia, offering new perspectives for drug development.}, }
@article {pmid41384118, year = {2025}, author = {Bautista, J and Cardona-Maya, WD and Gancino-Guevara, K and López-Cortés, A}, title = {Reprogramming prostate cancer through the microbiome.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1690498}, pmid = {41384118}, issn = {2296-858X}, abstract = {Prostate cancer (PCa) is a major global public health challenge, driven by a multifactorial interplay of genetic, epigenetic, hormonal and environmental determinants. In recent years, the human microbiome has emerged as a critical and previously underappreciated contributor to PCa initiation, progression, and therapeutic response. Emerging high-resolution multi-omics studies have demonstrated that microbial communities across the gut, urinary tract and prostate form a functional axis that shapes immune surveillance, hormonal metabolism, inflammatory tone and epigenetic regulation. Dysbiosis in these compartments promotes chronic inflammation, modulates androgen receptor signaling, and produces bioactive metabolites, including short-chain fatty acids, that activate oncogenic IGF-1/MAPK/PI3K and NF-κB/JAK/STAT pathways. Cross-compartmental trafficking of bacterial taxa and metabolites reinforces tumor-promoting circuits, while specific commensals such as Akkermansia muciniphila enhance antitumor immunity and improve responses to androgen deprivation therapy. Importantly, microbiota-derived factors also modulate microRNA (miRNAs) expression and epigenetic signatures, thereby affecting tumor plasticity and resistance to therapy. These mechanistic insights have catalyzed interest in microbiome-based therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, dietary modulation and bacteriophage therapy, which hold promise for restoring eubiosis and enhancing treatment efficacy. Nevertheless, clinical translation remains limited by inter-individual variability and the need for well-designed, longitudinal studies integrating shotgun metagenomics, metabolomics and host-microbe interactomics. Overall, the prostate, urinary and gut microbiomes represent interconnected targets that may inform precision diagnostics and novel therapeutic strategies in PCa.}, }
@article {pmid41385953, year = {2026}, author = {Pan, Z and Guo, J and Wang, H and Cai, Y and Wu, L and Zhang, J and Wu, L and Jia, X and Wang, Q and Yu, K and Shen, C and Zhao, L}, title = {Shenling Baizhu Powder attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157654}, doi = {10.1016/j.phymed.2025.157654}, pmid = {41385953}, issn = {1618-095X}, mesh = {Animals ; Male ; *Drugs, Chinese Herbal/pharmacology ; *Cognitive Dysfunction/drug therapy/etiology ; Diet, High-Fat/adverse effects ; Mice ; *Obesity/complications/drug therapy ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Brain/drug effects ; Mice, Obese ; Powders ; *Brain-Gut Axis/drug effects ; }, abstract = {BACKGROUND: Obesity is closely associated with cognitive dysfunction, and markedly increases the risk of developing neurodegenerative diseases. Currently, obesity-related cognitive impairment lacks effective therapeutic interventions. Shenling Baizhu Powder (SLBZ) is a classical formula used to strengthen the spleen and promote the ascent of clear qi in traditional Chinese medicine (TCM). According to the TCM, this formula has great potential for the treatment of obesity-related cognitive impairment. However, research on SLBZ has focused primarily on its gastrointestinal effects, leaving its neurocognitive mechanisms largely unexplored.<br><br>PURPOSE: This study aimed to elucidate the therapeutic mechanisms of SLBZ in obesity-related cognitive impairment.<br><br>MATERIALS AND METHODS: Obese mice were obtained by subjecting male mice to a 16-week high-fat diet (HFD, 60 kcal % fat). During the final four weeks of the study, a SLBZ decoction (10 and 20 g/kg/day) was administered orally. The mice were then subjected to two behavioral tests and a glucose tolerance test. To evaluate the therapeutic effects of HFD on metabolic dysregulation, neuroinflammation, and intestinal barrier impairment, a range of analytical techniques, including biochemical analysis, immunofluorescence, RT-qPCR, and Western blotting, were used. Subsequently, 16S rRNA gene sequencing and metabolomic profiling were used to detect changes in the gut microbes and metabolite levels. Finally, fecal microbiota transplantation was performed to assess the functional link between SLBZ remodeling of the gut microbiota, metabolic alterations, and hippocampal cognitive function.<br><br>RESULTS: Our study demonstrated that HFD-fed mice developed significant cognitive impairment, supporting the notion that obesity adversely affects cognitive function. In the Morris water maze and open-field tests, SLBZ administration effectively ameliorated HFD-induced cognitive dysfunction. This improvement was accompanied by the restoration of the hippocampal synaptic ultrastructure and the recovery of the key synaptic proteins BDNF and PSD95. In agreement with this, SLBZ suppressed microglial activation and associated neuroinflammatory responses in HFD-fed mice. In the colon, SLBZ administration markedly alleviated HFD-induced gut barrier impairment, as evidenced by increased colonic mucus thickness and elevated expression of tight junction proteins, ZO-1, Occludin, and Claudin-1. Furthermore, SLBZ reduced endotoxin translocation and downregulated the expression of pro-inflammatory cytokines TNF-&#x3b1;, IL-1&#x3b2;, and IL-6. Notably, HFD-induced gut microbiota dysbiosis was remodeled by the SLBZ treatment, which was characterized by an increased capacity for microbial vitamin B6 synthesis. SLBZ increased the serum levels of vitamin B6 in HFD-fed mice. Intriguingly, fecal microbiota transplantation from SLBZ-treated HFD-fed mice facilitated the amelioration of cognitive deficits, including superior performance in behavioral tests and synaptic repair in the hippocampus compared to recipients of HFD-microbiota.<br><br>CONCLUSION: Our findings highlight that SLBZ is a promising therapeutic agent mitigating obesity-related cognitive impairment via the "gut microbiota-vitamin B6-neuroprotection" axis.}, }
@article {pmid41385961, year = {2026}, author = {Zhao, H and Akram, MZ and Comer, L and Corion, M and Fako, E and Everaert, N}, title = {Early life fecal microbiota transplantation enhances fermentation potential by changing the microbial profiles in broiler chickens.}, journal = {Poultry science}, volume = {105}, number = {1}, pages = {106189}, pmid = {41385961}, issn = {1525-3171}, mesh = {Animals ; *Chickens/microbiology/physiology ; *Fecal Microbiota Transplantation/veterinary ; *Fermentation ; *Gastrointestinal Microbiome ; Female ; *Dietary Fiber/metabolism ; Feces/microbiology ; Fatty Acids, Volatile/metabolism ; Diet/veterinary ; Animal Feed/analysis ; }, abstract = {The early gut microbiota of broiler chickens plays a critical role in shaping physiological functions later in life. Broilers have a limited capacity to utilize dietary fiber at an early stage of life. Fecal microbiota transplantation (FMT) can modify the gut microbial composition of broilers, potentially enhancing their fiber utilization capability. In this study, fecal samples from different chicken donors (broilers, laying hens, and broiler breeders) were collected and used for in vitro fermentation with two structurally distinct fibers, inulin and citrus pectin. FMT was then performed on newly hatched broilers, followed by additional in vitro fermentation to evaluate changes in the recipients' fiber fermentation capacity. Laying hen fecal microbiota exhibited the fastest fermentation rates for both fibers, while broilers showed the slowest. Notably, laying hens produced the highest levels of propionic acid during fermentation. These donor-specific fermentation differences were likely driven by Bacteroides, Subdoligranulum, Collinsella, Clostridium, and Bifidobacterium. The in vivo experiment demonstrated that FMT significantly altered the microbial composition and volatile fatty acid production in recipient broilers up to 14 days of age. Subsequent in vitro fermentation of the recipients' cecal content revealed that fermentation capacity was influenced by both the donor microbiota and the fiber substrate, with recipients of laying hen microbiota showing significantly enhanced propionic acid production, mirroring donor patterns. In conclusion, differences in donor fecal microbiota composition reflect their distinct capacities to utilize different fibers. Through FMT, recipient's cecal microbiota composition can be changed, and the donor's fermentative capacity is reflected in the recipients. These findings highlight the potential of early microbial interventions to improve fiber utilization in broilers, offering a promising strategy to optimize gut health.}, }
@article {pmid41387927, year = {2025}, author = {Shi, F and Yang, Z and Zhang, L and Zou, D and Yu, J and Guo, N and Ren, S and Tang, X and Gu, C and Xu, R and Ru, Y and Zhang, Y and Wang, D}, title = {Deoxycholic acid derived from the gut microbiota involved in the regulation of adaptive thermogenesis in response to dietary protein restriction in plateau pika.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {29}, pmid = {41387927}, issn = {2049-2618}, support = {32301301//National Natural Science Foundation of China/ ; 32330012//National Natural Science Foundation of China/ ; 23-2-1-26-zyyd-jch//Natural Science Foundation of Qingdao/ ; ZR2024QC355//Natural Science Foundation of Shandong/ ; }, mesh = {*Thermogenesis ; Animals ; *Gastrointestinal Microbiome/physiology ; Fibroblast Growth Factors/metabolism/genetics ; *Deoxycholic Acid/metabolism ; Adipose Tissue, Brown/metabolism ; Energy Metabolism ; *Diet, Protein-Restricted ; Signal Transduction ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Dietary Proteins ; Uncoupling Protein 1/metabolism ; Liver/metabolism ; }, abstract = {BACKGROUND: Most winter-active mammals experience protein restriction. Gut microbiota is a key regulator of host energy homeostasis during nutrient deficiency, yet cross talk between microbiota and factors (e.g., hormones, signaling molecules) that regulate host energy metabolism in a low-protein (LP) context has not been studied sufficiently.<br><br>RESULT: The LP diet triggered the hepatic FGF21 adaptive metabolic pathway, which increased thermogenesis and reduced body weight, and this adaptive response was dependent on the composition and function of gut microbiota. Specifically, the LP diet induced a reshaping of the gut microbiota, altering its metabolic profile to increase deoxycholic acid levels and thereby increasing UCP1-induced thermogenesis of brown adipose tissue in an FGF21-dependent manner. Fecal transplantation with LP-associated microbiota increased thermogenesis through activation of GCN2-eIF2&#x3b1;-FGF21 signaling. Supplementation of the LP diet with yak fecal bacteria in plateau pika reduced UCP1-associated thermogenesis by altering the gut microbiome, decreasing deoxycholic acid production, suppressing activation of GCN2-eIF2&#x3b1;-FGF21 signaling, and alleviating LP-induced weight loss.<br><br>CONCLUSIONS: Our study reveals an association between the gut microbiota and LP diet-associated regulation of FGF21 signaling and thermogenesis and further demonstrates that this relationship is influenced by interspecies microbial transfer, indicating a critical mechanism whereby horizontal microbial exchange between sympatric species enhances host energy homeostasis. These findings provide novel insights into our understanding of the adaptations of mammals to high-elevation environments. Video Abstract.}, }
@article {pmid41388767, year = {2025}, author = {Hou, B and Shao, H and Yuan, D and Tham, EH}, title = {Skin and gut microbiome in atopic dermatitis: Mechanisms and therapeutic opportunities.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {36}, number = {12}, pages = {e70265}, pmid = {41388767}, issn = {1399-3038}, support = {//National Medical Research Council/ ; }, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Skin/microbiology/immunology ; *Dysbiosis/immunology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The pathogenesis of atopic dermatitis (AD) comprises a combination of genetic, immune, and microbial factors. An imbalance in skin and gut microbiota composition, termed dysbiosis, may contribute to AD pathogenesis and severity through overgrowth of pathogenic microbes and suppression of healthy commensal colonization. These, in turn, promote barrier disruption and pro-inflammatory responses. The skin and gut microbiota composition plays crucial roles in AD, namely as early predictive biomarkers of AD onset; indicators of treatment response; and as future novel therapeutics such as probiotics, fecal, and skin microbiota transplantation. Such interventions aim to directly "reset" and restore a healthy microbial equilibrium, thereby fundamentally repairing barrier function, regulating immune homeostasis, and establishing new adjunctive pathways for the long-term management of AD.}, }
@article {pmid41389450, year = {2026}, author = {Mittal, A and Sharma, S}, title = {Gut microbiota and nutritional interventions in alcohol-associated liver disease: Mechanisms and therapeutic advances.}, journal = {Nutrition research (New York, N.Y.)}, volume = {145}, number = {}, pages = {8-24}, doi = {10.1016/j.nutres.2025.11.004}, pmid = {41389450}, issn = {1879-0739}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Diseases, Alcoholic/therapy/microbiology ; Fecal Microbiota Transplantation ; *Dietary Proteins/administration &amp; dosage ; *Diet ; Nutritional Status ; }, abstract = {Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Despite growing awareness of its burden, treatment options remain limited, with abstinence as the only widely accepted intervention. Recent research underscores the critical role of the gut-liver axis and nutritional status, particularly dietary protein, in modulating ALD pathogenesis and progression. This review aims to integrate current knowledge on the interplay between gut microbiota, dietary protein, and alcohol-induced liver injury, and to evaluate microbiota-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), within this context. We examine how chronic alcohol intake reshapes the gut microbiome, impairs barrier function, and alters microbial metabolism. We discuss how dietary protein, based on source, quantity, and amino acid composition, influences microbial ecology and metabolite profiles, with plant and dairy proteins emerging as beneficial. The review also highlights advances in FMT, which shows promise in improving outcomes in severe alcoholic hepatitis. However, its efficacy is modulated by donor microbial composition and recipient compatibility, both of which may be influenced by diet. Furthermore, we address emerging evidence on the role of fungal and viral communities, which remain understudied contributors to ALD. Despite substantial progress, significant knowledge gaps persist. These include the need for clinical validation of preclinical findings, deeper exploration of nonbacterial microbiota, and a lack of personalized, nutrition-based interventions. Addressing these gaps through integrative, multiomic approaches will be essential to advancing precision therapeutics in ALD.}, }
@article {pmid41389504, year = {2026}, author = {Meenakshi, S and Amrutha, TV and Abubakar, M and Prakash, V and Kumar, N and Murti, K}, title = {Fluoride-induced gut dysbiosis in metabolic disorders: Mechanisms and public health implications.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {93}, number = {}, pages = {127806}, doi = {10.1016/j.jtemb.2025.127806}, pmid = {41389504}, issn = {1878-3252}, mesh = {Humans ; *Dysbiosis/chemically induced/metabolism ; *Fluorides/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Metabolic Diseases/microbiology/metabolism ; Animals ; *Public Health ; }, abstract = {AIM: This review explores the effects of fluoride exposure and metabolic alterations linked to obesity and diabetes, and highlights preventive and therapeutic approaches to mitigate fluoride-driven metabolic risks.<br><br>SUMMARY: While fluoride is beneficial to dental health, but excessive exposure disrupts gut microbiota composition, reducing short-chain fatty acids (SCFA) production and impairing intestinal barrier integrity. These disruptions alter the oxidative stress, inflammation and insulin resistance. Evidence from animal and human studies suggest a dose-dependent pattern, with depletion of beneficial bacteria such as Lactobacillus and Faecalibacterium and enrichment of pro-inflammatory microbes. Such microbial imbalances influence bile acid metabolism. lipopolysaccharide (LPS) translocation and glucose regulation. This review discusses potential microbiome modulating strategies include probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT) and glucose lowering agents such as metformin and GLP-1 receptor agonists as possible therapeutic interventions to restore microbial balance and improve metabolic outcome However, the long-term and epigenetic effects of fluoride on intestinal and metabolic health remain unclear.<br><br>CONCLUSION: Since fluoride contaminates drinking water in areas with an endemic tendency, defluoridation, exposure monitoring, and public awareness are essential preventive strategies. Future mechanistic and clinical studies are necessary to elucidate the pathways linking fluoride metabolic disease progression.}, }
@article {pmid41390118, year = {2025}, author = {Dai, Z and Bao, X and Jiang, H and Zhang, Y and Shen, Q and Xue, Y}, title = {Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.010}, pmid = {41390118}, issn = {2090-1224}, abstract = {INTRODUCTION: Consumption of gran proteins has been associated with lower risk of type 2 diabetes (T2D), but the underlying mechanisms remain unclear. Gut microbiota plays a key role in glucose metabolism, and dietary proteins can modulate microbial composition and function.<br><br>OBJECTIVE: This study aims to evaluate the effects of grain proteins on glucose metabolism, identify key gut microbiota-derived metabolites, and elucidate the molecular mechanisms underlying grain protein-mediated glucose metabolism regulation.<br><br>METHODS: Glucose homeostasis and gut microbiota composition were assessed in mice fed a high-fat diet (HFD) supplemented with proteins isolated from rice, soybean, highland barley (HB), oats, and quinoa. The alterations in gut microbiota and their causal roles in glucose regulation were determined by in vitro fermentation and fecal microbiota transplantation (FMT). Key tryptophan (Trp) metabolites in fecal and serum samples were identified, and their glucose-regulating effects were validated in mice and HepG2 cells. Liver transcriptomics and molecular analyses were subsequently performed to elucidate the underlying regulatory pathways.<br><br>RESULTS: HB, oat, and quinoa proteins significantly improved glucose metabolism, increased Lactobacillus and Bifidobacterium abundance, and enriched Trp-derived metabolites. FMT reproduced the metabolic improvements in recipient mice, supporting a microbiota-mediated mechanism. Among Trp metabolites, indole-3-ethanol (IEt), indole-3-acrylic acid (IArA), and indole-3-aldehyde (IAld) promoted glucose homeostasis via aryl hydrocarbon receptor (AhR) activation and intestinal homeostasis maintenance. Cell-based and liver transcriptomic analyses demonstrated that these metabolites suppressed hepatic gluconeogenesis by modulating the Nemo-like kinase (NLK)/forkhead box protein O1 (FOXO1)/phosphoenolpyruvate carboxykinase 1 (PCK1)/glucose-6-phosphatase (G6PC) pathway.<br><br>CONCLUSIONS: Grain proteins alleviate glucose metabolic disorders by enriching gut microbiota-derived indole metabolites, which improve intestinal homeostasis and inhibit hepatic gluconeogenesis through AhR and NLK/FOXO1 signaling. These findings highlight the therapeutic potential of grain proteins for T2D prevention and management.}, }
@article {pmid41390455, year = {2025}, author = {Isnard, S and Berini, CA and Parvathy, SN and Feng, H and Aiyana, O and Royston, L and Mabanga, T and Lakatos, PL and Bessissow, T and Klein, MB and Lebouché, B and Costiniuk, CT and Routy, B and Silverman, MS and Routy, JP}, title = {Fecal microbiota transplantation to reduce immune activation in ART-treated people with HIV with low CD4/CD8 ratio: protocol for the single-blind, randomized, placebo-controlled Gutsy study (CIHR/CTN PT038).}, journal = {Trials}, volume = {27}, number = {1}, pages = {52}, pmid = {41390455}, issn = {1745-6215}, support = {CTN PT038//Canadian HIV Trials Network, Canadian Institutes of Health Research/ ; Cell Therapy network//Fonds de Recherche du Qu&#xe9;bec - Sant&#xe9;/ ; }, mesh = {Humans ; *HIV Infections/immunology/drug therapy/diagnosis/therapy/microbiology/virology ; Single-Blind Method ; *Fecal Microbiota Transplantation/adverse effects ; *Lymphocyte Activation ; CD4-CD8 Ratio ; *Gastrointestinal Microbiome ; Treatment Outcome ; *Anti-HIV Agents/therapeutic use/adverse effects ; Viral Load ; Time Factors ; Randomized Controlled Trials as Topic ; *Anti-Retroviral Agents/therapeutic use ; Dysbiosis/immunology/therapy ; Male ; }, abstract = {BACKGROUND: Despite antiretroviral therapy (ART) controlling HIV viral replication, people with HIV (PWH) remain at risk for inflammatory non-AIDS comorbidities. Factors contributing to comorbidities in PWH on ART include spontaneous release of HIV products, CMV co-infection, microbial translocation, and gut dysbiosis, each driving systemic T-cell activation. In addition to ART, novel gut microbiota-modulating therapies could reduce epithelial gut permeability, microbial translocation, and immune activation. Fecal microbiota transplantation (FMT) from healthy volunteer is a promising therapy to counteract dysbiosis, protect from gut barrier damage, and lower systemic immune activation.<br><br>METHODS: The Gutsy study is a single-blind, randomized, placebo-controlled clinical trial evaluating the effects of FMT in PWH on ART for more than 3&#xa0;years, with a viral load below 50 copies/mL, a CD4 count above 200 cells/mL, and a CD4/CD8 ratio below 1.0. All participants undergo a bowel cleanse before receiving FMT or placebo capsules. In the treatment group, 10 participants receive a bowel cleanse then two high doses of FMT delivered via 30 to 40 capsules twice, 3&#xa0;weeks apart. The placebo group of 10 participants receive a bowel cleanse and capsules filled with microcrystalline cellulose for equivalence in weight and color, administered under the same time course. Peripheral blood mononuclear cells (PBMCs) and stool samples are collected at each visit: before bowel cleanse (baseline 1), before the first (baseline 2) and the 2nd (visit 4) FMT/placebo, 6&#xa0;weeks (visit 5) and 12&#xa0;weeks (visit 6) after the first FMT/placebo; colon biopsies are obtained at visits 3 and 6 in an optional sub-study. The primary objective is to assess the effect of FMT on plasma markers of gut epithelial permeability. Secondary objectives include microbial translocation, immune activation, and HIV latent reservoir biomarkers.<br><br>DISCUSSION: We hypothesize that large-dose FMT in capsules, but not placebo capsules, will increase the abundance of beneficial microbes in the gut of PWH on ART, leading to decreased gut damage markers and reduced immune activation. The results of the Gutsy pilot study will inform for the calculation of sample size of larger definitive randomized clinical trials assessing the influence of FMT on immune activation in PWH.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT06022406. Registered on 2024-08-01. https://clinicaltrials.gov/study/NCT06022406?cond=HIV&amp;term=Gutsy&amp;rank=1 .}, }
@article {pmid41390868, year = {2025}, author = {Iskander, O and Michot, N and Courtot, L and Bourbao-Tournois, C and Artus, A and Thiery, J and Deffain, A and Proutheau, G and Bouayed, A and Salame, E and Demtröder, CR and Giger-Pabst, U and Ouaïssi, M}, title = {Evaluating the influence of metabolic bariatric surgery on urinary and fecal incontinence outcomes: a one-year postoperative analysis.}, journal = {Langenbeck's archives of surgery}, volume = {411}, number = {1}, pages = {47}, pmid = {41390868}, issn = {1435-2451}, abstract = {PURPOSE: The most prevalent conditions affecting the pelvic floor include fecal incontinence (FI) and urinary incontinence (UI), both of which are particularly common among women with obesity. Although the effect of metabolic bariatric surgery (MBS) on FI remains a topic of ongoing discussion, the present study seeks to assess the impact of effective bariatric surgery on UI and FI in women with obesity. MATERIALS AND METHODS: An observational prospective study was conducted at the Tours University Hospital, involving 212 women who underwent MBS. Participants completed pre-operative and post-operative questionnaires to evaluate UI and FI one-year after surgery. Additionally, urinary symptom profile (USP) and Wexner score (WS) were utilized for the assessment of UI and FI, respectively. RESULTS: Of the 212 patients, 148 achieved a weight loss of more than 20% of their weight one-year after surgery, and of these 40 (27.0%) completed all questionnaires. The median pre-surgical BMI was found to be 41.8 kg/m[2], which reduced to 29.1 kg/m[2] one-year post-surgery. A significant improvement was observed in stress urinary incontinence (SUI), which decreased from 32.5% pre-operatively to 22.5% post-operatively (p < 0.0001). FI showed slight exacerbation, with an increase in moderate FI (from 5.0% to 10.0%), frequency of liquid stool per week (from 2.5% to 5.0%), and gas-related symptoms (from 0 to 2.5%). CONCLUSION: The findings of this study indicate that MBS significantly improves SUI in women with obesity, yet has minimal impact on FI one-year postoperatively. Further studies are required to more accurately assess the impact of metabolic bariatric surgery on postoperative FI.}, }
@article {pmid41391320, year = {2026}, author = {Tang, N and Deng, G and Jin, Z and Chen, J and Wang, D and Luo, Y and Luo, Y and Zhang, G}, title = {Bacillus sp. S361 isolated from bioaerosols in pharmaceutical wastewater treatment plants aggravates Klebsiella pneumoniae-induced lung injury in rats by modulating the gut microbiota.}, journal = {Journal of hazardous materials}, volume = {501}, number = {}, pages = {140669}, doi = {10.1016/j.jhazmat.2025.140669}, pmid = {41391320}, issn = {1873-3336}, mesh = {Animals ; *Bacillus/isolation &amp; purification/genetics ; *Klebsiella pneumoniae/pathogenicity ; Aerosols ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Wastewater/microbiology ; *Lung Injury/microbiology/chemically induced ; Male ; Rats, Sprague-Dawley ; *Klebsiella Infections/microbiology ; }, abstract = {Current research on bioaerosol diversity in pharmaceutical wastewater treatment plants (PWWTPs) remains limited, especially concerning pulmonary injury mechanisms. Bacterial diversity in two PWWTPs was investigated via high-throughput sequencing and culture-based isolation, revealing functional interactions with pathogenic Klebsiella pneumoniae (Kpn). Emissions showed bimodal size distributions: Plant A dominated by ≥ 7μm particles, Plant B by 0.65-1.1μm submicron fractions enriched with Pseudomonadota (formerly Proteobacteria). Strain S361 (Bacillus sp., Bacillota) isolated from AeT1 exhibited significant synergistic pathogenicity with Kpn. Whole-genome sequencing identified 51 antibiotic resistance genes (ARGs) across 12 resistance mechanisms and 86 virulence factors in Bacillus sp. S361. Mechanistically, Bacillus sp. S361 synergistically enhances pulmonary colonization and pathogenicity of Kpn via distinctive metabolic crosstalk. Co-exposure to S361 and Kpn disrupts gut microbiota homeostasis, inducing dysregulated short-chain fatty acid (SCFA) metabolism and intestinal barrier impairment. This gut-derived dysfunction mediates systemic inflammation through the gut-lung axis, ultimately amplifying Kpn-induced lung injury. Fecal microbiota transplantation (FMT) experiments confirmed gut microbiota's mediating role, as recipient rats developed pathological changes (alveolar septal thickening, inflammatory infiltration) mirroring co-infected groups. Notably, microbiota-depleted rats suffered more severe lung injury than protected counterparts, establishing gut dysbiosis as a critical determinant of pulmonary damage. These findings implicate PWWTP bioaerosols in driving Kpn pathogenicity via Bacillus sp. S361-mediated synergy and gut-lung dysregulation, necessitating targeted interventions for occupational risk mitigation.}, }
@article {pmid41391369, year = {2026}, author = {Wang, S and Wu, J and Xu, L and Wu, S and Pei, X and Wang, H and Deng, L and Xu, H and Chen, X}, title = {WenDan Decoction activates neuronal autophagy in the hippocampus via the gut-brain axis to improve depressive-like behavior in HFD mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157686}, doi = {10.1016/j.phymed.2025.157686}, pmid = {41391369}, issn = {1618-095X}, mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology ; *Autophagy/drug effects ; *Depression/drug therapy ; Mice ; Gastrointestinal Microbiome/drug effects ; Male ; *Hippocampus/drug effects ; *Antidepressive Agents/pharmacology ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Neurons/drug effects ; *Brain-Gut Axis/drug effects ; Behavior, Animal/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: High-fat diet (HFD) is implicated in depression pathogenesis. WenDan Decoction (WDD), a classical traditional Chinese medicine formula, shows promise for metabolic and psychiatric disorders, but its precise mechanisms require elucidation.<br><br>METHODS: The chemical constituents of WDD were characterized by UPLC-MS/MS. The antidepressant effects of WDD in HFD mice were evaluated through behavioral tests, ELISA, and histopathology. Gut-brain axis mechanisms were investigated via 16S rRNA sequencing, untargeted metabolomics, network pharmacology, Nissl staining, transmission electron microscopy, Western blot, and RT-qPCR. Validation was performed through antibiotic depletion, fecal microbiota transplantation (FMT), and exogenous prostaglandin F2&#x3b1; (PGF2&#x3b1;) supplementation experiments.<br><br>RESULTS: WDD administration significantly ameliorated depressive-like behaviors of HFD mice with relatively low hepatorenal toxicity. It restored intestinal mucosal integrity, mitigated inflammation, re-established gut microbial homeostasis and subsequently regulated arachidonic acid metabolism. Correlation analysis revealed that the strongest negative association between the differential microbiota Lactobacillus murinus and the arachidonic acid metabolite PGF2&#x3b1;. WDD attenuated blood-brain barrier disruption by diminishing pro-inflammatory metabolites, suppressed PI3K/AKT/mTOR pathway, and restored autophagic flux, thereby rescuing neuronal ultrastructural and functional impairments. The application of PI3K agonists reversed the effective regulation of WDD. Crucially, FMT experiments further confirmed that the gut microbiota and metabolite PGF2&#x3b1; are essential for WDD's antidepressant effects.<br><br>CONCLUSION: WDD ameliorates depressive-like behaviors in HFD mice by modulating the gut microbiota and metabolism to suppress PI3K/AKT/mTOR pathway activation and restore autophagic flux. This study provides crucial mechanistic insights into WDD's effects against depression.}, }
@article {pmid41392089, year = {2025}, author = {Wilson, BC and Tweedie-Cullen, RY and Albert, BB and Derraik, JGB and Ho, D and Depczynski, M and Creagh, C and Edwards, T and Gali, S and Thabrew, H and Cutfield, WS and O'Sullivan, JM}, title = {Encapsulated faecal microbiota transfer in young women with anorexia nervosa: an open-label feasibility pilot trial.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {571}, pmid = {41392089}, issn = {2041-1723}, mesh = {Humans ; *Anorexia Nervosa/therapy/microbiology ; Female ; Pilot Projects ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome/physiology ; Feasibility Studies ; Young Adult ; Adult ; Adolescent ; Treatment Outcome ; Feces/microbiology ; }, abstract = {Perturbations of the gut microbiome have been associated with anorexia nervosa (AN) suggesting microbiome-modulation treatments, like faecal microbiota transfer (FMT), may offer therapeutic benefits. This open-label feasibility pilot trial evaluated the tolerability and microbiological impact of encapsulated, multi-donor FMT in 18 young women with AN (Registration: ACTRN12621001504808). Participants completed clinical and microbiome assessments at enrolment (3 weeks pre-treatment), baseline, and 3, 6, and 12 weeks post-treatment. Fifteen participants completed FMT, and 11 completed the final follow-up. The primary outcome was the change in gut microbiome composition from baseline to 3 weeks compared with natural variation between enrolment and baseline. FMT produced a significantly greater shift post-treatment (mean ± SD Bray-Curtis dissimilarity 0.36 ± 0.11; p = 0.0007), with participants gaining 38 ± 16 new species. Donor-derived strains comprised 41 ± 12% of the microbiome at 3 weeks, with engraftment persisting at 6 and 12 weeks. FMT was generally well tolerated; adverse events were mostly mild to moderate and overlapped with typical AN symptomatology. Monitoring of clinical outcomes supported the safety profile and suggested potential improvements in anxiety and metabolic parameters; however, the small sample and absence of a control arm preclude safety and efficacy inference. Overall, these findings warrant further investigation through randomised controlled trials in AN.}, }
@article {pmid41392314, year = {2025}, author = {Abahussin, HM and Alotaibi, MS and Alhazzaa, OA and Alotaibi, AG and Alsaab, SM and Aljawini, NA and Alawad, AO}, title = {Exploring the intricate link between gut microbiota dysbiosis and the aging process: implications for age-related diseases.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {3}, pmid = {41392314}, issn = {1757-4749}, abstract = {Aging is a complex process marked by the gradual accumulation of impairments in molecules and tissues, leading to frailty and dysfunction. This decline is a significant risk factor for many debilitating conditions. Recently, gut microbiota dysbiosis has been identified as one of the hallmarks of aging. This review sheds light on the role of gut microbiota dysbiosis in accelerating aging and its relation to age-associated diseases, including neurodegenerative disorders, cardiovascular diseases, cancer and diabetes. Emerging research demonstrates a strong link between the gut microbiome and the aging process, although the underlying mechanisms remain under investigation. Animal studies suggest that targeting the gut microbiome may offer a promising approach to mitigate aging and related diseases. However, further human studies are needed to confirm these findings.}, }
@article {pmid41393108, year = {2025}, author = {Sun, Y and Yang, H and Zhang, J and Cong, S and Wang, L and Yu, T}, title = {Development and emerging trends in gastrointestinal dysfunction of Parkinson's disease: a decade-long bibliometric analysis.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1712302}, pmid = {41393108}, issn = {1663-4365}, abstract = {Gastrointestinal (GI) dysfunction represents a prevalent non-motor symptom of Parkinson's disease (PD) that not only contributes significantly to disease progression but also substantially compromises patients' quality of life. Over the past decade, research in this domain has expanded considerably. To systematically delineate the knowledge framework and evolving trends, we performed a bibliometric analysis of publications on GI and PD from 2015 to 2025. A total of 924 articles were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence, clustering, and collaboration network analyses were performed using VOSviewer, CiteSpace, and the R package Bibliometrix. For findings validation, the PubMed database was incorporated as an independent external validation dataset, providing complementary verification of keyword analyses derived from WoSCC. Our analysis revealed a steady annual increase in publication output. China and the United States emerged as the most prolific contributors globally, with the latter attaining the highest total citation count. At the institutional level, Capital Medical University led in publication output, whereas the University of Helsinki ranked highest in both total and average citations. Among journals, Parkinsonism &amp; Related Disorders published the most papers on this topic, while Movement Disorders received the most citations. Keyword cluster analyses identified three primary research frontiers: (1) pathogenesis, focusing on α-synuclein (α-syn), the brain-gut-microbiome axis, and the enteric nervous system; (2) clinical manifestations, especially dysphagia and constipation; and (3) therapeutic interventions, particularly fecal microbiota transplantation and probiotics. By integrating established knowledge and highlighting emerging trends, this review aims to inform and guide future research and clinical practice in the field of gastrointestinal dysfunction in PD.}, }
@article {pmid41393538, year = {2025}, author = {Manoria, PC}, title = {The Obesity Drug Revolution: New Frontiers in Pharmacotherapy.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96713}, pmid = {41393538}, issn = {2168-8184}, abstract = {Obesity is the most prevalent condition in high-income nations, primarily associated with increased risk of diabetes, cardiovascular disease (CVD), hypertension, and hyperlipidemia. Lifestyle modifications are a key determinant in non-pharmacological management that includes a combination of nutritional therapy, a low-calorie diet, and exercise. Earlier, anti-obesity drugs had been withdrawn from the market due to their safety profiles with cardiovascular and neuropsychiatric toxicity. The current FDA-approved pharmacotherapy consists of orlistat, setmelanotide, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide. Among these, semaglutide has a better clinical and regulatory profile with the feasibility of dosing and frequency. Orforglipron, a non-peptide oral glucagon-like peptide-1 receptor agonist, offers parenteral efficacy with convenient dosing. Probiotics, prebiotics, and fecal microbiota transplantation promote moderate weight loss by regulating metabolism and inflammation. Mitochondrial uncouplers help energy utilization rather than appetite regulation, which focuses on metabolic efficiency. A few challenges in obesity management are financial barriers, weight-promoting medications, inadequate obesity training, discomfort with prescribing, and lack of reimbursement. Innovative therapeutic approaches, multidisciplinary care, and a patient-centered plan are required for better clinical outcomes. This review highlights the current and emerging therapies designed to enhance long-term outcomes in obesity care.}, }
@article {pmid41395292, year = {2025}, author = {Ren, H and Wen, J and Liu, J and Wang, L}, title = {Gut microbiota in immunomodulation and infection prevention among multiple myeloma patients after chemotherapy: current evidence and clinical prospects.}, journal = {American journal of cancer research}, volume = {15}, number = {11}, pages = {4621-4638}, pmid = {41395292}, issn = {2156-6976}, abstract = {Multiple Myeloma (MM) is the second most common hematological malignancy, with its pathogenesis involving complex cytogenetic variations, tumor clonal evolution, and dynamic interactions between tumor cells and bone marrow stromal microenvironment. Recent studies highlight the role of the intestinal microbiota, a key component of the tumor-associated microenvironment, in regulates MM occurrence, progression, and treatment response via the "gut-bone marrow axis". Under physiological conditions, it protects the local microenvironment by regulating host metabolism and maintaining immune homeostasis. However, intestinal dysbiosis causes metabolic disorders and immune surveillance defects, promoting tumor growth, drug resistance, and poor prognosis. Though traditional treatments such as chemotherapy and hematopoietic stem cell transplantation have been optimized, chemotherapy disrupts intestinal mucosal integrity and impairs immunity, significantly increasing post-chemotherapy infections. These infections can interrupt treatment, worsen conditions, and reduce quality of life, leaving MM still intractable. Notably, microbiota-targeted interventions (e.g., probiotics, fecal microbiota transplantation [FMT]) have shown potential to reduce infection risk by restoring microbiota balance and repairing intestinal barriers. These interventions may also exert potential anti-tumor effects through immune microenvironment regulation and alleviate chemo/radiotherapy-related adverse reactions (e.g., nausea, diarrhea), offering a new direction for relapsed/refractory MM. This article summarizes the molecular regulatory network of the intestinal microbiota in the pathogenesis of MM and the research progress of microbiota-based interventions, aiming to provide a foundation for developing novel microbiome-oriented precision treatment regimens and improving chemotherapy tolerance and patient prognosis.}, }
@article {pmid41395459, year = {2025}, author = {Li, Q and Liu, Y}, title = {Analyzing the gut liver axis: a dual role of the microbiome in the genesis, progression, and treatment of liver cell carcinoma.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1701101}, pmid = {41395459}, issn = {1664-302X}, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, and the poor prognosis highlights the pressing need for innovative therapeutic strategies. The gut-liver axis, a critical bidirectional pathway linking the gut microbiota to the liver, plays a pivotal role in HCC pathogenesis. This review systematically delineates current evidence on how gut dysbiosis, compromised intestinal barrier function, and resultant microbial metabolites (e.g., bacterially metabolized bile acids) drive hepatocarcinogenesis via specific signaling pathways, while also addressing the loss of protective effects due to the depletion of beneficial microbes. Moving beyond descriptive summaries, this article focuses on elucidating the core molecular mechanisms of microbiome-regulated HCC-a key knowledge gap that remains unaddressed-and reconciles conflicting findings into a unified framework. We further explore the translational potential of microbiome signatures as non-invasive biomarkers and evaluate microbiota-targeting interventions (e.g., probiotics, dietary modulation, fecal microbiota transplantation) for enhancing treatment efficacy. Ultimately, this review aims to provide a clear roadmap for developing microbiome-based precision medicine in HCC, with the goal of improving clinical management and patient outcomes.}, }
@article {pmid41395479, year = {2025}, author = {Yang, J and Wang, J and Li, J and Yang, S}, title = {Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711299}, pmid = {41395479}, issn = {1664-302X}, abstract = {Pulmonary fibrosis (PF) is a progressive and life-threatening interstitial lung disease with irreversible lung function loss. The bidirectional interaction between respiratory and gut microbiota mediated by the "lung-gut axis" has emerged as a core regulatory link in PF pathogenesis. This review integrates clinical and preclinical data to systematically clarify the association between microbiota dysbiosis and PF. Clinical evidence shows that PF patients (including idiopathic pulmonary fibrosis, silicosis, and coal workers' pneumoconiosis) exhibit reduced pulmonary microbiota diversity, increased pro-inflammatory microbial abundance, and altered gut microbiota composition. Preclinical studies using bleomycin or silica-induced PF models confirm consistent microbiota changes and abnormal metabolites. Further, five core pathophysiological mechanisms (immune dysregulation, gut-lung barrier dysfunction, sustained activation of Type 2 epithelial-mesenchymal transition, autophagy modulation, and alveolar epithelial cell apoptosis mediated by microbial peptides) explain how microbiota alterations drive PF progression. Key microbial mediators (e.g., tryptophan metabolites, short-chain fatty acids, lipopolysaccharide, bile acid metabolites) exert bidirectional regulatory effects on PF through synergistic or antagonistic interactions. Additionally, microbiota-targeted strategies such as probiotic/prebiotic intervention, fecal microbiota transplantation, dietary adjustment, and antibiotics have shown experimental anti-fibrotic efficacy. This review highlights the gut microbiota as a potential therapeutic target for PF, while discussing current challenges (e.g., unclear causal relationship, lack of standardized intervention protocols) and future research directions, providing a new framework for PF mechanism research and clinical intervention.}, }
@article {pmid41395487, year = {2025}, author = {Bai, Z and Wang, Y and Li, Y and Xu, J and Lai, Z}, title = {The gut microbiota in liver transplantation recipients during the perioperative and postoperative recovery period.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1684303}, pmid = {41395487}, issn = {1664-302X}, abstract = {BACKGROUND: Chronic Liver Disease (CLD) is one of the frequent causes of death, especially in the developing world. Liver transplantation (LT) is an effective modality to treat end-stage liver disease. Perioperative management of liver transplantation patients and prevention of postoperative complications are the key to improving patient prognosis and quality of life, and the intestinal flora of these patients can affect postoperative complications and overall prognosis.<br><br>METHOD: We collected a total of 151 fecal samples from 59 liver transplantation patients at different stages from the First Hospital of Shanxi Medical University. Using 16S rRNA sequencing technology, we compared the characteristics and changes of their microbiota. We selected 42 samples for metagenomic sequencing using the microPITA method to further analyze the composition and functional differences of the microbiota during the perioperative period of liver transplantation across various time points.<br><br>RESULTS: After liver transplantation (LT), the diversity of gut microbiota initially decreased and then increased. Firmicutes, Proteobacteria, and Bacteroidota were the main bacterial groups during the perioperative period. Firmicutes and Proteobacteria initially decreased and then increased, while Bacteroidota exhibited the opposite process. Alpha diversity and beta diversity analyses indicated that 1 month post-transplantation was a turning point for microbiota recovery (P < 0.01). Metagenomic sequencing, analyzed using the LEfSe method, identified a total of 50 genera that played significant roles in this process. The changes in microbiota exhibited the same trend as the 16S rRNA results. KEGG pathway analysis also indicated that 1 month was a critical time point, with Ko02010 potentially being a key pathway for recovery in LT patients, and it showed a negative correlation with Bacteroidota (P < 0.05).<br><br>CONCLUSION: The diversity of intestinal flora in the perioperative period of LT patients decreased first and then increased, and the turning point of intestinal flora recovery was 1 month after LT surgery.}, }
@article {pmid41395840, year = {2025}, author = {Wang, J and Wei, Y and Chen, D and Li, X and Zhang, H and Feng, S and Lu, S and Yang, J and Zeng, Q and He, X and Wu, L}, title = {Targeted Therapy for Gut Microbiota: Candidates for a Novel Strategy to Ameliorate Type 2 Diabetes Mellitus.}, journal = {Microbial biotechnology}, volume = {18}, number = {12}, pages = {e70283}, pmid = {41395840}, issn = {1751-7915}, support = {2022B1111070006//the Key-Area Research and Development Program of Guangdong Province/ ; 2025A1515011113//the Basic and Applied Basic Research Fund of Guangdong Province/ ; 2023A1515012578//the Basic and Applied Basic Research Fund of Guangdong Province/ ; 2025KTSCX058//the Characteristic Innovation Project of Regular Colleges and Universities in Guangdong Province/ ; 32202380//the National Natural Science Foundation of China/ ; B2022209//the Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//the Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; }, mesh = {*Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Fecal Microbiota Transplantation/methods ; Probiotics/administration &amp; dosage/therapeutic use ; Prebiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; Animals ; }, abstract = {Type 2 diabetes mellitus (T2DM) poses a significant threat to public health and is associated with the gut microbiota. Gut microbiota modulators, including probiotics, prebiotics, and synbiotics, together with faecal microbiota transplantation (FMT), can restore the gut microbiota in patients and are recognised as powerful modulators of this ecosystem. Consequently, gut microbiota modulators are promising in the prevention and treatment of T2DM. The roles and mechanisms by which these therapeutic approaches target the gut microbiota in patients with T2DM warrant further investigation and elucidation. Key potential mechanisms associated with gut microbiota regulation include the modulation of gut microbiota composition alteration of gut microbiota metabolites, enhancement of intestinal barrier function, and suppression of inflammation. This study provides a comprehensive review of the relationship between the gut microbiota and T2DM, presents promising research findings and controversial issues, emphasises the potential roles and mechanisms of the gut microbiota in T2DM, and investigates the factors influencing the therapeutic efficacy of FMT. This review serves as a valuable reference for future studies on FMT.}, }
@article {pmid41397742, year = {2025}, author = {Kragsnaes, MS and Gilbert, BTP and Sofíudóttir, BK and Rooney, CM and Hansen, SM and Mauro, D and Mullish, BH and Bergot, AS and Mankia, KS and Goel, N and Bakland, G and Johnsen, PH and Miguens Blanco, J and Li, S and Dumas, E and Lage-Hansen, PR and Wagenaar, C and Bakdash, G and Robinson, M and Kristiansen, K and Marchesi, JR and Schett, G and Zaiss, MM and Orlu, M and van Schaadenburg, D and Scher, JU and McGonagle, D and Elewaut, D and Breban, M and Tugwell, P and Finckh, A and Ciccia, F and Kriegel, MA and Daien, C and Ellingsen, T and Christensen, R and , }, title = {Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e101593}, pmid = {41397742}, issn = {2044-6055}, mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; *Gastrointestinal Microbiome ; *Rheumatic Diseases/therapy/microbiology ; *Autoimmune Diseases/therapy/microbiology ; Probiotics/therapeutic use ; Research Design ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {INTRODUCTION: An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.<br><br>METHODS AND ANALYSIS: This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.<br><br>ETHICS AND DISSEMINATION: No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.<br><br>PROSPERO REGISTRATION NUMBER: CRD42025644244.}, }
@article {pmid41397823, year = {2025}, author = {Huang, YS and Tong, WD and Xiao, GD and Li, Q and Guo, M}, title = {[Transformation and evidence-based progress of chronic constipation treatment mode].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {12}, pages = {1411-1416}, doi = {10.3760/cma.j.cn441530-20251013-00379}, pmid = {41397823}, issn = {1671-0274}, support = {82370547//National Natural Science Foundation of China/ ; CSTB2023NSCQZDJ0012//Key Project of Chongqing Natural Science Foundation/ ; 2022XLC05//Clinical Innovation Research Project of Army Medical University/ ; }, mesh = {Humans ; *Constipation/therapy ; Chronic Disease ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, significant progress has been made in the treatment of chronic constipation, with high-quality studies emerging in areas such as fecal microbiota transplantation (FMT), sacral neuromodulation (SNM), acupuncture, and surgical techniques. The therapeutic approach is shifting from a traditional "medication and surgery" model toward an integrated strategy that includes dietary and defecation habit adjustment, FMT, SNM, acupuncture, pharmacotherapy, and surgery. Although FMT can partially improve stool frequency and consistency, its standardization and long-term efficacy require further validation. SNM demonstrates limited effectiveness in treating chronic constipation and is relatively cost-inefficient. Electroacupuncture remains controversial, though some studies support its value. Biofeedback therapy is recommended by multiple guidelines as the first-line treatment for dyssynergic defecation (DD), with portable home-based biofeedback systems showing considerable potential. For internal rectal prolapse (IRP) and rectocele (RC), various surgical options exist without a clear superiority, though laparoscopic ventral rectopexy (VMR) is increasingly favored due to its low recurrence rate and high patient satisfaction. In the surgical management of slow transit constipation (STC), total colectomy with ileorectal anastomosis remains the mainstream approach, while subtotal colectomy is gaining attention as an alternative.}, }
@article {pmid41397827, year = {2025}, author = {Mei, ZB and Cao, YL and Lv, BB and Wang, SY and Tian, K and Liu, QL and Ma, LZ and Wang, YS and Wei, D}, title = {[Efficacy observation of pelvic floor autologous fascia integrated repair based on membrane anatomy for complete rectal prolapse].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {12}, pages = {1441-1447}, doi = {10.3760/cma.j.cn441530-20250810-00300}, pmid = {41397827}, issn = {1671-0274}, support = {LHGJ20250781//Medical Science and Technology Project of Henan Province/ ; }, mesh = {Humans ; Retrospective Studies ; *Pelvic Floor/surgery ; *Fascia/transplantation ; *Rectal Prolapse/surgery ; Female ; Treatment Outcome ; Male ; Laparoscopy ; Middle Aged ; Aged ; Adult ; Quality of Life ; }, abstract = {Objective: To compare the clinical efficacy of laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy versus transperineal proctosigmoidectomy (Altemeier procedure) in the treatment of patients with complete rectal prolapse (CRP). Methods: This study employed a retrospective observational cohort design. Clinical data were collected from a total of 55 CRP patients who underwent surgical treatment between January 2018 and July 2023, including 25 patients from Luoyang Central Hospital, affiliated with Zhengzhou University, and 30 patients from the 989th Hospital of the Joint Logistics Support Force &amp; Military Anorectal Surgery Research Institute. All patients undergoing surgery met the following criteria: aged ≥ 18 years, rectal prolapse protruding outside the anus, prolapse length > 5 cm with inability to self-reduce, conforming to the diagnostic criteria for CRP, and being first-time treated patients. Twenty-seven patients who underwent the Altemeier procedure between January 2018 and March 2021 were assigned to the Altemeier group; 28 patients who underwent laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy between April 2021 and July 2023 were assigned to the integral repair group. The therapeutic efficacy differences between the two groups were analyzed and compared, including the CRP length (DCRP), Wexner Constipation Score, Wexner Fecal Incontinence Score, and Gastrointestinal Quality of Life Index (GIQLI) before surgery and at 6, 12, and 24 months after surgery, as well as postoperative complications and recurrence at 24 months after surgery. Results: There were no statistically significant differences between the two groups in terms of gender distribution, age, preoperative body mass index (BMI), defecation frequency, DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI (all P>0.05). All patients completed the surgery. The length of hospital stay and intraoperative blood loss in the integral repair group were significantly less than those in the Altemeier group (both P<0.01). At 6, 12, and 24 months after surgery, the DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in both groups significantly improved compared with the preoperative values (all P<0.001). At 6, 12, and 24 months after surgery, the CRP treatment effect, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in the integral repair group were significantly better than those in the Altemeier group (χ[2]=15.821, P<0.001; χ[2]=18.238, P<0.001; χ[2] = 12.558, P=0.001; and χ[2] =22.413, P<0.001, respectively). In the integral repair group, 4 patients (14.3%) developed grade I-III postoperative complications, including 2 cases of urinary retention, 1 case of anastomotic bleeding, and 1 case of anastomotic stenosis. In the Altemeier group, 11 patients (40.7%) developed grade I-III postoperative complications, including 4 cases of urinary retention, 3 cases of anastomotic bleeding, 1 case of anastomotic stenosis, 2 cases of intestinal fistula, and 1 case of fecal incontinence. The difference between the two groups was statistically significant (χ[2]=4.850, P=0.028). There was no recurrence of CRP in the integral repair group at 24 months after surgery, while 7 cases of CRP recurrence were observed in the Altemeier group at 24 months after surgery. The difference between the two groups was statistically significant (χ[2]=6.148, P=0.013). Conclusion: The autologous fascia repair technique based on membrane anatomy and the pelvic floor integral theory is superior to the transperineal Altemeier procedure in the treatment of CRP. Furthermore, it is an effective surgical method for CRP.}, }
@article {pmid41398400, year = {2025}, author = {Myagmankhuu, S and Tsuji, S and Akagawa, S and Kino, J and Akagawa, Y and Yamanouchi, S and Kaneko, K}, title = {Depletion of gut microbiota alleviates proteinuria in puromycin aminonucleoside-induced nephrosis in rats.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {41398400}, issn = {1530-0447}, abstract = {BACKGROUND: The gut-kidney axis has been implicated in chronic kidney disease, however its role in minimal change nephrotic syndrome (MCNS) is poorly understood. We investigated the impact of gut microbiota on proteinuria in MCNS.<br><br>METHODS: A puromycin aminonucleoside (PAN)-induced rat model of MCNS was used. Rats received a cocktail of antibiotics, PBS (control), or antibiotics plus indoxyl sulfate (IS). To assess causality, fecal microbiota transplantation (FMT) was performed in additional PAN rats. Urinary protein, kidney histology, urinary IS, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and gut microbiota composition were evaluated.<br><br>RESULTS: On day 8 after PAN injection, antibiotic-treated rats exhibited markedly reduced proteinuria (1.4&#x2009;g/gCre) compared with controls (16.8&#x2009;g/gCre, p&#x2009;=&#x2009;0.014), whereas IS-treated rats developed severe proteinuria (117.3&#x2009;g/gCre). Electron microscopy revealed podocyte foot process effacement in control and IS-treated rats but not in antibiotic-treated rats. Antibiotic-treatment decreased indole-producing bacteria, lowered urinary IS, and reduced 8-OHdG levels, indicating attenuation of oxidative stress. Importantly, FMT abolished the protective effect of antibiotics, re-emerging proteinuria.<br><br>CONCLUSION: Depletion of the gut microbiota by antibiotic treatment in a rat MCNS model alleviated proteinuria, which was reversed by FMT. This causally implicates gut microbiota, particularly indole-producing bacteria that generate toxins including IS, as a key therapeutic target for MCNS.<br><br>IMPACT: This study demonstrated that depleting the gut microbiota with antibiotics reduced proteinuria in a rat model of minimal change nephrotic syndrome, suggesting that harmful gut bacteria play a critical role in this disease. This research also identified indoxyl sulfate as a key uremic toxin produced by gut bacteria that worsens proteinuria and kidney damage, highlighting its role in disease progression. These findings could lead to novel treatments that target gut microbiota, including antibiotics or activated charcoal adsorbents that reduce proteinuria in minimal change nephrotic syndrome, and potentially minimize steroid use.}, }
@article {pmid41398688, year = {2025}, author = {Zhong, W and Feng, R and Liang, H and Hu, J and Zhou, S and Liu, D and Li, S and Liao, G and Liao, J and Yang, S and Zhang, Y and Xiao, X and Qian, J and Chen, H and Fan, L and Li, M and Zhao, M and Chen, J and Liu, Y}, title = {Longitudinal profiling of gut microbiota dynamics in kidney transplant recipients.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {91}, pmid = {41398688}, issn = {1479-5876}, support = {No. 2022A1515012304 &amp; 2023A1515110205//Basic and Applied Basic Research Foundation of Guangdong Province/ ; No. 82170764 &amp; 82403882//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The gut microbiota undergoes substantial alterations in kidney transplant recipients, which are linked to postoperative complications and renal function recovery. However, the underlying mechanisms of these associations remain unclear.<br><br>METHODS: We conducted a prospective, longitudinal cohort study at our center. Fecal samples were collected from 88 kidney transplant recipients at multiple time points before and after surgery. The gut microbiota dynamics were profiled using 16S rRNA sequencing.<br><br>RESULTS: Significant shifts in gut microbiota diversity and composition were observed following transplantation. At 30 days post-surgery, a significant enrichment of Enterobacteriaceae was associated with an increased risk of urinary tract infections (UTIs) and a concomitant reduction in multiple peripheral blood lymphocyte subsets. While Enterobacteriaceae enrichment was not correlated with renal function, patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m&#xb2; at 30 days post-transplantation exhibited a marked increase in Bifidobacterium.<br><br>CONCLUSIONS: Our findings suggest that post-transplant enrichment of Enterobacteriaceae may be associated with an increased incidence of UTIs and immune dysregulation. In contrast, Bifidobacterium may play a beneficial role in supporting renal function recovery. These results highlight specific gut microbiota taxa as potential biomarkers or targets for improving outcomes in kidney transplant recipients.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07465-4.}, }
@article {pmid41399025, year = {2025}, author = {Zhao, D and Wang, X and Wang, K and Yang, B and Zhu, H and Xu, Y and Ye, C and Li, L and Lv, X and Zhou, S and Ma, C and Chen, X and Yin, F and Zhu, Y and Cao, Z and Li, N and Zuo, T and Qin, H and Chen, Q}, title = {Recipients' native bacteria determine the outcome of FMT treatment in inflammatory bowel disease.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2600055}, pmid = {41399025}, issn = {1949-0984}, mesh = {Humans ; Male ; Female ; Adult ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/adverse effects ; Middle Aged ; *Bacteria/classification/isolation &amp; purification/genetics ; Treatment Outcome ; Retrospective Studies ; Feces/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Young Adult ; Prospective Studies ; Aged ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for inflammatory bowel disease (IBD), achieving clinical response rate of ~50% for ulcerative colitis (UC), and Crohn's disease (CD). While prior research has emphasized donor selection and treatment protocols, the role of the patient's native intestinal microbiota in FMT outcomes remains underexplored.<br><br>METHODS: This study analyzed a retrospective cohort of 96 IBD patients (45 CD, 51 UC) undergoing FMT, with 192 paired stool samples collected pre- and post-treatment, alongside 332 healthy donor samples from 18 donors. A prospective cohort of 45 IBD patients provided 45 baseline stool samples, and a validation cohort of 112 non-IBD patients contributed 224 paired samples. Retrospective cohort patients were monitored for 4 weeks to assess FMT responsiveness and 52 weeks for treatment effectiveness. Microbiome analysis identified enterotype-specific bacteria and native bacterial genera influence FMT outcomes. Random forest, permissivity, and mathematical models predicted treatment response, characterized microbiome remodeling, and defined microecological remission thresholds.<br><br>RESULTS: The FMT regimen was safe, with no serious adverse events reported. At week 4, the clinical response rates were 58.8% (26/45) for CD patients and 66.7% (34/51) for UC patients; by week 52, the remission rates were 82.4% (37/45) for CD patients and 84.4% (43/51) for UC patients. Microbiome analysis identified 54 bacterial genera linked to enterotype classification, 57 to UC response, and 93 to CD response. Notably, 38 high-frequency retentions of recipient native bacteria after FMT were predictive of FMT responsiveness. The permissivity model revealed a shift toward Bacteroidetes-dominated enterotypes in IBD patients post-FMT, which was validated in 112 non-IBD patients. The abundance ranges of recipients' native bacteria predictive of treatment responsewere determined by mathematical interpretation model.<br><br>CONCLUSION: The patient's native microbiota significantly influences FMT efficacy in IBD, influencing microbiome remodeling and clinical outcomes, highlighting the importance of baseline microbial profiles in predicting FMT responsiveness and optimizing therapy.}, }
@article {pmid41399387, year = {2026}, author = {Yu, Y and Zhao, W and Yang, M and Wu, B and Yuan, X}, title = {Tumor-Promoting Gut Microbes in Colorectal Cancer: Mechanisms and Translational Perspectives.}, journal = {International journal of medical sciences}, volume = {23}, number = {1}, pages = {63-75}, pmid = {41399387}, issn = {1449-1907}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/therapy/diagnosis/pathology/immunology ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/microbiology/complications/therapy/immunology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Carcinogenesis/immunology ; Translational Research, Biomedical ; }, abstract = {Colorectal cancer (CRC) represents a predominant global malignancy, characterized by increasing incidence and mortality rates. Recent investigations have underscored the gut microbiota as a pivotal element in the pathogenesis and progression of CRC. This review synthesizes current evidence regarding the association between gut microbial dysbiosis and CRC, with a particular emphasis on pathogenic bacteria such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks[+] Escherichia coli, and Enterococcus faecalis, among others. The mechanisms through which these microbes contribute to tumorigenesis include the induction of DNA damage, the promotion of chronic inflammation, and the induction of immunosuppression, and the production of oncogenic metabolites. Additionally, the review examines the clinical implications of gut microbiota, highlighting their potential as non-invasive biomarkers for early CRC detection and their impact on the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Furthermore, emerging microbiota-targeted interventions, such as fecal microbiota transplantation, dietary modification, and probiotics, are evaluated for their therapeutic potential. Despite substantial progress, challenges remain in standardizing microbial markers and optimizing individualized microbiota modulation strategies. Future studies integrating multi-omics and machine learning approaches may pave the way for microbiome-based precision medicine in CRC.}, }
@article {pmid41399411, year = {2025}, author = {Li, X and Ji, J and Li, J and Li, S and Luo, Q and Gu, M and Yin, X and Zhang, M and Fan, H and Yao, R}, title = {Gut microbiota-bile acid metabolic disorder involved in the cognitive impairments in epilepsy through HO-1 dependent ferroptosis.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {11}, pages = {101291}, pmid = {41399411}, issn = {2214-0883}, abstract = {Abnormal bile acid (BA) metabolism has been implicated in the pathogenesis of central nervous system (CNS) diseases, but its role in epilepsy remains unclear. In this study, we investigated the relationship between gut microbiota-driven dysregulation of BA metabolism and seizure-induced ferroptotic neuronal death in epilepsy. Our targeted metabolomic analysis revealed elevated levels of deoxycholic acid (DCA) in the serum and cerebrospinal fluid (CSF) of epileptic patients, which correlated with cognitive impairment. In a pentylenetetrazol (PTZ)-induced mouse model of epilepsy, 16S ribosomal RNA (16S rRNA) sequencing showed significant alterations in gut microbiota composition. Importantly, fecal microbiota transplantation (FMT) from healthy mice into epileptic mice significantly reduced seizure activity and improved cognitive function, primarily by normalizing serum and brain levels of secondary bile acids (SBAs), including DCA. Both in vitro and in vivo experiments demonstrated that DCA promotes ferroptosis in hippocampal neurons by activating the farnesoid X receptor (FXR). This activation triggered the nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway, known to be involved in oxidative stress and cell death regulation. Our findings suggest that the upregulation of DCA, through its effects on FXR and HO-1, plays a critical role in the progression of epilepsy by inducing ferroptosis in hippocampal neurons. Targeting the DCA-FXR-HO-1 axis may provide a novel therapeutic strategy for treating seizures and associated cognitive deficits in epilepsy.}, }
@article {pmid41399570, year = {2025}, author = {Bheemaneni, RS and Sakarkar, P and Nigam, A and Nwachukwu, EC and Sekar Lakshmisai, S and Mohammed, L}, title = {Unraveling the Association Between Fibromyalgia and Irritable Bowel Syndrome: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96801}, pmid = {41399570}, issn = {2168-8184}, abstract = {Fibromyalgia (FM) and irritable bowel syndrome (IBS) often occur together. Patients with FM and IBS present similar symptoms, such as pain and fatigue; this leads to a delay in diagnosis and management. This systematic review explored the shared pathophysiology of these conditions in adults, focusing on the roles of immune dysfunction, gut dysbiosis, neurotransmitter imbalances, and disturbances in the gut-brain axis. We searched five databases, PubMed, PubMed Central, Google Scholar, Cochrane, and ScienceDirect, for relevant free full-text English articles from 2015 to 2025. Ten studies were selected after screening, identification, and quality assessment, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Our review found that immune system dysregulation involves mast cells and pro-inflammatory cytokines that damage the gut barrier. The gut microbiome and neurotransmitter levels seem to have a reciprocal influence on each other, and their alteration contributes to pathogenesis, with an increase of certain species showing an association with symptom severity. Serotonin and tryptophan metabolism appear to have a crucial role in pain perception, particularly visceral hypersensitivity. Therapeutic strategies targeting the gut microbiome, such as probiotics and fecal microbiota transplantation, have potential but require further research. Overall, this review identified overlapping mechanisms of FM-IBS comorbidity, which can pave the way to effective and combined treatment approaches. Future research should explore gender distinctions in the mechanisms, medications that act on neurotransmitter receptors (especially serotonergic pathways), and the utility of fecal microbiota transplantation and probiotics.}, }
@article {pmid41400783, year = {2025}, author = {Wei, Q and Wang, Y and Rui, M and You, JHS}, title = {Health economic evaluations of fecal microbiota transplantation for non-clostridioides difficile related diseases: a systematic review.}, journal = {Health economics review}, volume = {15}, number = {1}, pages = {103}, pmid = {41400783}, issn = {2191-1991}, abstract = {OBJECTIVES: This study aimed to conduct a systematic review on health economic evaluations of fecal microbiota transplantation (FMT) for non-Clostridioides difficile infection (non-CDI) related diseases. METHODS: A systematic search of literature was conducted up to October 2025 in MEDLINE (Ovid), Embase (Ovid), APA PsycINFO, Web of Science, Scopus, and CINAHL Ultimate. Studies inclusion criteria were: (1) Non-CDI related diseases; (2) FMT as a treatment; (3) health economic evaluations; and (4) original research articles published in English. The quality of included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Six studies were included. All studies were conducted from the healthcare provider’s perspective, and one additionally considered the societal perspective. Three studies (50%) were cost analyses (n = 1 inflammatory bowel disease (IBD); n = 2 fecal donor screening for treatment of melanoma and metabolic syndrome-associated diseases), two (33%) were cost-effectiveness analyses (IBD), and one (17%) was cost-consequence analyses (urinary tract infection (UTI) caused by multidrug-resistant organisms (MDROs)). The studies were classified as excellent (n = 1), very good (n = 2), and insufficient (n = 3). Four studies (67%) reported that FMT was a potentially cost-saving intervention for IBD (n = 3) and UTI (n = 1). One cost-effectiveness study of 3 FMT regimens for IBD treatment showed the number FMT administrations was influential to total treatment cost. CONCLUSIONS: The included health economic evaluations of FMT for non-CDI related diseases are scarce and quality is diverse. The small number of analyses highlights the research gap of health economic evaluation of FMT for non-CDI related diseases with positive clinical benefits.}, }
@article {pmid41400824, year = {2026}, author = {Liu, M and Liu, W and Zhao, K and Zhang, W and Lei, B and Zhang, Y and Li, L and Yuan, W}, title = {Adult duck fecal microbiota transplantation alleviates short beak and dwarfism syndrome in ducklings by inhibiting Th17 cell differentiation.}, journal = {Virulence}, volume = {17}, number = {1}, pages = {2605745}, pmid = {41400824}, issn = {2150-5608}, mesh = {Animals ; *Ducks ; *Fecal Microbiota Transplantation/veterinary ; *Poultry Diseases/therapy/virology/microbiology ; Gastrointestinal Microbiome ; Cell Differentiation ; *Th17 Cells/immunology/cytology ; *Dwarfism/therapy/veterinary/virology ; *Parvoviridae Infections/veterinary/therapy/virology ; Parvovirinae/pathogenicity ; Beak/pathology ; Dysbiosis ; }, abstract = {Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.}, }
@article {pmid41402129, year = {2026}, author = {Wang, J and Li, J and Li, Y and Huang, W and Huang, C and Xu, Q and Sun, J and Gong, J and Ma, X and Wang, G and Meng, Y and Li, X}, title = {Angiotensin-(1-7) alleviates intestinal barrier dysfunction and dysbiosis in mice with polymicrobial sepsis.}, journal = {British journal of pharmacology}, volume = {183}, number = {9}, pages = {2028-2048}, doi = {10.1111/bph.70248}, pmid = {41402129}, issn = {1476-5381}, support = {82170641//National Natural Science Foundation of China/ ; 82470663//National Natural Science Foundation of China/ ; 82270089//National Natural Science Foundation of China/ ; 81873583//National Natural Science Foundation of China/ ; 2021A1515012595//Guangdong Provincial Science and Technology Projects under Grant/ ; 2024A1515220136//Guangdong Provincial Science and Technology Projects under Grant/ ; 202312121006//National College Students' Innovation and Entrepreneurship Training Program/ ; S202012121056//Guangdong Provincial Innovation Training Projects under Grant/ ; 2017B020209003//Guangdong Science and Technology Project under Grant/ ; JCYJ20210324112807021//Technical Research and Development Project of Shenzhen/ ; }, mesh = {Animals ; *Dysbiosis/drug therapy/microbiology ; *Sepsis/drug therapy/microbiology/metabolism ; Mice, Inbred C57BL ; *Peptide Fragments/pharmacology/therapeutic use/blood ; Male ; *Angiotensin I/pharmacology/therapeutic use/blood ; Mice ; Gastrointestinal Microbiome/drug effects ; Humans ; *Intestinal Mucosa/drug effects/metabolism ; Disease Models, Animal ; *Intestines/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND AND PURPOSE: The intestine plays a key role in the initiation of sepsis. The gut barrier impedes the translocation of commensal bacteria to the liver in sepsis. Previous studies have reported that angiotensin-(1-7) [Ang-(1-7)] attenuated sepsis-induced organ injury and mortality. However, its role in sepsis-induced intestinal barrier dysfunction remains unclear. Here we have investigated therapeutic effects of Ang-(1-7) on the intestinal barrier dysfunction and dysbiosis in a murine model of sepsis.<br><br>EXPERIMENTAL APPROACH: We used a model of sepsis in C57BL/6 mice with caecal ligation and puncture (CLP), to assess mortality and histological and biochemical changes in the gut and liver tissues. Faecal microbiota transplantation (FMT) was used to assess the role of the gut microbiome. 16-s rDNA and metabolomics analyses were performed to characterize differences in the gut microbiome signatures and metabolic profiles.<br><br>KEY RESULTS: Plasma Ang-(1-7) was decreased in patients with sepsis. In CLP mice, exogenous Ang-(1-7) attenuated intestinal barrier dysfunction and liver damage. FMT experiments showed that the protective effects of Ang-(1-7) on the gut depended on the gut microbiota. Furthermore, 16-s ribosomal DNA analysis revealed that Ang-(1-7) treatment increased the abundance of Lactobacillus gasseri (L. gasseri) among commensal bacteria. Mechanistically, L. gasseri regulated the production of antimicrobial peptides in intestinal epithelia by activating NLRP6 inflammation.<br><br>CONCLUSION AND IMPLICATIONS: Ang-(1-7) protected against sepsis-induced intestine barrier dysfunction and liver injury in mice by modulating gut homeostasis and NLRP6 inflammasome. Ang-(1-7) is a promising candidate drug for protecting intestinal homeostasis in sepsis, offering new insights for clinical treatment.}, }
@article {pmid41403286, year = {2025}, author = {Yoshinami, Y and Yamaguchi, S and Shoji, H and Okita, N and Takamaru, H and Hirose, T and Hirano, H and Takashima, A and Imazeki, H and Yamamoto, S and Koyama, S and Ishikawa, D and Terauchi, J and Tanaka, K and Ogawa, K and Watanabe, H and Kato, K}, title = {Feasibility of antibiotic-assisted fecal microbiota transplantation with immunotherapy for esophageal and gastric cancer.}, journal = {Future oncology (London, England)}, volume = {21}, number = {30}, pages = {3903-3912}, pmid = {41403286}, issn = {1744-8301}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; *Esophageal Neoplasms/therapy/mortality/immunology/pathology ; Feasibility Studies ; *Fecal Microbiota Transplantation/methods/adverse effects ; Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Immunotherapy/methods/adverse effects ; *Stomach Neoplasms/therapy/mortality/immunology ; Treatment Outcome ; }, abstract = {AIMS: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.<br><br>METHODS: This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.}, }
@article {pmid41403899, year = {2025}, author = {Shi, W and Wu, L and Qin, Q and Li, Y and Chen, W}, title = {Research progress on the role of microbiome-immune-neurotransmitter network in post-stroke sleep disorders.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1694709}, pmid = {41403899}, issn = {1663-4365}, abstract = {Post-stroke sleep disorders, as a significant complication affecting patient rehabilitation, are closely associated with dysregulation of the microbiome-immune-neurotransmitter network. Following stroke, activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system triggers intestinal barrier disruption (reduced tight junction proteins and intestinal permeability) along with microbial imbalance (decreased Bifidobacterium and increased Enterobacteriaceae). Reduced short-chain fatty acids and lipopolysaccharide (LPS) translocation exacerbate systemic inflammatory responses and neurotransmitter imbalances (inhibited serotonin synthesis and excitotoxic glutamate production). These changes further disrupt circadian regulation by the hypothalamic suprachiasmatic nucleus, leading to reduced REM sleep and disrupted slow-wave sleep architecture. Future research should prioritize interventional strategies targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, integrated with multi-omics technologies and neural circuit modulation approaches, to elucidate the spatiotemporal dynamics of the microbiome-immune-neurotransmitter network and provide a theoretical basis for clinical translation. Restoring brain-gut axis homeostasis is expected to improve post-stroke sleep disorders and neurological functional outcomes in patients.}, }
@article {pmid41405935, year = {2026}, author = {D'Amico, F and Nardone, OM and Bruno, A and Allocca, M and Zilli, A and Furfaro, F and Parigi, TL and Solitano, V and Ungaro, F and Faggiani, I and La Mantia, A and Calabrese, G and Fiorino, G and Jairath, V and Peyrin-Biroulet, L and Massimino, L and Castiglione, F and Danese, S}, title = {Bowel Urgency Improvement Correlates With Clinical, Biochemical, and Intestinal Ultrasound Improvements in Inflammatory Bowel Disease: A Cross Sectional Multicenter Study.}, journal = {United European gastroenterology journal}, volume = {14}, number = {1}, pages = {}, pmid = {41405935}, issn = {2050-6414}, mesh = {Humans ; Male ; Female ; Adult ; Retrospective Studies ; Cross-Sectional Studies ; *Colitis, Ulcerative/drug therapy/complications/diagnostic imaging ; Ultrasonography ; *Crohn Disease/drug therapy/complications/diagnostic imaging ; Leukocyte L1 Antigen Complex/analysis ; Severity of Illness Index ; Treatment Outcome ; Middle Aged ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Remission Induction ; Intestines/diagnostic imaging ; }, abstract = {BACKGROUND: Bowel urgency (BU) is reported by over 80% of patients with ulcerative colitis (UC) and 60% of those with Crohn's disease (CD). However, the impact of advanced therapies on BU has not been consistently evaluated.<br><br>OBJECTIVES: To assess the effect of advanced therapies on BU improvement in patients with UC and CD.<br><br>METHODS: This retrospective cohort study included all consecutive patients with confirmed UC or CD who started an advanced therapy with available data regarding BU before and after induction therapy between 2023 and 2024 at two tertiary centers. BU was assessed using the numeric-rating-scale urgency score (NRS-us), with BU defined as NRS-us &#x2265;&#xa0;3. The primary endpoint was BU improvement (NRS-us &#x2264;&#xa0;3 or reduction of at least two points) after the induction phase. Multivariate logistic regression analysis identified factors associated with BU improvement.<br><br>RESULTS: A total of 159 patients were included (56% male; 65% UC; median age: 36&#xa0;years (Interquartile range [IQR] 27-25)). TNF&#x3b1; inhibitors were the most frequently used agents (49.6%). At baseline, the median NRS-us was 7. After induction, 50.9% of patients achieved BU improvement, with a mean reduction of 2.3&#xa0;&#xb1;&#xa0;2.9 points. BU improvement was significantly associated with clinical remission (false-discovery-rate [FDR]&#xa0;=&#xa0;0.009 in CD and FDR&#xa0;=&#xa0;0.010 in UC), normalization of fecal calprotectin (FDR&#xa0;=&#xa0;0.001), CRP (FDR&#xa0;=&#xa0;0.008), and bowel wall thickness on intestinal ultrasound (FDR&#xa0;=&#xa0;0.001). No significant differences were observed between therapeutic classes.<br><br>CONCLUSION: BU improved in approximately half of IBD patients following induction with advanced therapies. Its improvement correlated with clinical, biochemical, and ultrasound remission, supporting the incorporation of BU assessment into routine clinical monitoring.}, }
@article {pmid41406837, year = {2026}, author = {Wu, C and Hu, S and Li, D and Jiang, X and Bi, G and Wang, P and OuYang, H and Fang, J and Yang, X and Bi, H}, title = {Gut microbiota affects the role of mPXR agonist PCN in alleviating sepsis-induced liver injury by regulating YAP activation.}, journal = {International immunopharmacology}, volume = {169}, number = {}, pages = {116013}, doi = {10.1016/j.intimp.2025.116013}, pmid = {41406837}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Sepsis/complications/drug therapy ; YAP-Signaling Proteins ; Male ; Mice, Inbred C57BL ; Mice ; *Pregnane X Receptor/agonists/metabolism ; *Pregnenolone Carbonitrile/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Liver/pathology/drug effects ; *Adaptor Proteins, Signal Transducing/metabolism ; *Liver Diseases/etiology ; Disease Models, Animal ; Lipopolysaccharides ; Signal Transduction ; }, abstract = {BACKGROUND: Sepsis severity is primarily driven by exaggerated inflammatory responses that contribute to hepatic injury. The pregnane X receptor (PXR), a nuclear receptor that regulates xenobiotic and endobiotic metabolism, plays a crucial protective role against sepsis-induced liver injury and modulates hepatic regeneration. Concurrently, the gut microbiota contributes to sepsis pathogenesis via intestinal signaling and the gut-liver axis. This study aimed to evaluate how the gut microbiota mediates the protective effects exerted by the mouse PXR (mPXR) agonist pregnenolone-16α‑carbonitrile (PCN) against sepsis-induced liver injury and to elucidate the underlying mechanisms.<br><br>METHODS: Sepsis was induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) treatment. Mice were pretreated with PCN for three consecutive days prior to model construction. Gut microbiota depletion was achieved using a cocktail of broad-spectrum antibiotics (ABX), and fecal microbiota transplantation (FMT) was performed to restore microbial communities.<br><br>RESULTS: We found that depletion of gut microbiota abrogated PCN-mediated hepatoprotection in septic mice. Conversely, FMT from PCN-treated donors attenuated sepsis-induced liver injury. Furthermore, PCN-activated PXR significantly altered the gut microbiota composition in septic mice. Mechanistically, PCN treatment enhanced activation of the Yes-associated protein (YAP) signaling pathway, an effect that was diminished upon depletion of gut microbiota. Correspondingly, FMT from PCN-treated donors enhanced YAP activation and upregulated its downstream target proteins in septic mice.<br><br>CONCLUSIONS: In summary, this study demonstrated that the gut microbiota mediated the protective effects of PCN against sepsis-induced liver injury by activating the YAP pathway. These findings provide novel insights into the role of gut microbiota in PXR-mediated protection during sepsis.}, }
@article {pmid41408007, year = {2025}, author = {Abrishami, M and Sabouri, M and Joneidi, F and Haghshenas, Z and Khalili-Tanha, G and Nazari, E}, title = {The role of gut microbiota in breast cancer: biomarker identification and therapeutic applications.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {1}, pages = {14}, pmid = {41408007}, issn = {1572-9699}, support = {1403-1121//Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran/ ; }, mesh = {Humans ; *Breast Neoplasms/therapy/microbiology/diagnosis ; *Gastrointestinal Microbiome/physiology ; Female ; *Biomarkers, Tumor ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Recent studies have established the gut microbiome as a crucial player in breast cancer diagnosis, progression, and treatment. Distinct microbial patterns have shown promise as non-invasive diagnostic and prognostic biomarkers, supporting patient stratification and risk assessment based on microbiota composition. The gut microbiome also modulates estrogen metabolism, influencing the risk of hormone receptor-positive breast cancer, while dysbiosis can promote chronic inflammation and tumor expansion. Moreover, accumulating evidence demonstrates that gut bacteria can alter responses to chemotherapy and immunotherapy, suggesting that microbiota modulation may enhance treatment efficacy. With the advent of omics technologies and machine learning, intricate host-microbe interactions are being decoded, revealing new molecular targets and therapeutic opportunities. Importantly, early clinical and interventional studies using probiotics, prebiotics, and fecal microbiota transplantation (FMT) are being explored to restore microbial balance, mitigate therapy-related side effects, and improve antitumor immunity in breast cancer patients. Together, these advances underscore the translational potential of microbiome research, paving the way for microbiota-guided diagnostic, prognostic, and therapeutic strategies in personalized breast cancer management.}, }
@article {pmid41408061, year = {2025}, author = {Wang, Z and Cui, Y and Li, D and Yan, L and Zhu, S and Ma, X and Lu, Z and Li, C and Feng, J and Yuan, W and He, X}, title = {Alternate-day fasting ameliorates α-synuclein pathology and suppresses inflammation via the gut-brain axis in an MPTP-induced subacute mouse model of Parkinson's disease.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {228}, pmid = {41408061}, issn = {2055-5008}, support = {2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; }, mesh = {Animals ; Mice ; *Fasting ; *alpha-Synuclein/metabolism/genetics ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Parkinson Disease/pathology/metabolism/therapy ; *Brain/metabolism/pathology ; *Inflammation ; Male ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; Mice, Inbred C57BL ; Dopaminergic Neurons/metabolism ; }, abstract = {Dietary restrictions like alternate-day fasting (ADF) can counteract several age-related disorders, but its role in Parkinson's disease (PD) is still controversial. Recent findings highlight the imbalances in the gut-brain axis in PD, herein, we aim to study whether ADF can confer protection in PD mice through the gut-brain axis. Firstly, we assessed the neuroprotective effect of ADF in a time-dependent manner and found that 16 -week ADF could confer the optimal neuroprotection by preserving dopaminergic neurons and reducing the level of α‑synuclein (α‑syn) in the substantia nigra (SN), and it could decrease inflammatory cytokine levels in both the brain and the gut. Furthermore, ADF reshaped gut microbial composition and altered metabolites associated with PD. Relative abundances of several intestinal flora, including Alistipes, Helicobacter and Lactobacillus, were identified as potential mediators. In addition, we conducted fecal microbiota transplantation (FMT) to further investigate the role of the gut-brain axis in the neuroprotective effects of ADF. Notably, we found that FMT from ADF mice conferred equal protection to ADF in ameliorating the pathology and inflammation in both the brain and the gut. Collectively, our findings suggest that the microbiota-gut-brain axis is crucial to the neuroprotective effect of ADF in PD.}, }
@article {pmid41409175, year = {2025}, author = {Ng, DZW and Low, A and Khairul Sani, KRB and Liu, L and Zhang, Z and Koh, XQ and Zhu, M and Mitra, K and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY}, title = {Dysbiosis-Driven Reprogramming of Secondary Bile Acid Metabolism in Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights from an Ex Vivo Human Fecal Microbiota Model.}, journal = {ACS pharmacology &amp; translational science}, volume = {8}, number = {12}, pages = {4335-4344}, pmid = {41409175}, issn = {2575-9108}, abstract = {Gut microbial dysbiosis-induced perturbations in bile acid (BA) metabolism are implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), yet evidence remains largely associative. Using an optimized ex vivo fecal microbiota model, we modeled the metabolism kinetics of conjugated- and primary-BA between MASLD and healthy donors. Enzymes for known BA metabolic reactions were inferred using functional metagenomics. MASLD cultures exhibited impaired deconjugation capacity but preserved downstream primary-BA clearance and demonstrated a substrate-independent shift that favored oxidative metabolism over 7α-dehydroxylation. This was marked by increased formation clearance of 7-keto-deoxycholic acid (175%) and 3-oxo-cholic acid (51.7%) from cholic acid (CA) and 7-keto-lithocholic acid (77.9%) from chenodeoxycholic acid (CDCA). C7-oxidized BA constituted the major proportion of total BA clearance (CA = 56.0%, CDCA = 72.3%) in MASLD cultures. Enrichment of C3- and C7-hydroxysteroid dehydrogenases in MASLD compared to control corroborated the differential secondary BA profiles. Together, microbes catalyzing C7-oxidation warrants further investigation as potential pharmacological targets of MASLD.}, }
@article {pmid41413564, year = {2025}, author = {Han, M and Xie, B and Yu, Y and Xu, D and Shi, Y and Xu, M and Wu, Y and Zhang, Y and Wen, X and Wang, X and Zhen, Z and Zhang, X and Sun, X and Yuan, Y and Shang, Y and Yuan, S and Hashimoto, K and Zhang, J}, title = {Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {24}, pmid = {41413564}, issn = {1742-2094}, support = {82402568//National Natural Science Foundation of China/ ; 82302471//National Natural Science Foundation of China/ ; 82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, mesh = {Animals ; *Hippocampus/metabolism/drug effects ; Mice ; *Ketamine/pharmacology/therapeutic use/analogs &amp; derivatives ; *Stress, Psychological/metabolism/complications ; *Interleukin-17/metabolism ; *Mitophagy/drug effects/physiology ; Male ; *Depression/metabolism/etiology/drug therapy ; Mice, Inbred C57BL ; Signal Transduction/drug effects/physiology ; *Intraepithelial Lymphocytes/metabolism/drug effects ; *Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Gastrointestinal Microbiome/drug effects ; Antidepressive Agents/pharmacology/therapeutic use ; }, abstract = {Chronic stress precipitates depression, yet how gut-immune-brain interactions translate stress into mood pathology remains unclear. We tested the hypothesis that stress-primed small intestinal γδ T cells drive hippocampal mitochondrial dysfunction and depression-like behavior via interleukin-17A (IL-1A). In mice exposed to chronic restraint stress (CRS), we combined behavioral assays (open-field, sucrose-preference, tail-suspension, forced-swim), 16S rRNA profiling, fecal microbiota transplantation, Kaede photoconversion, conditional CD8α deletion in γδ T cells, hippocampal IL-17A overexpression, rapamycin treatment, and administration of the antidepressant arketamine. CRS increased gut and brain permeability, induced gut-microbiota dysbiosis, and promoted migration of small intestinal CD8α[+] γδ T17 cells to the meninges and brain; γδ T cells were the predominant IL-17A source in the brain. Kaede tracing confirmed an intestinal origin, and CRS-associated microbiota alone transferred γδ T cell trafficking and depression-like behavior to recipients. In the hippocampus, CRS elevated IL-17A and impaired PINK1/Parkin-mediated mitophagy (decreased PINK1, Parkin, Beclin-1, and LC3B-II/I; increased p62), reduced ATP, and produced mitochondrial and synaptic ultrastructural deficits. IL-17A overexpression further worsened mitophagy and behavior, whereas rapamycin restored both. Conditional deletion of CD8α in γδ T cells reduced brain γδ T17 infiltration, lowered hippocampal IL-17A, rescued mitophagy and synapses, and improved behavior. Arketamine normalized dysbiosis and barrier markers, curtailed γδ T cell trafficking, decreased hippocampal IL-17A, restored mitophagy, and alleviated depression-like behavior in both sexes. These findings delineate a stress-responsive microbiota-γδ T cell-IL-17A pathway that compromises hippocampal mitophagy and identify arketamine as a candidate modulator of this axis, nominating mitophagy and γδ T cell trafficking as translational targets.}, }
@article {pmid41415268, year = {2025}, author = {Wei, YF and Wang, YS and Song, JY and Wang, H and He, XX and Zhong, HJ}, title = {Restoration of peripheral ILC3s by washed microbiota transplantation improves lipid profiles in hyperlipidemia patients.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1688070}, pmid = {41415268}, issn = {1664-3224}, mesh = {Humans ; *Hyperlipidemias/therapy/immunology/blood/metabolism ; Animals ; Mice ; Male ; Gastrointestinal Microbiome/immunology ; Female ; Middle Aged ; *Lymphocytes/immunology/metabolism ; *Fecal Microbiota Transplantation/methods ; Immunity, Innate ; *Lipid Metabolism ; *Lipids/blood ; Interleukin-22 ; Interleukins/blood ; Adult ; Liver/metabolism/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Prospective Studies ; }, abstract = {BACKGROUND: The contribution of circulating group 3 innate lymphoid cells (ILC3s) to lipid dysregulation has remained poorly defined, and the mechanisms through which washed microbiota transplantation (WMT) improves lipid metabolism require further clarification.<br><br>METHODS: Peripheral ILC subsets and plasma IL-22 were assessed in hyperlipidemia patients and healthy controls. The lipid-lowering effects of WMT were evaluated in a prospective cohort without lipid-lowering medications. Gut microbial and plasma metabolite profiles before and after WMT were analyzed. A hyperlipidemic mouse model was used to determine whether healthy microbiota promote hepatic ILC3 homing via integrin &#x3b1;4.<br><br>RESULTS: Hyperlipidemia was characterized by reduced circulating ILC3s, integrin &#x3b1;4[+] ILC3s, and plasma IL-22, all of which showed inverse correlations with TC, TG, LDL-C, non-HDL-C, and ApoB. Significant lipid improvements were achieved after WMT, accompanied by increased circulating ILC3s and integrin &#x3b1;4[+] ILC3s, paralleling reductions in TC and LDL-C. WMT induced marked remodeling of gut microbiota and plasma metabolites, including taxa and metabolites positively associated with ILC3 restoration and lipid improvement. In hyperlipidemic mice, healthy microbiota transplantation increased hepatic ILC3 and integrin &#x3b1;4[+] ILC3 accumulation and improved lipid levels, whereas integrin &#x3b1;4 blockade impaired ILC3 liver homing and attenuated the metabolic benefit.<br><br>CONCLUSION: Hyperlipidemia is associated with depletion of circulating ILC3s and reduced IL-22. Restoration of ILC3 subsets and enhancement of integrin &#x3b1;4-dependent hepatic homing are achieved after WMT, accompanying improvements in lipid metabolism.}, }
@article {pmid41415394, year = {2025}, author = {Barcena-Varela, M and Shang, J and Mogno, I and Lozano, A and Liebling, I and Mead, KR and Li, Z and Grinspan, LT and Lindblad, KE and Ruiz de Galarreta, M and Donne, R and Gnjatic, S and Merad, M and Jun, T and Ang, C and Marron, TU and Faith, J and Lujambio, A}, title = {Bacteroidetes promote hepatocellular carcinoma progression and resistance to immunotherapy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41415394}, issn = {2692-8205}, support = {S10 OD026880/OD/NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; T32 CA078207/CA/NCI NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R37 CA230636/CA/NCI NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Growing evidence highlight the critical role of the gut microbiome in tumorigenesis and response to immunotherapies. However, the impact of gut microbes on hepatocellular carcinoma (HCC) progression and response to immune-checkpoint blockade (ICB) remains unclear due to the lack of combined preclinical and clinical studies.<br><br>APPROACH &amp; RESULTS: We performed 16S rRNA of cross-cohort stool samples from 10 HCC responders (R) and 40 non-responders (NR) to ICB at baseline and on-treatment time-points. We identified an enrichment of Bacteroidetes in NR. To study the role of the microbiome in the cancer immune response, we generated an immunogenic mouse model of HCC via hydrodynamic tail-vein injection (HDTVI) of DNA plasmids mimicking common HCC alterations and immunogenicity by expressing model antigens (MYC-lucOS;CTNNB1 tumors). We found that antibiotic (ABX)-induced dysbiosis promoted a pro-tumorigenic effect in the MYC-lucOS;CTNNB1 HCC model by the expansion of a specific Bacteroidetes, Parabacteroides distasonis. Colonization of mice carrying MYC-lucOS;CTNNB1 HCCs with Parabacteroides distasonis confirmed its pro-tumorigenic effect in vivo. Furthermore, we explored the effects of colonizing with microbiotas from patients and showed that microbiota from a NR donor enriched in Bacteroidetes promoted faster tumorigenesis than microbiota from a R donor with reduced Bacteroidetes. We isolated 6 Bacteroidetes species from the NR donor, cultured them, and used them as a cocktail to colonize mice; similarly, mice transplanted with this cocktail showed increased tumorigenesis and reduced survival.<br><br>CONCLUSIONS: This study identified Bacteroidetes enrichment as a potential biomarker of ICB resistance in HCC and, by using immunogenic mouse models, established that Bacteroidetes abundance influences tumor development.}, }
@article {pmid41416026, year = {2025}, author = {Wan, L and Park, A and Lio, P}, title = {Fecal Microbiota Transplantation as a Potential Treatment for Pediatric Atopic Dermatitis.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {18}, number = {10}, pages = {16}, pmid = {41416026}, issn = {1941-2789}, }
@article {pmid41416604, year = {2025}, author = {Rychlik, A}, title = {Fecal microbiome transplantation in the treatment of chronic enteropathies.}, journal = {Polish journal of veterinary sciences}, volume = {28}, number = {4}, pages = {691-700}, doi = {10.24425/pjvs.2025.157285}, pmid = {41416604}, issn = {2300-2557}, mesh = {*Fecal Microbiota Transplantation/veterinary ; Animals ; *Intestinal Diseases/therapy/veterinary ; *Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {The intestinal microbiome is essential for the proper functioning of the immune system and the course of metabolic processes in the living organism. Intestinal bacteria produce a variety of metabolites that affect the health of many organs, especially the intestines. Disturbances in the composition of the intestinal microflora are referred to as dysbiosis. Dysbiosis occurring in chronic enteropathies may exacerbate intestinal inflammation. Therefore, effective methods of treating enteropathy are still being sought, which involve restoring the proper composition of the intestinal microbiome. In recent years, many scientific centers have drawn attention to the possibility of treating enteropathy by transplanting intestinal contents from a healthy donor. This review presents the advantages and disadvantages of this therapeutic method, described in the latest available literature and the newest guidelines regarding the donor and transplant administration methods.}, }
@article {pmid41417461, year = {2026}, author = {Drew, G and Kraft, CS and Mehta, N}, title = {Fecal Microbiota Therapy: Clinical Laboratory Testing and Metabolomic Approaches for Donor Screening, Product Assessment, and Patient Monitoring.}, journal = {Clinical chemistry}, volume = {72}, number = {5}, pages = {554-563}, doi = {10.1093/clinchem/hvaf156}, pmid = {41417461}, issn = {1530-8561}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/prevention &amp; control ; *Feces/microbiology/chemistry ; *Metabolomics/methods ; *Donor Selection ; Clostridioides difficile ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: The safety and efficacy of fecal microbiota transplantation for prevention of recurrent Clostridioides difficile infection relies on complex interactions between the donor and recipient microbiome.<br><br>CONTENT: Screening of donor stool has largely aimed to ensure safety; however, metagenomic and metabolic features of the stool, which may affect efficacy of the fecal microbiota transplantation (FMT), have been largely overlooked.<br><br>SUMMARY: In this review, we discuss the nascent field of metagenomic and metabolic donor and recipient characteristics that may affect efficacy of FMT and future directions for this field to allow for more precise and personalized therapies.}, }
@article {pmid41419954, year = {2025}, author = {Huang, SJ and Ye, HL and Xu, S and Liu, T and Zhang, WC and Wang, YL and Duan, SZ}, title = {T cell KAT6A deficiency relieves inflammatory bowel disease in mice.}, journal = {Cell &amp; bioscience}, volume = {15}, number = {1}, pages = {167}, pmid = {41419954}, issn = {2045-3701}, support = {82330015//the National Natural Science Foundation of China/ ; 81991503//the National Natural Science Foundation of China/ ; 2023YFA1801100//the National Key Research and Development Program of China/ ; 2023YFA1801104//the National Key Research and Development Program of China/ ; 2024R01003//Zhejiang Provincial Leading Innovation and Entrepreneurship/ ; }, abstract = {The incidence of inflammatory bowel disease (IBD) has been increasing, and while the interaction between T cells and intestinal microorganisms is crucial in its pathogenesis, the related epigenetic mechanisms remain unclear. This study found that the expression of lysine acetyltransferase 6A (KAT6A) was increased in T cells of patients with acute colitis. Knocking out KAT6A in CD4[+] T cells alleviated dextran sulfate sodium (DSS)-induced colitis in mice, as manifested in body weight, disease activity index, colon length, inflammation, and the expression of proinflammatory factors. Mechanistically, KAT6A deficiency upregulated the senescence of CD4[+] T cells and affected the expression of related genes. Moreover, the regulation of colitis by CD4[+] T cell KAT6A was dependent on the gut microbiota. Antibiotic treatment could reverse the protective effect in T cell KAT6A knockout (TK6AKO) mice, and fecal transplantation experiments confirmed that it was related to the change of the microbiota. 16S rRNA sequencing showed that the composition of the gut microbiota was changed, and specific bacteria such as Akkermansia muciniphila were enriched in TK6AKO mice. This study reveals that KAT6A affects colitis through the interaction between regulating T cell senescence and the gut microbiota, providing a new strategy for treatment.}, }
@article {pmid41421285, year = {2026}, author = {Sun, C and Tian, Y and Zheng, Y and Yang, K and Liu, S and Zhao, D and Li, L and Yin, X and Li, H and Duan, J and Mu, H and Liu, Q and Luo, J}, title = {KuiAnNingFang alleviates ulcerative colitis by modulating gut microbiota and NF-κB/NLRP3 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157677}, doi = {10.1016/j.phymed.2025.157677}, pmid = {41421285}, issn = {1618-095X}, mesh = {*Colitis, Ulcerative/drug therapy/microbiology ; Animals ; *Gastrointestinal Microbiome/drug effects ; *NF-kappa B/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Humans ; Male ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Female ; Fecal Microbiota Transplantation ; Dextran Sulfate ; Middle Aged ; Adult ; }, abstract = {BACKGROUND: Ulcerative colitis (UC), a major form of inflammatory bowel disease, is a chronic and relapsing inflammatory condition of the colonic mucosa. Despite the efficacy of the Traditional Chinese Medicine formula KuiAnNingFang (KANF) in alleviating UC, its therapeutic mechanisms remain incompletely understood.<br><br>PURPOSE: This study aimed to elucidate the ameliorative effect of Chinese medicine KANF and its potential mechanism against UC.<br><br>METHODS: The therapeutic efficacy of KANF against UC was initially assessed in clinical cohorts. A murine model of UC was subsequently established by administering DSS in drinking water and oral treatment with KANF extracts. The prototype components of KANF absorbed into the bloodstream were identified using UPLC-MS/MS. RNA-seq was conducted to identify differentially expressed genes and altered signaling pathways in colonic tissue. Furthermore, 16S rDNA sequencing and fecal microbiota transplantation were employed to determine whether KANF ameliorates UC by modulating the gut microbiota.<br><br>RESULTS: KANF demonstrated significant therapeutic efficacy in alleviating UC in both clinical patients and animal models. Integrated analysis combining network pharmacology and RNA-seq validated that KANF attenuates intestinal inflammation by inhibiting NF-&#x3ba;B/NLRP3 activation. Furthermore, 16S rDNA sequencing revealed that KANF restores gut microbial homeostasis, and fecal microbiota transplantation experiments confirmed that the suppressive effect of KANF on NF-&#x3ba;B/NLRP3 signaling is primarily mediated through gut microbiota remodeling.<br><br>CONCLUSION: KANF can significantly ameliorate symptoms in both clinical UC patients and DSS-induced colitis mice. KANF exerts its multi-target anti-colitic effects through regulation of the gut microbiota and subsequent suppression of the NF-&#x3ba;B/NLRP3 signaling cascade.}, }
@article {pmid41424069, year = {2025}, author = {Prokopidis, K}, title = {Probiotics, prebiotics, and synbiotics to counteract sarcopenia: where are we now and what challenges need to be faced?.}, journal = {The Proceedings of the Nutrition Society}, volume = {}, number = {}, pages = {1-6}, doi = {10.1017/S0029665125102036}, pmid = {41424069}, issn = {1475-2719}, abstract = {Sarcopenia, the age-related decline in muscle mass and strength, is a contributor to frailty and reduced quality of life. Emerging evidence suggests an emerging role of the gut microbiome in modulating skeletal muscle through microbial species and metabolites, such as short-chain fatty acids (SCFAs), potentially influencing inflammation, nutrient absorption, and glucose and protein metabolism. This review considers the potential of probiotics, prebiotics, and synbiotics as interventions to mitigate sarcopenia based on animal and human studies, while providing a critique of present barriers that need to be addressed. Preclinical models, including germ-free mice and faecal microbiota transplantation, demonstrate that gut microbiota from healthy or young donors may enhance overall muscle health via reductions in inflammatory and muscle atrophy markers. Limited human studies show that probiotics such as Lactobacillus and Bifidobacterium could improve branched-chain amino acid (BCAA) bioavailability and potentially sarcopenia indices, although findings have been inconsistent. Particularly, challenges including inconsistent microbial assessments, lack of dietary control and interindividual variability due to diet, age, genetics, comorbidities and medications may hinder progress in this field. Delivery methods (e.g. capsules, fermented foods or fortified products) could further complicate efficacy through probiotic stability and dietary restrictions in older adults. Standardised protocols [e.g. Strengthening The Organisation and Reporting of Microbiome Studies (STORMS) checklist] and multi-omics approaches may be critical to address these limitations and identify microbial signatures linked to sarcopenia outcomes. While preclinical evidence highlights mechanistic pathways pertinent to amino acid metabolism, translating findings to humans requires rigorous experimental trials.}, }
@article {pmid41424605, year = {2025}, author = {Kay, E and Kazi, M and Burton, J and Parvathy, SN}, title = {Therapeutic properties of plant-derived prebiotics in melanoma.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002354}, pmid = {41424605}, issn = {2692-3114}, abstract = {Immune checkpoint inhibitor (ICI) therapy has revolutionized metastatic melanoma treatment, yet only a subset of patients respond effectively, and the treatment can induce a variety of immune-related adverse events (irAEs), including colitis. The gut microbiome plays a critical role in determining patient responses to immunotherapy, prompting exploration of gut-modifying strategies such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) to overcome both primary and acquired resistance and improve treatment outcomes. Prebiotics, defined as dietary substrates that selectively support the growth and/or activity of beneficial gut microorganisms, represent a feasible and safe strategy for microbiome reshaping. Plant-derived prebiotics like castalagin, inulin, fructooligosaccharides, galactooligosaccharides, mushroom extract, kale extract, and konjac glucomannan offer unique advantages over synthetic or animal-derived alternatives due to their natural fiber content alongside their ability to enhance gut microbial diversity. Prebiotics are known to achieve health benefits by selectively stimulating beneficial gut bacteria, producing short-chain fatty acids (SCFAs) that modulate the host immune system, suppressing pathogenic microbes, enhancing mucin production, and modulating systemic and gut-associated immune responses. SCFAs generated through prebiotic fermentation influence host innate and adaptive immunity and regulate metabolic activity via inhibition of histone deacetylases (HDACs), influencing mTOR/MAPK signaling and cytokine production. They also act as ligands for G-protein-coupled receptors (GPCRs), altering intracellular calcium and cAMP to modulate immune cell gene expression. However, the specific mechanisms by which individual prebiotics interact with host genetics, beneficial gut bacteria, and their metabolites are not very well understood. This is crucial to optimize their therapeutic potential in cancer immunotherapy. This review synthesizes current evidence on plant-derived prebiotics, highlighting the impact of beneficial gut bacteria and their metabolites. Given their established safety for human consumption, prebiotics represent a promising, low-risk option to improve gut microbiome composition and potentially enhance immunotherapy and clinical outcomes in cancer.}, }
@article {pmid41424618, year = {2025}, author = {Pandey, SN and Goyal, K and Rana, M and Menon, SV and Ray, S and Ali, H and Kumbhar, PS and Disouza, J and Singh, SK and Gupta, G and Wong, LS and Kumarasamy, V and Subramaniyan, V}, title = {Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {681-690}, pmid = {41424618}, issn = {2352-3204}, abstract = {The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome-derived bile acid metabolites are potent endogenous mediators of hepatic regeneration. Beyond their canonical role in lipid emulsification, these chemically diverse molecules engage nuclear and membrane receptors, most notably the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to stimulate hepatocyte proliferation, modulate inflammatory responses, and reactivate quiescent progenitor cells. In this review, we integrate mechanistic insights from partial hepatectomy, germ-free, and antibiotic-treated animal models with early clinical observations to illuminate how primary and secondary bile acids orchestrate cell cycle progression, cytokine balance, and extracellular matrix remodeling. We then examined the therapeutic landscape, from synthetic FXR/TGR5 agonists to live-biotherapeutic approaches, genetically modified probiotic strains, and fecal microbiota transplantation. We highlight the preliminary indicators of efficacy and challenges in manufacturing consistency, safety profiling, and regulatory classification. We address the interindividual variability in microbiome composition, potential biomarkers such as serum FGF19, imaging-based measures of functional liver mass, and considerations for optimal trial design. This is the first comprehensive review to frame microbiome-driven bile acids as direct modulators of liver regeneration and chart a coherent translational development pathway. By integrating stem cell biology, hepatology, microbiology, and bioengineering perspectives, we demonstrate the underexplored therapeutic potential of these approaches to transform the future of hepatic repair.}, }
@article {pmid41424968, year = {2025}, author = {Shayya, M and Wehbi, Z and Matar, M and Elzein, M and Safieddine, Z and El Khoury, K and Ibrahim, JN and Hassan, HF and Jamal, O and Chatila, R and Kobeissy, PH}, title = {Awareness and perception of fecal microbiota transplantation in Lebanon: a cross-sectional survey among the general population, healthcare workers, physicians, and patients.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251399034}, pmid = {41424968}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI) and shows promise for other dysbiosis-related conditions such as inflammatory bowel disease (IBD). Awareness and acceptance remain underexplored in the Middle East, where cultural and social factors may influence adoption.<br><br>OBJECTIVES: To evaluate awareness, perceptions, willingness, and acceptance of FMT among the Lebanese population.<br><br>DESIGN: A nationwide cross-sectional survey with nonprobability sampling was conducted between April and November 2024.<br><br>METHODS: A total of 725 participants were recruited through mixed sampling across Lebanon's governorates: 379 from the general population, 109 healthcare workers, 155 physicians, and 82 IBD or CDI patients. A structured bilingual questionnaire assessed awareness, perceptions, treatment preferences, and willingness to disclose or undergo FMT. Analyses included Chi-square tests, logistic regression, and false discovery rate-adjusted comparisons.<br><br>RESULTS: Overall, 31% of participants had prior awareness of FMT, while 60.1% reported positive perception. Awareness and perception were significantly associated (p&#x2009;=&#x2009;0.0017) and were highest among physicians (59.4% and 70.2%) and lowest among patients (17.1% and 52.4%). Sources varied by group: universities for the general population, media for patients, and professional networks for healthcare workers and physicians. Logistic regression identified physician status, younger age, and prior awareness as predictors of favorable perception. Capsules were the preferred delivery route across groups. Willingness to disclose (81.4%) and to donate stool (68.4%) were high, while 17.2% expressed stigma-related concerns. Major concerns included hygiene, infection risk, and psychological discomfort.<br><br>CONCLUSION: FMT awareness in Lebanon remains limited, particularly among patients and the public. Although perceptions are generally positive, misconceptions, stigma, and unrealistic expectations persist. These findings stem from a nonprobability sample that overrepresents younger, female, and highly educated participants and is not nationally representative. Targeted education, stronger physician-patient communication, and culturally sensitive approaches are needed to promote FMT acceptance and integration into practice.}, }
@article {pmid41425837, year = {2025}, author = {Oladele, P and Johnson, TA}, title = {Trehalose and maltodextrin preserve microbial community structure in freeze-dried fecal samples for fecal microbiota transplantation.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf204}, pmid = {41425837}, issn = {2730-6151}, abstract = {Fecal microbiota transplantation (FMT) is a promising approach for restoring gut microbial balance in both humans and animals. However, the logistical limitations of transplanting fresh fecal samples have increased interest in freeze-dried (lyophilized) fecal material as a transplant inoculum. While lyophilization facilitates storage, it can compromise bacterial viability, which is essential for FMT effectiveness. Lyoprotectants are often used to protect bacterial cultures during freeze-drying, but their effect on complex microbial communities remains unclear, as they may preferentially preserve some taxa over others. This study investigated the impact of four lyoprotectants-mannitol, maltodextrin, trehalose, and a maltodextrin-trehalose mixture-on bacterial viability and community structure in pig fecal samples post-lyophilization. Propidium monoazide (PMA) treatment combined with 16S rRNA sequencing (PMAseq) was used to differentiate viable from non-viable bacteria. In the total community (without PMA), microbial profiles appeared similar across treatment groups. However, when focusing on the viable community (PMA-treated), lyoprotectant choice significantly influenced the post-lyophilization community composition. Gram-negative bacterial viability was especially sensitive to lyophilization. Trehalose and maltodextrin preserved bacterial viability and community structure more effectively than mannitol. Mannitol-treated samples had reduced viable bacterial cells and altered community composition, while trehalose and maltodextrin better maintained diversity and structure of the viable (PMA-treated) communities. Taken together, lyoprotectants have differential effects on microbial composition during lyophilization. Among those tested, trehalose and maltodextrin best preserved both viability and community structure, making them promising candidates for FMT applications. Future research should explore optimizing lyoprotectant formulations to enhance microbiome stability and functional outcomes.}, }
@article {pmid41425939, year = {2025}, author = {Chen, J and Sun, K and Zhang, X and Chen, X and Chu, Y and Geng, L and Bian, Z and Su, Y and Cong, X and Wang, G}, title = {Psoriasis and gut microbes: research advances from mechanism to therapy.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711288}, pmid = {41425939}, issn = {1664-302X}, abstract = {BACKGROUND: Psoriasis is a chronic, immune-mediated, relapsing inflammatory skin condition, with its pathogenesis remaining incompletely understood and clinical eradication presenting significant challenges. Recent studies have highlighted the role of gut microbiota in psoriasis pathogenesis, emerging as a focal point of research.<br><br>OBJECTIVE: This review aims to systematically elucidate the core mechanisms by which gut microbiota contribute to psoriasis pathogenesis, summarize advances in gut microbiota-based therapeutic strategies, and provide theoretical support and innovative insights for both basic research and clinical treatment of psoriasis.<br><br>METHODS: Comprehensively retrieve and analyze recent research literature on the gut microbiota characteristics of psoriasis patients, the regulatory mechanisms of the gut-skin axis, and related therapeutic interventions, focusing on the microbiota's effects on immune modulation, intestinal barrier integrity, and metabolic products.<br><br>RESULTS: Accumulating evidence supports a complex, bidirectional regulatory relationship between gut dysbiosis and skin inflammation, with notable alterations in the diversity and relative abundance of gut microbial communities in patients with psoriasis compared to healthy individuals. This review comprehensively examines the mechanisms through which gut microbes contribute to psoriasis development via the gut-skin axis, influencing immune regulation, intestinal barrier integrity, and related metabolites. Additionally, the potential of gut microbiota-based therapies-such as oral probiotics, prebiotics, synbiotics, and fecal microbiota transplantation-in alleviating psoriasis symptoms and reducing disease recurrence is emphasized.<br><br>CONCLUSION: Dysbiosis of the gut microbiota is a key factor in the pathogenesis of psoriasis. The regulatory mechanisms of the gut-skin axis offer new insights into the multisystemic associations of psoriasis. Gut microbiota-based therapeutic strategies hold promise as important adjuncts to conventional treatments, laying the foundation for developing novel targeted therapies. This approach carries significant clinical implications for improving the prognosis of psoriasis patients.}, }
@article {pmid41429215, year = {2026}, author = {Korenblik, V and Schilder, NKM and de Lange, IGS and Daams, JG and Bockting, CLH and Brul, S and Nieuwdorp, M and Lok, A and Korosi, A}, title = {From gut to glee: Is butyrate a promising antidepressant? A systematic review and mechanistic insights.}, journal = {Brain, behavior, and immunity}, volume = {132}, number = {}, pages = {106237}, doi = {10.1016/j.bbi.2025.106237}, pmid = {41429215}, issn = {1090-2139}, mesh = {Humans ; *Butyrates/pharmacology/therapeutic use ; Animals ; *Depression/drug therapy ; *Antidepressive Agents/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Anxiety/drug therapy ; }, abstract = {INTRODUCTION: Despite available therapies for depression, many patients do not achieve adequate improvement, illustrating the need for innovative treatment strategies. Nutritional psychiatry is an emerging area, with increasing evidence that microbially derived butyrate contributes to the beneficial effects of dietary, pre-, pro- and synbiotics interventions - raising the exciting possibility that direct butyrate administration might alleviate depressive symptoms. The main objective was to systematically review the effects of butyrate on depressive symptoms in humans and depressive-like behavior in animals (PROSPERO; CRD42023g0739).<br><br>METHODS: A search was conducted in MEDLINE, Embase, PsycINFO, and Web of Science, ICTPR and ClinicalTrials.gov up to October 2025. Studies were included if they examined depressive symptoms in humans or relevant behaviors in animal models of depression/anxiety, involved treatment with butyrate formulations, included a control or pre-post comparison, and reported behavioral or clinical outcomes. Eligible designs included case-control, cohort, (randomized) controlled trials, experimental, or in vivo studies published in English or Dutch. Studies were excluded if depression was not the primary focus or if butyrate was combined with another treatment. Risk of bias was assessed with SYRCLE for animal studies and RoB 2 for the human studies.<br><br>RESULTS: Of the two randomized controlled trials, one found no measurable effect of 1-week oral butyrate in healthy males, whereas the other found reductions in depressive and anxiety symptoms in patients with ulcerative colitis after 12-weeks oral butyrate. Thirty-two animal studies showed that butyrate generally modulated depressive- and anxiety-like phenotypes in rodents, potentially via anti-inflammatory, neuroplastic, epigenetic and gut-mediated mechanisms.<br><br>DISCUSSION: Preclinical findings support the therapeutic promise of butyrate as a novel intervention for depression, warranting further clinical investigation.<br><br>ABBREVIATIONS: BDNF, Brain-derived neurotrophic factor; CRS, Chronic restraint stress; CSD, Chronic social defeat; CUMS, Chronic unpredictable mild stress; DASS, Depression, anxiety, Stress Scales; EPM, Elevated plus maze; FMT, Fecal microbiota transplant; FST, Forced swim test; HDAC, Histone deacetylase; HFD, High-fat diet; HPA, Hypothalamic-pituitary-adrenal; ICTRP International Clinical Trials Registry Platform; IL, Interleukin; LDB, Light-dark box; LEIDS-R, Leiden Index of Depression Severity-Revised; LPS, Lipopolysaccharide; MD, Maternal deprivation; MDD, Major depressive disorder; MGBA, Microbiota-gut-brain axis; NORT, Novel object recognition test; OFT, Open field test; PFC, Prefrontal cortex; PRISMA Preferred reporting items for systematic reviews and meta-analyses; SCFA, Short-chain fatty acid; SPT, Sucrose preference test; SYRCLE, Systematic Review Centre for Laboratory Animal Experimentation; TCA, Tricarboxylic acid; TNF, Tumor necrosis factor; TST, Tail suspension test; ZO-1, Zonulin-1.}, }
@article {pmid41429881, year = {2025}, author = {Hanzely, P and Holm, K and Bjørnholt, JV and Melum, E and Hov, JR and Rasmussen, H}, title = {Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {45099}, pmid = {41429881}, issn = {2045-2322}, support = {802544/ERC_/European Research Council/International ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Administration, Oral ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Administration, Rectal ; Feces/microbiology ; Male ; Disease Models, Animal ; Female ; Bacteria/genetics/classification ; }, abstract = {The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota-host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies.}, }
@article {pmid41430282, year = {2025}, author = {He, Y and Zhang, Y and Zhao, L and Zhou, Z and Su, N and Zhang, C and Wang, K and Jin, L and Yang, B and Hu, X and Fu, Y}, title = {Vagus nerve stimulation alleviates S. aureus-induced mastitis by regulating gut microbiota S24-7-PPARγ and NF-ΚB/NLRP3 signaling in mice.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {32}, pmid = {41430282}, issn = {1742-2094}, support = {212558JC010286222//Jilin Province Department of Science and Technology/ ; 32422086//the National Natural Science Foundation of China/ ; 32301247//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Vagus Nerve Stimulation/methods ; Female ; Signal Transduction/physiology ; PPAR gamma/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Mastitis/therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Staphylococcus aureus ; NF-kappa B/metabolism ; *Staphylococcal Infections/therapy/complications/metabolism ; Mice, Inbred BALB C ; }, abstract = {Gut microbiota dysbiosis has been implicated in the pathogenesis of mastitis. While the vagus nerve exerts well-documented anti-inflammatory effects and modulates gut microbiota, its potential influence on mastitis progression via gut microbiota modulation remains unclear. To investigate this, we employed vagus nerve stimulation (VNS) in Staphylococcus aureus (S. aureus)-induced mastitis in mice. We demonstrate that VNS significantly attenuated mammary gland inflammation and restored epithelial barrier integrity following S. aureus challenge. Crucially, antibiotic depletion of the gut microbiota abrogated the protective effects of VNS, and fecal microbiota transplantation (FMT) from VNS-treated mice conferred protection against mastitis, establishing a causal role for the gut microbiota in mediating the VNS effect. Specifically, VNS markedly increased the abundance of Muribaculaceae. in the gut. Replenishment with S24-7, a representative strain of this genus, alleviated S. aureus-induced mammary gland inflammation in mice. Transcriptomic analysis revealed that S24-7 exerted its effects by activating peroxisome proliferator-activated receptor gamma (PPARγ), which subsequently suppressed the NF-κB/NLRP3 signaling pathway. Overall, our findings suggest that targeting the vagus nerve - mediated Muribaculaceae/PPARγ axis may represent a promising strategy for mastitis treatment.}, }
@article {pmid41431379, year = {2026}, author = {Al-Btoosh, S and Donnelly, RF and Kelly, SA}, title = {Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604867}, pmid = {41431379}, issn = {1949-0984}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Probiotics ; *Bacteria/drug effects/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Pharmaceutical Preparations/metabolism ; Prebiotics ; Biotransformation ; }, abstract = {The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modulation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunotherapeutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihypertensives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceuticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment outcomes and mitigate adverse drug effects.}, }
@article {pmid41432256, year = {2026}, author = {He, F and Liu, G and Wu, H and Elsabagh, M and Huang, Y and Wang, J and Wang, M and Zhang, H}, title = {Maternal intestinal and placental mitochondrial dysfunction, autophagy, and ferroptosis involving intestinal microbiota by gut microbiota transplantation from sheep to mice†.}, journal = {Biology of reproduction}, volume = {114}, number = {3}, pages = {1030-1044}, doi = {10.1093/biolre/ioaf253}, pmid = {41432256}, issn = {1529-7268}, support = {2024YFD1300203//Project of National Key Research and Development Program of China/ ; }, mesh = {Animals ; Female ; Pregnancy ; *Placenta/drug effects ; Mice ; *Autophagy/physiology/drug effects ; *Gastrointestinal Microbiome/physiology ; Sheep ; *Ferroptosis/physiology/drug effects ; *Mitochondria ; *Intestines/microbiology ; *Fecal Microbiota Transplantation ; Fetal Growth Retardation/chemically induced ; }, abstract = {Exposure to testosterone (T) in pregnant ewes resulted in placental dysfunction and fetal growth restriction (FGR). However, the impact of T on gut microbiota and its contribution to exacerbating intestinal and placental pathologies remains uncharacterized. Pregnant sheep received intramuscular injections of 100 mg T propionate or a control vehicle. To examine the gut microbiota' s role in T-induced FGR, gut microbiota transplantation (GMT) was conducted from T-exposed and control ewes into antibiotic-treated pregnant mice. The findings demonstrated that T exposure exacerbated mitochondrial impairment, autophagy, and ferroptosis in placental and intestinal tissues, alongside inducing gut microbial dysbiosis. GMT further revealed that pathological alterations were mechanistically linked to gut microbiota imbalance. The findings demonstrated that gut-placental axis play a central role in mediating T-induced mitochondrial dysfunction, autophagy, and ferroptosis in maternal intestinal and placental tissues. These results underscore novel therapeutic opportunities, which operate via the gut-placental axis to mitigate FGR.}, }
@article {pmid41436018, year = {2026}, author = {Yue, CB and Luan, WW and Qiu, D and Ding, X and Gu, HW and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM}, title = {A vagus-dependent gut microbiota-metabolite axis drives chronic inflammatory pain and working-memory deficits in mice.}, journal = {Brain research bulletin}, volume = {234}, number = {}, pages = {111702}, doi = {10.1016/j.brainresbull.2025.111702}, pmid = {41436018}, issn = {1873-2747}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Vagus Nerve/metabolism ; Mice ; Male ; *Inflammation/metabolism ; *Chronic Pain/metabolism/microbiology/physiopathology ; *Memory, Short-Term/physiology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Memory Disorders/metabolism/microbiology ; Hippocampus/metabolism ; Neuroinflammatory Diseases/metabolism ; Vagotomy ; }, abstract = {Chronic inflammatory pain (CIP) has been increasingly linked to gut microbiota (GM)-brain interactions, yet whether these effects rely on vagal signaling remains unclear. Here, we investigated whether GM from CIP mice is sufficient to transfer pain-like behaviors to healthy recipients and whether this process depends on the vagus nerve. Fecal microbiota transplantation (FMT) from mice treated with complete Freund's adjuvant induced mechanical and thermal hypersensitivity and impaired working memory in recipients, accompanied by hippocampal neuroinflammation and GM dysbiosis. Subdiaphragmatic vagotomy (SDV) performed prior to FMT attenuated these behavioral and neuroinflammatory alterations and partially normalized microbial community structure. Plasma metabolomics further showed that SDV restored phosphatidylcholines while reducing pro-inflammatory lipid classes, with several metabolites and bacterial taxa correlating significantly with pain sensitivity and hippocampal cytokine levels. Collectively, these findings demonstrate that a vagus-dependent GM-metabolite-brain axis contributes to CIP-like behaviors and neuroinflammation. Targeting vagal pathways and GM-regulated lipid metabolism may offer therapeutic strategies and pharmacodynamic biomarkers for inflammatory pain.}, }
@article {pmid41437305, year = {2025}, author = {Gong, Z and Zou, J and Fang, Y and Li, J and Luo, Y and Xue, Q and Yu, B and Hua, B and Liu, Z}, title = {The role of gut microbiota in neuropathic pain: insights into immune mechanisms.}, journal = {The journal of headache and pain}, volume = {27}, number = {1}, pages = {28}, pmid = {41437305}, issn = {1129-2377}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Neuralgia/immunology/microbiology/metabolism ; Animals ; }, abstract = {Neuropathic pain (NP), characterized by its complex pathophysiological mechanisms, has long posed a formidable therapeutic challenge. The burden of NP is further exacerbated by the increasing prevalence of chronic diseases. Emerging evidence highlights the pivotal role of gut microbiota in modulating immune responses, offering novel insights into NP pathogenesis. This review explores recent advancements in understanding how gut microbiota-derived metabolites - including short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives - regulate immune processes that influence neuroinflammation and nociceptive signaling. We focus on key immune mediators, including macrophages, microglia, T cells, and astrocytes, elucidating their involvement in microbiota-driven immune regulation via pathways such as TLR4/NF-κB signaling, histone deacetylase (HDAC) inhibition, and aryl hydrocarbon receptor (AhR) activation. Additionally, we examine emerging evidence of sex-specific immune mechanisms in NP. Despite promising preclinical findings on microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation, translational challenges, such as microbiota heterogeneity and sex-specific responses, necessitate further investigation. This review aims to bridge microbiology, neuroimmunology, and pain research, offering a multidimensional perspective and actionable insights for the future management of NP.}, }
@article {pmid41438339, year = {2026}, author = {Van Espen, L and Brol, MJ and Close, L and Schierwagen, R and Gu, W and Keller, MI and Balogh, B and Fullam, A and De Coninck, L and Nakamura, T and Kuhn, M and Bork, P and Laleman, W and Bajaj, JS and Papp, M and Schnabl, B and Trebicka, J and Matthijnssens, J and , }, title = {L actococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101622}, pmid = {41438339}, issn = {2589-5559}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND &amp; AIMS: As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).<br><br>METHODS: The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters.<br><br>RESULTS: Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of proven systemic bacterial infection. The presence of both phage families was linked to increased 90-day mortality rates.<br><br>CONCLUSION: ACLF is characterized by increased fecal virome diversity and a shift from virulent toward temperate phages at disease onset. Our study links Lactococcus A phages to ACLF development, and Enterococcus B phages to bacterial infection, while both are associated with increased 90-day mortality.<br><br>CLINICAL TRIAL NUMBER: NCT03056612.<br><br>IMPACT AND IMPLICATIONS: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.}, }
@article {pmid41438381, year = {2025}, author = {Chen, X and Zhang, Y and Zhang, G and Wang, D and Dou, L and Wang, Y and Huang, Z and Liu, X}, title = {Spatial microbiome-metabolic crosstalk drives CD8[+] T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1704491}, pmid = {41438381}, issn = {1664-302X}, abstract = {BACKGROUND: The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.<br><br>METHODS: We integrated single-cell RNA-seq, spatial transcriptomics, and microbial multi-omics from a discovery cohort of 23 treatment-na&#xef;ve CRC patients. Findings were validated in an independent validation cohort from The Cancer Genome Atlas (TCGA-CRC, n&#x202f;=&#x202f;159).<br><br>RESULTS: Spatial depletion of Streptococcus and Acetivibrio in tumor niches disrupts butyrate-histone deacetylase (HDAC) signaling, leading to programmed cell death 1 (PDCD1) hyperacetylation and CD8[+] T-cell exhaustion. The Colorectal Cancer Microbiome Score (CMS) may serve as a predictive biomarker for immunotherapy response and HDAC inhibitor-based combination therapy. We developed the CMS, a spatial biomarker that stratifies patients by microbial-metabolic dysfunction, predicting immunotherapy resistance (e.g., higher tumor immune dysfunction and exclusion (TIDE) scores; p&#x202f;<&#x202f;0.01) and guiding combinatorial HDAC inhibition for CMS-defined subgroups. In silico fecal microbiota transplantation (FMT) validated CMS as an actionable target for microbiota modulation. Butyrate supplementation in vitro restored HDAC activity and reduced PD-1 expression on CD8[+] T cells, validating the proposed mechanism.<br><br>CONCLUSION: Our study unveils a spatially defined, microbiome-driven metabolic niche that epigenetically programs CD8[+] T-cell exhaustion via the butyrate-HDAC axis, revealing a targetable mechanism to overcome immunotherapy resistance in CRC.}, }
@article {pmid41438742, year = {2025}, author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD}, title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1568962}, pmid = {41438742}, issn = {1664-3224}, mesh = {Animals ; Humans ; *Bacteria/classification/isolation &amp; purification ; *Biomarkers/analysis ; *Carcinoma, Hepatocellular/diagnosis/immunology/microbiology/therapy ; *Gastrointestinal Microbiome ; Immunotherapy ; Inflammation/immunology/pathology ; *Liver Neoplasms/diagnosis/microbiology ; Tumor Microenvironment ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.}, }
@article {pmid41439197, year = {2025}, author = {Liang, J and Qiu, Y and Fu, T and Li, J and Yang, J and Tong, Y}, title = {The Gut-Kidney Axis in Uric Acid Nephropathy: Microbiota, Metabolic Crosstalk, and Translational Prospects.}, journal = {Journal of multidisciplinary healthcare}, volume = {18}, number = {}, pages = {8111-8132}, pmid = {41439197}, issn = {1178-2390}, abstract = {Uric acid nephropathy (UAN) represents a critical and multifactorial renal disorder closely linked to hyperuricemia, inflammation, and gut microbiota dysregulation. Recent advances have revealed the pivotal role of the gut-kidney axis in modulating urate metabolism, immune activation, and oxidative stress. This review synthesizes emerging preclinical and clinical evidence to construct an integrative framework for understanding UAN, highlighting both crystal-dependent and crystal-independent mechanisms that drive tubular injury and fibrosis. Accumulating data underscore the reciprocal crosstalk between renal dysfunction and gut dysbiosis, mediated by microbial metabolites such as short-chain fatty acids (SCFAs), indoxyl sulfate, and p-cresol sulfate. We further evaluate therapeutic interventions targeting the gut-kidney axis-including probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and engineered microbial therapies-which have shown promise in restoring microbial balance and improving urate handling. By integrating multi-omics profiling with systems biology, this review proposes a precision-medicine roadmap that leverages microbiome signatures and metabolic phenotyping for risk stratification and personalized intervention. Moreover, we emphasize the need for supportive regulatory frameworks and interdisciplinary collaboration to enable the clinical translation of microbiota-based strategies. Collectively, this work provides a strengthened conceptual foundation for microbiome-informed prevention and treatment of uric acid-related kidney disease.}, }
@article {pmid41439235, year = {2026}, author = {Zou, B and Huo, Q and Zhou, X and Lv, Y and Li, G and Fu, G and Shen, H and Shu, S}, title = {Characteristics and longitudinal stability of Gut Microbiota in healthy individuals across different age groups.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100512}, pmid = {41439235}, issn = {2666-5174}, abstract = {Fecal microbiota transplantation (FMT) efficacy relies on donor microbiome composition and temporal stability, yet the influence of donor age remains inadequately investigated. This longitudinal analysis addressed this gap by examining 81 healthy individuals (3-30 years), stratified into four age groups, who provided monthly fecal samples over 12 months (n = 972 samples). Gut microbiota composition (16S rDNA sequencing) and temporal stability were assessed using Bray-Curtis dissimilarity, intraclass correlation coefficient (ICC), and genus-level co-occurrence network analysis. Results demonstrated a strong age-dependency in microbiota stability. The teenage cohort (13-17 years) exhibited the highest stability, characterized by minimal fluctuations in α- and β-diversity and significantly stronger network centrality. Furthermore, specific genera, notably Faecalibacterium and Bifidobacterium, displayed exceptionally high ICC values (>0.90), identifying them as core taxa associated with temporal consistency. These findings underscore the critical role of donor age in microbial stability and highlight teenagers as possessing optimal microbiota characteristics for FMT. They strongly support the development of an ICC-based screening framework to enhance donor selection protocols.}, }
@article {pmid41439481, year = {2026}, author = {Zou, Y and Li, N and Li, X and Kuang, M and Xu, X and Guan, L and Li, X and Zheng, P and Li, L and Wan, J and Lu, N and Liu, J and He, C and Zhu, Y}, title = {Gut microbiota dysbiosis exacerbates acute pancreatitis via Escherichia coli-driven neutrophil heterogeneity and NETosis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606480}, pmid = {41439481}, issn = {1949-0984}, mesh = {Animals ; *Dysbiosis/microbiology/immunology/complications ; *Gastrointestinal Microbiome ; Mice ; Humans ; *Neutrophils/immunology ; *Extracellular Traps/immunology/metabolism ; *Escherichia coli/physiology ; *Pancreatitis/microbiology/immunology/pathology ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Specific Pathogen-Free Organisms ; }, abstract = {Gut microbiota dysbiosis contributes to acute pancreatitis (AP) severity, but the specific microbes and mechanisms remain unclear. In this study, we employed both germ-free (GF) and specific-pathogen-free (SPF) murine models of AP to investigate the role of the intestinal microbiota. Our findings demonstrate that GF mice exhibited markedly attenuated pancreatic injury, inflammatory cell infiltration, and neutrophil extracellular traps (NETs) formation. Through fecal microbiota transplantation (FMT) from AP patients, differential antibiotic modulation, and single-bacterial colonization experiments, we identified Gram-negative bacteria, particularly Escherichia coli (E. coli), as critical microbial drivers of disease exacerbation. Single-cell RNA sequencing revealed that microbiota dysbiosis profoundly reprogrammed both local pancreatic and systemic immune landscapes. Specifically, dysbiosis promoted emergency granulopoiesis in the bone marrow, enhanced neutrophil mobilization and activation, and facilitated the expansion of pro-inflammatory neutrophil subpopulations (Neutrophils_2 and Neutrophils_3). These subsets exhibited upregulated signaling through NETosis-associated pathways, including TLR, NF-κB, and IL-17 axes. Conversely, in GF conditions, we observed a predominance of an anti-inflammatory neutrophil subset (Neutrophils_4), characterized by the expression of tissue repair-associated genes such as Reg1 and Reg2. Shotgun metagenomic profiling of fecal samples from patients with AP revealed an enrichment of E. coli during the acute phase, positively correlating with circulating cell-free DNA, a marker of NETosis. Together, these insights suggest that gut microbiota dysbiosis, notably increased E. coli abundance, may aggravate AP by reshaping immunity and promoting aberrant NETs formation, supporting microbiota or NETs targeted therapies.}, }
@article {pmid41439929, year = {2025}, author = {Geladari, EV and Kalergi, AC and Evangelopoulos, AA and Sevastianos, VA}, title = {Sepsis and the Liver.}, journal = {Diseases (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {41439929}, issn = {2079-9721}, abstract = {BACKGROUND/OBJECTIVES: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes.<br><br>METHODS: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently.<br><br>RESULTS: The initial inflammatory response activates pathways such as NF-&#x3ba;B and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPAR&#x3b1; and HNF4&#x3b1;. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity.<br><br>CONCLUSION: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI.}, }
@article {pmid41439979, year = {2025}, author = {Mostafavi Abdolmaleky, H and Pirani, A and Pettinato, G}, title = {Psychosomatic Disorders, Epigenome, and Gut Microbiota.}, journal = {Cells}, volume = {14}, number = {24}, pages = {}, pmid = {41439979}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Epigenome/genetics ; *Psychophysiologic Disorders/genetics/microbiology ; Animals ; *Epigenesis, Genetic ; }, abstract = {Psychosomatic disorders are conditions in which physical (somatic) symptoms are triggered or aggravated by psychological distress. These disorders result from complex interactions among the endocrine, central nervous, and immune systems. Emerging evidence indicates that gut microbiota (GM) dysbiosis, epigenetic alterations, and immune system dysregulation play pivotal roles in the pathogenesis of psychosomatic disorders and may serve as potential biomarkers for disease states and therapeutic outcomes. This review first outlines how epigenetic dysregulation contributes to psychosomatic disorders through altered expression of genes such as GRM2, TRPA1, SLC6A4, NR3C1, leptin, BDNF, NAT15, HDAC4, PRKCA, RTN1, PRKG1, and HDAC7. We then examine current evidence linking psychosomatic disorders with changes in GM composition and GM-derived epigenetic metabolites, which influence immune function and neurobiological pathways. The core focus of this review is on therapeutic interventions-including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and targeted dietary approaches-that modulate the gut-brain axis through epigenetic mechanisms for the management of psychosomatic disorders. Finally, we highlight the current challenges and future directions in elucidating the interplay between epigenetics, the GM, and psychosomatic disease mechanisms. In this context, human iPSC-derived multicellular organoids may serve as powerful platforms to unravel mechanistic pathways underlying inter-organ interactions.}, }
@article {pmid41440201, year = {2025}, author = {Ye, G and Zhang, H and Feng, Q and Xiao, J and Wang, J and Liu, J}, title = {Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.}, journal = {Current oncology (Toronto, Ont.)}, volume = {32}, number = {12}, pages = {}, pmid = {41440201}, issn = {1718-7729}, support = {2021ZQNZD009//Major Scientiffc Research Program for Young and Middle-aged Health Professionals of Fujian Province, China/ ; 2023Y9416//Fujian Science and Technology Innovation Joint Fund Project/ ; }, mesh = {*Carcinoma, Hepatocellular/immunology/microbiology/therapy ; *Bacteria/metabolism ; *Gastrointestinal Microbiome ; Humans ; Probiotics ; Fecal Microbiota Transplantation ; Tumor Microenvironment ; Animals ; Fatty Acids, Volatile/metabolism ; }, abstract = {Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.}, }
@article {pmid41440729, year = {2025}, author = {Hirji, I and John, D and Jith, J and Khoshnaw, H and Ganeshananthan, M}, title = {Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {41440729}, issn = {2308-3417}, abstract = {BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.<br><br>CASE PRESENTATIONS: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk.<br><br>DISCUSSIONS: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings.<br><br>CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.}, }
@article {pmid41440851, year = {2025}, author = {Tao, Y and Zhang, N and Wang, Z and Pan, Y and Zhong, S and Liu, H}, title = {SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.}, journal = {Journal of cardiovascular development and disease}, volume = {12}, number = {12}, pages = {}, pmid = {41440851}, issn = {2308-3425}, abstract = {Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated significant cardiovascular and renal benefits beyond glycemic control, yet their integrated mechanisms remain incompletely understood. Emerging evidence highlights the gut-kidney-heart axis as a pivotal pathological network, wherein gut dysbiosis, toxic metabolite accumulation, intestinal barrier disruption, and systemic inflammation synergistically drive cardiorenal injury. This review systematically elucidates how SGLT2i modulate this axis through multi-level interventions: reshaping gut microbiota composition, enriching short-chain fatty acid-producing bacteria, suppressing trimethylamine and other toxin-generating microbes, restoring tight junction integrity, and regulating bile acid metabolism. These upstream effects reduce systemic inflammatory and metabolic stress, interrupt kidney-derived toxin amplification, and mitigate myocardial remodeling. Unlike previous reviews focusing on single-organ pathways, this work integrates microecological regulation, metabolite reprogramming, and cross-organ protection into a unified "three-axis convergence to the heart" framework. We also highlight potential species-specific microbiota regulatory profiles among different SGLT2i and propose future directions, including fecal microbiota transplantation and microbiota-targeted co-therapies, to clarify causal relationships and optimize therapeutic strategies. By positioning the gut as a modifiable upstream driver, this framework provides novel mechanistic insight and translational potential for expanding SGLT2i applications in metabolic cardiovascular disease, including in non-diabetic populations.}, }
@article {pmid41443865, year = {2025}, author = {Takeda, T and Hojo, M and Asaoka, D and Nagahara, A}, title = {Targeting Gut Microbiota in the Management of Functional Constipation: A Narrative Review.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.6457-25}, pmid = {41443865}, issn = {1349-7235}, abstract = {Functional constipation (FC) is a prevalent gastrointestinal disorder that negatively affects the quality of life. Recent studies have suggested that the gut microbiota plays a key role in the pathophysiology of FC, with dysbiosis, reduced diversity, and altered production of short-chain fatty acids that influence intestinal motility. Probiotics have shown potential for improving bowel movements and related symptoms in adults with FC. However, clinical outcomes vary depending on strain, dosage, and study design. Fecal microbiota transplantation has also emerged as a promising treatment, demonstrating improved stool frequency and colonic transit in selected patients. This narrative review summarizes the current understanding of the relationship between gut microbiota and FC and highlights the therapeutic potential of probiotics and fecal microbiota transplantation. Further research is warranted to clarify the underlying mechanisms and optimize microbiota-targeted interventions for effective management of FC.}, }
@article {pmid41444511, year = {2025}, author = {Tang, M and Li, H and Tang, F and Shu, Y and Meng, B and Zhang, Q and Li, C and Xu, Y and Xu, Y and Pan, J and Liu, Y and Hu, L and Wang, C and Wu, T and Li, J}, title = {GPR43 deficiency aggravates sepsis by promoting gut microbiota-dependent barrier disruption and HIF-1α-ENO1 axis-mediated M1 polarization of macrophages.}, journal = {Cellular &amp; molecular biology letters}, volume = {31}, number = {1}, pages = {12}, pmid = {41444511}, issn = {1689-1392}, support = {82400132//National Natural Science Foundation of China/ ; 82470108//National Natural Science Foundation of China/ ; U24A20643//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: GPR43, a receptor for short-chain fatty acids (SCFAs), is broadly expressed in intestinal epithelial and immune cells and is essential for preserving barrier integrity and immune homeostasis. Nevertheless, how GPR43 influences gut microbiota composition and intestinal barrier integrity while also regulating macrophage immunometabolism in the context of sepsis remains poorly understood. METHODS: A cecal ligation and puncture model was used to induce sepsis in mice. Survival, histopathology, and immune responses were compared between Gpr43−/− and wild-type mice; 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomics were performed to evaluate gut microbiota composition and metabolic profiles. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation were used to assess functional impacts. Bone marrow-derived macrophages were employed to investigate the effects of GPR43 deficiency on macrophage polarization. RNA sequencing, metabolic flux analysis, and Western blotting were conducted to explore the molecular mechanisms involved. Peripheral blood mononuclear cell samples from patients with sepsis were analyzed for clinical correlation. RESULTS: Gpr43−/− mice exhibited significantly reduced survival following CLP, along with impaired intestinal barrier function and elevated proinflammatory cytokine levels. Microbiota diversity and SCFA-producing bacteria were markedly decreased, accompanied by reduced SCFA levels in fecal metabolites. Fecal microbiota transplantation (FMT) partially restored gut function and survival in Gpr43−/− mice. GPR43-deficient macrophages displayed a strong M1-polarized phenotype with the upregulation of the glycolytic enzyme ENO1 and its upstream regulator HIF-1α. The inhibition of either ENO1 or HIF-1α reversed the proinflammatory phenotype. A clinical data analysis revealed that GPR43 expression was negatively correlated with IL-6, ENO1, and lactate levels. CONCLUSIONS: GPR43 exerts a dual protective role in sepsis by maintaining gut microbiota homeostasis and barrier integrity and by modulating macrophage metabolism and polarization via the HIF-1α–ENO1 axis. This study provides novel insights into the GPR43 in pathogenesis of sepsis and suggests potential therapeutic targets for intervention.}, }
@article {pmid41444705, year = {2025}, author = {Oladele, P and Dong, W and Richert, BT and Johnson, TA}, title = {Route of fecal microbiota transplantation delivery determined the dynamics and predictability of donor microbe colonization.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {130}, pmid = {41444705}, issn = {2524-4671}, support = {ICASASHTWG0000000082//Foundation for Food and Agriculture Research,United States/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and the colonization of delivered donor microbes has been reported to improve the negative effects (decrease in body weight, diarrhea, and gut barrier disruption) associated with weaning in pigs. However, delivery of FMT in pigs is still invasive and predicting the colonization or rejection of donor microbes remains challenging. Therefore, this study developed a non-invasive in-feed delivery of FMT and evaluated the effect of FMT mode of delivery on growth performance, gut physiology, microbiota dynamics, and predictability of colonization or rejection of donor microbes in recipient pigs. Forty weaned piglets (10 per group) were administered FMT through one of three routes; oral, rectal, or amended in-feed. The control group was orally administered sterile saline to simulate handling stress. RESULTS: Pigs in the FMT groups had higher average daily weight gain (ADG) from day 0–2 post-weaning. An increase in community diversity and a shift in the recipient community towards the donor in all FMT groups was observed on day 5. The oral group had the highest colonization (15.12%) and the lowest rejection (19.34%) rates, while colonization was 13.82% and 11.78% in rectal and in-feed group respectively. On day 4, colon crypt depth was increased in all FMT groups but an increase in villus length was only observed in the in-feed group. Colonization and rejection of donor microbes in the recipient animals could be predicted in all routes of administration, but the efficacy of prediction was influenced by the route of delivery. In-feed FMT had the lowest colonization prediction which may have been influenced by the need for voluntary consumption of fecal materials in the in-feed group. The ten most abundant genera (Prevotella, Alloprevotella, Phascolarctobacterium, Lactobacillus, Cloacibacillus, Bacteroides, Lachnoclostridium, Escherichia-Shigella, unclassified Lachnospiraceae sequences, and archaea Methanobrevibacter) in the recipient prior to FMT (background community) was the most important feature in predicting colonization for all routes of fecal microbiota transplant. CONCLUSION: FMT administered as a lyophilized feed additive shows promise in altering microbiome community structure. While colonization and rejection of donor microbes within the recipient community are predictable, the efficacy of these predictions varies with the route of transplant. This suggests that different prediction models are necessary for each delivery mode of FMT in pigs.}, }
@article {pmid41445729, year = {2025}, author = {Yu, S and Zhang, M and Dou, Z and Tian, B and Lu, J}, title = {Gut microbiota metabolites in the immunoregulation of enteritis: research progress.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1706472}, pmid = {41445729}, issn = {1664-3224}, mesh = {Animals ; Humans ; Bile Acids and Salts/metabolism ; *Enteritis/immunology/metabolism/microbiology/therapy ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/immunology ; Immunomodulation ; Probiotics ; }, abstract = {The interaction between gut microbiota metabolites and the host immune system plays a crucial role in maintaining intestinal homeostasis and in the development of inflammatory bowel disease and other enteric conditions. This article presents a systematic review of the sources and functions of short-chain fatty acids, tryptophan metabolites, bile acids, and other microbial metabolites, focusing on how these metabolites regulate the function of immune cells, such as T cells, B cells, neutrophils, macrophages, and dendritic cells, as well as key inflammatory signaling pathways, including the NF-κB, NLRP3 inflammasome, and JAK-STAT pathways, thereby influencing intestinal barrier integrity. Also explored are potential therapeutic strategies based on microbial metabolites, including the application status and prospects of probiotic and prebiotic interventions, the direct administration of metabolites, and fecal microbiota transplantation. Although current research faces challenges such as unclear mechanisms, significant differences among individuals, and barriers to clinical translation, the development of multiomics technologies and precision medicine holds promise for providing more effective and personalized treatment strategies targeting gut microbiota metabolites for patients with enteritis.}, }
@article {pmid41447757, year = {2026}, author = {Mandala, A and Undi, RB and Janssen, RC and Sugino, KY and Zhao, W and Nelson, BN and Teague, AM and Patil, NY and Zemsky Berry, K and Varshney, R and Bergman, BC and Rudolph, MC and Joshi, AD and Rajala, RVS and Jonscher, KR and Friedman, JE}, title = {Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106098}, pmid = {41447757}, issn = {2352-3964}, support = {P30 DK048520/DK/NIDDK NIH HHS/United States ; R01 DK121951/DK/NIDDK NIH HHS/United States ; P30 GM154635/GM/NIGMS NIH HHS/United States ; P30 CA225520/CA/NCI NIH HHS/United States ; R01 DK122028/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Female ; *Indoles/administration &amp; dosage/pharmacology ; Mice ; Humans ; Pregnancy ; Male ; Gastrointestinal Microbiome/drug effects ; *Liver/metabolism/pathology/drug effects ; *Dietary Supplements ; *Fatty Liver/prevention &amp; control/etiology/metabolism/pathology ; Disease Models, Animal ; Prenatal Exposure Delayed Effects ; Receptors, Aryl Hydrocarbon/metabolism ; Diet, Western/adverse effects ; Maternal Exposure ; Ceramides/metabolism ; Fecal Microbiota Transplantation ; Hepatic Stellate Cells/metabolism/drug effects ; Indoleacetic Acids ; }, abstract = {BACKGROUND: Disruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored.<br><br>METHODS: WD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to na&#xef;ve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-&#x3b2;-induced fibrosis.<br><br>FINDINGS: Maternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition.<br><br>INTERPRETATION: Maternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD.<br><br>FUNDING: See Acknowledgements.}, }
@article {pmid41447836, year = {2026}, author = {Qiao, Z and Tong, H and Wang, Z and Liu, J and Chen, X and Song, Z and Wang, Y}, title = {Dehydrodiisoeugenol attenuates ulcerative colitis via regulating Anaerostipes caccae-mediated uric acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157721}, doi = {10.1016/j.phymed.2025.157721}, pmid = {41447836}, issn = {1618-095X}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Uric Acid/metabolism ; Fecal Microbiota Transplantation ; Male ; Mice, Inbred C57BL ; *Eugenol/analogs &amp; derivatives/pharmacology ; Disease Models, Animal ; Dextran Sulfate ; *Eubacteriales/drug effects ; }, abstract = {BACKGROUND: The gut microbiota plays a crucial role in the pathogenesis of ulcerative colitis (UC). Dehydrodiisoeugenol (DEH) is a major benzofuran-type neolignane isolated from Myristica fragrans Houtt., a plant whose fruit has been incorporated into traditional Chinese medicine (TCM) formulations for clinical treatment of gastrointestinal disorders. However, the pharmacological mechanisms underlying the anti-colitic efficacy of DEH remain to be elucidated.<br><br>PURPOSE: The present study aimed to investigate the anti-colitic efficacy of DEH and its therapeutic mechanism, with a specific focus on the role of gut microbiota regulation.<br><br>METHODS: A dextran sulfate sodium (DSS)-induced murine model of UC was utilized to assess the effects of DEH on UC progression. Co-housing experiments and fecal microbiota transplantation (FMT) were conducted to verify whether DEH's anti-colitic effects depend on the gut microbiota. 16S rRNA gene sequencing and quantitative PCR (qPCR) were performed to identify gut bacterial taxa altered by DEH. Bacterial colonization was carried out to evaluate the effects of differential species on symptoms of UC. Metabolomic analyses and in vitro incubations were conducted to identify key metabolites.<br><br>RESULTS: First, DEH exerted potent anti-colitic efficacy in DSS-induced UC mice by alleviating colonic inflammation and enhancing intestinal epithelial integrity. Administration of DEH at 50 mg/kg significantly prolonged the colon length to 6.27 &#xb1; 0.19 cm, which was longer than that of the vehicle group (4.85 &#xb1; 0.18 cm) and the positive control drug SASP group (200 mg/kg, 5.83 &#xb1; 0.18 cm). Co-housing and FMT validated that DEH's efficacy is dependent on the gut microbiota. Subsequently, we found that DEH significantly upregulated the abundance of Anaerostipes caccae, the colonization with which could alleviate symptoms of UC. Furthermore, we identified A. caccae as a uric acid (UA)-metabolizing microbe, and its colonization in UC mice obviously reduced UA levels. Blocking UA synthesis with allopurinol (Allo) completely abolished A. caccae's anti-colitic effects, verifying its therapeutic effects rely on the UA-lowering capacity. Finally, we found the pathologically elevated UA exacerbated UC via activating the p38 mitogen-activated protein kinase (MAPK) signaling pathway.<br><br>CONCLUSION: Our study highlights that the A. caccae-mediated maintenance of UA metabolic homeostasis restrains UC pathogenesis, a process that is the core mechanism through which DEH exerts its anti-colitic efficacy.}, }
@article {pmid41448004, year = {2026}, author = {Gao, J and Li, L and Zhang, S and Zhao, H and Feng, B and Liu, C and Wang, X and Li, S and Li, Y and Zhao, D}, title = {Taurodeoxycholic acid alleviates intestinal inflammation by modulating gut microbiota and TGR5-NF-kappaB axis in DSS-induced colitis.}, journal = {International immunopharmacology}, volume = {170}, number = {}, pages = {116056}, doi = {10.1016/j.intimp.2025.116056}, pmid = {41448004}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate ; *Colitis/chemically induced/drug therapy/microbiology/immunology ; NF-kappa B/metabolism ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Mice ; Mice, Inbred C57BL ; Male ; Bile Acids and Salts/metabolism ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Disease Models, Animal ; Feces/microbiology ; Humans ; }, abstract = {Taurodeoxycholic acid (TDCA), a metabolite of cholesterol, has been shown to be able to regulate various inflammatory responses and improve intestinal inflammation. However, its potential to alleviate colitis through modulating the gut microbiota-bile acid axis remains unclear. Mice were simultaneously administered dextran sulfate sodium (DSS) and TDCA via drinking water to estimate the effect of TDCA on colitis. TDCA-treated mice showed markedly relieved DSS-induced colitis. 16S rDNA sequencing revealed TDCA selectively remodeled the gut microbiota, notably decreasing the abundances of Desulfovibrionaceae_unclassified, Escherichia-Shigella and increasing Akkermansia. Furthermore, the reshaping of the microbial community was functionally characterized by a marked alteration in the gut bile acid profile, specifically a significant increase in secondary bile acids. Fecal microbiota transplantation (FMT) confirmed the protective role of the TDCA-shaped microbiota, which also transferred the reduction of Desulfovibrionaceae_unclassified and the characteristic bile acid profile to recipient mice. Similarly, transplanting feces after TDCA intervention into recipient mice still increased secondary bile acid levels in the gut to a certain extent. Spearman's correlation analysis further solidified the negative correlation between Desulfovibrionaceae_unclassified and secondary bile acids. Mechanistically, the altered bile acid profiles restored the activation of the bile acid receptor TGR5, but not FXR, thereby inhibiting the NF-κB signaling pathway. The essential role of TGR5 was substantiated as its inhibitor, SBI-115, largely abolished the protective effects of TDCA. In conclusion, our findings demonstrate that TDCA alleviates colitis by orchestrating a microbiota-bile acid-TGR5 signaling cascade, positioning it as a promising therapeutic candidate for inflammatory bowel disease.}, }
@article {pmid41450949, year = {2025}, author = {Perzon, O and Ilan, Y}, title = {Understanding gut microbial diversity using systems based on the Constrained-Disorder Principle provides a novel approach to targeting gut microbiome therapies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1713775}, pmid = {41450949}, issn = {1664-302X}, abstract = {BACKGROUND/AIMS: The diverse composition of the gut microbiome is vital for human health, influencing digestion, immune regulation, and disease resistance. While higher diversity is generally associated with resilience, reduced and excessive diversity can lead to health issues.<br><br>METHODS: This paper introduces the Constrained Disorder Principle (CDP) as a new framework for understanding microbial diversity.<br><br>RESULTS: The CDP emphasizes the significance of maintaining variability within certain boundaries to sustain ecosystem stability and promote health. It considers intra- and inter-individual variability, illustrating how microbial ecosystems adapt throughout different life stages, genetic backgrounds, and environmental exposures. Integrating CDP-based artificial intelligence systems may enable the establishment of personalized diversity thresholds, predict dysbiosis, and refine interventions such as probiotics, prebiotics, fecal microbiota transplantation, and customized dietary strategies. CDP-driven platforms enhance therapeutic precision by utilizing variability induction, feedback loops, and microbial signature analysis to optimize diversity goals and identify actionable biomarkers.<br><br>CONCLUSION: This platform can pave the way for adaptive, individualized disease prevention and treatment strategies, bridging the gap between microbial ecology and precision medicine. It provides a powerful tool for harnessing the therapeutic potential of gut microbial diversity to enhance human health.}, }
@article {pmid41452451, year = {2025}, author = {Zhang, X and Li, C and Feng, X and Yuan, X}, title = {The interplay of microbiome, molecular mechanisms, and fertility -an integrated review.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41452451}, issn = {1874-9356}, support = {LBH-Z21218//Postdoctoral funding of Heilongjiang Province/ ; }, abstract = {The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.}, }
@article {pmid41453546, year = {2026}, author = {Huang, S and Huang, F and Yang, L and Li, J and Qin, B and Zhou, R and Zhou, D and Tang, Y}, title = {Shentao Ruangan Granule Ameliorates Cholestatic Liver Disease via a Microbiota-Dependent Gut-Liver Axis.}, journal = {Journal of ethnopharmacology}, volume = {359}, number = {}, pages = {121069}, doi = {10.1016/j.jep.2025.121069}, pmid = {41453546}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Mice ; *Liver/drug effects/metabolism/pathology ; Male ; Toll-Like Receptor 4/metabolism ; *Cholestasis/drug therapy/microbiology/chemically induced ; NF-kappa B/metabolism ; Disease Models, Animal ; 1-Naphthylisothiocyanate ; }, abstract = {The Shentao Ruangan (STR) Granule, developed under Traditional Chinese Medicine (TCM)'s "Gan Bing Zhi Pi" (treating liver via spleen) theory, shows promise in cholestatic liver disease (CLD). TCM's "Pi Xu" (spleen deficiency) in CLD links to gut microbiota dysregulation, but STR's mechanisms remain unclear.<br><br>AIM OF THE STUDY: To decipher the anti-CLD mechanisms of STR, focusing on how it translates the "Gan Bing Zhi Pi" theory into biological effects via the gut-liver axis.<br><br>MATERIALS AND METHODS: This study employed an &#x3b1;-naphthyl isothiocyanate (ANIT)-induced C57BL/6 mouse model to verify the therapeutic efficacy of STR. Network pharmacology was utilized to predict underlying mechanisms; 16S sequencing characterized STR's effects on gut microbiota composition, and analysis via the gutMGene database helped elucidate STR's role in CLD. Finally, in vivo experiments assessed TLR4/NF-&#x3ba;B pathway expression and intestinal barrier function, with dual validation through gut microbiota depletion and transplantation assays, to unravel the molecular mechanisms underlying STR-mediated CLD amelioration.<br><br>RESULTS: STR ameliorated CLD by normalizing gallbladder index and serum ALP, TBA, TBIL, ALT, and AST, while attenuating hepatic inflammation. Network pharmacology identified 134 potential STR targets related to CLD, underscoring microbiota dysbiosis and inflammation and revealing LPS-related TLR4-mediated inflammatory pathways as regulatory hubs. 16S sequencing demonstrated STR-modulated gut microbiota, enriching Bacteroidetes and Akkermansia while depleting Enterococcus. These changes were associated with enhanced fecal bile acid excretion, intestinal barrier repair, and suppressed TLR4-mediated inflammatory cascades. Integrated network pharmacology/16S/gutMGene analyses established TLR4-mediated inflammation as the core microbiota-dependent mechanism. In vivo experiments confirmed STR reduced serum LPS, increased fecal bile acids, inhibited hepatic TLR4/NF-&#x3ba;B activation, and enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin). These mechanisms were validated via gut microbiota depletion and transplantation assays.<br><br>CONCLUSION: STR ameliorates CLD via a microbiota-dependent "Gan Bing Zhi Pi" mechanism. By reshaping the gut microbiota, it coordinates bile acid excretion, repairs intestinal barrier, and suppresses LPS-driven hepatic inflammation to regulate the gut-liver axis. This bridges TCM theory with modern microbiology, validating the therapeutic potential of STR for CLD.}, }
@article {pmid41454342, year = {2025}, author = {Song, H and Ma, Y and Peng, L and Gao, F and Fan, X and Yang, M and Hua, T and Yang, Y and Fan, R and Li, Z and Yuan, H}, title = {Platinum-doped emodin carbon dots mitigate sepsis-induced lung injury by targeting the gut-lung axis.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {84}, pmid = {41454342}, issn = {1477-3155}, support = {82471239//National Natural Science Foundation of China/ ; JDLCZDZK//Military clinical key specialty project fund/ ; }, abstract = {UNLABELLED: Sepsis-induced acute lung injury is a life-threatening complication with limited therapeutic options. Although the gut-lung axis is crucial in sepsis pathogenesis, effective interventions targeting this pathway remain scarce. Here, we developed multi-enzymatic platinum-doped emodin carbon dots (Pt-ECDs) via a hydrothermal method. Pt-ECDs exhibited superior catalase, superoxide dismutase, glutathione peroxidase and peroxidase-like activities, enabling potent reactive oxygen species (ROS) scavenging. In a murine sepsis model, oral Pt-ECDs significantly improved survival, reduced systemic inflammation, and ameliorated lung injury. Transcriptomic analysis revealed that Pt-ECDs suppressed oxidative stress and macrophage pyroptosis in lung tissues. Mechanistically, integrated metabolomic and microbiome analyses demonstrated that Pt-ECDs modulated the gut microbiota, specifically inhibiting g_Bacteroides-derived palmitic acid (PA) production. We further confirmed that PA exacerbates macrophage pyroptosis and pro-inflammatory polarization by directly binding to NOX2 and NLRP3. Crucially, fecal microbiota transplantation from Pt-ECDs-treated mice attenuated septic lung injury, whereas microbiota depletion abolished the therapeutic benefits. Collectively, our findings identify Pt-ECDs as a promising nanotherapeutic that alleviates septic lung injury by targeting the gut microbiota-palmitic acid-pyroptosis axis.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-025-03972-0.}, }
@article {pmid41454672, year = {2026}, author = {Aldriwesh, MG and Alotibi, RS and Alqurainy, N and Alrabiah, S and Arafah, AM and Alghoribi, MF and Ajina, R}, title = {The role of gut microbiome in aging-associated diseases: where do we stand now and how technology will transform the future.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2607076}, pmid = {41454672}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Precision Medicine ; }, abstract = {The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.}, }
@article {pmid41455033, year = {2025}, author = {Liu, Y and Eirin, A and Lerman, LO}, title = {Novel Therapeutic Strategies for Obesity-Related Glomerulopathy.}, journal = {Current hypertension reports}, volume = {28}, number = {1}, pages = {3}, pmid = {41455033}, issn = {1534-3111}, support = {R01 HL158691/HL/NHLBI NIH HHS/United States ; AG062104/AG/NIA NIH HHS/United States ; R01 DK122734/DK/NIDDK NIH HHS/United States ; HL158691/HL/NHLBI NIH HHS/United States ; DK122734/DK/NIDDK NIH HHS/United States ; R21 AG062104/AG/NIA NIH HHS/United States ; R01 DK120292/DK/NIDDK NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW:: Conventional management primarily focuses on weight reduction and renin-angiotensin-aldosterone blockade; however, these approaches are often insufficient to halt disease progression.<br><br>RECENT FINDINGS:: Recent advances have identified novel therapeutic targets and strategies aimed at addressing the metabolic, inflammatory, and hemodynamic abnormalities, as well as gut microbiome dysbiosis, driving obesity-related glomerulopathy (ORG). Pharmacological agents like sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, finerenone, mitochondrial transfer, and fecal microbiota transplantation have demonstrated renoprotective effects through improving weight, insulin sensitivity, blood pressure, inflammation, and gut microbiome. The potential direct renoprotective effects of these medications in ORG, independent of weight loss, warrant further investigation. Additionally, artificial intelligence and emerging biomarkers represent promising strategies for personalized and precise management, early non-invasive diagnosis, and prognostic evaluation of ORG.}, }
@article {pmid41455148, year = {2025}, author = {Uoti, A and Neulasalmi, O and Hiippala, K and Oksanen, T and Arkkila, P and Puustinen, L and Satokari, R and Sjöstedt, N}, title = {Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {53}, number = {12}, pages = {100205}, pmid = {41455148}, issn = {1521-009X}, abstract = {Gut bacterial β-glucuronidase (GUS) enzymes contribute to the intestinal toxicity and/or enterohepatic recycling of glucuronidated compounds by cleaving glucuronide conjugates excreted into the intestinal lumen. The activities and substrate specificities of several GUS isoforms have been recently described. However, the extent of intraindividual and interindividual variability in gut microbial deglucuronidation activity has remained poorly characterized. In this study, we used pan-GUS reporter substrates as well as drug and steroid glucuronides to study the deglucuronidation activities of fecal lysates produced from individual fecal samples from healthy donors (n = 12), and sequential samples collected from fecal microbiota transplantation (FMT) donors (n = 3) and patients with recurrent Clostridioides difficile infection who underwent FMT (n = 7). To determine relationships between fecal deglucuronidation activity and gut microbiota composition, we used 16S rRNA gene sequencing to characterize the healthy donors' fecal microbiotas. Although we observed considerable interindividual variability specifically in the processing of steroid glucuronides, intraindividual variability in the fecal deglucuronidation activity of FMT donors was relatively modest. We observed the female sex and Alistipes, Faecalibacterium, and Gemmiger taxa to be associated with higher deglucuronidation activity, whereas the abundance of Roseburia correlated negatively with deglucuronidation activity. In addition, the baseline deglucuronidation activity of patients with recurrent C. difficile infection was low but increased by FMT treatment. The results of this study further highlight deglucuronidation as a function of a healthy gut microbiota. Moreover, these results improve our understanding of deglucuronidation activity as a source of individual variability in the pharmacokinetics and pharmacodynamics of glucuronidated drugs that undergo enterohepatic recycling. SIGNIFICANCE STATEMENT: Gut microbial deglucuronidation rates of specific compounds may vary considerably between individuals. Deglucuronidation activity is relatively stable within healthy individuals for ≥1 year, but fecal microbiota transplantation can significantly alter the deglucuronidation activity of an individual.}, }
@article {pmid41458114, year = {2025}, author = {Pan, D and Li, J and Chen, S and Gu, S and Jiang, M and Xu, Q}, title = {Microbiota-gut-brain axis pathogenesis and targeted therapeutics in sleep disorders.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1721606}, pmid = {41458114}, issn = {1664-2295}, abstract = {Sleep constitutes an essential physiological process that is vital for maintaining physical and mental wellbeing. However, the science of sleep focusing on basic questions such as "how" we sleep and "why" we sleep is still not clear. Over the past decade, substantial progress has also been made in elucidating the interactions between sleep and other biological processes, providing insights into the basic questions of sleep. Among these, emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a pivotal bidirectional network that connects gut microorganisms with the central nervous system to regulate sleep architecture and homeostasis. This interaction is inherently bidirectional: sleep deprivation alters gut motility, mucosal integrity, and microbial composition, while microbial metabolites in turn influence neurotransmission (γ-aminobutyric acid, serotonin), immune-endocrine balance, and inflammatory signaling. In this article, we will review recent studies about MGBA-targeted therapeutic strategies for sleep disorders, such as probiotics, prebiotics, and fecal microbiota transplantation, which aim to restore microbial homeostasis and improve sleep quality. Furthermore, we discuss emerging interventions that modulate microbial metabolites and neuroimmune-endocrine signaling, as well as innovative pharmacological approaches targeting MGBA dysfunction. Collectively, we hope this review will contribute to a deeper understanding of MGBA-mediated mechanisms in sleep disorders promises to inform novel preventive and therapeutic strategies, ultimately improving clinical outcomes and quality of life for affected individuals.}, }
@article {pmid41459210, year = {2025}, author = {Yang, W and Wu, H and Li, X and Wan, Z and Kong, W and Huang, C}, title = {Gut-lung axis in allergic rhinitis: microbial dysbiosis and therapeutic strategies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1654997}, pmid = {41459210}, issn = {1664-302X}, abstract = {BACKGROUND: Allergic rhinitis (AR) affects an estimated 10%-30% of people worldwide and places a significant burden on both health and healthcare systems. Recent research suggests that imbalances in the gut microbiota may contribute to the development of AR by disrupting immune regulation along the gut-lung axis. However, these insights have yet to be fully translated into clinical practice.<br><br>METHODS: We performed a systematic review of studies published between 2010 and 2025, including clinical research, animal experiments, and multi-omics analyses, retrieved from PubMed, Web of Science, Embase, Cochrane, CNKI, and Wanfang databases. The review aimed to evaluate immune mechanisms mediated by the gut microbiota and assess microbiota-targeted interventions in AR.<br><br>RESULTS: Patients with AR consistently show reduced fecal butyrate levels, with several studies reporting significant declines, alongside elevated serum IgE concentrations. These changes are closely linked to gut dysbiosis, characterized by reduced abundance of Faecalibacterium and imbalances in the Bacteroidetes/Firmicutes ratio. Dysbiosis appears to drive activation of the aryl hydrocarbon receptor (AhR) pathway, evidenced by a 1.5-fold increase in the kynurenine/tryptophan ratio (p&#x202f;<&#x202f;0.05), and contributes to impaired regulatory T-cell function. Experimental evidence supports these associations: in murine models, fecal microbiota transplantation (FMT) reduced nasal IL-13 levels by as much as 60% in one study. In human trials, probiotic supplementation, particularly with Clostridium butyricum, was linked to reductions in serum IgE in some cohorts. Integration of multi-omics datasets further reveals conserved mechanisms, including butyrate-mediated histone deacetylase inhibition and vagus nerve-dependent suppression of mast cell activity. Moreover, combinatorial approaches, such as combining probiotics with FXR agonists, have yielded significant improvements in preclinical models, notably reducing nasal symptom scores.<br><br>CONCLUSION: Gut dysbiosis contributes to the development of AR by disrupting immune-metabolic pathways along the gut-lung axis. Microbiota-targeted interventions hold promise for both the prevention and management of AR, especially in pediatric populations. To achieve long-term impact, public health strategies that combine dietary modifications with measures to reduce air pollution are urgently needed.}, }
@article {pmid41459234, year = {2025}, author = {Xu, X and Zhang, Y and Zu, Y and Xu, Y and Liao, T and Li, X and Yan, J}, title = {The role of gut microbiota imbalance in preeclampsia pathogenesis: insights into FMO3-mediated inflammatory mechanisms.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1682007}, pmid = {41459234}, issn = {1664-302X}, abstract = {BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication linked to systemic inflammation and metabolic dysregulation. Emerging evidence suggests gut microbiota imbalance may contribute to PE pathogenesis, but the underlying mechanisms remain unclear. This study investigated whether gut dysbiosis triggers PE through flavin-containing monooxygenase 3 (FMO3)-mediated inflammatory pathways.<br><br>METHODS: We transplanted fecal microbiota from PE rats, healthy pregnant (HP) rats, and non-pregnant (NP) rats into antibiotic-treated dysbiotic rats, with a control group receiving normal saline (CON). Additionally, FMO3 expression was inhibited using FMO3-RNAi in parallel groups. We measured blood pressure, urine protein, FMO3 protein and mRNA expression, inflammatory markers, liver and kidney function, embryo resorption rate, and fetal weight. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. The impact of interleukin-8 (IL-8) on trophoblast cell function was assessed using cell counting kit-8 (CCK-8), transwell invasion, and tube formation assays.<br><br>RESULTS: Rats receiving PE fecal microbiota transplantation (FMT) exhibited a gradual rise in blood pressure post-pregnancy, varying degrees of liver and kidney damage, markedly elevated serum inflammatory cytokines, higher fetal resorption rates, and reduced placental weights. FMO3 protein and mRNA expressions were significantly higher in the PE-FMT group. FMO3 knockdown partially improved these perinatal outcomes. Antibiotic treatment significantly decreased gut microbiota alpha and beta diversity. At the genus level, the PE-FMO3-RNAi group showed increased Escherichia-Shigella and decreased Lactobacillus compared to the PE-CON-RNAi group. In cell experiments, elevated IL-8 levels decreased the viability and invasiveness of HTR-8/SVneo cells and diminished the angiogenic potential of human umbilical vein endothelial cells (HUVECs).<br><br>CONCLUSION: A disruption of gut microbiota could result in PE through the FMO3-driven inflammatory response, and targeting FMO3 may prove valuable in treating PE.}, }
@article {pmid41459433, year = {2025}, author = {Bhojiya, AA and Saurabh, A and Jain, D}, title = {Editorial: Microbial therapeutics: harnessing the human microbiome for disease treatment and prevention.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1751147}, doi = {10.3389/fmedt.2025.1751147}, pmid = {41459433}, issn = {2673-3129}, }
@article {pmid41459531, year = {2025}, author = {Nikolaidis, CG and Gyriki, D and Stavropoulou, E and Karlafti, E and Didangelos, T and Tsigalou, C and Thanopoulou, A}, title = {Targeting the TLR4 axis with microbiota-oriented interventions and innovations in diabetes therapy: a narrative review.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1701504}, pmid = {41459531}, issn = {1664-3224}, mesh = {Humans ; *Toll-Like Receptor 4/metabolism/immunology ; *Gastrointestinal Microbiome/immunology/drug effects ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2/therapy/immunology/microbiology/metabolism ; Animals ; Signal Transduction ; NF-kappa B/metabolism ; *Diabetes Mellitus, Type 1/therapy/immunology/microbiology/metabolism ; Insulin Resistance ; }, abstract = {The gut microbiota-Toll-like receptor 4(TLR4)-nuclear factor kappa B(NF-κB) signaling is a key controller of low-grade chronic inflammation and insulin resistance in type 1 (T1DM) and type 2 diabetes mellitus (T2DM). While TLR4-mediated inflammation contributes to both T1DM and T2DM, the bulk of microbiota-targeted interventions have been studied in T2DM. The focus of the current review is on T2DM, with relevant parallels in T1DM noted where appropriate. Modulation of this pathway by dietary natural bioactive molecules, fecal microbiota transplantation (FMT), and technological innovations hold therapeutic promise for the reconstitution of metabolic and immune homeostasis. Agents like celastrol, berberine, paeoniflorin, and licorice extract exhibit anti-inflammatory and antidiabetic effects by TLR4/Myeloid differentiation primary response 88(MyD88)/NF-κB signaling inhibition. FMT enhanced β-cell function and insulin sensitivity with evidence of immune-metabolic modulation. New technologies, like ingestible biosensors and gut-on-chip platforms, allow real-time monitoring and precision modulating of the microbiota. Gastric bypass-induced microbial remodeling is linked to long-term glycemic benefit. Pharmacological, surgical, and technological manipulation of gut microbiota-immune interactions is a potential complementary strategy to diabetes. The future encompasses personalized microbiota-matching, controlled FMT regimens, and incorporation of digital therapeutics into microbiome-based precision medicine.}, }
@article {pmid41460363, year = {2025}, author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X}, title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {57}, pmid = {41460363}, issn = {1573-2630}, support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; }, mesh = {Animals ; Humans ; Dysbiosis/complications ; *Eye Diseases/microbiology/therapy ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; }, abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.<br><br>METHODS: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.<br><br>RESULTS: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.<br><br>CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.}, }
@article {pmid41461024, year = {2026}, author = {Ng, DZW and Koh, M and Low, A and Liu, L and Jumat, NHB and Zhang, Z and Koh, XQ and Zhu, M and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY}, title = {Robust Workflow for Multiclass Host-Gut Microbial Cometabolite Quantitation in Human Stool via 3-Nitrophenylhydrazine Derivatization and LC-MS/MS: A Validated Analytical Platform for Translational Studies.}, journal = {Analytical chemistry}, volume = {98}, number = {1}, pages = {555-570}, doi = {10.1021/acs.analchem.5c05360}, pmid = {41461024}, issn = {1520-6882}, mesh = {Humans ; Tandem Mass Spectrometry/methods ; *Gastrointestinal Microbiome ; *Feces/chemistry/microbiology ; Chromatography, Liquid ; *Phenylhydrazines/chemistry ; *Fatty Acids, Volatile/analysis/metabolism ; *Bile Acids and Salts/analysis/metabolism ; Workflow ; Amino Acids, Branched-Chain/analysis/metabolism ; Tryptophan/analysis/metabolism ; Liquid Chromatography-Mass Spectrometry ; }, abstract = {Host-gut microbial co-metabolites, including short-chain fatty acids (SCFA), bile acids (BA), tryptophan metabolites, and branched-chain amino acids (BCAA), have key immune-metabolic functions affecting human health. Dysbiosis-induced alterations in their levels are implicated in the pathogenesis of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). However, simultaneous quantitation of these chemically diverse analytes in stool remains analytically challenging due to their diverse physicochemical properties and wide concentration ranges. Here, we developed and rigorously validated a derivatization and targeted liquid chromatography tandem mass spectrometry workflow for the simultaneous quantitation of host-gut microbial cometabolites in human stool. A 3-nitrophenylhydrazine derivatization protocol was optimized by systematically adjusting reagent concentrations and introducing postreaction quenching to suppress in-line acetic acid derivatization. Chromatographic separation was enhanced by using a novel dual-additive mobile-phase strategy (formic acid and ammonium acetate in aqueous and organic phase, respectively) coupled to a mixed-mode C18-anion-exchange stationary phase, enabling improved resolution and sensitivity across chemically diverse metabolite classes. Our optimized analytical method achieved accurate, sensitive, and efficient quantitation of 38 metabolites (15 SCFA, 16 BA, 4 tryptophan metabolites, 3 BCAA) within 23 min, demonstrating excellent linearity (r[2] > 0.99) and precision (CV < 15%), with short- (autosampler, 4 °C) and long-term (freezer, -20 °C) stability. Comparative analysis of healthy controls and MASLD stools revealed distinct metabolic signatures, including reduced SCFA and C6-oxidized BA, and elevated conjugated and secondary BA derivatives in MASLD. Our study establishes an analytically rigorous platform for multiclass host-gut cometabolite quantitation in stool, with demonstrated utility for translational research into gut-liver axis disorders.}, }
@article {pmid41461285, year = {2026}, author = {Bharathi, S and Soundara Rajan, YAPA and Prakash, S and Immanuel, G and Ramasubburayan, R}, title = {Pathobionts in the microbiome: Drivers of disease and targets for treatment.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108268}, doi = {10.1016/j.micpath.2025.108268}, pmid = {41461285}, issn = {1096-1208}, mesh = {Humans ; *Microbiota/physiology ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; Gastrointestinal Microbiome ; Mouth/microbiology ; Anti-Bacterial Agents/therapeutic use ; Vagina/microbiology ; Female ; Phage Therapy ; }, abstract = {Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.}, }
@article {pmid41461744, year = {2025}, author = {Cho, H and Nam, H and Kim, HE and Kim, JE and Park, JI and Park, J and Kim, YC and Lee, JP and Kim, DK and Joo, KW and Kim, YS and Kim, BS and Park, S and Lee, H}, title = {Gut microbiome and metabolite signatures for predicting acute kidney transplant rejection: a prospective study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44709}, pmid = {41461744}, issn = {2045-2322}, support = {2021R1I1A1A01060190//National Research Foundation grants funded by the Korean government/ ; 2018R1A3B1052328//National Research Foundation grants funded by the Korean government/ ; 2022R1A2C2011190//by National Research Foundation grants funded by the Korean government/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation/adverse effects ; Female ; Male ; Prospective Studies ; Middle Aged ; *Graft Rejection/metabolism/microbiology/diagnosis/etiology ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Dysbiosis/microbiology ; *Metabolome ; }, abstract = {Acute rejection (AR) remains a significant challenge in kidney transplantation (KT) despite advances in immunosuppressive treatment. Recognizing the critical influence of the gut microbiome on modulating host immunity, we investigated the association between gut dysbiosis and AR in KT recipients. A total of 97 patients with KT were prospectively enrolled from two centers, and their samples were collected at multiple time points, such as pre-transplant (n = 97), three months (n = 66), and twelve months (n = 37) post-transplant. Microbial profiling was performed using 16S rRNA sequencing and fecal metabolomics was done via nuclear magnetic resonance spectroscopy. Thirty-three patients developed AR after KT, exhibiting reduced bacterial richness and diversity compared with KT recipients without AR. In addition, these patients had increased Escherichia-Shigella and decreased Phascolarctobacterium abundance. Pathway analysis identified 47 enriched pathways in AR patients, notably those involved in lipopolysaccharide biosynthesis and short-chain fatty acid metabolism. Consistent results were obtained from stool metabolomics, showing reduced propionate and lactate concentrations compared with patients without AR. Finally, combining pre-KT bacterial and fecal metabolite features with clinical parameters significantly improved AR prediction accuracy. Our results suggest that integrating clinical, microbial, and metabolomic data may provide a more holistic patient care regimen across both pre- and post-transplant phases.}, }
@article {pmid41462485, year = {2025}, author = {Wang, D and Chen, Y and Yang, J and Zhang, Y and Deng, X and Liu, Y and Chen, Y and Yang, X and Wang, X and Liang, C and Xie, Q and Hao, Y and Yuan, H}, title = {Modulation of gut microbiota in Graves' orbitopathy: Prevotella dominance and atorvastatin's impact.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {258}, pmid = {41462485}, issn = {2049-2618}, support = {82270865//National Natural Science Foundation of China under Grant/ ; 231111313200//Henan Provincial Key Research and Development Projects/ ; SBGJ202301001//Henan Provincial Medical Science and Technology Research Program-the Provincial and Ministerial Major Projects/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; *Atorvastatin/pharmacology/therapeutic use/administration &amp; dosage ; Humans ; Animals ; Mice ; Male ; Female ; Feces/microbiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Prevotella/drug effects/isolation &amp; purification/genetics ; Middle Aged ; *Graves Ophthalmopathy/microbiology/drug therapy ; Adult ; Glucocorticoids/therapeutic use/administration &amp; dosage ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: The gut microbiota in patients with Graves' orbitopathy (GO) may influence the disease's progression, but its specific role and function in the progression of GO treatment are not well understood.<br><br>METHODS: We performed fecal microbiota sequencing using the 16S rRNA-gene sequencing on patients with GO (n&#x2009;=&#x2009;48), Graves' disease (GD, n&#x2009;=&#x2009;40), and healthy controls (HC, n&#x2009;=&#x2009;36). Subsequently, fecal samples from patients with GO, GD, and healthy donors were transplanted into antibiotic-treated pseudo-germ-free mice. Finally, the 48 patients with GO were randomly divided into two groups: one group received intravenous glucocorticoids (ivGC) and atorvastatin (n&#x2009;=&#x2009;24), while the other group received ivGC only (n&#x2009;=&#x2009;24), to observe the effects of atorvastatin on GO progression and its impact on gut microbiota.<br><br>RESULTS: Patients with GO exhibit a distinct gut microbiota composition, particularly marked by increased levels of Prevotella and Bacteroides, compared to patients with GD and HC. Correlation analysis revealed a direct positive association between Prevotella and thyrotropin receptor antibody levels. Antibiotic-treated pseudo-germ-free mice that received fecal transplants from patients with GO exhibited a slower rate of weight gain, significant impairment of intestinal barrier integrity, and markedly increased levels of serum LBP and inflammatory factors. A combined treatment regimen of ivGCs and atorvastatin significantly reduced ocular clinical symptoms in patients with GO, including clinical activity score, exophthalmos, and intraocular pressure, while also promoting a healthier gut microbiota composition and a reduction in Prevotella levels.<br><br>CONCLUSIONS: Gut microbiota imbalance, particularly involving Prevotella, contributes to GO's development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella. Video Abstract.}, }
@article {pmid41463403, year = {2025}, author = {Sun, X and Li, P and Chen, B and Chen, C and Zhao, J and Sun, S}, title = {Fucoidan Therapy for Extraintestinal Diseases: Targeting the Microbiota-Gut-Organ Axes.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, pmid = {41463403}, issn = {2218-273X}, support = {82374218//National Natural Science Foundation of the People's Republic of China/ ; 82405310//National Natural Science Foundation of the People's Republic of China/ ; 2023DYPLHGG-09//The First Batch of Joint Research Projects of the China Association of Traditional Chinese Medicine/ ; MS2021002//Jiangsu Province Traditional Chinese Medicine Science and Technology Development Project/ ; 1020241792//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, mesh = {*Polysaccharides/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Prebiotics ; Obesity/drug therapy/microbiology ; }, abstract = {The microbiota-gut-organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson's disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota-gut-organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation.}, }
@article {pmid41464526, year = {2025}, author = {Ichim, C and Boicean, A and Todor, SB and Boeras, I and Anderco, P and Birlutiu, V}, title = {Dynamics of Fecal microRNAs Following Fecal Microbiota Transplantation in Alcohol-Related Cirrhosis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, pmid = {41464526}, issn = {2077-0383}, abstract = {Background: Micro-RNAs (miRNAs) are emerging as pivotal regulators of pathophysiological processes, reflecting systemic responses to stress, inflammation and metabolic imbalance. Their role in advanced liver disease and in modulating responses to therapeutic interventions, such as fecal microbiota transfer (FMT), remains insufficiently characterized. Methods: We conducted a prospective study including six male patients with toxic ethanolic liver cirrhosis undergoing FMT and six healthy controls. Stool and blood samples were collected pre- and post-FMT. Fecal micro-RNA expression (miR-21, miR-122, miR-125, miR-146 and miR-155) was quantified using RT-qPCR and normalized to miR-26c. Associations with noninvasive fibrosis markers (FIB-4, APRI, elastography, CAP) and biological parameters were analyzed through multivariable regression and Pearson correlation, with internal validation by bootstrapping. Results: One week after fecal microbiota transfer, miR-21 and miR-146 exhibited significant expression changes, while miR-122, miR-125, and miR-155 showed non-significant trends toward increased expression. Post-FMT increases in miR-21, miR-122, miR-146 and miR-155 were consistently associated with reductions in hepatic fibrosis markers (FIB-4, APRI and liver stiffness), whereas no significant associations were observed with CAP. Conclusions: Fecal micro-RNAs reflect interconnected molecular networks that capture systemic adaptations to FMT. Despite a limited cohort, these findings highlight their potential as integrative biomarkers and as therapeutic targets in advanced liver disease. Larger-scale studies are warranted to validate clinical utility.}, }
@article {pmid41464856, year = {2025}, author = {Sylwestrzak, T and Ciosek, M and Pastuszak, K and Jastrzębski, T}, title = {Fecal Short-Chain Fatty Acids in Colorectal Cancer Patients Versus Healthy Controls: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, pmid = {41464856}, issn = {2077-0383}, abstract = {Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD -0.37; 95% CI -0.63 to -0.10; p = 0.006; I[2] = 0%) and butyrate (pooled SMD -0.59; 95% CI -1.10 to -0.07; p = 0.026; I[2] = 64.4%), whereas propionate did not differ significantly (pooled SMD -0.02; 95% CI -0.85 to 0.82; p = 0.971; I[2] = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC.}, }
@article {pmid41465322, year = {2025}, author = {Rzeczycki, P and Pęciak, O and Plust, M and Droździk, M}, title = {Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465322}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Intestinal Mucosa/metabolism ; Multidrug Resistance-Associated Protein 2 ; *Membrane Transport Proteins/metabolism ; }, abstract = {Gut microbiota, through both its species composition and its metabolites, impacts expression and activity of intestinal drug transporters. This phenomenon directly affects absorption process of orally administered drugs and contributes to the observed inter-individual variability in pharmacotherapeutic responses. This review summarizes mechanistic evidence from in vitro and animal studies and integrates clinical observations in which alterations in gut microbiota are associated with changes in oral drug exposure, consistent with potential regulation of key intestinal drug transporters-such as P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2), MRP2/3 proteins (ABCC2/3), and selected Organic Anion-Transporting Polypeptides (OATPs, e.g., SLCO1A2, SLCO2B1)-by major bacterial metabolites including short-chain fatty acids (SCFAs), secondary bile acids, and tryptophan-derived indoles. The molecular mechanisms involved include activation of nuclear and membrane receptors (PXR, FXR, AhR, TGR5), modulation of transcriptional and stress-response pathways (Nrf2, AP-1) with simultaneous suppression of pro-inflammatory pathways (NF-κB), and post-translational modifications (e.g., direct inhibition of P-gp ATPase activity by Eggerthella lenta metabolites). The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. In conclusion, the significance of "drug-transporter-microbiome" interactions for personalized medicine is discussed. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.}, }
@article {pmid41466105, year = {2025}, author = {Zhang, H and Shen, C and Lei, W and Wang, J and Liu, J and Qiu, Z}, title = {Pilot Clinical Trial of Fecal Microbiota Transplantation for Constipation in Parkinson's Disease.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2509029}, pmid = {41466105}, issn = {1738-8872}, mesh = {Humans ; *Constipation/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Parkinson Disease/complications/therapy/microbiology ; Aged ; Pilot Projects ; Middle Aged ; Male ; Gastrointestinal Microbiome ; Female ; Prospective Studies ; Feces/microbiology ; Treatment Outcome ; Dysbiosis/therapy ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {The purpose of this study was to evaluate the safety and efficacy of fecal microbiota transplantation in patients with constipation due to parkinson's disease. Gut dysbiosis has long been associated with parkinson's and recent studies have shown that FMT can restore the normal flora of the gut. Therefore, this clinical trial aimed to test the therapeutic efficacy of FMT in 5 patients aged 55 to 71 diagnosed with PD who presented with constipation. The study was conducted as an open label, prospective trial and consisted of FMT performed every 3 days via nasojejunal tube placement followed by 8 weeks of patient follow-up to evaluate response to drug therapy and to assess neurological function using UPDRS-III OFF scores, and improvement in constipation assessed with Wexner scores. Samples taken before and after FMT were collected for shotgun metagenomic sequencing to analyze the composition of the microbial communities present in patients. Untargeted non-targeted metabolomic studies were performed to investigate the impact of FMT on metabolome changes due to FMT. The results indicate an improvement in constipation and neurological functioning following FMT, and significant alteration of the gut microbiota. Significant increases in Bifidobacteria bifidus, Alistipes shahi, Anaerotruncus coli, and uncharacterized Flavonifractor were found post-treatment compared to the baseline. Many of the other strains present prior to treatment, including Acinetobacter sp. and Proteobacteria sp., had significantly decreased after the FMT. The metabolomic studies found shifts in metabolic pathways involved with unsaturated fatty acid synthesis and amino acid metabolism due to FMT. FMT may be an effective treatment option for constipation and neurological symptoms associated with PD.}, }
@article {pmid41466331, year = {2025}, author = {Li, J and Zhang, X and Zhao, X and Gong, G and Li, J and Dalai, B and Mo, Z and Xu, X and Jia, X and Li, Y and Lai, J and Wang, P and Sun, L and Liu, Y and Luo, X}, title = {Characterising gut microbiome dysbiosis in diarrhoea calves from multiple farms in Inner Mongolia using 16S and metagenomics.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {259}, pmid = {41466331}, issn = {2049-2618}, support = {2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/genetics ; *Diarrhea/microbiology/veterinary/epidemiology ; RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; China/epidemiology ; *Dysbiosis/microbiology/veterinary ; *Cattle Diseases/microbiology/epidemiology ; Feces/microbiology ; Escherichia coli/genetics/isolation &amp; purification/pathogenicity ; *Bacteria/classification/genetics/isolation &amp; purification ; Farms ; }, abstract = {BACKGROUND: The pathogenesis of neonatal calf diarrhoea (NCD), a critical disease that contributes to neonatal mortality in calves, remains nebulous.<br><br>RESULTS: Inner Mongolia, a key region for cattle farming in China, was selected as a study area to provide a comprehensive overview of the epidemiology and treatment of calf diarrhoea. No significant correlation was found between the incidence of diarrhoea and sampling points or medications. The severity of diarrhoea cases was stratified into five levels based on faecal characteristics. To elucidate the pathogenesis of NCD, 16S rRNA gene and metagenomic sequencing analyses were performed across severity levels. Microbial diversity analyses revealed distinct variations in microbial communities at different severity levels. Employing binning and LEfSe methodologies, two potential bacterial pathogens were identified: Escherichia coli (bin.216), leveraging non-canonical virulence mechanisms; and Streptococcus ruminantium (bin.338), an uncharacterised diarrhoeagenic bacterium. Furthermore, the viral agent Escherichia phage VpaE1_ev108 was significantly associated with disease progression. Gene function enrichment analysis revealed a broad spectrum of antibiotic resistance genes even in farms without direct antibiotic treatment, underscoring the pervasive prevalence of drug resistance.<br><br>CONCLUSIONS: The findings of this study revealed significant gut microbial dysbiosis in calves with severe diarrhoea, through which two putative NCD-associated pathogens were identified: E. coli (bin.216) and S. ruminantium (bin.338). Marked enrichment of Bacteroides spp. and Methanobrevibacter_A sp. 900313645 was observed in healthy cohorts, suggesting their potential protective roles. Therapeutic strategies employing phage-mediated pathogen targeting combined with probiotic transplantation have demonstrated dual benefits, potentially reducing antimicrobial dependency and preserving microbial homeostasis through ecological network reconstruction. Video Abstract.}, }
@article {pmid41466423, year = {2025}, author = {Chen, L and Tang, C and Hu, D and Yu, S and Liao, P}, title = {Brevilin A reverses colitis of inflammatory bowel disease via modulation of TNF-α signaling and microbiome dysregulation.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {1}, pmid = {41466423}, issn = {1757-4749}, support = {2024000003-09//Middle-aged Backbone Talents in the Province/ ; }, abstract = {BACKGROUND: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.<br><br>METHODS: Colitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20&#xa0;mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of action.<br><br>RESULTS: Br significantly alleviated DSS-induced colitis and modulated the gut microbiota profile. Specifically, Br enriched beneficial bacteria such as Lactobacillus, while suppressing pathogenic bacteria including Escherichia coli and Clostridium perfringens. Metabolomic analysis revealed that Br significantly altered bacterial metabolites, including 7-Oxolithocholic Acid, Kudinoside A, Veratrine, and Soyasaponin. These metabolites were linked to key pathways such as GPCR signaling, DNA damage response, aminoacyl-tRNA biosynthesis, riboflavin metabolism, and central carbon metabolism in cancer. Transcriptomic profiling indicated that Br inhibited the TNF-&#x3b1; signaling pathway, and this inhibition was confirmed as TNF-&#x3b1; overexpression reversed its anti-inflammatory effects. Furthermore, the therapeutic effects of Br were partially recapitulated in microbiota-depleted mice through fecal microbiota transplantation from Br-treated donors.<br><br>CONCLUSION: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-&#x3b1; highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.}, }
@article {pmid41466538, year = {2026}, author = {Zheng, B and Liu, L and Li, J and Chen, Y and Xie, J and Zhao, X and Feng, J and Zhou, Q and Hu, X and Yu, Q}, title = {Bound Polyphenols in Rice Bran Insoluble Dietary Fiber Ameliorate Intestinal Barrier Damage via Butyrate-Mediated Regulation of Apoptosis-Autophagy Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {1}, pages = {885-896}, doi = {10.1021/acs.jafc.5c12877}, pmid = {41466538}, issn = {1520-5118}, mesh = {Animals ; *Dietary Fiber/metabolism/analysis/administration &amp; dosage ; *Autophagy/drug effects ; *Oryza/chemistry/metabolism ; Mice ; Humans ; *Polyphenols/metabolism/chemistry/administration &amp; dosage ; *Apoptosis/drug effects ; Male ; Mice, Inbred C57BL ; *Intestinal Mucosa/metabolism/drug effects ; *Butyrates/metabolism ; Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; Caco-2 Cells ; Signal Transduction/drug effects ; *Obesity/metabolism/physiopathology/drug therapy/microbiology/genetics ; *Intestines/drug effects ; }, abstract = {Bound polyphenols (BPs) are critical to the anti-obesity effects of dietary fiber. However, their role in dietary-fiber-mediated intestinal barrier protection remains unclear. In this study, we demonstrated that rice bran insoluble dietary fiber (RIDF) alleviated intestinal barrier damage in high-fat-diet (high-fat diet)-fed mice, and this beneficial effect was dependent on BPs, as it was attenuated in mice treated with polyphenol-removed dietary fiber (RIDF_DF). Furthermore, fecal supernatant transplantation from RIDF-treated (not RIDF_DF-treated) mice alleviated obesity and reshaped the gut microbiota in recipient mice. Additionally, the fecal supernatant enhanced the intestinal barrier function and augmented the synthesis of short-chain fatty acids. Notably, butyrate administration upregulated intestinal tight junction proteins in Caco-2 cells and HFD-fed mice and increased Oscillospira abundance. Mechanistically, butyrate inhibited apoptosis and promoted autophagy, accompanied by alterations in the AMPK-Akt signaling pathway. These results indicate that BPs contribute to the ameliorative effect of RIDF on intestinal damage.}, }
@article {pmid41467904, year = {2026}, author = {Maruyama, D and Tian, X and Doan, TNM and Liao, WI and Chaki, T and Taenaka, H and Maishan, M and Matthay, MA and Prakash, A}, title = {Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606486}, pmid = {41467904}, issn = {1949-0984}, support = {P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL146753/HL/NHLBI NIH HHS/United States ; T32 GM008440/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Macrophages, Alveolar/metabolism/immunology ; Mice ; *Lung Injury/microbiology/metabolism/immunology ; Dietary Fiber/metabolism/administration &amp; dosage ; Fatty Acids, Volatile/metabolism ; *Propionates/metabolism ; Mice, Inbred C57BL ; Male ; Bacteria/metabolism/classification/genetics/isolation &amp; purification ; Lung/metabolism/immunology ; }, abstract = {Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.}, }
@article {pmid41469027, year = {2026}, author = {Bu, T and Zhao, X and Kong, X and Huang, Z and Zhu, H and Sun, P and Yang, K and Chen, S and Cai, M}, title = {The Mechanism of Dendrobium officinale Polysaccharides in Alleviating Osteoporosis via Regulation of Wnt/β-Catenin Signaling Pathways and Modulation of Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {1}, pages = {713-730}, doi = {10.1021/acs.jafc.5c10301}, pmid = {41469027}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/administration &amp; dosage/chemistry ; *Wnt Signaling Pathway/drug effects ; *Dendrobium/chemistry ; Mice ; Female ; *Osteoporosis/metabolism/drug therapy/microbiology/genetics ; Humans ; Mice, Inbred C57BL ; Bacteria/classification/isolation &amp; purification/genetics/metabolism/drug effects ; beta Catenin/metabolism/genetics ; *Plant Extracts/administration &amp; dosage ; Fatty Acids, Volatile/metabolism ; }, abstract = {Osteoporosis (OP) poses a significant global health burden, with emerging therapies targeting the gut microbiota (GM). This study investigated the effects of Dendrobium officinale polysaccharides (DOP), characterized as an acetylated glucomannan with a linear β-(1 → 4)-mannose backbone, on ovariectomy (OVX)-induced OP through the gut-bone axis. DOP administration significantly attenuated bone loss in OVX mice by modulating bone turnover and inflammation markers, activating Wnt/β-catenin signaling, and preserving intestinal barrier function. Furthermore, DOP dose-dependently reshaped the GM composition, increasing the Firmicutes/Bacteroidetes ratio, especially enriching short chain fatty acids (SCFA)-producing genera Allobaculum and Clostridia_UCG-014, which consequently restored butyric and isovaleric acid levels. Crucially, fecal microbiota transplantation from DOP-treated donors reproduced the osteoprotective phenotype in recipient mice, establishing a causal role for DOP-modulated GM. These findings demonstrate that DOP alleviates OP via GM-driven SCFA production, barrier integrity, anti-inflammation, and Wnt/β-catenin signaling activation, underscoring its prebiotic potential for OP management.}, }
@article {pmid41469665, year = {2025}, author = {Zheng, SH and Li, KZ and Feng, G and Wang, YT and Wang, JN and Li, SQ and Sun, YD}, title = {Gut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy.}, journal = {Molecular cancer}, volume = {24}, number = {1}, pages = {313}, pmid = {41469665}, issn = {1476-4598}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/immunology ; *Pancreatic Neoplasms/therapy/immunology/etiology/pathology/microbiology/metabolism ; *Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Pancreatic cancer remains one of the deadliest malignancies, primarily due to its highly immunosuppressive tumor microenvironment (TME) and poor response to conventional therapies. Increasing evidence highlights the gut microbiota as a pivotal regulator of antitumor immunity, modulating T cell activation, macrophage polarization, and dendritic cell function. Microbial communities and their metabolites can either inhibit or enhance immune surveillance, thereby influencing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy. Approaches including dietary modulation, probiotics, fecal microbiota transplantation (FMT), and microbial metabolite supplementation show promise in restoring immune homeostasis and improving treatment outcomes. Additionally, gut microbiome profiling has emerged as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events. This review summarizes current insights into microbiota-immune interactions in pancreatic cancer, emphasizes microbiome-targeted therapeutic strategies, and explores future opportunities for precision immunotherapy guided by microbial modulation.}, }
@article {pmid41470815, year = {2025}, author = {Wei, X and Lang, F and Liu, H and Wang, S and Wang, T}, title = {Soluble Dietary Fiber from Highland Barley Bran Reduces Hepatic Lipid Accumulation in Mice via Gut Microbiota Modulation.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, pmid = {41470815}, issn = {2072-6643}, support = {2024-ZJ-963//Qinghai Provincial Natural Science Youth Foundation Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber/pharmacology ; *Hordeum/chemistry ; *Liver/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice ; *Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Obesity/prevention &amp; control/etiology/metabolism ; Lipidomics ; }, abstract = {BACKGROUND: Obesity has emerged as a significant public health challenge largely attributed to excessive dietary fat consumption. A growing body of evidence indicates that soluble dietary fiber (SDF) can prevent high-fat-diet (HFD)-induced obesity by modulating the gut microbiota. Our previous studies have shown that SDF derived from highland barley bran exhibits favorable lipid-lowering activity in vitro, but its lipid-lowering effect in vivo remains to be elucidated.<br><br>METHODS: This study aimed to investigate the lipid-lowering effects of SDF from highland barley bran in HFD-fed mice based on the gut microbiota. Mice were fed an HFD, and the intervention effects of SDF on hepatic lipid metabolism and its underlying molecular mechanisms were systematically evaluated using liver lipidomics, 16S rDNA sequencing, molecular biological techniques, and fecal microbiota transplantation (FMT).<br><br>RESULTS: Liver lipidomics analysis revealed that potential lipid biomarkers responsive to barley bran-derived SDF included phosphatidylethanolamines (PE, 18:2-20:3), phosphatidylserine (PS, 18:0-18:2), and PS (18:1-22:3). Furthermore, SDF modulated the composition and structure of the gut microbiota in HFD-fed mice. Notably, SDF increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Dubosiella, as well as elevated SCFA levels.<br><br>CONCLUSIONS: The increase in SCFAs activated the hepatic AMP-activated protein kinase &#x3b1; (AMPK) signaling pathway, thereby ameliorating HFD-induced disturbances in lipid metabolism, reducing hepatic lipid accumulation, and lowering serum lipid concentrations.}, }
@article {pmid41471163, year = {2025}, author = {Ziaka, M}, title = {Targeting Gut-Lung Crosstalk in Acute Respiratory Distress Syndrome: Exploring the Therapeutic Potential of Fecal Microbiota Transplantation.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41471163}, issn = {2076-0817}, mesh = {*Respiratory Distress Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Lung/microbiology/immunology ; Animals ; *Gastrointestinal Tract/microbiology ; }, abstract = {The gastrointestinal (GI) tract contributes significantly to the pathogenesis of acute respiratory distress syndrome (ARDS) by influencing systemic inflammation and sepsis, which are key factors in the development of multiple organ dysfunction syndrome (MODS), while the significant impact of gut microbiota in critically ill patients, including those with sepsis and ARDS, further underscores its importance. The intestinal microbiota is vital to immune system function, responsible for triggering around 80% of immune responses. Therefore, it may be hypothesized that modifying fecal microbiota, such as through fecal microbiota transplantation (FMT), could serve as a valuable therapeutic approach for managing inflammatory diseases like lung injury (LI)/ARDS. Indeed, emerging experimental research suggests that FMT may have beneficial effects in ARDS models by improving inflammation, oxidative stress, LI, and oxygenation. However, well-designed randomized clinical trials in patients with ARDS are still lacking. Our study seeks to examine how therapeutic interventions such as FMT might benefit LI/ARDS patients by exploring the interactions between the gut and lungs in this context.}, }
@article {pmid41471872, year = {2025}, author = {Yang, B and Zhong, S and Wang, J and Yu, W}, title = {Dietary Modulation of the Gut Microbiota in Dogs and Cats and Its Role in Disease Management.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471872}, issn = {2076-2607}, support = {No. 20242BAB20315//Natural Science Foundation for Youth of Jiangxi Province/ ; GJJ2200410//The Science and Technology Program of Jiangxi Provincial Department of Education/ ; }, abstract = {Food has a massive influence on the gut microbiota and is one of the most useful therapeutic levers in disease. Recent developments have highlighted how macronutrient balance, food format, and functional ingredients can regulate microbial diversity, metabolism, and host physiology in companion animals such as dogs and cats. This narrative review condenses evidence on the bidirectional gut microbiota-diet connection and on nutritional therapy for gastrointestinal, metabolic, renal, hepatic, and immune-mediated disorders. Protein-based diets including high or hydrolyzed protein, omega-3 acids, fermentative fiber, and probiotics can positively affect microbial composition, stimulate short-chain fatty acid synthesis, and enhance intestinal barrier functions. Conversely, excess fats or refined carbohydrates may cause dysbiosis, inflammation, and metabolic imbalances. Numerous studies have shown that therapeutic nutrition-e.g., low-protein renoprotective, hepatoprotective antioxidants, and allergen-elimination diets-holds enormous potential for treatment. In addition, fecal microbiota transplantation (FMT) can be used as an additive therapy for resistant gastrointestinal illnesses. Despite these developments, constraints remain in terms of standardization, study duration, and species-specific data, especially for cats. This review underscores dietary modification as a clinically actionable tool for microbiota-targeted therapy and calls for integrative, multi-omics research to translate microbiome modulation into precision nutrition for companion animals.}, }
@article {pmid41471996, year = {2025}, author = {Zhang, X and Mao, G and Pei, Z and Sun, Y and Cen, J and Zhang, S and Li, S and Meng, W and Xiao, K and Xu, Q and Sun, M}, title = {Microbial Ecology of Sulfur Mustard Toxicity: From Dysbiosis to Restoration.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471996}, issn = {2076-2607}, support = {82103885//National Natural Science Foundation of China/ ; 82273672//National Natural Science Foundation of China/ ; 20ZR1470300//Natural Science Foundation of Shanghai Municipality/ ; 21ZR1477700//Natural Science Foundation of Shanghai Municipality/ ; GWV-10.2-YQ48//Shanghai Municipal Health Commission-Outstanding Youth Foundation of Public Health/ ; }, abstract = {Sulfur mustard (SM) causes multi-organ toxicity, yet its impact on intestinal tissue and the associated gut microbiota remains poorly characterized. This study demonstrates that in a mouse model of SM exposure, gut microbial ecological collapse occurs, characterized by depletion of protective taxa (Bifidobacteriales, Gordonibacter, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated Escherichia/Shigella. Mendelian randomization analysis established causal relationships between these SM-perturbed taxa and human inflammatory bowel disease. Fecal microbiota transplantation effectively restored microbial diversity (Simpson index: 0.85 to 0.95), suppressed Escherichia/Shigella by 97.4%, and ameliorated intestinal pathology. Longitudinal tracking revealed persistent vulnerability of Bifidobacteriales compared to other depleted taxa. Our findings establish the gut microbiota as a key mediator in SM intestinal toxicity and provide new insights for microbiota-targeted interventions against chemical injuries.}, }
@article {pmid41472066, year = {2025}, author = {Vestad, B and Hanzely, P and Karaliūtė, I and Ramberg, O and Skiecevičienė, J and Lukoševičius, R and Bjørnholt, JV and Holm, K and Kupčinskas, J and Rasmussen, H and Hov, JR and Melum, E}, title = {Modulation of Dextran Sodium Sulfate-Induced Colitis in Germ-Free Mice by Enterococcus faecalis Monocolonization.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472066}, issn = {2076-2607}, support = {LT08-2-LMT-K-01-060//EEA Grants 2014-2021/ ; 802544/ERC_/European Research Council/International ; }, abstract = {Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host-microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.}, }
@article {pmid41472740, year = {2025}, author = {Chen, Q and Zhong, M and Lin, Y}, title = {Exploring gut microbiota and spinal cord injury: pathogenesis, treatment strategies and prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1693883}, pmid = {41472740}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Spinal Cord Injuries/therapy/microbiology/etiology ; Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Spinal cord injury (SCI) is a disabling central nerve system (CNS) injury, often caused by factors such as traffic accidents, falls from heights, violent trauma, and sports injuries, commonly resulting in permanent loss of motor and sensory function below the level of injury. Increasing evidence suggests that gut microbiota influences the occurrence and development of CNS diseases through the brain-gut axis. Recent studies indicate that patients with SCI frequently exhibit gut microbiota dysbiosis. Changes in gut microbiota can lead to gut barrier disruption, triggering neurogenic inflammatory responses, thereby hindering recovery after SCI, while reshaping gut microbiota may benefit the recovery of intestinal function and neurofunction after SCI. In this review, we summarize emerging literature on the role of microbiota after SCI. We elucidate the intrinsic connection between gut microbiota and SCI, explore the role of gut microbiota in the pathogenesis of SCI, and investigate potential intervention strategies targeting gut microbiota, including probiotic therapy, fecal microbiota transplantation (FMT), and regulation of metabolites, aiming to provide theoretical basis and translational prospects for developing innovative microecological targeted therapeutic approaches.}, }
@article {pmid41472805, year = {2025}, author = {Tian, Z and Li, C}, title = {The role of gut microbiota in the onset and development of sepsis and its therapeutic potential: mechanisms and research progress.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1718549}, pmid = {41472805}, issn = {1664-302X}, abstract = {Sepsis is a life-threatening disease triggered by infection-induced immune dysregulation, characterized by multi-organ dysfunction, and is one of the leading causes of death among critically ill patients worldwide. Recent studies have shown that gut microbiota (GM) imbalance plays a crucial role in the progression of sepsis. This review identifies the core mechanisms of GM imbalance: it disrupts the integrity of the intestinal mucosal barrier, induces bacterial and endotoxin translocation, activates systemic inflammatory responses, and forms a vicious cycle of "gut-organ" cross-damage, becoming a key driver of sepsis-associated multi-organ dysfunction. Existing research has confirmed that microbiota modulation strategies, such as probiotic supplementation and fecal microbiota transplantation (FMT), have potential therapeutic value. However, due to issues like strain specificity, lack of standardized protocols, and insufficient clinical evidence, the clinical translation of these strategies still faces significant barriers. Therefore, future research should focus on the identification of sepsis-specific GM core functional biomarkers, the development of personalized combined regulatory strategies, and the advancement of targeted delivery technologies. Multi-center large-scale clinical trials are needed to validate their efficacy and safety, providing innovative solutions for precision treatment of sepsis.}, }
@article {pmid41472816, year = {2025}, author = {Lan, T and Hou, Q and Zhao, H and Luan, Y and Shi, Y and Hu, S and Wang, N and Yan, S and Gong, X and Song, Y}, title = {Gut microbiota dysbiosis impairs TGF-β/Smad4 signaling to drive postoperative metastasis in colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1654227}, pmid = {41472816}, issn = {1664-302X}, abstract = {BACKGROUND: After surgical intervention, metastasis remains the primary contributor of mortality rates in colorectal cancer (CRC). While compelling evidence implicates gut microbiota dysbiosis as a key driver of CRC progression, its role in postoperative metastasis remains unclear.<br><br>METHODS: A total of 97 participants were recruited, comprising 21 postoperative CRC patients with metastasis (M group), 37 postoperative CRC patients without metastasis (C group), and 39 healthy individuals (H group). Fecal microbiota composition, short-chain fatty acid (SCFA) concentrations, and serum cytokines were quantified. Spearman correlation was used to assess the relationship between microbiota and SCFAs. Fecal microbiota transplantation (FMT) was performed by transferring patient specimens into antibiotic-pretreated orthotopic CRC mice models. Epithelial-mesenchymal transition (EMT) markers and TGF-&#x3b2;/Smad4 signaling were subsequently analyzed.<br><br>RESULTS: In humans, M group patients exhibited significant gut dysbiosis, characterized by enriched Fusobacterium and depleted Gemmiger, concomitant with markedly diminished fecal butyrate, propionate, and acetate (vs. H group, p&#x202f;<&#x202f;0.05). In these patients, this dysbiosis was directly correlated with SCFA depletion (Padj &#x202f;<&#x202f;0.05). Serologically, patients in the M group exhibited elevated TGF-&#x3b2; while suppressed IL-10 compared to C group (p&#x202f;<&#x202f;0.05). In the mouse model, the FMT from M group significantly increased Fusobacterium abundance and reduced fecal acetate/butyrate, concomitantly accelerating tumor progression with elevated hepatic and cecal tumor weights and upregulated EMT markers (N-cadherin and MMP9). This pro-metastatic phenotype was associated with downregulated hepatic mRNA expression of the key SCFA receptors, FFAR2 and FFAR3. Notably, in the animal model, the FMT-M group exhibited elevated hepatic TGF-&#x3b2; and a trend toward reduced Smad4 expression, suggesting a potential dysregulation of the TGF-&#x3b2;/Smad4 signaling pathway. Conversely, the fecal microbiota from C group markedly suppressed Fusobacterium colonization and restored acetic acid, butyric acid levels which ameliorates pathological changes by attenuating N-cadherin expression and normalizing TGF-&#x3b2;/Smad4 signaling.<br><br>CONCLUSION: Gut microbiota dysbiosis and SCFA depletion exert profound regulatory effects on postoperative CRC metastasis, potentially by promoting EMT through mechanisms involving the TGF-&#x3b2;/Smad4 signaling axis. Thus, targeting gut microbiota may offer promising therapeutic strategies to mitigate CRC metastasis.}, }
@article {pmid41472848, year = {2025}, author = {Tang, B and Cao, Y and Li, J and Gao, N and Gao, P and Chen, X and Ming, Z and Li, Z and Hou, W}, title = {Whole microbiota transplantation restores gut homeostasis throughout the gastrointestinal tract.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70091}, pmid = {41472848}, issn = {2770-596X}, abstract = {This study introduces whole microbiota transplantation (WMT), a synergistic therapeutic approach that concurrently transplants small intestinal and fecal microbiota. In germ-free mice, WMT outperforms conventional fecal microbiota transplantation (FMT) in restoring gut microbiota diversity and abundance. Moreover, in a chemotherapy-induced intestinal mucositis model, WMT alleviates intestinal inflammation and reverses microbiota dysbiosis. Encapsulation in layer-by-layer self-assembled nanocapsules further boosts microbial survival and colonization, amplifying WMT's anti-inflammatory effects and microbiota restoration in a mouse model of pan-intestinal infection. Overall, WMT represents a precise strategy for reshaping microbial homeostasis across the entire gastrointestinal tract, with therapeutic promise for inflammatory bowel diseases and small-intestinal disorders.}, }
@article {pmid41473248, year = {2025}, author = {Zhang, Y and Cao, J and Wang, Y and Fan, X and Deng, R and Mi, J}, title = {Effects of fecal microbiota transplantation on glycemic and lipid profiles in overweight or obese patients with metabolic disorders: a systematic review and meta-analysis.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1737543}, pmid = {41473248}, issn = {1664-2392}, mesh = {Humans ; *Blood Glucose/analysis/metabolism ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Lipid Metabolism ; *Lipids/blood ; *Metabolic Diseases/blood/complications/therapy ; *Obesity/therapy/blood/complications ; *Overweight/blood/complications/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {UNLABELLED: Obesity and its associated metabolic disorders (such as type 2 diabetes, metabolic syndrome, and NAFLD/MASLD) represent a global health challenge. Fecal microbiota transplantation (FMT), as a therapy regulating the gut microbiome, has demonstrated inconsistent clinical efficacy. This systematic review aims to evaluate the impact of FMT on key indicators of glucose and lipid metabolism in overweight/obese adults with metabolic diseases. We systematically searched PubMed, Embase, Cochrane, and Web of Science databases up to September 28, 2025, to identify randomized controlled trials evaluating FMT for obesity and metabolic disorders. Data were pooled using a random-effects model, with primary outcomes being changes in BMI, HOMA-IR, and HbA1c relative to baseline. A total of 11 RCTs (320 participants) were included. The primary analysis showed that FMT intervention demonstrated a trend toward improvement in the primary outcome measures, BMI (MD: -0.65, p = 0.070) and HOMA-IR (MD: -0.64, p = 0.062), but these trends did not reach statistical significance. There was no significant effect on HbA1c (MD: 0.06, p = 0.742). However, this negative conclusion based on the conventional assumption (Corr = 0.5) exhibited high instability: sensitivity analysis revealed that FMT's improvement effects on BMI became statistically significant (p = 0.010) when the correlation coefficient (Corr) used to estimate the standard deviation of change was adjusted to 0.75. Furthermore, meta-regression analysis revealed that treatment regimen, follow-up duration, and patient baseline characteristics were significantly associated with HbA1c efficacy. Based on the current "low" certainty evidence, the overall improvement of metabolic parameters in overweight or obese patients with metabolic diseases following FMT did not reach statistical significance in the primary analysis. However, the robustness of this negative finding is limited, exhibiting high sensitivity to statistical hypotheses and likely being significantly confounded by methodological factors (e.g., administration protocols) and donor variability. Consequently, the true efficacy of FMT for treating systemic metabolic disorders remains uncertain. Future trials should shift toward precision medicine, prioritizing the standardization of donor selection and optimization of administration protocols.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251172011, identifier CRD420251172011.}, }
@article {pmid41473261, year = {2025}, author = {Zhou, Y and Yang, L and Nan, Y and , }, title = {Expert Consensus on Clinical Applications of Fecal Microbiota Transplantation for Chronic Liver Disease (2025 edition).}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {12}, pages = {1107-1116}, pmid = {41473261}, issn = {2310-8819}, abstract = {The gut microbiota is crucial in maintaining host health and liver function. Fecal microbiota transplantation (FMT) has shown promising potential in treating chronic liver diseases. To help clinicians quickly master and standardize the clinical application of FMT for chronic liver disease, the Liver Related Digestive Diseases Group of the Chinese Society of Hepatology of the Chinese Medical Association has developed the "Expert Consensus on the Clinical Application of FMT for Chronic Liver Disease." This consensus addresses the key aspects of FMT, including the indications, contraindications, efficacy, safety, donor selection, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions, such as chronic hepatitis, cirrhosis, and liver cancer, thereby offering reference and guidance to clinicians implementing FMT in the treatment of chronic liver disease.}, }
@article {pmid41474687, year = {2026}, author = {Abulaiti, A and Yu, H and Ma, J and Wuji, A and Chi, H}, title = {Advancement on the Association between Gut Microbiota and Autism Spectrum Disorder in Children.}, journal = {Annals of nutrition &amp; metabolism}, volume = {82}, number = {2}, pages = {115-129}, pmid = {41474687}, issn = {1421-9697}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology/etiology ; *Gastrointestinal Microbiome/physiology ; Child ; Probiotics/therapeutic use ; Diet ; Diet, Gluten-Free ; Female ; }, abstract = {<p>Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of restricted, repetitive behaviors. The rising global prevalence of ASD suggests a multifactorial etiology involving genetic, environmental, and neurodevelopmental factors. This review explores the establishment of the early life microbiome, highlighting rapid microbial colonization from maternal and environmental sources. Emerging evidence indicates that delivery mode and infant feeding practices may influence ASD susceptibility. Although the concept of a sterile intrauterine environment remains debated, its investigation is valuable. Summary: This review provides a comprehensive analysis of the interplay between diet, gastrointestinal symptoms, and ASD, evaluates the gut-brain axis as a mechanistic framework, and assesses the therapeutic potential of microbial interventions. The bidirectional "microbiota-gut-brain axis" has emerged as a critical pathway linking gut microbiota and brain function, offering potential therapeutic targets for ASD. Dietary patterns in children with ASD are often characterized by selectivity and restriction, which may disrupt gut microbiota composition and exacerbate gastrointestinal symptoms, thereby increasing ASD risk. Nutritional interventions and early behavioral therapies are thus essential. Key Messages: The gluten-free, casein-free diet remains controversial, with inconsistent evidence regarding its efficacy. Probiotic supplementation shows strain-specific effects, necessitating rigorous evaluation before clinical application. Given the heterogeneity of ASD, pharmacological treatments have shown limited universal efficacy. While promising findings have emerged from research on probiotics, prebiotics, and fecal microbiota transplantation, further well-designed clinical studies are needed to elucidate the complex etiology of ASD and validate therapeutic strategies. </p>.}, }
@article {pmid41475279, year = {2026}, author = {Singh, G and Ansari, S and Yadav, S and Aran, KR}, title = {Gut microbiota's role in NAFLD- and HBV/HCV-related hepatocellular carcinoma: Mechanisms and therapeutic implications.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108273}, doi = {10.1016/j.micpath.2025.108273}, pmid = {41475279}, issn = {1096-1208}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Carcinoma, Hepatocellular/microbiology/therapy/etiology ; *Liver Neoplasms/microbiology/therapy/etiology ; *Non-alcoholic Fatty Liver Disease/microbiology/complications ; Dysbiosis/complications/microbiology ; *Hepatitis C/complications ; Liver/pathology ; *Hepatitis B/complications ; Animals ; Fecal Microbiota Transplantation ; Probiotics ; Hepatitis B virus ; }, abstract = {Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally and has been closely linked to chronic liver conditions, such as viral hepatitis and non-alcoholic fatty liver disease. Recent research has demonstrated that the gut microbiota significantly impacts the gut-liver axis, a crucial aspect of the pathophysiology of HCC. This review emphasizes the mechanisms by which gut dysbiosis contributes to liver inflammation, fibrosis, and tumor formation. In NAFLD-related HCC, modification in the microbiota composition facilitates intestinal barrier dysfunction, endotoxemia, and metabolic disturbances. In HCC associated with HBV/HCV, the microbiome modulates immune surveillance and viral persistence. Shared pathogenic pathways, such as LPS-TLR4 signaling, bile acid dysregulation, and immunosuppressive microenvironments, highlight the role of microbial imbalance across varied etiologies. We also discuss how antibiotics, diet, probiotics, and postbiotics influence gut-liver homeostasis, as well as their therapeutic potential in primary and secondary prevention and treatment of HCC. Short-chain fatty acids and valeric acid are examples of postbiotics with anti-inflammatory and pro-apoptotic anti-IBD effects, while fecal microbiota transplantation and dietary modulation have shown potential in improving outcomes. The review also identifies significant research gaps, particularly in establishing causality, understanding intrahepatic metastasis, and investigating the roles of the fungal and viral microbiome (mycobiome and virome). Finally, the incorporation of microbiome-based interventions into clinical practice could represent an effective future strategy for risk stratification, prevention, and adjuvant therapy of HCC. Future studies focusing on longitudinal analysis, mechanistic validation, and multi-kingdom profiling are essential for translating microbiome research into effective clinical applications.}, }
@article {pmid41475542, year = {2026}, author = {Nayak, A and Bera, S and Purohit, S and Jain, CK}, title = {Gut microbiota mediated neuroinflammation in psychiatric disorders: Current perspectives and challenges.}, journal = {Behavioural brain research}, volume = {501}, number = {}, pages = {116019}, doi = {10.1016/j.bbr.2025.116019}, pmid = {41475542}, issn = {1872-7549}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Mental Disorders/microbiology/immunology/therapy ; *Neuroinflammatory Diseases/microbiology/immunology ; Animals ; *Dysbiosis/immunology ; Probiotics ; Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; }, abstract = {Psychiatric disorders remain a major global health concern, with complex diagnostic criteria and a lack of clear biological markers that continue to challenge therapeutic strategies. Current treatment methods, such as psychotherapy, brain stimulation therapy, and pharmacological interventions, often come with their own set of side effects, thus warranting the need to explore alternative approaches. Emerging research highlights the gut brain axis (GBA) and gut microbiota (GM) as key modulators of brain health and disease. Dysbiosis, a disruption in gut microbial composition, can influence blood brain barrier (BBB) integrity, immune signaling, and microbial metabolite production, collectively modulating neuroimmune homeostasis and contributing to the onset of neuroinflammation. While growing preclinical and clinical evidence links altered GM to depression, anxiety, schizophrenia, bipolar disorder (BD), and autism spectrum disorder (ASD), causal relationships remain incompletely defined. This review examines the established and emerging mechanisms connecting the GM to neuroinflammation underlying psychiatric disorders and evaluates current microbiome targeted interventions, such as diet based strategies, probiotics, next generation probiotics (NGPs), and fecal microbiota transplantation (FMT). We also discuss speculative microbiome engineering approaches and highlight translational limitations that must be addressed before clinical implementation. A holistic approach integrating these strategies with conventional psychiatric treatments could facilitate more effective and personalized interventions.}, }
@article {pmid41475679, year = {2026}, author = {Morel, C and Li, R and Luces, CF and Brougham, MF and Pascual-Gazquez, JF and Torquati, L and Iniesta, RR}, title = {Interventions Targeting the Gut Microbiome to Improve Cancer Treatment Outcomes and Their Gastrointestinal Side Effects: A Systematic Review and Meta-analysis.}, journal = {The Journal of nutrition}, volume = {156}, number = {2}, pages = {101300}, pmid = {41475679}, issn = {1541-6100}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Neoplasms/therapy/microbiology ; *Gastrointestinal Diseases/prevention &amp; control/microbiology/etiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Improvements in cancer treatment are essential to reduce premature mortality. Emerging evidence highlights the role of the gut microbiome (GM) in influencing treatment responses and modulating gastrointestinal adverse events (GIAEs). Because cancer therapy disrupts GM composition, restoring gut health may help mitigate side effects and support gut-associated immunity.<br><br>OBJECTIVES: This study aimed to systematically evaluate and assess the effectiveness of GM interventions on the occurrence of GIAEs and clinical responses to cancer treatment.<br><br>METHODS: Three databases (PubMed, Web of Science, and Cochrane Library) were systematically searched up to February 2025 for studies assessing GM interventions during cancer treatment. Risk of bias was evaluated using the Effective Public Healthcare Panacea Project Quality Assessment tool. Meta-analyses were conducted in Stata 18 using random-effects models to estimate the pooled relative risk of GM interventions on gut microbiome interventions, gastrointestinal adverse events (GIAEs) (primary outcome) and objective disease response rates (secondary outcome).<br><br>RESULTS: Fifty-six studies were included in the systematic review, and 40 were meta-analyzed (n = 37 for GIAE outcomes, n = 8 for treatment response). GM interventions reduced the overall risk of GIAEs [relative risk (RR)]: 0.59; 95% CI: 0.53, 0.65; I[2]: 76.8%; 95% prediction interval (PI): 0.32, 1.08], including diarrhea, constipation, nausea, and vomiting, but with considerable heterogeneity between studies. There was insufficient evidence to suggest improvements in objective disease response rates (RR: 1.06; 95% CI: 0.93, 1.20; I[2]: 0%; 95% PI: 0.93, 1.20).<br><br>CONCLUSIONS: GM interventions show promise in improving cancer care by reducing GIAEs, although evidence for direct effects on-treatment response remains limited. Standardizing intervention protocols and outcome reporting in future RCTs is essential to strengthen the evidence base and guide clinical recommendations. This trial was registered at PROSPERO as CRD42023443332 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023443332).}, }
@article {pmid41475736, year = {2026}, author = {Wu, J and Xu, Q and Yang, Y and Yang, Z and Li, Z and Chen, L and Song, Y and Che, H and Wang, G and Lv, Q and Han, J}, title = {A novel fructan from Atractylodes macrocephala ameliorates ulcerative colitis through gut microbiota-mediated PI3K/Akt signaling.}, journal = {Carbohydrate polymers}, volume = {375}, number = {}, pages = {124764}, doi = {10.1016/j.carbpol.2025.124764}, pmid = {41475736}, issn = {1879-1344}, mesh = {Animals ; *Atractylodes/chemistry ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism/pathology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Mice ; Signal Transduction/drug effects ; *Fructans/pharmacology/chemistry/isolation &amp; purification/therapeutic use ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Polysaccharides from edible and medicinal plants are promising natural agents for intestinal health. In this study, a homogeneous polysaccharide (AMP) was isolated from Atractylodes macrocephala Koidz. Structural characterization revealed that AMP (Mw = 3.56 kDa) primarily consisted of fructose (92.4 %) and glucose (7.6 %), with β-D-fructofuranose and α-d-glucopyranose residues linked through →1)-β-D-Fruf-(2→, →1,6)-β-D-Fruf-(2→, and α-D-Glcp-(1 → glycosidic bonds. In vivo studies confirmed the efficacy of AMP against ulcerative colitis (UC) in a DSS-induced mouse model, as evidenced by a significant improvement in disease symptoms, including increased body weight, longer colon length, and elevated goblet cell counts, coupled with a reduction in the disease activity index and histological damage. Mechanistically, AMP attenuated inflammation by restoring intestinal barrier integrity and regulating the gut microbiota to maintain its homeostasis. These regulatory effects were further validated through fecal microbiota transplantation (FMT) and antibiotic intervention (Abx). Olink proteomics and western blotting demonstrated that the ameliorative effect of AMP on UC, mediated via the PI3K/Akt pathway, was entirely dependent on the homeostasis of the gut microbiota. Collectively, these findings position AMP as a promising functional food ingredient or natural therapeutic for UC, providing a scientific basis for the high-value exploitation of A. macrocephala.}, }
@article {pmid41475762, year = {2026}, author = {Wu, X and Wei, J and Deng, R and Wang, J and Wu, B and Yan, T and Jia, Y}, title = {The Akkermansia muciniphila-tryptophan metabolism-aromatic hydrocarbon receptor axis mediates the protective effect of Schisandra chinensis pectin polysaccharide against colitis.}, journal = {Carbohydrate polymers}, volume = {375}, number = {}, pages = {124808}, doi = {10.1016/j.carbpol.2025.124808}, pmid = {41475762}, issn = {1879-1344}, mesh = {Animals ; *Tryptophan/metabolism ; *Schisandra/chemistry ; *Receptors, Aryl Hydrocarbon/metabolism ; Mice ; *Pectins/pharmacology/chemistry/therapeutic use ; Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism ; Mice, Inbred C57BL ; Male ; Dextran Sulfate/toxicity ; Akkermansia/drug effects/metabolism ; *Colitis/drug therapy/chemically induced/metabolism ; *Polysaccharides/pharmacology/chemistry ; Fecal Microbiota Transplantation ; Protective Agents/pharmacology ; }, abstract = {Current therapies for ulcerative colitis (UC) remain inadequate, necessitating novel treatment strategies. This study isolated SCPII-1, a homogeneous pectin polysaccharide (Mw: 278.153 kDa, DM: 57.21 %) from Schisandra chinensis, primarily composed of →4)-α-D-GalpA-(1 → units. In dextran sulfate sodium (DSS)-induced colitis mice, SCPII-1 alleviated symptoms, repaired mucosal ultrastructure (microvilli, mitochondria), and enhanced barrier integrity. Mechanistically, SCPII-1 ameliorated gut dysbiosis in UC mice, notably through the selective enrichment of the beneficial bacterium Akkermansia muciniphila (AKK). Interestingly, SCPII-1 not only promoted the proliferation of AKK but also modulated its tryptophan metabolism, particularly enhancing the production of the tryptophan-derived metabolite indole-3-ethanol (I3E). The beneficial role of SCPII-1-induced microbiota in UC was validated using pseudo-germ-free mice and fecal microbiota transplantation experiments. Moreover, I3E was identified as a key microbiota-derived active metabolite regulated by SCPII-1, and exogenous supplementation of I3E further confirmed its therapeutic efficacy in UC. Importantly, I3E activated the aryl hydrocarbon receptor (AhR), upregulated IL-22 expression, and promoted mucosal repair and immune homeostasis, thereby confirming the protective role of the SCPII-1-AKK-tryptophan metabolism axis in colitis. These findings highlight SCPII-1 as a promising prebiotic agent for UC treatment by modulating AKK-dependent tryptophan metabolism and activating the AhR/IL-22 signaling pathway, offering a novel microbiota-based therapeutic strategy.}, }
@article {pmid41476057, year = {2025}, author = {Wu, Y and Wong, O and Chen, S and Wang, Y and Lu, W and Cheung, CP and Ching, JYL and Cheong, PK and Chan, S and Leung, P and Chan, FKL and Su, Q and Ng, SC}, title = {Distinct diet-microbiome associations in autism spectrum disorder.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {41476057}, issn = {2041-1723}, mesh = {*Autism Spectrum Disorder/microbiology ; Humans ; Female ; Male ; Child ; *Gastrointestinal Microbiome/genetics/physiology ; *Diet/adverse effects ; Feces/microbiology ; Child, Preschool ; Adolescent ; Food Additives/adverse effects ; Metagenomics ; }, abstract = {Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers-specifically polysorbate-80 and carrageenan-were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors-particularly synthetic food additives-and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.}, }
@article {pmid41476793, year = {2025}, author = {Jin, S and Cheng, X and Han, F and Li, Q and Shang, J and Xie, G and Qin, M}, title = {Total alkaloids of Corydalis saxicola Bunting ameliorate ulcerative colitis through regulation of metabolite networks and gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1721116}, pmid = {41476793}, issn = {1663-9812}, abstract = {BACKGROUND: Yanhuanglian (YHL), derived from the dried herb of Corydalis saxicola Bunting, can inhibit diarrhea and alleviate bleeding in traditional Chinese medicine. YHL is used to treat dysentery and hematochezia, which are recognized as ulcerative colitis (UC) in traditional Chinese medicine. However, the effectiveness and mechanisms of YHL treating UC remain largely unknown. This study aimed to reveal anti-colitis effect and mechanisms of YHL's total alkaloids (YTA) against UC.<br><br>METHODS: Three graded doses of YTA were introduced to DSS-induced colitis mice for 7&#xa0;days to evaluate the anti-colitis effect. Colon, serum, and fecal untargeted metabolomics were applicated to analyze the differential metabolites. 16S rRNA sequencing was used to analyze changes in the gut bacteria, while gut microbiota depletion and fecal microbiota transplantation further verified the effects of gut microbiota. Lactobacillus spp. isolated from the mice feces were screened based on the enrichment abundance of YTA in vivo and in vitro, and the therapeutic effect of Lactobacillus johnsonii enriched with YTA was evaluated in colitis mice.<br><br>RESULTS: YTA alleviated weight loss, diarrhea, and hematochezia in colitis mice, reducing inflammation and oxidative stress while restoring intestinal barrier impairment. Untargeted metabolomics profiling of colon, serum, and feces demonstrated that YTA restored the disrupted metabolite profiles, with linoleic acid consistently identified as a key differential metabolite. Through the pathway enrichment, linoleic acid metabolism pathway was highlighted. YTA also ameliorated imbalance of the gut microbiota by significantly increasing the abundance of Lactobacillus. Gut microbiota depletion and fecal microbiota transplantation confirmed that the benefits of YTA depended on the presence of gut microbiota. Furthermore, Lactobacillus johnsonii enriched by YTA protected colitis mice against UC.<br><br>CONCLUSION: YTA exhibited potential anti-colitis activity by modulating metabolomic profiles and the gut microbiota, suggesting its potential as a complementary and alternative therapy in phytomedicine.}, }
@article {pmid41476963, year = {2025}, author = {Ma, S and Zheng, L and Zhuang, X and Wang, M and Zou, Y}, title = {Pathogenic mechanisms and therapeutic potential of the microbiome in premature ovarian insufficiency.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1734367}, pmid = {41476963}, issn = {1664-3224}, mesh = {Humans ; *Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology ; Female ; Animals ; *Microbiota ; Ovary/metabolism/microbiology ; Probiotics/therapeutic use ; }, abstract = {The postponement of childbearing age has become a global issue. Factors such as increased work pressures on women and environmental changes have led to a rising incidence and younger onset of premature ovarian insufficiency (POI). POI not only impacts patients' reproductive function but also heightens the risk of depression, anxiety, cognitive decline, premature mortality, osteoporosis, and cardiovascular disease. Exploring effective prevention and treatment strategies for POI can slow ovarian ageing and safeguard female reproductive health. Microbiome research confirms that most human tissues and organs form dynamic, interactive systems with symbiotic microbes that play a crucial role in female reproductive function. Previous studies on the microbiome and female reproductive health have rarely focused on POI. The proposed 'Microbiota-Ovary Axis' aims to establish an integrated regulatory framework. This theoretical model systematically elucidates how microbial signals influence ovarian function through four core pathways: the hypothalamic-pituitary-ovarian (HPO) axis, metabolism and endocrine regulation, immunoregulation, and oxidative stress. Evaluating the efficacy of dietary modifications, probiotics, and microbiota transplantation in animal models and preliminary clinical studies will establish a robust theoretical foundation for developing microbiota-targeted innovative diagnostic and therapeutic strategies for POI, thereby enhancing reproductive health throughout the female lifespan.}, }
@article {pmid41477763, year = {2026}, author = {He, Z and Zhang, Y and Feng, C and Xie, T and Zhu, K and Yuan, W and Liu, Y and Xie, P and Zhang, N and Zhao, C and Bian, W and Hu, X and Fu, Y}, title = {Gut microbiota induces mammary gland sIgA production to alleviate S. aureus mastitis.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116782}, doi = {10.1016/j.celrep.2025.116782}, pmid = {41477763}, issn = {2211-1247}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; *Immunoglobulin A, Secretory/metabolism/biosynthesis ; *Staphylococcus aureus ; Mice ; *Mammary Glands, Animal/microbiology/immunology/metabolism ; *Mastitis/microbiology/immunology ; Dysbiosis/microbiology ; *Staphylococcal Infections/microbiology/immunology ; gamma-Aminobutyric Acid/metabolism ; B-Lymphocytes/immunology ; Milk/immunology ; Macrophages ; Glutamate Dehydrogenase/metabolism ; }, abstract = {Mastitis threatens dairy cow health and public safety. While gut dysbiosis increases mastitis susceptibility, the mechanism is unclear. We hypothesized that gut dysbiosis exacerbates Staphylococcus aureus (S. aureus)-induced mastitis by reducing milk secretory immunoglobulin A (sIgA). In mice, vancomycin-induced gut dysbiosis reduced sIgA and IgA[+] B cells in milk, gut, and Peyer's patches, impairing the blood-milk barrier and worsening mastitis, effects reversed by fecal microbiota transplantation. Dysbiosis specifically reduced intestinal M. intestinale abundance and GABA levels. Supplementing with M. intestinale or GABA restored sIgA, increased IgA[+] B cells, and alleviated mastitis. We identified an NADP-specific glutamate dehydrogenase (GDH) in M. intestinale; a GDH-expressing E. coli-produced glutamate, elevating gut GABA, enhancing sIgA, and mitigating mastitis. Mechanistically, GABA activated the mTOR pathway to drive macrophage M2 polarization and B cell differentiation. Thus, M. intestinale-derived GABA boosts sIgA to protect against mastitis, offering novel prevention strategies.}, }
@article {pmid41478268, year = {2026}, author = {Chen, J and Xu, J and Xu, J and Xu, F and Gong, F and Xiao, P and Ma, H and Zhang, Q and Feng, J and Min, Y}, title = {Gut microbiota-derived propionic acid mitigates age-related albumen quality deterioration by modulating magnum functions.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106357}, pmid = {41478268}, issn = {1525-3171}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Chickens/physiology/microbiology ; *Propionates/metabolism/administration &amp; dosage ; Diet/veterinary ; Fecal Microbiota Transplantation/veterinary ; Animal Feed/analysis ; *Albumins/metabolism ; Aging/physiology ; Dietary Supplements/analysis ; }, abstract = {The declined albumen quality during the late laying phase is associated with age-related magnum dysfunction, in which to the roles of gut microbiota is unclear. This study aimed to elucidate the relationship between gut microbiota and magnum function, and its impact on albumen quality. Hy-Line Brown layers at peak (30 wk) and late (70 wk) laying phases were compared to assess age-related changes in albumen quality, magnum function, and gut microbiota. Fecal microbiota transplantation (FMT) from peak- to late-phase hens was conducted to assess functional effects. Microbiome and metabolome analyses were then integrated to identify key bacterial taxa and metabolites. The role of the leading candidate metabolite was further validated through dietary supplementation. Results showed that late-phase hens exhibited significant reductions in albumen height, magnum mucosal fold height, and tubular gland diameter (P < 0.05), alongside gut microbial dysbiosis. FMT from peak-phase donors effectively reversed age-related declines in magnum histomorphology and albumen height in late-phase hens. It also up-regulated the expression of barrier function genes (Claudin-1, ZO-2, MUC2, AGR2) and magnum secretory markers (OVOA), while down-regulating pro-inflammatory cytokines (IL-4, IFN-γ) (P < 0.05). Microbial analysis identified Anaerotruncus as the only genus consistently enriched following FMT and positively correlated with improved albumen height and magnum morphology. Metabolomic analysis revealed that propionic acid was the top metabolite associated with Anaerotruncus abundance. Crucially, dietary supplementation with sodium propionate recapitulated the key benefits of FMT. In summary, our findings revealed a gut microbiota-oviduct axis through which microbiota from peak-laying hens ameliorate age-related magnum decline and improve albumen quality in aging hens.}, }
@article {pmid41478424, year = {2026}, author = {Zhang, Y and Chen, L and Jin, J and Xin, Y and Wang, J and Zhang, A}, title = {Therapeutic application of fecal microbiota transplantation for neurological diseases: Exploring novel mechanisms and perspectives.}, journal = {Experimental neurology}, volume = {398}, number = {}, pages = {115631}, doi = {10.1016/j.expneurol.2025.115631}, pmid = {41478424}, issn = {1090-2430}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/trends ; *Nervous System Diseases/therapy ; *Gastrointestinal Microbiome/physiology ; Animals ; }, abstract = {Recently, fecal microbiota transplantation (FMT) has garnered widespread attention as an emerging therapeutic approach in the field of neurological disorders. In this study, we review the research progress of FMT in treating neurological disorders. First, the development, safety, and efficacy of FMT are introduced. Subsequently, the application and potential mechanisms of FMT in neurodegenerative diseases (such as Parkinson's disease and Alzheimer's disease), neurodevelopmental disorders (such as autism spectrum disorder and attention deficit hyperactivity disorder), and other neurological conditions are elaborated in detail. Particularly, we explore the pivotal role of the microbiota-gut-brain axis in FMT for treating neurological disorders, as well as how FMT influences neurological function by regulating the gut microbiota and its metabolites, immune system and inflammatory responses, and neurotransmitters. However, FMT also faces numerous challenges in the treatment of neurological disorders, such as ethical issues, safety concerns, and standardization problems. Therefore, this review also prospects the future development directions of FMT in the treatment of neurological diseases, including personalized therapy and combination therapies. FMT may be a feasible and promising option for treating various neurological disorders, but a comprehensive understanding of its working principles and continuous improvement of its application in clinical practice are still ongoing.}, }
@article {pmid41479037, year = {2026}, author = {El-Daly, SM and Fayed, B and Talaat, RM and Gouhar, SA and Fahmy, CA and El-Jawad, AMA and Hamdy, NM and Abd Elmageed, ZY}, title = {The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.}, journal = {Sub-cellular biochemistry}, volume = {114}, number = {}, pages = {61-121}, pmid = {41479037}, issn = {0306-0225}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastrointestinal Neoplasms/microbiology/genetics/pathology/metabolism ; *RNA, Untranslated/genetics/metabolism ; *Endocrine Gland Neoplasms/microbiology/genetics/metabolism/pathology ; Dysbiosis/microbiology/genetics ; Animals ; }, abstract = {The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.}, }
@article {pmid41479552, year = {2025}, author = {Qian, C and Hong, J and Shi, W and Liu, F and Li, W and Ma, L and Gao, X and Tang, YW and Wu, Q and Xia, L and Hong, M}, title = {Impact of Xpert[®] Carba-R-based screening for carbapenem-resistant organisms on infection-related mortality in hematopoietic stem cell transplant recipients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1698525}, pmid = {41479552}, issn = {2235-2988}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins/genetics ; beta-Lactamases/genetics ; *Carbapenem-Resistant Enterobacteriaceae/isolation &amp; purification ; *Carbapenems/pharmacology ; Feces/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Mass Screening/methods ; Prospective Studies ; Transplant Recipients ; }, abstract = {BACKGROUND: The emergence of carbapenem-resistant organisms (CROs) poses a major challenge to clinical infection control in hospitals. Patients undergoing hematopoietic stem cell transplants (HSCTs) infected with CROs are at high risk of mortality. Proactive screening of HSCT patients for CRO colonization may enable early and accurate preemptive anti-CRO therapy, reduce the probability of secondary infections, and contribute to infection prevention and control measures. However, screening CRO colonization with stool/rectal swab culture and sensitivity has a low positivity rate with a long turnaround time, which limits the effectiveness of the interventions. A more rapid and accurate method to detect CRO colonization is urgently needed. Xpert Carba-R assay provides a rapid and accurate detection of carbapenemase types, enabling targeted anti-infective therapy selection based on the identified resistance mechanism.<br><br>METHODS: We conducted a historically controlled prospective study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2021 and July 2022. The study population comprised adult HSCT patients (&#x2265;18 years old) who received preemptive anti-CRO therapy based on rectal culture and Xpert Carba-R screening during this period. A total of 381 patients who underwent HSCT from August 2020 to July 2022 were included in the study, and CRO colonization screening was performed on admission and weekly thereafter. In the historic control group from August 2020 to July 2021, HSCT patients were screened only by rectal swab traditional CRO culture, and CRO colonization was determined if the rectal culture was positive. In the study group from August 2021 to July 2022, two rectal swab specimens were collected from HSCT patients for both CRO traditional culture (RS-culture) and Xpert Carba-R testing (RS-Carba-R). CRO colonization was determined if either of the screening methods was positive. CRO-active antibiotics were immediately provided on the first febrile episode of neutropenia (FN) in CRO-colonized patients. Clinical outcome data for the CRO monthly colonization rate and anti-infection efficiency were collected and contrasted between the two groups.<br><br>RESULTS: In the historic group, 47 out of 197 patients (23.9%) were identified as colonized with CRO, detected only by RS-culture. In the study group, 41 out of 184 patients (22.3%) were identified as colonized with CRO, detected by either RS-culture or RS-Carba-R; among them, Escherichia coli was the most common CP-CRO strain, and the most prevalent carbapenemase type was NDM. This indicated a slightly lower annual detection rate of CRO gut colonization in the study group compared to the historic group, but no significant difference was observed (22.3% vs. 23.9%, p = 0.715). The incidence of CRO-related bloodstream infections (CRO-BSI) was significantly lower in the study group compared to the historic group (4.8% vs. 25.5%, p = 0.012), and the CRO-related mortality in colonized patients decreased from 19.4% in the historic group to 2.4% in the study group (p = 0.046). The monthly detection rate of CRO gut colonization by RS-culture in the historic group remained steady, with no significant fluctuation (19.7% in the first month and 18.8% in the last month). In contrast, the monthly detection rate of CRO gut colonization by either RS-culture or RS-Carba-R in the study group was higher in the first month compared to the historic group (21.2% in August 2021 vs. 18.8% in July 2021). However, a gradual decline in the monthly detection rates of CRO gut colonization by RS-culture and/or RS-Carba-R was observed in the study group, dropping from 21.2% in the first month to 2.9% in the last month. The univariate and multivariate analyses indicated that the study group had a shorter length of hospitalization (OR = 0.94, 95% CI 0.88-0.99, p = 0.038) and CRO-related mortality (OR = 0.12, 95% CI 0.01-0.75, p = 0.021) than the historic group.<br><br>CONCLUSIONS: Our study showed a positive effect of more rapid CRO colonization screening using rectal swabs with Xpert Carba-R and culture, which can guide potent CRO preemptive therapy for subsequent infections based on the detected carbapenemase mechanism, thereby reducing mortality and the spread of CRO infection in HSCT patients.<br><br>CLINICAL TRIAL REGISTRATION: chictr.org, identifier ChiCTR2100041976.}, }
@article {pmid41479812, year = {2025}, author = {Song, YJ and Yang, B and Feng, QS and Ma, FF and Xing, B and Bin, XL and Ha, XQ}, title = {Gut microbiota-derived trimethylamine N-oxide exacerbates diabetic nephropathy by promoting renal fibrosis.}, journal = {World journal of nephrology}, volume = {14}, number = {4}, pages = {112066}, pmid = {41479812}, issn = {2220-6124}, abstract = {BACKGROUND: Background diabetic nephropathy (DN), a major complication of diabetes, is linked to gut microbiota dysbiosis. Elevated trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, plays a central role in inducing renal injury during DN pathogenesis.<br><br>AIM: To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN, hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.<br><br>METHODS: A DN model was successfully established using Zucker diabetic fatty (ZDF) rats. Blood samples were analyzed for renal function parameters, and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry. Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining, respectively. Additionally, 16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN. Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.<br><br>RESULTS: After 8 weeks of modeling, the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L, and compared to the control group, renal function indicators, including &#x3b2;2-microglobulin, cystatin C, uric acid, and creatinine, were significantly elevated (P < 0.05). Renal fibrosis was more pronounced in the ZDF model group, accompanied by heightened P-smad3 expression, in contrast to the TMAO inhibition group. Although Masson staining results did not reach statistical significance (P > 0.05), notable alterations in intestinal flora structure were observed in DN rats, and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls (P > 0.05).<br><br>CONCLUSION: DN is associated with gut microbiota alterations that potentiate TMAO generation, contributing to renal injury and fibrotic progression. While TMAO's role in fibrosis warrants further validation, these findings implicate the gut-kidney axis in DN pathogenesis.}, }
@article {pmid41479898, year = {2025}, author = {Abdel-Gaber, R and Albasyouni, S and Santourlidis, S and Al Quraishy, S and Al-Shaebi, E}, title = {Commiphora myrrha extract protects pigeons from Eimeria labbeana-like-triggered inflammatory dysregulation.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1714313}, pmid = {41479898}, issn = {1664-3224}, mesh = {Animals ; *Eimeria/drug effects/immunology ; *Coccidiosis/veterinary/immunology/parasitology/drug therapy ; *Commiphora/chemistry ; *Plant Extracts/pharmacology ; *Columbidae/parasitology/immunology ; Cytokines/metabolism ; *Bird Diseases/parasitology/immunology/prevention &amp; control/drug therapy ; *Inflammation ; *Resins, Plant/pharmacology ; }, abstract = {BACKGROUND: Coccidiosis, caused by Eimeria species, is a major enteric disease in birds, with Eimeria labbeana-like isolates frequently inducing severe intestinal lesions, diarrhea, and reduced weight gain in pigeons. Conventional anticoccidial drugs face limitations due to resistance, residue concerns, and environmental impact, highlighting the need for alternative strategies. Commiphora myrrha (myrrh) is a resinous plant extract rich in bioactive compounds with antioxidant, antimicrobial, antiparasitic, and anti-inflammatory properties. This study evaluated the protective effects of C. myrrha resin in pigeons experimentally infected with E. labbeana-like isolates.<br><br>METHODS: Resin of C. myrrha was collected from Riyadh, Saudi Arabia, authenticated, and extracted with 70% methanol to prepare a crude extract (MyE). Its chemical composition was characterized using GC-MS. A laboratory strain of Eimeria labbeana-like oocysts was propagated in pigeons, sporulated, and used for experimental infection. Twenty-five pigeons were randomly assigned to five groups: uninfected control, uninfected + myrrh extract (MyE), infected control, infected + MyE, and infected + amprolium (standard drug). MyE and amprolium treatments were administered orally for 5 days post-infection. Parasitological, histological, immunohistochemical (NF-&#x3ba;B and IFN-&#x3b3;), gene expression (MUC2, IL-1&#x3b2;, IL-10, IFN-&#x3b3;, and TNF-&#x3b1;), and cytokine (IL-10 and TNF-&#x3b1;) analyses were conducted.<br><br>RESULTS: In this study, myrrh resin was methanol-extracted and characterized by GC-MS, revealing 29 phytochemical components. Experimental infection of pigeons with E. labbeana-like oocysts resulted in peak fecal oocyst shedding (~5.25 &#xd7; 10[5] oocysts/g.feces), extensive development of intracellular parasite stages (meronts, gamonts, and developing oocysts), a marked reduction in goblet cell numbers, and elevated intestinal inflammatory responses, including increased NF-&#x3ba;B and IFN-&#x3b3; immunoreactivity, as well as upregulated mRNA expression of IL-1&#x3b2;, IL-10, IFN-&#x3b3;, and TNF-&#x3b1;. Oral administration of MyE significantly suppressed oocyst shedding by 60%, reduced the number of intracellular parasitic stages, restored goblet cell counts, and downregulated both gene and protein levels of pro-inflammatory markers while enhancing MUC2 expression, indicating effective modulation of Eimeria-induced intestinal damage and inflammatory dysregulation.<br><br>CONCLUSION: These findings demonstrate that C. myrrha extract effectively mitigates Eimeria-induced intestinal damage, inflammation, and immune dysregulation, highlighting its potential as a natural, plant-based intervention for managing pigeon coccidiosis.}, }
@article {pmid41480095, year = {2025}, author = {Wang, B and Ma, D and Li, N and Luo, T}, title = {The application of fecal microbiota transplantation in Parkinson's disease.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1713899}, pmid = {41480095}, issn = {1663-4365}, abstract = {BACKGROUND: Parkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) in dopaminergic neurons of the substantia nigra. The pathogenesis of PD remains incompletely understood, and disease-modifying therapies are lacking. Emerging evidence suggests that gut microbiota and their metabolites influence both intestinal and central nervous system (CNS) functions via the microbiota-gut-brain axis (MGBA). Recent studies have identified dysbiosis in the gut microbiota of PD patients, which may contribute to disease progression through two primary mechanisms: First, increased intestinal permeability, allowing pro-inflammatory factors and microbial metabolites to affect the enteric nervous system (ENS) and subsequently spread to the CNS via the vagal neurons; Secondly, disruption of the Blood-Brain barrier (BBB), leading to neuroinflammation and aberrant α-syn aggregation, ultimately resulting in dopaminergic neuron degeneration. These findings underscore the critical role of the MGBA in PD pathogenesis, which makes gut microbiota modulation a promising therapeutic target.<br><br>HIGHLIGHTS: This review synthesizes current knowledge on gut microbiota alterations in PD and evaluates the potential of fecal microbiota transplantation (FMT) as an adjunctive therapy to alleviate motor and non-motor symptoms and slow disease progression.<br><br>CONCLUSION: FMT has demonstrated efficacy in ameliorating PD symptoms via the MGBA. However, further preclinical and clinical studies are needed to fully elucidate its mechanisms and optimize therapeutic protocols. Targeting the gut microbiota may offer novel biomarkers and intervention strategies for PD.}, }
@article {pmid41480316, year = {2025}, author = {Majeed, AA and Butt, AS}, title = {Gut microbiota: An overlooked target in dyslipidemia management.}, journal = {World journal of gastroenterology}, volume = {31}, number = {48}, pages = {113178}, pmid = {41480316}, issn = {2219-2840}, mesh = {Humans ; Bile Acids and Salts/metabolism ; Cardiovascular Diseases/prevention &amp; control ; Circadian Rhythm ; *Dyslipidemias/therapy/microbiology/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology/immunology ; Lipid Metabolism ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {With the global rise in sedentary lifestyles, obesity, and unhealthy dietary patterns, dyslipidemia has emerged as a leading modifiable risk factor for atherosclerotic cardiovascular disease. Beyond host genetics and diet, the gut microbiota has gained recognition as a critical regulator of lipid homeostasis through mechanisms involving bile acid metabolism, short-chain fatty acid signaling, and microbial modulation of inflammation. Lv et al provide a comprehensive synthesis of the diet microbe-lipid axis and therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. In this correspondence, we expand on their framework by highlighting underexplored yet clinically relevant dimensions, including circadian rhythm alignment, pharmacotherapy microbe crosstalk, population-specific microbial signatures, and functional microbial phenotyping. Addressing these overlooked aspects could accelerate the translation of microbiome science into precision dyslipidemia management, with the potential to improve cardiovascular outcomes worldwide.}, }
@article {pmid41481427, year = {2026}, author = {Wang, J and Zi, F and Liu, W and Liu, C and Zhang, Z and Kong, L and Xu, X and Wei, J and Chen, T and Li, J}, title = {Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609455}, pmid = {41481427}, issn = {1949-0984}, mesh = {*Clostridium butyricum/physiology/metabolism ; Animals ; *Multiple Myeloma/microbiology/therapy/metabolism/pathology ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Bone Marrow/metabolism/pathology ; Signal Transduction ; Tumor Microenvironment ; Dysbiosis/microbiology ; Female ; Th17 Cells/immunology ; }, abstract = {Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished butyrate levels in the MM cohort. Subsequent fecal microbiota transplantation demonstrated that the gut microbiota critically modulates MM progression, with healthy donor-derived microbiota reducing the tumor burden and concomitantly elevating serum butyrate. Furthermore, through function-based culturomics screening, Clostridium butyricum (C. butyricum) was identified as a key butyrate-producing specialist. C. butyricum or its metabolite butyrate significantly reduced the systemic tumor burden in 5TGM1 mice. Notably, C. butyricum and butyrate alleviated bone marrow inflammation and osteolytic lesions by suppressing Th17 cells and IL-17 levels in the bone marrow. Moreover, cellular assays and transcriptome sequencing further revealed that butyrate could induce MM cells' apoptosis via HDAC inhibition-mediated upregulation of PPARγ, leading to sequential suppression of the PI3K/AKT pathway and antiapoptotic BCL-2 expression. This apoptotic signaling cascade was reversed by PPARγ antagonism. The direct antitumor effect was further confirmed in M-NSG mice. Our research systematically verifies the specific role of the gut microbiota in MM and provides the first evidence of the immune and molecular mechanisms by which C. butyricum alleviates MM progression, offering preclinical support for probiotic-based therapies against MM.}, }
@article {pmid41482085, year = {2026}, author = {Yang, B and Xia, Q and Ji, X and Su, K and Yu, T and Xiao, Z and Shi, C and Luo, Z and Wang, X and Xu, W and Gao, Y and Hua, H and Shan, J}, title = {Ganjie Decoction protects against respiratory syncytial virus infection by activating PI3K/AKT-apoptosis axis and regulating gut microbiota metabolism.}, journal = {Journal of ethnopharmacology}, volume = {360}, number = {}, pages = {121142}, doi = {10.1016/j.jep.2025.121142}, pmid = {41482085}, issn = {1872-7573}, mesh = {Animals ; *Respiratory Syncytial Virus Infections/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Proto-Oncogene Proteins c-akt/metabolism ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Mice, Inbred BALB C ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Humans ; *Antiviral Agents/pharmacology ; Lung/drug effects/pathology/virology ; Molecular Docking Simulation ; Female ; Male ; }, abstract = {Ganjie Decoction (GJD), a traditional Chinese medicine (TCM) formula commonly used for respiratory diseases, has shown therapeutic potential against RSV pneumonia. However, its pharmacological mechanisms against respiratory syncytial virus (RSV) pneumonia are not fully understood.<br><br>AIM OF STUDY: This study aimd to characterize the active components of GJD and systematically investigate its therapeutic effects and underlying mechanisms in RSV-induced pneumonia.<br><br>MATERIALS AND METHODS: To evaluate the therapeutic efficacy of GJD in RSV-infected mice, we monitored body weight, performed qPCR, and conducted histopathological examination of lung tissues. The chemical constituents of GJD were characterized using UPLC-MS. Key bioactive compounds and their potential targets were predicted using network pharmacology and molecular docking. The underlying mechanisms were further elucidated using immunohistochemistry and western blotting. The interactions between GJD and the gut microbiota were explored using antibiotic depletion, fecal microbiota transplantation (FMT), metagenomic sequencing, and in vitro co-culture assays. Untargeted metabolomics was employed to assess GJD-induced metabolic alterations. Finally, the role of the key metabolite 4-hydroxyphenylacetic acid (4-HPA) was investigated in vivo and in vitro through qPCR, immunohistochemistry, ELISA, Western blot, cell viability assays and immunofluorescence.<br><br>RESULTS: GJD significantly mitigated weight loss, attenuated pulmonary viral load, and suppressed inflammation in RSV-infected mice. Network pharmacology and molecular docking revealed that specific compounds in GJD target the PI3K/AKT signaling pathway. This finding was validated by western blotting and immunohistochemistry, which demonstrated that GJD suppresses PI3K/AKT pathway activation, thereby attenuating apoptosis and ameliorating RSV-induced pneumonia. Notably, these protective effects were markedly attenuated in mice with depleted gut microbiota, while therapeutic effects of GJD against RSV pneumonia were transferable via gut microbiota transplantation. GJD restored RSV-induced dysbiosis of the gut microbiota, with Lactobacillus reuteri emerging as one of the most enriched microbes following treatment. Metabolomics analysis identified 4-HPA as a microbiota-dependent metabolite significantly upregulated by GJD. Remarkably, administration of 4-HPA reproduced GJD's therapeutic effects in RSV-infected mice and activated the KEAP1/NRF2 antioxidant pathway, suggesting that 4-HPA functions as a key mediator of GJD's anti-RSV activity.<br><br>CONCLUSIONS: These findings suggest that GJD alleviates RSV pneumonia through a synergistic mechanism that modulates the PI3K/AKT-apoptosis pathway, restores gut microbial balance, and normalizes metabolic disturbances. This study systematically elucidates the mechanistic basis underlying the therapeutic effects of GJD against RSV pneumonia.}, }
@article {pmid41482667, year = {2026}, author = {Chen, Y and Du, H and Zhou, W and Qin, M and Li, M and Jin, Y and Xu, Y and Ma, C and Xia, J and Mo, Y and Chen, N and Huang, H and Li, H and Xie, Z and Wang, P and Hong, Y}, title = {Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2610077}, pmid = {41482667}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Tamoxifen/adverse effects/toxicity ; Mice ; *Chemical and Drug Induced Liver Injury/metabolism/microbiology ; Dysbiosis/microbiology/chemically induced ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; Bile Acids and Salts/metabolism ; Humans ; Fecal Microbiota Transplantation ; Male ; Feces/chemistry ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Receptor, Farnesoid X-Activated ; }, abstract = {Tamoxifen (TAM) is a widely used estrogen receptor modulator for breast cancer treatment. However, TAM exhibits significant hepatotoxicity in the clinic, affecting nearly 50% of patients and thereby limiting its clinical utility. The specific mechanisms underlying TAM-induced liver injury remain poorly understood. In this study, we elucidated the mechanistic role of the gut microbiota in the hepatotoxicity associated with TAM. TAM administration induced substantial liver injury and gut microbiota dysbiosis in mice, characterized by an increased abundance of Escherichia and a reduction in Lachnospiraceae NK4A136 group. These microbial shifts resulted in decreased levels of total fecal bile acids (BA), particularly hyodeoxycholic acid (HDCA), which was inversely correlated with TAM-induced liver injury. Additionally, TAM disrupted BA homeostasis by enhancing intestinal Farnesoid X receptor (FXR) activity and concurrently stimulating hepatic BA synthesis through an alternative nonintestinal FXR mechanism. Notably, gut microbiota depletion reversed these effects, demonstrating the critical role of the microbiota in modulating the gut‒liver FXR axis in TAM-induced liver injury. Fecal microbiota transplantation (FMT) further confirmed that TAM directly stimulated hepatic BA synthesis through a microbiota-dependent mechanism. The disruption of the gut‒liver BA‒FXR axis impaired enterohepatic BA circulation, contributing to the liver toxicity associated with TAM administration. Importantly, HDCA supplementation restored the gut‒liver BA‒FXR axis and alleviated TAM-induced liver injury. These findings highlight the intricate relationship between TAM, gut microbiota, and BA metabolism, suggesting that targeting the gut-liver FXR axis with HDCA may serve as a promising therapeutic strategy for alleviating TAM-associated liver injury.}, }
@article {pmid41483189, year = {2026}, author = {Rathee, S and Sen, D and Jain, A and Jain, SK}, title = {Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {399}, number = {6}, pages = {7741-7762}, pmid = {41483189}, issn = {1432-1912}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/epidemiology/diagnosis/physiopathology ; Animals ; Risk Factors ; Ammonia/metabolism ; }, abstract = {This comprehensive review explores the multifaceted landscape of hepatic encephalopathy (HE), encompassing its epidemiology, pathophysiology, classification, and evolving therapeutic approaches. Delving into the prevalence and incidence of HE, it is found that the burden of this condition is on individuals and healthcare systems. The intricate mechanisms underlying HE, including abnormalities in synapse transmission, the ammonia hypothesis, the false neurotransmitter theory, the GABAergic theory, and the benzodiazepine theory, are scrutinized, providing a nuanced understanding of the disorder. The review examines altered gene expression, hyponatremia, neurosteroids, oxidative stress, electrolyte imbalance, and manganese accumulation as contributing factors to HE. Classifying HE and identifying precipitating risk factors form crucial aspects of the discussion, shedding light on the most widely used diagnostic tools. Conventional approaches for HE management are discussed, focusing on reducing elevated ammonia formation, improving ammonia-detoxifying liver capacity, and inhibiting false neurotransmitters. Antibiotics, metabolic ammonia scavengers, albumin, probiotics, dietary management, zinc, and secondary prophylaxis are analyzed as current therapeutic targets. Furthermore, the review examines emerging therapies at various stages, including clinical and pre-clinical development, such as glycerol/sodium phenylbutyrate, ornithine phenylacetate, fecal microbiota transplantation, engineered bacteria, liposome-supported peritoneal dialysis, GABAA receptor modulating steroid antagonists (GAMSA), activated carbon microspheres, and glutamine synthetase replacement. This review consolidates knowledge on HE, providing a comprehensive resource for clinicians, researchers, and healthcare professionals involved in managing this complex disorder. The synthesis of epidemiological data, pathophysiological insights, and therapeutic advancements offers a holistic view of HE, paving the way for improved diagnosis and targeted interventions.}, }
@article {pmid41483363, year = {2026}, author = {Yang, J and Yan, H and Liu, J and Shen, X and Liu, H and Kang, X and Yang, X and Che, Y and Wang, X and Guo, L and Zhang, F and Fan, W}, title = {Lactobacillus Acidophilus Protects against alcohol-associated Liver Disease in Mice Via Gut Microbiota Modulation and Alleviation of Inflammation and Oxidative Stress.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41483363}, issn = {1867-1314}, support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; }, abstract = {Alcohol-associated liver disease (ALD) is a severe liver disease caused by excessive alcohol consumption. ALD remains a clinical challenge with limited therapeutic options. Following 5-day pretreatment with Lactobacillus acidophilus (Lac), mice were administered ethanol by gavage to induce ALD. Tissues were collected and analyzed for serum markers, hepatic pathology/inflammation/oxidative stress, ileal morphology/tight junctions, and cecal microbiota via 16 S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was performed, and tissues were then collected and analyzed as above. Moreover, the anti-inflammatory and antioxidant properties of Lac-derived particulate matter (pLac) were evaluated on RAW264.7 macrophages in vitro. Lac administration improved gut microbiota composition, enhanced intestinal barrier integrity and reduced lipopolysaccharide (LPS) translocation to the liver, thereby inhibiting the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) pro-inflammatory pathway and activating the adenosine monophosphate activated protein kinase (AMPK)- peroxisome proliferator activated receptor α (PPARα) signaling axis. This led to significant attenuation of hepatic inflammation, oxidative stress and steatosis. The FMT experiments further validated that Lac-mediated protection is dependent on gut microbiota modulation. In vitro studies revealed that pLac exhibit direct anti-inflammatory and antioxidant properties. These findings elucidate the mechanistic basis for Lac in alleviating acute ALD, positioning it as a promising treatment or dietary intervention to enhance clinical management.}, }
@article {pmid41483616, year = {2026}, author = {Zhong, Y and Liu, J and Huang, J and Yu, J and Liu, Y and Zhuo, W and Xu, Y and Zhang, Y and Zhou, Z and Chen, L and Xiao, Q and Liu, D}, title = {Astragaloside IV alleviates ulcerative colitis via gut microbiota - butyrate metabolism axis to reshape Th17/Treg balance.}, journal = {International immunopharmacology}, volume = {171}, number = {}, pages = {116135}, doi = {10.1016/j.intimp.2025.116135}, pmid = {41483616}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/immunology ; *Th17 Cells/immunology/drug effects ; *T-Lymphocytes, Regulatory/immunology/drug effects ; *Saponins/therapeutic use/pharmacology ; *Colitis, Ulcerative/drug therapy/immunology/chemically induced/microbiology ; *Triterpenes/therapeutic use/pharmacology ; Mice ; *Butyrates/metabolism ; Dextran Sulfate ; Mice, Inbred C57BL ; Colon/drug effects/pathology/immunology ; Male ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Disease Models, Animal ; Humans ; }, abstract = {Gut microbiota dysbiosis and Th17/Treg cell imbalance play critical roles in the pathogenesis of ulcerative colitis (UC). Astragaloside IV (AS-IV) exhibits extensive anti-inflammatory and immunomodulatory activities; however, the crosstalk between gut microbiota and Th17/Treg cells modulated by AS-IV remains unreported. Here, chronic colitis was induced in mice by free access to 2.5 % dextran sulfate sodium (DSS) solution over three 7-day cycles, with concurrent AS-IV administration. AS-IV effectively alleviated DSS-induced chronic colitis in mice, as evidenced by increased body weight and colon length, decreased disease activity index (DAI), colon weight, colon weight/colon length, and colon weight index, and enhanced the gene and protein expression of tight junction molecules Claudin-1, Occludin, ZO-1. Notably, AS-IV not only effectively regulated the differentiation balance of Th17/Treg cells, but also significantly improved the composition of gut microbiota and butyric acid metabolism in chronic colitis mice. Intriguingly, Th17/Treg cells and butyric acid were significantly correlated with α/β diversity, as well as the genera Enterorhabdus, Mucispirillum, and Helicobacter. However, AS-IV lost its therapeutic efficacy against colitis and its regulatory effects on Th17/Treg cell balance and butyric acid metabolism following gut microbiota depletion. Critically, FMT from AS-IV-treated mice restored the protective effects against colitis and the regulation of Th17/Treg cell balance and butyric acid metabolism. Collectively, AS-IV inhibits chronic colitis by regulating gut microbiota composition, butyric acid metabolism, and Th17/Treg cell differentiation balance, whose protective effects are dependent on the regulatory mechanism of Th17/Treg cell differentiation balance mediated by gut microbiota-derived butyrate metabolism.}, }
@article {pmid41484558, year = {2026}, author = {Zhang, B and Zheng, T and He, Z and Su, S and Yuan, S and Chen, D and Li, H and Guan, W and Zhang, S}, title = {Maternal purified fiber supplementation-enriched Akkermansia muciniphila regulates lactation and offspring growth via the gut-mammary axis.}, journal = {Science China. Life sciences}, volume = {69}, number = {2}, pages = {542-556}, pmid = {41484558}, issn = {1869-1889}, mesh = {Animals ; Female ; *Lactation/drug effects/physiology ; Mice ; *Gastrointestinal Microbiome/drug effects/physiology ; *Dietary Fiber/administration &amp; dosage/pharmacology ; Dietary Supplements ; Swine ; Milk/metabolism/chemistry ; *Mammary Glands, Animal/metabolism/drug effects ; Akkermansia ; Fatty Acids, Volatile/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Immunoglobulins/metabolism ; *Verrucomicrobia ; }, abstract = {Maternal fiber intake alters the maternal gut microbiota and metabolites, which benefits offspring health through unclear mechanisms. Using a sow model, the study showed that supplementing with purified fiber (cellulose:guar gum=3:1) increased weaning weight and resistance to LPS-induced intestinal injury. Milk analysis revealed higher levels of immunoglobulins and milk fat. Fecal microbiota transplantation (FMT) from fiber-fed sows to mice replicated these benefits, increasing milk fat, immunoglobulins, and pup growth. Akkermansia muciniphila (AKK) abundance was positively associated with milk quality in both models. Supplementing with AKK mimicked the effects of fiber, boosting milk fat and immunoglobulins. In in vitro experiments with HC11 mammary epithelial cells showed that AKK metabolites enhanced milk fat synthesis and immunoglobulin transporter expression. Metabolite analysis indicated that AKK influences mammary gland function by increasing acetate and propionate levels, with acetate promoting milk fat synthesis via GPR43 and propionate regulating immunoglobulin transport through GPR41. Therefore, maternal fiber intake promotes intestinal AKK abundance, increases short-chain fatty acids (SCFAs) production, and influences lactation via GPR41/43 signaling.}, }
@article {pmid41484843, year = {2026}, author = {Sadeghi, R and Abdol Homayuni, MR and Fateh, A and Ebrahimzadeh, N and Riazi-Esfahani, H and Yazdani Moghadam, M and Nikfar, R and Pakzamir, P and Siadat, SD}, title = {The gut-eye axis: microbiota and their role in diabetic retinopathy: a systematic review and meta-analysis.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {7}, pmid = {41484843}, issn = {1471-2415}, abstract = {PURPOSE: To systematically evaluate the relationship between gut microbiota dysbiosis and diabetic retinopathy (DR), exploring microbial diversity, composition, metabolic function, and causal associations via the gut–eye axis. METHOD: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across PubMed, Scopus, Embase, and Web of Science identified studies examining gut microbiota in diabetic patients with and without DR. Eighteen eligible studies—including observational, cohort, and Mendelian randomization (MR) designs—were critically appraised. Meta-analyses pooled standardized mean differences (SMDs) for alpha diversity indices (Chao1, ACE, OTUs, Shannon, Simpson) between DR, diabetes without retinopathy (DM), and healthy controls (HC), using random-effects models with heterogeneity assessments. RESULTS: Gut microbiota in DR patients showed inconsistent alpha diversity changes but consistent beta diversity shifts, indicating distinct microbial community structures. Meta-analysis across eight studies (268 DR, 269 DM, 99 HC) revealed no significant differences in alpha diversity between DR and DM (e.g., Shannon SMD 0.01, 95% CI -0.44 to 0.45; I[2]=74%) or DR and HC (e.g., Shannon SMD 0.02, 95% CI -1.30 to 1.33; I[2]=71%), with moderate to high heterogeneity. DR cohorts exhibited altered Firmicutes/Bacteroidetes ratios, reduced short-chain fatty acid (SCFA)-producing genera (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia-Shigella, Pseudomonas). Functional analyses revealed dysregulated amino acid and lipid metabolism, with specific taxa-metabolite correlations. CONCLUSION: This review substantiates gut microbiota dysbiosis as a potential contributor to DR pathogenesis via the gut–eye axis. While no robust changes in alpha diversity were found, compositional and functional alterations highlight specific microbial taxa and pathways as potential therapeutic targets. Microbiota modulation through diet, probiotics, or fecal transplantation may offer novel strategies to complement conventional DR management. However, high heterogeneity, demographic limitations, and methodological variations warrant further longitudinal and ethnically diverse studies to validate these findings and guide clinical translation.}, }
@article {pmid41485293, year = {2026}, author = {Meng, Y and Hou, Y and Zhang, R and Guo, Z and Zhang, Z and Li, J and Yan, Y and Chang, Y and Li, D and Chang, L and Li, M and Gao, H}, title = {Jinlida ameliorates diabetic kidney disease via gut microbiota-dependent production of pyridoxamine targeting renal AGEs/RAGE and TGF-β pathways.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157744}, doi = {10.1016/j.phymed.2025.157744}, pmid = {41485293}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Pyridoxamine/metabolism/pharmacology ; *Diabetic Nephropathies/drug therapy/metabolism ; Mice ; Male ; Transforming Growth Factor beta/metabolism ; Glycation End Products, Advanced/metabolism ; Mice, Inbred C57BL ; *Drugs, Chinese Herbal/pharmacology ; Fecal Microbiota Transplantation ; Receptor for Advanced Glycation End Products/metabolism ; Kidney/drug effects/metabolism ; Signal Transduction/drug effects ; Vitamin B 6/metabolism ; }, abstract = {BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease (ESRD), necessitating novel therapies beyond conventional approaches. Emerging evidence indicates that gut microbiota dysbiosis promotes DKD progression through metabolite-mediated renal injury. Jinlida (JLD) is a clinically validated traditional Chinese medicine with antidiabetic activity, but its microbiota-mediated renoprotective mechanism remains unclear.<br><br>PURPOSE: This study investigates whether JLD alleviates DKD by modulating gut microbiota and vitamin B6 metabolism, and elucidates the renoprotective mechanism of its key metabolite, pyridoxamine (PM).<br><br>METHODS: To assess JLD's microbiota-dependent effects, we employed antibiotic-induced pseudo-germ-free mice and fecal microbiota transplantation (FMT). Metagenomics and untargeted metabolomics delineated gut microbiota and metabolite compositional changes. Renal PM levels were quantified by LC-MS/MS. The renoprotective effects and mechanisms of direct PM supplementation against DKD were further evaluated in vivo and in vitro.<br><br>RESULTS: JLD's therapeutic effects on proteinuria and glomerulosclerosis were shown to partially depend on microbiota homeostasis. Metabolomic analysis demonstrated that JLD significantly upregulated the vitamin B6 metabolic pathway and increased levels of related metabolites, including PM and pyridoxine (PN). Metagenomic analyses indicated that JLD remodeled the gut microbiota composition and enriched pathways related to cofactor biosynthesis, and markedly increased the relative abundance of key enzyme genes involved in the de novo (DXP-dependent) vitamin B6 biosynthesis pathway - namely pdxJ, pdxB, dxs and dxr. Genes related to vitamin B6 activation and conversion (pdxH, aldH) showed no significant changes, suggesting that JLD may promote PM accumulation by enhancing the microbiota's capacity for vitamin B6 biosynthesis rather than its subsequent activation/conversion. Source-tracking pinpointed Paramuribaculum intestinale as the core functional species. In vitro culture experiments showed that JLD markedly promoted the growth of this strain and elevated PM production, and that the strain's conditioned culture medium effectively inhibited formation of advanced glycation end-products (AGEs). Notably, direct supplementation with PM recapitulated the renoprotective effects of JLD in vivo. Mechanistically, PM inhibited the AGEs-RAGE-NF-&#x3ba;B-AP-1 axis and TGF-&#x3b2; receptor signaling, thereby suppressing NF-&#x3ba;B-driven inflammation and Smad2-mediated fibrosis.<br><br>CONCLUSION: JLD remodels the gut microbiota and enhances its de novo vitamin B6 biosynthetic capacity, leading to accumulation of PM. Gut-derived PM enters the circulation and functions as an effector molecule targeting the kidney; through PM's direct carbonyl-trapping activity it scavenges AGEs and suppresses the AGEs-RAGE axis as well as downstream inflammatory and profibrotic signaling, thereby exerting renoprotective effects. This study reveals PM as a microbially derived metabolite with therapeutic potential in DKD and offers a new metabolism-directed strategy for DKD treatment.}, }
@article {pmid41485442, year = {2026}, author = {Ma, C and Liu, Y and Zeng, T and Li, X and Tan, X and Ma, X and Lu, X and Wang, Y and Wu, X}, title = {Zexie-Baizhu herb pair attenuates MASH via the gut-liver Axis by suppressing NLRP3 Inflammasome activation and M1-macrophage polarization.}, journal = {Bioorganic chemistry}, volume = {169}, number = {}, pages = {109451}, doi = {10.1016/j.bioorg.2025.109451}, pmid = {41485442}, issn = {1090-2120}, mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; Animals ; *Inflammasomes/metabolism/antagonists &amp; inhibitors ; Mice ; *Macrophages/drug effects/metabolism ; *Drugs, Chinese Herbal/pharmacology/chemistry ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects ; *Liver/drug effects/metabolism ; Male ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; Molecular Structure ; }, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD lacking effective treatments, may be therapeutically targeted by the Traditional Chinese Medicine herb pair Zexie-Baizhu (ZB), known for its lipid-modulating and anti-inflammatory properties. This study investigated ZB's effects and mechanisms in diet-induced MASH mouse models. We began by identifying potential active ingredients in ZB using UPLC-MS/MS. When administered preventively over an 8-week period, ZB significantly improved serum lipids, reduced hepatic inflammation, and alleviated liver lipid accumulation. Mechanistic studies revealed that ZB restores beneficial gut microbiota, enhances intestinal barrier integrity, modulate the hepatic bile acid receptor FXR signaling pathway to regulate bile acid metabolism, and crucially suppresses NLRP3 inflammasome activation and M1 macrophage polarization. Fecal microbiota transplantation confirmed the role of gut microbiota modulation. Collectively, these results demonstrate that ZB alleviates MASH progression primarily via the gut-liver axis by inhibiting NLRP3 inflammasome and M1 macrophage polarization, highlighting this axis as a promising therapeutic target.}, }
@article {pmid41485542, year = {2026}, author = {Allani, M and Nath, G and Juyal, G and Chandra Joshi, M and Tiwari, V}, title = {Fecal microbiota transplantation attenuates neuropathic pain in rats via gut microbiota-mediated immunomodulation of ion channels and nociceptors.}, journal = {Microbial pathogenesis}, volume = {212}, number = {}, pages = {108275}, doi = {10.1016/j.micpath.2026.108275}, pmid = {41485542}, issn = {1096-1208}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; *Neuralgia/therapy/microbiology ; Rats ; *Nociceptors/metabolism/immunology ; Male ; Rats, Sprague-Dawley ; *Immunomodulation ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/therapy/microbiology ; Ganglia, Spinal ; TRPA1 Cation Channel/metabolism ; TRPM Cation Channels/metabolism ; Hyperalgesia/therapy ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {INTRODUCTION: Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.<br><br>OBJECTIVES: This study aimed to determine the relationship between gut microbiota and neuropathic pain using fecal microbiota transplantation (FMT) in rats with chronic constriction injury (CCI). Additionally, it sought to identify microbial species associated with pain modulation.<br><br>METHODS: CCI was performed in wildtype and antibiotic-treated pseudo-germ-free (PGF) rats. FMT was performed using fecal matter slurry from healthy (hFMT) and CCI-dysbiotic (dFMT) donors, transplanted into nerve-injured and healthy rats, respectively. Pain-related behaviors were assessed and microbial composition was analyzed via 16sRNA sequencing. Western blot and RT-PCR assays were conducted on dorsal root ganglion (DRG) and spinal cord tissues.<br><br>RESULTS: CCI induced gut microbial dysbiosis, characterized by increased Proteobacteria and Fusobacteriota and decreased Actinobacteria. hFMT from healthy rats alleviated mechanical, thermal, and cold hyperalgesia but did not reverse mechanical allodynia in CCI rats. Conversely, dFMT from CCI rats induced pain-like hypersensitivity in healthy rats, mimicking nerve injury effects. Correlation analysis identified microbial species linked to pain modulation: Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger were associated with reduced pain behaviors, while Pasteurellaceae bacterium, Bacillus sp., and Staphylococcus arlettae were linked to nerve injury-induced dysbiosis. hFMT restored claudin-5 and anti-inflammatory markers TGF-&#x3b2; and IL-10 while downregulating pain-related proteins TRPM8, Nav 1.8, Nav 1.7, and TRPA1 in CCI rats. In contrast, dFMT promoted neuroinflammation by increasing IBA1, TNF-&#x3b1;, and IL-1&#x3b2;, leading to microglial activation in healthy rats.<br><br>CONCLUSION: Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger could serve as a promising alternative for managing neuropathic pain.}, }
@article {pmid41485840, year = {2026}, author = {Jurgiel, J and Gromowski, T and Król, J and Bomba-Opoń, D and Kościółek, T and Wielgoś, M}, title = {The impact of maternal microbial transfer on the infant gut microbiome after cesarean delivery: a systematic review.}, journal = {American journal of obstetrics and gynecology}, volume = {233}, number = {6S}, pages = {S541.e1-S541.e16}, doi = {10.1016/j.ajog.2025.09.001}, pmid = {41485840}, issn = {1097-6868}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cesarean Section ; Female ; Infant, Newborn ; Pregnancy ; *Fecal Microbiota Transplantation ; Vagina/microbiology ; Bacteroides ; Lactobacillus ; Bifidobacterium ; }, abstract = {OBJECTIVE: To systematically review the results of maternal microbial transfer in shaping microbial diversity, improving neonatal development, and evaluating the microbial transfer procedure's adverse events.<br><br>DATA SOURCES: A comprehensive search was conducted on April 25, 2024, using PubMed/MEDLINE, Academic Search Ultimate, and ClinicalTrials.gov for studies published in English from 2000 to 2023. The following keywords were used: "vaginal seeding," "microbiota," "maternal fecal microbiota transplantation," "maternal microbial transfer," and "bacterial baptism."<br><br>STUDY ELIGIBILITY CRITERIA: The review included English-language, peer-reviewed randomized controlled trials and nonrandomized interventional studies investigating maternal microbial transfer in neonates born via elective cesarean delivery.<br><br>Data were extracted and analyzed for key outcomes, including severe adverse effects, alpha diversity, beta diversity, and the abundance of key taxa such as Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp.<br><br>RESULTS: A total of 10 studies, including 4 randomized controlled trials and 6 nonrandomized interventional studies with 1450 participants, were included in this qualitative review. The findings regarding changes in alpha diversity (a measure of microbial richness within individual samples) were inconclusive, while several studies indicated a potential increase in beta diversity (reflecting differences in microbial composition between samples) associated with the procedure. Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp. were the most frequently assessed taxa, with some studies suggesting beneficial changes in their abundance. Developmental outcomes, such as anthropometric measures and allergy risks, showed limited evidence of benefit, with one study reporting preliminary findings of improved neurodevelopmental scores. No significant increase in severe adverse effects was observed in any of the included studies.<br><br>CONCLUSION: The efficacy of maternal microbial transfer in restoring neonatal microbiota and promoting health outcomes remains uncertain, with neonatal outcomes addressed in only 3 of the included studies-one on allergy and one on neurodevelopment. However, while no serious adverse effects have been consistently reported, data on safety remain limited.}, }
@article {pmid41486262, year = {2026}, author = {Wu, J and Xiu, M and Wang, X and Zhang, P and Qin, Y and Li, J and Jiang, X and Duan, Y and Liu, Y and He, J}, title = {Dunhuang Gancao Fuling Xingren decoction and its components alleviate CPT-11 induced intestinal mucositis by regulating gut microbiota related innate immunity and inflammatory response in Drosophila and mice.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {4}, pmid = {41486262}, issn = {1749-8546}, support = {DHYX24-15//Foundation from Key Laboratory of Dunhuang Medicine/ ; 2024-QN-35//Lanzhou Youth Science and Technology Talent Innovation Project/ ; 25JRRA1177//Natural Science Foundation of Gansu Province/ ; 25JRRA303//Gansu Natural Science Foundation/ ; }, abstract = {BACKGROUND: Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.<br><br>PURPOSE: To investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using&#xa0;Drosophila melanogaster&#xa0;and C57BL/6&#xa0;J mouse models.<br><br>METHODS: The therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H&amp;E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC-MS), and their efficacy was validated in CPT-11-treated&#xa0;Drosophila.<br><br>RESULTS: GFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus,&#xa0;Prevotella) and reducing pathogens (Bacteroides,&#xa0;Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury.<br><br>CONCLUSIONS: GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.}, }
@article {pmid41486395, year = {2026}, author = {Hajjar, R and Mars, RAT and Kashyap, PC}, title = {Harnessing the microbiome for cancer therapy.}, journal = {Nature reviews. Microbiology}, volume = {24}, number = {6}, pages = {392-407}, pmid = {41486395}, issn = {1740-1534}, support = {R01 DK114007/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/therapy/microbiology ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Prebiotics/administration &amp; dosage ; *Microbiota ; Fecal Microbiota Transplantation ; Tumor Microenvironment ; Animals ; }, abstract = {The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.}, }
@article {pmid41487047, year = {2026}, author = {Xie, W and Wang, X and Liu, Y and Cai, L and Song, B and Zhang, S and Shao, Y and Wang, W and Xue, X and Li, J and Cui, W and Jiang, Y and Wang, X and Tang, L}, title = {Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {1}, pages = {647-662}, doi = {10.1021/acs.jafc.5c08687}, pmid = {41487047}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Ursodeoxycholic Acid/metabolism ; Swine ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Mice ; Colon/immunology/microbiology ; Bile Acids and Salts/metabolism ; Humans ; Fecal Microbiota Transplantation ; Male ; *Swine Diseases/microbiology/immunology ; NF-kappa B/immunology/genetics ; }, abstract = {Microbes in the gut are crucial for host health, yet their role in disease resistance remains unclear. Using fecal microbiota transplantation from disease-resistant Min pigs to Duroc × Landrace × Yorkshire (DLY) pigs, combined with 16S rRNA sequencing and metabolomics, we investigated this relationship. The transferred microbiota alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in the DLY piglets. Key bacterial genera and bile acid metabolites have been identified, with in vitro evidence showing that the gut microbiome can convert bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA). Subsequent mechanistic validation in a mouse model demonstrated that UDCA acts via the gut-liver axis on the farnesoid X receptor, inhibiting PI3K/AKT/NF-κB pathways and reducing inflammatory responses, thereby preserving tissue structure in the liver and colon. These findings establish a causal link between gut microbiota and disease resistance, indicating that targeting microbial bile acid metabolism may restore intestinal and hepatic health.}, }
@article {pmid41488302, year = {2025}, author = {Liu, S}, title = {Mechanisms of gut microbiota in host fat deposition: metabolites, signaling pathways, and translational applications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1675155}, pmid = {41488302}, issn = {1664-302X}, abstract = {Obesity and metabolic diseases are global health challenges, with gut microbiota playing a critical role in host fat deposition through symbiotic interactions. In recent years, the gut microbiota, as an important factor regulating fat deposition, has received widespread attention. Numerous studies have confirmed that gut microbes influence host fat accumulation by regulating energy metabolism, inflammatory response, and gut barrier function. In this review, we summarized the key roles of gut microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, lipopolysaccharides (LPS), branched-chain amino acids (BCAAs), and trimethylamine N-oxide (TMAO) in host epigenetic regulation and lipid metabolism, and explored their regulatory mechanisms through mediated signaling pathways, including Wnt/β-catenin signaling pathway, transforming growth factor beta/SMAD3 pathway (TGF-β/SMAD3), peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In terms of translational applications, we described the research progress and application potentials of intervention strategies, such as probiotics, prebiotics, synbiotics, postbiotics, and fecal transplantation in obesity control and animal production. Finally, we proposed the current bottlenecks and translational challenges in obesity control by precision nutrition and microecological intervention, and look forward to future directions. This review provides a theoretical basis for the in-depth understanding of the interactions between gut microbiota and host metabolism, and serves as a reference for the prevention and control of metabolic diseases by developing nutritional intervention strategies for animals.}, }
@article {pmid41488304, year = {2025}, author = {Duan, Y and Li, X and Chai, Y and Chen, H and Hou, H}, title = {Adlercreutzia-modulated polyunsaturated fatty acid metabolism underlies nicotine's anti-obesity effects.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1682370}, pmid = {41488304}, issn = {1664-302X}, abstract = {BACKGROUND: The regulatory effects of nicotine on energy balance through central and peripheral mechanisms have been reported. However, its impact on obesity and gut microbiota at safe doses remains unclear.<br><br>RESULTS: In this study, it was found that chronic oral nicotine administration daily at relative low dose (0.5 mg/kg) significantly alleviated high-fat diet (HFD)-induced obesity phenotypes in mice, including body weight gain, fat deposits, hepatic steatosis, inflammation and metabolic dysfunction. Gut microbiota depletion and fecal microbiota transplantation (FMT) confirmed that these beneficial effects were microbiota-dependent. Metagenomic sequencing confirmed that nicotine administration reshaped gut microbiota composition, and specifically enriched the commensal genus Adlercreutzia, whose increased abundance correlated with improved biochemical indicators related to obesity. Furthermore, transplantation of Adlercreutzia reproduced anti-obesogenic effects, suggesting it was a key factor for nicotine reducing HFD-induced obesity. Untargeted metabolomics analysis combined association analysis further demonstrated that nicotine modulated host metabolic profiles via gut microbiota-metabolite axis, particularly enhancing Adlercreutzia-linked lipid metabolites involved in polyunsaturated fatty acid (PUFA) metabolism.<br><br>CONCLUSION: Collectively, our study elucidates the critical involvement of gut microbiota in nicotine-induced obesity amelioration, uncovers a novel Adlercreutzia-PUFA metabolic axis mediating nicotine's anti-obesity effects, and highlight Adlercreutzia potentiation as a promising microbiota-directed invention strategy for obesity and metabolic syndrome.}, }
@article {pmid41488894, year = {2025}, author = {Lin, B and Zhu, Z and Yang, X and Li, Z and Zhou, H and Luo, M and Guan, J and Zou, Y and Chen, H and Zhuang, Z and Meng, S and Li, W and Yang, Q and Dai, D}, title = {Protocol for the efficacy and safety of fecal microbiota transplantation in children with autism spectrum disorder: a prospective single-center, single-arm interventional study.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1660773}, pmid = {41488894}, issn = {2296-2360}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 0.7% of children globally, with 90% experiencing comorbid gastrointestinal (GI) symptoms. Fecal microbiota transplantation (FMT) may modulate ASD symptoms via the microbiota-gut-brain axis (MGBA).<br><br>METHODS: This open-label single-arm trial enrolls 30 children (2-12 years) with moderate-to-severe ASD, defined as a Childhood Autism Rating Scale (CARS) score of &#x2265;36. Participants receive 3 nasojejunal FMTs (5&#x2005;mL/kg) over 5 days. The primary outcomes are GI symptom improvement, assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and ASD severity, assessed using the CARS. Secondary outcomes include social responsiveness (Social Responsiveness Scale, SRS), aberrant behaviors (Aberrant Behavior Checklist, ABC), and gut microbiota changes assessed by metagenomic next-generation sequencing (mNGS).<br><br>ETHICS AND DISSEMINATION: Ethical approval obtained from Shenzhen Children's Hospital Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=229136, identifier ChiCTR2400083998. Registered on 2024-05-08. Registered title: "Efficacy and safety of fecal microbiota transplantation in treatment of autism spectrum disorder: a prospective single-center intervention study".}, }
@article {pmid41490238, year = {2026}, author = {Ni, S and Chen, K and Wang, H and Chen, S and Qiu, Y and Wang, T and Mo, F and Wang, S and Li, B and Bai, Y and Zhao, J and Zhai, X and Li, Z}, title = {A new paradigm of bidirectional regulation of the gut-spinal cord axis.}, journal = {Neural regeneration research}, volume = {21}, number = {9}, pages = {4100-4111}, doi = {10.4103/NRR.NRR-D-25-01016}, pmid = {41490238}, issn = {1673-5374}, abstract = {The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut-spinal cord axis, rather than being fully explained by the conventional gut-brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut-spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut-spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut-spinal cord axis provides a conceptual shift that extends beyond the gut-brain framework.}, }
@article {pmid41490547, year = {2026}, author = {Wang, Y and He, Y and Xie, J and Li, J and Guo, J}, title = {Escherichia coli Nissle 1917 Modulates the RNF150/ELAVL1 Ubiquitination Pathway to Ameliorate Obesity-driven Insulin Resistance in High-fat Diet-fed Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {20}, number = {5}, pages = {101719}, pmid = {41490547}, issn = {2352-345X}, mesh = {Animals ; *Insulin Resistance ; Diet, High-Fat/adverse effects ; *Obesity/etiology/metabolism/therapy ; Mice ; Male ; Ubiquitination ; *Ubiquitin-Protein Ligases/metabolism/genetics ; Gastrointestinal Microbiome ; Humans ; *ELAV-Like Protein 1/metabolism/genetics ; Mice, Inbred C57BL ; *Escherichia coli ; Macrophages/metabolism ; *Probiotics/pharmacology/administration &amp; dosage ; Mice, Knockout ; Fecal Microbiota Transplantation ; Adipose Tissue/metabolism ; Disease Models, Animal ; }, abstract = {BACKGROUND &amp; AIMS: Obesity, a global epidemic, fuels metabolic dysfunction through complex gut microbiota‒immune system crosstalk. The probiotic Escherichia coli Nissle 1917 (EcN) holds promise for alleviating obesity-related complications, yet its mechanistic underpinnings remain unclear. This study explored the therapeutic potential of EcN, focusing on its ability to regulate the ring finger protein 150 (RNF150)/embryonic lethal abnormal vision-like 1 (ELAVL1) axis in macrophages to counter high-fat diet (HFD)-induced obesity and insulin resistance.<br><br>METHODS: We employed a 12-week dietary intervention in male C57BL/6J mice and administered EcN. Fecal microbiota transplantation (FMT) and myeloid-specific RNF150 and ELAVL1 knockout models were used to establish mechanistic causality. The gut microbiota composition was analyzed via 16S rRNA sequencing, whereas metabolic parameters, adipose tissue inflammation, and RNF150/ELAVL1 interactions were assessed via glucose/insulin tolerance tests, immunohistochemistry, Western blotting, coimmunoprecipitation, and ubiquitination assays. RNF150 expression was also evaluated in adipose tissue and peripheral blood mononuclear cells from overweight and normal-weight human subjects.<br><br>RESULTS: EcN treatment significantly reduced HFD-induced weight gain, adipose accumulation, and insulin resistance while restoring the gut microbiota balance (decreased the Firmicutes/Bacteroidetes ratio and increased Muribaculaceae). FMT from EcN-treated mice recapitulated these benefits. EcN attenuated inflammation across the liver, adipose, and colon, reducing proinflammatory cytokine levels and macrophage infiltration. RNF150 was upregulated in HFD-fed mice and human overweight samples but downregulated by EcN. Myeloid RNF150 deletion mirrored the effects of EcN, promoting anti-inflammatory M2 macrophages and insulin sensitivity. RNF150 mediated ELAVL1 ubiquitination and degradation, whereas ELAVL1 stabilization enhanced anti-inflammatory responses. Myeloid ELAVL1 deletion worsened metabolic outcomes.<br><br>CONCLUSIONS: EcN ameliorates obesity and insulin resistance by modulating the gut-adipose axis via RNF150/ELAVL1 in macrophages, suggesting novel therapeutic targets for metabolic disorders.}, }
@article {pmid41490552, year = {2026}, author = {Ren, L and Chen, P and Xu, S and Liang, J and Wang, Y and Lin, C and Yu, Y and Li, Y}, title = {Gut microbiota-based bile acid metabolism mediates the intestinal barrier protection of Phellodendri chinensis Cortex polysaccharide against ulcerative colitis.}, journal = {Journal of ethnopharmacology}, volume = {360}, number = {}, pages = {121143}, doi = {10.1016/j.jep.2025.121143}, pmid = {41490552}, issn = {1872-7573}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/microbiology/metabolism/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; *Polysaccharides/pharmacology/isolation &amp; purification/therapeutic use ; Mice ; Male ; Mice, Inbred C57BL ; Intestinal Mucosa/drug effects/metabolism/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Colon/drug effects/pathology/metabolism/microbiology ; *Phellodendron/chemistry ; }, abstract = {Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is marked by the occurrence of colonic mucosal damage and immune system dysfunction. A notable challenge in the management of UC is the paucity of long-term effective and safe medications. Phellodendri Chinensis Cortex polysaccharide (PCP), one of the main bioactive compounds in Phellodendri Chinensis Cortex, exerts anti-inflammatory and immunomodulatory effects. However, the effects and mechanisms of PCP on mice with ulcerative colitis remain unclear.<br><br>AIM OF THE STUDY: This study explores that PCP attenuates colitis mice via regulation of gut microbiota and bile acid metabolism.<br><br>MATERIALS AND METHODS: Monosaccharide composition, molecular weight analysis, infrared spectroscopy, scanning electronic microscopy was used to analyze the chemical characterization of PCP. Mice were administrated by 3&#xa0;% DSS for establishment of ulcerative colitis model and treated with PCP for 7 days. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) experiments was performed to evaluate the effect of gut microbiota in PCP-treated colitis mice. Targeted metabolomics analysis of bile acids (BAs) and in vivo inhibition of FXR were performed to analyze the key b BAs and key mechanism of PCP in colitis mice.<br><br>RESULTS: PCP alleviated colitis-associated symptoms, repaired, injured intestinal barrier and promoted FXR activation in DSS-induced colitis mice. 16S rRNA gene sequencing found that PCP increased beneficial microbiota such as Bifidobacterium and Lactobacillus, while reducing pathogenic microbiota such as Bacteroides and Romboutsia in colitis mice. FMT experiment confirmed that PCP improved colitis mice and enhanced intestinal barrier integrity through gut microbiota. Simultaneously, PCP altered BA profiles, notably reducing the ratios of primary to secondary BAs and conjugated to unconjugated BAs, with a particularly pronounced effect on the T&#x3b1;MCA/&#x3b1;MCA ratio. Finally, FXR antagonist Gly-&#x3b2;-MCA reversed the protect effect of PCP against colitis.<br><br>CONCLUSION: Taken together, our study demonstrates that PCP alleviates DSS-induced colitis symptoms and restores intestinal barrier by gut microbiota-BA metabolism-FXR axis.}, }
@article {pmid41490838, year = {2026}, author = {Gao, W and Yan, S and Zhang, L and Chen, L and Che, J and Huang, W and Chen, Y and Liu, A and Zhu, Y and Yang, Y and Peng, Z and Tan, C and Schnabl, B and Hou, X and Yang, L and Chu, H}, title = {Escherichia coli expressing the kpsM gene exacerbates drug-induced liver injury through up-regulating α1,2-fucosyltransferase and disturbing the host taurine metabolism-from animal models and clinical studies.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.012}, pmid = {41490838}, issn = {2090-1224}, abstract = {BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Patients with DILI have disorders of the gut microbiota, yet little is known about the influence of gut microbes on this disease. Herein, we investigated the alterations of gut microbiota in DILI patients, and elucidated the mechanism by which Escherichia coli expressing kpsM gene (kpsM[+]E. coli) exacerbates DILI, in order to provide targets for intervention of related signaling pathways to improve DILI.<br><br>METHODS: Full-length 16S sequencing was performed on fecal samples from a prospective cohort of patients with DILI (n&#xa0;=&#xa0;42). Quantitative PCR was employed for analysis of E. coli and its kpsM gene in human feces. The DILI model was established by intraperitoneal injection of acetaminophen (300&#xa0;mg/kg) into mice (n&#xa0;=&#xa0;5-12). Two hours later, kpsM[+] or kpsM knockout E. coli strains were gavaged to determine their roles during DILI. Intestinal epithelial Fut2 gene knockout mice (Fut2[&#x394;IEC]) and hepatic metabolome were used to assess the pathogenic mechanisms of the kpsM[+]E. coli. Plasma metabolome of DILI patients was further validated the discoveries in mice.<br><br>RESULTS: The percentage of subjects carrying kpsM were 14.7&#xa0;%, 40.0&#xa0;%, 76.5&#xa0;% in healthy controls, patients with mild DILI, and patients with moderate-to-severe DILI, respectively. Mice transplanted with kpsM[+]E. coli exhibited more severe DILI, primarily achieved through impaired gut barrier function and enhanced expression of intestinal Fut2. Fut2[&#x394;IEC] mice alleviated the aggravation of DILI caused by E. coli via up-regulating the hepatic levels of taurine and tauroursodeoxycholic acid. In addition, the level of plasma taurine was lower in patients with moderate-to-severe DILI than in those with mild DILI.<br><br>CONCLUSIONS: The kpsM[+] E. coli was associated with the severity of DILI in human. This strain can exacerbate DILI in mice through up-regulating intestinal Fut2 expression and disrupting taurine metabolism.}, }
@article {pmid41491103, year = {2026}, author = {Bryant, JA and Vulić, M and Walsh, EA and Allen, EG and Beauchemin, NJ and Chafee, ME and Diao, L and Fenn, K and Ford, KA and Hasson, BR and Litcofsky, KD and Lombardo, MJ and Martinez, A and O'Brien, EJ and Straub, TJ and Sykes, SM and Marshall, LF and Winkler, JA and McGovern, BH and Ford, CB and Wortman, JR and Henn, MR}, title = {The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome.}, journal = {Nature medicine}, volume = {32}, number = {1}, pages = {186-196}, pmid = {41491103}, issn = {1546-170X}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Clostridium Infections/microbiology/therapy/prevention &amp; control ; Clostridioides difficile/pathogenicity ; Administration, Oral ; Male ; Female ; Double-Blind Method ; Feces/microbiology ; Middle Aged ; Bacillota ; Adult ; *Fecal Microbiota Transplantation/methods ; Aged ; }, abstract = {VOWST (VOWST oral spores, VOS; fecal microbiota spores, live-brpk, formerly SER-109) is an FDA-approved, orally administered consortium of purified Firmicutes spores developed to prevent recurrent Clostridioides difficile infection (CDI). Although 86.7% (26/30) of patients with recurrent CDI did not experience a subsequent recurrence over 8 weeks in an open-label phase 1b study, a subsequent double-blind phase 2 study (NCT02437487) did not demonstrate a significant benefit over placebo (rate of recurrence at 8 weeks in SER-109 versus placebo: 44.1% versus 53.3%). These discordant outcomes were hypothesized to be due to suboptimal dosing. This hypothesis was addressed in a pivotal phase 3 trial (NCT03183128) using an approximately tenfold higher dose. In phase 3, only 12% of VOS-treated patients versus 40% of placebo patients recurred by week 8 (relative risk 0.32, P < 0.001). Here in this follow-up post hoc analysis, across-trial comparisons confirmed that the higher, efficacious phase 3 dose is associated with improved pharmacokinetics, assessed by VOS engraftment (patients with available samples: phase 1b: 28, phase 2: 79, phase 3: 170). In-depth phase 3 analyses revealed that VOS significantly altered microbial composition, significantly enriching the diversity and abundance of Firmicutes species and reducing the prevalence and abundance of C. difficile and opportunistic pathogens (for example, Enterobacteriaceae species). Consistent with these taxonomic changes, significant changes in key bioactive metabolites were observed, including depletion of conjugated and deconjugated primary bile acids, enrichment of secondary bile acids and increases in short-chain and medium-chain fatty acids. In vitro, VOS batches produced these C. difficile-inhibiting metabolites. These findings on the pharmacology of VOS underscore the importance of rapidly restoring key protective functions of the microbiome in patients with recurrent CDI to achieve durable prevention of recurrence, as observed in the phase 3 study; they also highlight the need to include the microbiome in the clinical management of CDI. ClinicalTrials.gov registrations: NCT02437487 and NCT03183128 .}, }
@article {pmid41491927, year = {2026}, author = {Yao, T and Xiong, Y and Hu, Q and Chen, Y and Li, D and Yan, J and Yang, J and Wang, Y and Cao, H and Zhang, F and Zhuang, R and Sun, J}, title = {Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41491927}, issn = {1471-2180}, support = {2023YFF1104301//National Key R&amp;D Program of China/ ; BK20241756//Basic Research Program of Jiangsu/ ; HB2023063//Medical Key Discipline Program of Wuxi Health Commission/ ; KX-25-A14; KX-25-C108//The Soft Science Project of Wuxi Science and Technology Association/ ; }, abstract = {BACKGROUND: Gestational diabetes mellitus (GDM) is an important risk factor for metabolic diseases such as obesity in its offspring, and this effect may be mediated by altering the infant’s gut microbiota.<br><br>METHODS: Fecal samples from offspring born to mothers with GDM (G-O, n&#x2009;=&#x2009;29) and non-GDM mothers (C-O, n&#x2009;=&#x2009;30) was collected and analyzed by 16&#xa0;S rRNA gene sequencing. Subsequently, two types of infant fecal microbiota were transplanted into pseudo-sterile mouse models maintained on normal diet (ND) and high-fat diet (HFD) for 16 weeks, to investigate the relationship between the fecal microbiota of offspring of GDM and the risk of diseases such as obesity and dysglycemia in their later life.<br><br>RESULTS: Significant differences in gut microbial composition between G-O and C-O (p&#x2009;<&#x2009;0.05). Fecal microbiota transplantation (FMT) from G-O resulted in obesity, hypertrophy of adipocytes in white adipose tissue (WAT), and abnormal glucose tolerance compared to mice that received FMT from C-O. The 16&#xa0;S rRNA sequencing results showed that under ND, the abundance of the potentially pathogenic bacteria Eubacterium_nodatum_group and Lachnoclostridium was significantly increased in the FMT from G-O group, while the abundance of the beneficial bacteria Acetatifactor, Muribaculum, and Lactobacillus was significantly decreased (all p&#x2009;<&#x2009;0.05). Further analysis showed that fecal isobutyrate levels were significantly lower in the FMT from G-O group compared to the FMT from C-O group (p&#x2009;<&#x2009;0.05). In addition, under HFD, the FMT from G-O group enriched the abundance of Alistipes, Rikenellaceae_RC9_gut_group, Rikenella, and Bilophila, while the abundance of Akkermansia, Faecalibaculum, and Lactobacillus showed a decrease (all p&#x2009;<&#x2009;0.05). Meanwhile, the fecal acetate content in the FMT from G-O group was significantly higher than that in the FMT from C-O group (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: Mothers with GDM are associated with significant gut microbiota dysbiosis in G-O, and transplantation of G-O fecal microbiota is associated with increased fat accumulation and impaired glucose tolerance in mice Therefore, the gut microbiota dysbiosis in G-O is associated with later-life growth abnormalities and increased disease risk, suggesting a potential role in this association.<br><br>GRAPHICAL ABSTRACT: This study focused on the impact of gestational diabetes mellitus (GDM) on offspring&#x2019;s long-term health, especially the role of the gut microbiota in infant feces. Fecal samples were collected from offspring born to mothers with (G-O) and without GDM(C-O) and analysed changes in the gut microbiota in infant feces using 16&#xa0;S rRNA sequencing; A pseudo-sterile mouse model was established by administering water containing antibiotics; FMT of the gut microbiota in infant feces from C-O and G-O was given by gavage to pseudo-sterile male C57BL/6 mice, which were fed either ND or HFD daily for 16 weeks. The results demonstrated significant differences in gut microbiota between mice receiving FMT from C-O and G-O, regardless of whether they were maintained on ND or HFD. Under ND, FMT from G-O results in increased body weight, hypertrophy of adipocytes in both iWAT and eWAT, and impaired glucose tolerance compared to those FMT with C-O. 16&#xa0;S rRNA sequencing revealed a significant increase in the abundance of potentially pathogenic bacteria, including Eubacterium_nodatum_group and Lachnoclostridium, in mice receiving FMT from G-O. Conversely, the abundance of beneficial bacteria such as Acetatifactor, Muribaculum, and Lactobacillus was significantly reduced. Further analyses indicated that isobutyrate levels were markedly lower in the feces of mice receiving FMT from G-O transplants compared to those receiving FMT from C-O. Under HFD, mice receiving FMT of the gut microbiota in infant feces from G-O exhibited increased body weight and eWAT, hypertrophy of iWAT adipocytes, and impaired glucose tolerance. In addition, these mice showed an increased abundance of Alistipes, Rikenellaceae_RC9_gut_group, Rikenella and Bilophila in their feces compared to those transplanted with feces from C-O; conversely, the abundance of Akkermansia, Faecalibaculum and Lactobacillus was significantly reduced, while the concentration of acetate in the feces was significantly increased. This study provides a scientific basis for exploring the association between gut microbiota and the intergenerational effects of GDM, with further mechanistic studies needed to clarify the underlying pathways. [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04591-3.}, }
@article {pmid41492376, year = {2026}, author = {Huang, L and Zheng, Y and Liu, Q and Feng, Y and Ma, Z and Zhao, X and Wei, X and Yu, X and Lv, X and Lv, J and Li, L and Liu, H and Ze, X and Zhang, M}, title = {Milk fat globule membrane ameliorates depressive-like behaviors in chronic unpredictable mild stress rats by modulating the microbiota-gut-brain axis.}, journal = {Bioscience of microbiota, food and health}, volume = {45}, number = {1}, pages = {66-78}, pmid = {41492376}, issn = {2186-6953}, abstract = {Depression is one of the common psychiatric disorders, and it has been reported that the imbalance in the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Milk fat globule membrane (MFGM) can impact the gut-brain axis by regulating the intestinal flora and metabolite production. The aim of this study was to investigate whether MFGM could ameliorate depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) and further elucidate the potential mechanism through a fecal microbiota transplantation (FMT) experiment. Male Sprague-Dawley rats were provided with an MFGM diet for 5 weeks after the induction with CUMS. Depressive-like behaviors were assessed, and the levels of neurotransmitters, neuroendocrine hormones, microbiota, short-chain fatty acids (SCFAs), and tight junction proteins, including occludin and zonula occludens-1 (ZO-1), were measured. It was revealed that MFGM could alleviate the depressive-like behaviors in CUMS rats. MFGM up-regulated the expression of occludin and ZO-1 and ameliorated intestine pathological changes in CUMS rats. Moreover, MFGM increased the levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine and decreased the levels of neuroendocrine hormones in CUMS rats. Furthermore, it was confirmed that the concentrations of SCFAs, DA, 5-HT, and tight junction proteins significantly increased in the recipient rats that were inoculated with the fecal microbiota from the rats after MFGM treatment. These findings demonstrated that MFGM could alleviate depressive-like behaviors in CUMS rats and was possibly associated with modulation of the gut microbiota and up-regulation of SCFAs and monoamine neurotransmitters.}, }
@article {pmid41492974, year = {2026}, author = {Qiu, Y and Lyu, X and Zhang, D and Xu, H and He, X and Chen, J and Liu, H and Liu, Y and Xie, L}, title = {Gut Microbiota in Pulmonary Arterial Hypertension: Murine Models and Human Microbial Signatures, Pathogenic Mechanisms, and Emerging Therapeutic Avenues.}, journal = {Comprehensive Physiology}, volume = {16}, number = {1}, pages = {e70094}, doi = {10.1002/cph4.70094}, pmid = {41492974}, issn = {2040-4603}, support = {U21A20333//National Natural Science Foundation of China/ ; 2023YFC2705701//National Key Research and Development Program of China/ ; XZ202501ZY0116//Science and Technology Projects of Xizang Autonomous Region/ ; XZ202401ZY0013//Science and Technology Projects of Xizang Autonomous Region/ ; 2023NSFSC0530//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Pulmonary Arterial Hypertension/microbiology/therapy/metabolism ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Pulmonary arterial hypertension (PAH) is a chronic, severe cardiopulmonary disease characterized by the progressive increase in pulmonary vascular resistance (PVR) because of the proliferation and fibrosis of the pulmonary arterioles. Although the disease originates in the pulmonary vasculature, it ultimately leads to right heart failure and death. PAH is associated with high mortality rates and poor prognosis, with no therapies currently available to reverse pulmonary vascular remodeling, imposing substantial socioeconomic burdens. Growing interest in the gut-lung axis has highlighted the role of gut microbiota and their metabolites in the occurrence and development of PAH. Evidence showed that gut dysbiosis and metabolite imbalances, involving reduced short-chain fatty acids (SCFAs), increased trimethylamine-N-oxide (TMAO), and dysregulated tryptophan metabolism, contributed to pulmonary vascular remodeling. This review systematically compares gut microbiota and metabolites across PAH murine models (including chronic hypoxia, SU5416/hypoxia [SuHx], monocrotaline [MCT], and non-classical models) and patients (adults and children). The analysis aims to identify disease-specific microbial and metabolic signatures. It is also discussed how the microbiota and their metabolites may influence inflammation around the pulmonary vasculature. Furthermore, the potential of probiotic therapy, fecal microbiota transplantation (FMT), and mesenchymal stem cells (MSCs) therapies as novel treatment strategies for PAH is discussed.}, }
@article {pmid41493848, year = {2026}, author = {Kawaguchi, Y and Terui, K and Fumita, T and Shibata, R and Yoshizawa, H and Ogasawara, S and Kondo, T and Ozawa, Y and Inaba, Y and Hishiki, T}, title = {Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial.}, journal = {Hepatology communications}, volume = {10}, number = {1}, pages = {}, pmid = {41493848}, issn = {2471-254X}, mesh = {Humans ; Male ; Female ; *Bezafibrate/therapeutic use/administration &amp; dosage ; *Biliary Atresia/complications/surgery ; *Cholestasis/drug therapy/etiology ; Prospective Studies ; Adult ; *Hypolipidemic Agents/therapeutic use/administration &amp; dosage ; Young Adult ; Adolescent ; Alkaline Phosphatase/blood ; Liver ; Treatment Outcome ; Survivors ; gamma-Glutamyltransferase/blood ; }, abstract = {BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study.<br><br>METHODS: In this single-center, single-arm, open-label, uncontrolled, prospective phase II trial, patients were enrolled from a central registry system at the Chiba University Data Center. Postoperative patients (n=10) aged older than 18 years (median age, 29&#xa0;y) with BA and increased serum ALP levels were enrolled between July 2021 and March 2022. Patients with high total bilirubin or alanine aminotransferase levels, recent changes in BA medication, cholangitis within 3 months, renal dysfunction, or liver transplantation were excluded. Participants were administered 400&#xa0;mg BZF orally in 2 daily doses for 12 weeks and subsequently underwent a 12-week observation. Other drugs were continued. The primary endpoint was the change in ALP levels after 12 weeks of oral BZF administration. The secondary and exploratory endpoints were changes in gamma-glutamyl transpeptidase and triglyceride levels, fecal microbiota, and bile acids.<br><br>RESULTS: The mean change in the ALP level was -67&#xa0;U/L (&#xb1;20&#xa0;U/L; p=0.0042). Changes in ALP and gamma-glutamyl transpeptidase levels differed between week 0 and week 6. Adverse events occurred in 5 patients. BZF administration increased the number of Fusicatenibacter without affecting microbiome diversity or bacterial phylum abundance while decreasing lithocholic acid levels and increasing chenodeoxycholic acid levels.<br><br>CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.}, }
@article {pmid41494100, year = {2026}, author = {Wang, D and Dai, S and Li, D and Du, P and Zhao, Y and Chen, Y and Ye, Y and Zhou, M and Ren, W and Liu, X and Zhao, B}, title = {Bovine Milk-Derived Extracellular Vesicles Attenuate Liver Injury by Modulating the Gut-Liver Axis via Faecalibaculum-Mediated SCFA Production.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {2}, pages = {2157-2171}, doi = {10.1021/acs.jafc.5c12208}, pmid = {41494100}, issn = {1520-5118}, mesh = {Animals ; *Extracellular Vesicles/metabolism/chemistry ; Gastrointestinal Microbiome ; *Milk/chemistry/metabolism ; *Fatty Acids, Volatile/metabolism/biosynthesis ; *Liver/metabolism/injuries/microbiology/drug effects ; Cattle ; Mice ; Male ; Mice, Inbred C57BL ; Humans ; Carbon Tetrachloride/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Chronic liver injury represents a core pathological substrate in a spectrum of hepatic disorders, wherein gut-liver axis homeostasis critically drives progression. Although bovine milk extracellular vesicles (mEVs) positively regulate intestinal homeostasis, the mechanisms underlying their gut microbiota-linked hepatoprotection remain unclear. Herein, we demonstrated that mEVs (0.6 mg/kg/d) effectively alleviated carbon tetrachloride (CCl4, 1 mg/kg)-induced liver injury, as evidenced by reduced hepatic inflammation and fibrosis. Concurrently, mEVs also markedly attenuated colonic barrier disruption and inflammation concomitant with liver injury. Gut microbiota analysis revealed that mEVs notably enriched the relative abundances of Faecalibaculum and Lactobacillus, which correlated positively with mEV-enhanced colonic short-chain fatty acid (SCFA)/free fatty acid receptor (FFAR) signaling. Furthermore, a causal link between the mEV-reshaped gut microbiota and the resulting hepatoprotection was further established via fecal microbiota transplantation (FMT). In summary, these findings revealed that mEVs attenuated liver injury in a gut microbiota-dependent manner, offering valuable insights into microbiota-targeted and mEV-based therapeutic strategies for hepatic disorders.}, }
@article {pmid41494302, year = {2026}, author = {Yi, J and Tang, Y and Chen, Y and Chen, L and Geng, D and Liu, L and Yu, J and Zou, L and Zeng, J and Lan, M and Gao, W and Gao, M}, title = {Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy.}, journal = {Biomaterials}, volume = {329}, number = {}, pages = {123967}, doi = {10.1016/j.biomaterials.2025.123967}, pmid = {41494302}, issn = {1878-5905}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Carbon/chemistry ; *Macrophages/drug effects/metabolism ; *Plant Roots/chemistry ; *Diabetes Mellitus, Experimental/therapy/drug therapy/metabolism ; Mice ; Male ; Mice, Inbred C57BL ; *Pueraria/chemistry ; *Diabetes Mellitus, Type 2/therapy/drug therapy ; Fecal Microbiota Transplantation ; Diet, High-Fat ; }, abstract = {Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root-derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota-metabolite-macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.}, }
@article {pmid41496048, year = {2026}, author = {He, C and Zhou, F and Fang, X}, title = {Meta-analysis of the effectiveness of fecal microbiota transplantation in the treatment of metabolic-associated fatty liver disease: A systematic review based on liver inflammation indicators and fat content.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46886}, pmid = {41496048}, issn = {1536-5964}, support = {jkws202318//Health and Sanitation Scientific Research Project of the Metallurgical Safety and Health Branch of the Chinese Society for Metals/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Randomized Controlled Trials as Topic ; Body Mass Index ; Treatment Outcome ; *Fatty Liver/therapy ; Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy ; Male ; Middle Aged ; Liver/pathology ; }, abstract = {BACKGROUND: Metabolic-associated fatty liver disease (MASLD) affects over 25% of the global population, progressing from hepatic steatosis to fibrosis. Current therapies show limited efficacy, and gut microbiota dysbiosis via the gut-liver axis highlights fecal microbiota transplantation (FMT) as a novel intervention.<br><br>METHODS: Following preferred reporting items for systematic reviews and meta-analyses guidelines, 8 randomized controlled trials were systematically selected from PubMed, Cochrane, Embase, and Web of Science (inception to September 2025). MASLD patients receiving FMT (any protocol) versus standard care were evaluated for alanine aminotransferase (ALT), aspartate aminotransferase (AST), proton density fat fraction, and body mass index (BMI). Risk of bias was assessed using Cochrane ROB 1.0.<br><br>RESULTS: FMT significantly reduced ALT (mean difference [MD]&#x2005;=&#x2005;-6.81, 95% confidence interval [-10.29, -3.33], P&#x2005;=&#x2005;.0001) and AST (MD&#x2005;=&#x2005;-7.13, [-10.45, -3.80], P&#x2005;<&#x2005;.0001) versus standard care. Subgroup analysis revealed greater ALT improvement in patients aged <50 years (MD&#x2005;=&#x2005;-14.00, [-22.79, -5.20], P&#x2005;=&#x2005;.002). Proton density fat fraction decreased markedly (MD&#x2005;=&#x2005;-3.50, [-5.12, -1.87], P&#x2005;<&#x2005;.0001), while BMI showed no significant change (MD&#x2005;=&#x2005;-0.69, [-1.49, 0.11], P&#x2005;=&#x2005;.09).<br><br>CONCLUSION: FMT effectively improves hepatic inflammation and steatosis in MASLD, with age modulating ALT response. Lack of BMI improvement suggests localized liver effects rather than systemic metabolic impact, supporting FMT as a targeted adjunctive therapy.}, }
@article {pmid41496455, year = {2026}, author = {Ramesh, A and Subbarayan, R and Shrestha, R and Adtani, PN}, title = {Exploring Fecal Microbiota Transplantation: Potential Benefits, Associated Risks, and Challenges in Cancer Treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {9}, number = {1}, pages = {e70455}, pmid = {41496455}, issn = {2573-8348}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects/standards ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Tumor Microenvironment/immunology ; Animals ; Immunotherapy/methods ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a groundbreaking strategy for modulating the gut microbiome and improving cancer treatment outcomes. This review synthesizes the current evidence on the role of FMT in oncology, focusing on its potential to enhance the efficacy of immunotherapy, restore microbiome homeostasis, and mitigate cancer-associated complications.<br><br>RECENT FINDINGS: Preclinical and clinical studies have demonstrated that FMT can reprogram the tumor microenvironment, augment immune checkpoint inhibitor responses, and reduce chemotherapy-induced toxicity. However, risks such as pathogen transmission, immune dysregulation, and unintended microbial shifts necessitate rigorous donor screening and a personalized approach. Challenges in standardization, regulatory frameworks, and mechanistic understanding further complicate their clinical translation. Emerging innovations, including precision microbial consortia, synthetic biology, and biomarker-driven strategies, have the potential to address these limitations.<br><br>CONCLUSION: While FMT holds transformative potential in cancer care, its integration into oncological practice requires robust clinical validation, long-term safety assessments, and interdisciplinary collaboration to harness its full therapeutic potential.}, }
@article {pmid41497693, year = {2025}, author = {Rusman, RD and Akil, F and Parewangi, ML and Daud, NA and Bachtiar, R and Kusuma, SH and Rifai, A}, title = {Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.}, journal = {World journal of experimental medicine}, volume = {15}, number = {4}, pages = {107316}, pmid = {41497693}, issn = {2220-315X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut-liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.}, }
@article {pmid41498910, year = {2026}, author = {Li, Y and Shen, X and Wang, D and Sun, K}, title = {The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.}, journal = {Discover oncology}, volume = {17}, number = {1}, pages = {181}, pmid = {41498910}, issn = {2730-6011}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally. Beyond established genetic and environmental risk factors, the gut microbiome is now recognized as a pivotal contributor to CRC pathogenesis, progression, and therapeutic response. This review synthesizes current evidence on how dysbiosis and specific pathogenic bacteria—notably Fusobacterium nucleatum (Fn), Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli carrying the polyketide synthase genomic island (pks+ E. coli)—may drive carcinogenesis through chronic inflammation, genotoxic metabolite production, immune evasion, and epigenetic reprogramming. Critically, we explore the microbiome’s dual role in modulating conventional therapies: Fn is linked to chemotherapy resistance and metastasis, while certain commensals may enhance radiotherapy and immunotherapy efficacy. We further evaluate emerging microbiota-targeted strategies, including fecal microbiota tra nsplantation (FMT), probiotics, prebiotics, postbiotics and precision antibiotics, which hold promise for restoring microbial balance and overcoming treatment resistance. By integrating mechanistic insights with clinical evidence, this review provides a foundation for leveraging the microbiome in CRC diagnosis, prognosis, and next-generation therapeutic approaches.}, }
@article {pmid41500422, year = {2026}, author = {Jin, J and Li, F and Hu, Y and Zhang, Z and Zhang, R and Xing, F}, title = {Gut microbiota dysbiosis transmits deoxynivalenol toxicity and triggers liver inflammation.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.01.011}, pmid = {41500422}, issn = {2090-1224}, abstract = {INTRODUCTION: Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is known to compromise gut barrier integrity and induce systemic inflammation.<br><br>OBJECTIVES: This study demonstrates that intestinal microbiota play a central role in DON-induced liver inflammation.<br><br>METHODS: Through oral exposure and fecal microbiota transplantation (FMT) experiments in mice, we observed that DON disrupts intestinal structure, alters microbial composition, and activates liver inflammation via the TLR4/MyD88/NF-&#x3ba;B pathway.<br><br>RESULTS: Notably, liver inflammation was replicated in pseudo-germ-free mice colonized with microbiota from DON-exposed donors, even in the absence of direct DON exposure. Microbial analysis identified Alloprevotella, a mucin-degrading genus associated with increased intestinal permeability, and Pseudomonas, a pathogenic genus enriched in the liver, as key candidate microbial drivers of this effect.<br><br>CONCLUSION: These findings underscore that dysbiosis, especially involving specific bacterial genera, can independently trigger liver inflammation, highlighting a microbiota-mediated pathogenic mechanism in mycotoxin toxicity.}, }
@article {pmid41502951, year = {2025}, author = {Oliveira, RA and McSpadden, E and Pandey, B and Lee, K and Yousef, M and Chen, RY and Triebold, C and Haro, F and Aksianiuk, V and Patel, R and Shriram, K and Ramanujam, R and Kuehn, S and Raman, AS}, title = {Statistical design of a synthetic microbiome that suppresses diverse gut pathogens.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41502951}, issn = {2692-8205}, support = {R35 GM146702/GM/NIGMS NIH HHS/United States ; }, abstract = {Engineering functional microbiomes is challenging due to complex interactions between bacteria and their environments[1-6]. Using a set of 848 gut commensal strains and clearance of multi-drug resistant Klebsiella pneumoniae (Kp-MH258) as a target function, we engineered a functional 15-member synthetic microbiome-SynCom15-through a statistical approach agnostic to strain phenotype, mechanism of action, bacterial interactions, or composition of natural microbiomes. Our approach involved designing, building, and testing 96 metagenomically diverse consortia, learning a generative model using community strain presence/absence as input, and distilling model constraints through statistical inference. SynCom15 cleared Kp-MH258 across in vitro, ex vivo, and in vivo environments, matching the efficacy of a fecal microbiome transplant in a clinically relevant murine model of infection. The mechanism of suppression by SynCom15 was related to fatty acid production coupled with environmental acidification. SynCom15 also suppressed other pathogens-Clostridioides difficile, Escherichia coli, and other K. pneumoniae strains-but through different mechanisms. Sensitivity analysis revealed models trained on strain presence/absence captured the statistical structure of pathogen suppression, illustrating that community representation was key to our approach succeeding. Our framework, 'Constraint Distillation', could be a general and efficient strategy for building emergent complex systems, offering a path towards synthetic ecology more broadly.}, }
@article {pmid41503356, year = {2025}, author = {Alobaidi, S}, title = {The gut-kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1675458}, pmid = {41503356}, issn = {2296-858X}, abstract = {Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut-kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral-gut-kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions-including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation-are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies.}, }
@article {pmid41503571, year = {2026}, author = {Bajaj, JS and Fagan, A and Sterling, RK and Sikaroodi, M and Gallagher, ML and Lee, H and Matherly, SC and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Thacker, LR and McGinley, JP and Khoruts, A and Gillevet, PM}, title = {The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101634}, pmid = {41503571}, issn = {2589-5559}, abstract = {BACKGROUND &amp; AIMS: The THEMATIC trial demonstrated that fecal microbiota transplantation (FMT) reduces recurrence of hepatic encephalopathy (HE) in patients already receiving lactulose and rifaximin. The aim of this analysis was to identify multi-omic predictors of HE recurrence among THEMATIC trial participants.<br><br>METHODS: The THEMATIC trial enrolled patients with cirrhosis and HE who received oral or enema FMT vs. placebo (1-3 administrations) and were followed for 6 months. Outcomes included safety and HE recurrence. Serum, urine, and stool samples were collected at baseline and post-FMT for all participants. Stool metagenomics, serum and urine metabolomics, inflammatory cytokines, and clinical data were analyzed. Differences between patients with and without HE recurrence were assessed using pathway, random forest, and latent factor analyses.<br><br>RESULTS: HE recurred in 10 of 60 patients (17%), with significantly higher recurrence in the placebo vs. the FMT groups (40% vs. 8%; p = 0.005). Due to the low recurrence rate in the FMT arms, all patients with recurrence were combined and compared with those without recurrence. Stool metagenomics showed that the abundance of short-chain fatty acid (SCFA) producers (Faecalibacterium, Eubacterium, Bacteroides, Blautia spp.) was lower, while that of GABA-producing taxa (Lactobacillus, Bifidobacterium spp.) was higher, in patients with recurrence. Urine and serum metabolomes separated HE recurrence groups on PLS-DA, with serum butyrate and isobutyrate being most significantly associated (p = 0.008). Pathway analyses revealed upregulation of GABA and neurotransmitter pathways in patients with HE recurrence. Random forest and latent factor analysis indicated that SCFA producers and secondary bile acids were protective, whereas IL-6, GABA producers, nicotine metabolites, and primary bile acids were associated with HE recurrence.<br><br>CONCLUSIONS: Secondary analysis of the THEMATIC randomized controlled trial indicates that HE recurrence in patients on lactulose and rifaximin is associated with distinct microbiome and metabolomic profiles, particularly involving SCFAs, GABA metabolism, bile acids, and IL-6.<br><br>IMPACT AND IMPLICATIONS: Fecal microbiota transplantation (FMT) reduced hepatic encephalopathy (HE) recurrence in patients receiving lactulose and rifaximin in the THEMATIC trial, but the multi-omic mechanisms underlying this effect were unclear. In this secondary analysis, we found that HE recurrence - regardless of FMT or placebo assignment - was associated with distinct multi-omic signatures, including reduced short-chain fatty acid-producing and increased pathobiont taxa, lower urinary and serum short-chain fatty acids, secondary bile acids, and acetaminophen derivatives, and higher GABA-related and nicotine metabolites, along with elevated IL-6 levels. Notably, patients with greater donor microbiota engraftment had lower rates of HE recurrence. These findings suggest that HE recurrence after FMT reflects a multifactorial process involving alterations in gut metagenomics, systemic metabolomics, inflammation, and donor engraftment.<br><br>TRIAL REGISTRATION: www.clinicaltrials.gov: NCT03796598.}, }
@article {pmid41503678, year = {2026}, author = {Zhou, S and Guo, L and Chen, N and Liu, H and Liu, X and Li, J and Dong, S and Liu, J and Wang, X and Ran, Y and Liu, M and Chu, H and Li, Y and Yang, H and Zhao, J and Zhou, L}, title = {Depression Aggravates Immune-Mediated Hepatitis Through NLRP3 Overactivation Induced by Intestinal Microbiota.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {32}, number = {1}, pages = {e70743}, pmid = {41503678}, issn = {1755-5949}, support = {81860109//National Natural Science Foundation of China/ ; 21JCZDJC00880//Natural Science Foundation of Tianjin Municipality/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/immunology ; Male ; Humans ; Mice ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; *Hepatitis, Autoimmune/metabolism/immunology/psychology ; Female ; Mice, Inbred C57BL ; Adult ; Concanavalin A ; *Depression/immunology/metabolism ; Inflammasomes/metabolism ; Middle Aged ; *Major Depressive Disorder/immunology ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Depression is associated with adverse effects in patients with autoimmune hepatitis (AIH). However, the underlying mechanism remains unclear. This study explores the impact of depression and related intestinal microbiota on immune-mediated hepatitis.<br><br>METHODS: We assessed depression in 260 AIH patients receiving 2-year standardized treatment and 173 healthy controls. In mice, depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS), and immune-mediated hepatitis was induced by intravenous injection of concanavalin A (ConA). Fecal microbiota transplantation (FMT) was performed using samples from patients with major depressive disorder (MDD) and controls.<br><br>RESULTS: Depression was common in patients with AIH (106/260, 40.8%) and was associated with cirrhosis. Compared with nondepressed AIH patients, those with depression showed exacerbated intestinal barrier dysfunction and hepatic NLR family pyrin domain containing 3 (NLRP3) inflammasome overactivation. In the ConA-induced hepatitis model, CUMS exposure aggravated these abnormalities, which were then attenuated by mirtazapine. Furthermore, mice colonized with MDD microbiota exhibited greater intestinal barrier disruption and hepatic NLRP3 inflammasome overactivation than those colonized with control microbiota. Notably, gut-derived Lactococcus formosensis, isolated from the livers of MDD microbiota-colonized mice, could translocate to the liver and induce hepatic NLRP3 inflammasome overactivation. In addition, vaccination against L. formosensis prevented translocation and alleviated liver injury in monocolonized mice.<br><br>CONCLUSION: Depression aggravates immune-mediated hepatitis through disruption of intestinal barrier integrity and overactivation of hepatic NLRP3 inflammasome. Gut-derived L. formosensis could translocate to the liver and induce liver injury in mice. This study provides the necessity of screening for depression in patients with AIH.}, }
@article {pmid41503704, year = {2026}, author = {De Palma, G and Costanzini, A and Mohan, V and Sidani, S and Saqib, Z and Pigrau, M and Lu, J and Causada Calo, N and Pinto-Sanchez, I and Verdu, EF and Marcon, M and Barbara, G and Stanghellini, V and De Giorgio, R and Collins, SM and Bercik, P}, title = {The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2610597}, pmid = {41503704}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Animals ; Humans ; *Intestinal Pseudo-Obstruction/therapy/microbiology/physiopathology ; Mice ; *Gastrointestinal Microbiome ; Male ; Bacteria/classification/genetics/isolation &amp; purification ; Chronic Disease/therapy ; Female ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Adult ; Middle Aged ; Gastrointestinal Transit ; }, abstract = {Chronic intestinal pseudo-obstruction (CIPO) is characterized by bowel dilation and obstructive symptoms without any structural blockage. Although the microbiota is known to affect gastrointestinal function, its role in CIPO is poorly understood. We aimed to characterize the CIPO microbiota, investigate its role in disease expression and explore the therapeutic role of fecal microbiota transplantation (FMT). CIPO patients (n = 14) and healthy controls (HC, n = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.}, }
@article {pmid41503791, year = {2026}, author = {Jin, J and Yao, G and Zhang, X and Zhang, T and Ye, H and Zhou, X and Yu, Y and Zhao, Y and Qin, Z and Chen, H and Bi, Y and Wang, X and Ren, X and Zhang, Y and Wang, Z and Zhang, Q}, title = {Gut virome dysbiosis contributes to premature ovarian insufficiency by modulating gut bacteriome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2611645}, pmid = {41503791}, issn = {1949-0984}, mesh = {Female ; *Dysbiosis/virology/complications/microbiology ; Animals ; *Primary Ovarian Insufficiency/microbiology/virology/therapy/etiology ; Humans ; *Gastrointestinal Microbiome ; Rats ; *Virome ; Adult ; Fecal Microbiota Transplantation ; Feces/virology/microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; Ovary/physiopathology ; Young Adult ; }, abstract = {BACKGROUND: Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored.<br><br>RESULTS: Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function.<br><br>CONCLUSIONS: Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.}, }
@article {pmid41503825, year = {2026}, author = {Kang, K and Kim, JY and Yim, JJ and Kim, D}, title = {Gut-lung axis and microbiome alterations in mycobacterial infections: from pathogenesis to therapeutic potential.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612428}, pmid = {41503825}, issn = {1949-0984}, mesh = {Humans ; *Lung/microbiology/immunology ; *Dysbiosis/microbiology/therapy ; Animals ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage ; Prebiotics ; Fecal Microbiota Transplantation ; *Mycobacterium Infections/microbiology/therapy ; }, abstract = {Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.}, }
@article {pmid41503829, year = {2026}, author = {Zhang, H and Wang, Y and Ning, B and Wang, Y and Sun, T and Xu, J}, title = {The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2611203}, pmid = {41503829}, issn = {1365-2060}, mesh = {Humans ; *Obesity/complications/microbiology/immunology ; *Breast Neoplasms/microbiology/immunology/pathology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Female ; *Dysbiosis/microbiology/complications/immunology ; Prognosis ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC.<br><br>METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening.<br><br>DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived &#x3b2;-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies.<br><br>CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.}, }
@article {pmid41504254, year = {2026}, author = {Lin, P}, title = {The importance of the microbiome in uveitis.}, journal = {Current opinion in ophthalmology}, volume = {37}, number = {2}, pages = {137-140}, doi = {10.1097/ICU.0000000000001197}, pmid = {41504254}, issn = {1531-7021}, support = {R01 EY032882/EY/NEI NIH HHS/United States ; }, mesh = {*Uveitis/microbiology ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; *Microbiota/physiology ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review was to summarize the literature on preclinical and clinical studies demonstrating the impact of the intestinal microbiome in noninfectious uveitis.<br><br>RECENT FINDINGS: Preclinical studies using the experimental autoimmune uveitis (EAU) model have shown commensals such as Desulfovibrio and Prevotella , as well as Ruminococcaceae , associated with uveitis, which overlap with some clinical studies in uveitis patients. Interventions that target the microbiome that can be developed for the treatment of uveitis include antibiotics, fecal metabolites or metabolite agonists that are protective in uveitis, probiotics, dietary interventions, or fecal microbial transplant.<br><br>SUMMARY: There is significant data supporting the importance of the intestinal microbiome in noninfectious uveitis through enrichment or depletion of certain gut bacteria as well as their metabolites. Targeting the intestinal microbiome or their metabolites might be a viable option for the treatment of noninfectious uveitis.}, }
@article {pmid41505077, year = {2026}, author = {Ghaemi, M and Ghaemi, A and Tavakkoli, H and Mashhadinejad, M and Kheradmand, D}, title = {The MOF-Microbiome Axis: a New Paradigm for Precision Nanomedicine.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41505077}, issn = {1867-1314}, abstract = {The gut microbiome is crucial for human health, and its imbalance, known as dysbiosis, is associated with diseases such as inflammatory bowel disease, metabolic disorders, and neurological disorders. Traditional treatments, such as probiotics and fecal microbiota transplants, often lack precision, making the emerging field of nanomedicine a promising alternative. This review introduces the "MOF-Microbiome Axis," which explores the interactions between metal-organic frameworks (MOFs), versatile, porous materials, and the gut microbiome. It focuses on designing gastrointestinal-targeted MOFs that are biocompatible and responsive to stimuli. We discuss how MOFs can serve as scaffolds, controlled-release vehicles, and metabolite scavengers, highlighting their therapeutic applications in targeted antimicrobial therapy, enhanced probiotic delivery, and immunomodulation. The review also addresses important challenges in biosafety, scalable production, and personalized treatment, suggesting future directions such as bio-hybrid systems and precision microbiome editing. Overall, the MOF-Microbiome Axis offers a new perspective on microbiome engineering and advanced therapeutic approaches.}, }
@article {pmid41506296, year = {2026}, author = {He, D and Chen, Y and Xue, M and Gao, X and Yan, A and Sun, Y and Li, X and Liu, J and Hu, G and Fu, S}, title = {Orally Administered Neohesperidin (Neo) Alleviates Lipopolysaccharide-Induced Mastitis by Suppressing TLR4/NF-κB and Activating AMPK/Nrf2/HO-1 Signaling, and Regulating Intestinal Flora Structure.}, journal = {Journal of agricultural and food chemistry}, volume = {74}, number = {2}, pages = {2140-2156}, doi = {10.1021/acs.jafc.5c12129}, pmid = {41506296}, issn = {1520-5118}, mesh = {Animals ; Female ; *Mastitis/drug therapy/genetics/microbiology/metabolism/chemically induced/immunology ; *NF-E2-Related Factor 2/genetics/metabolism ; *NF-kappa B/genetics/metabolism ; *Hesperidin/analogs &amp; derivatives/administration &amp; dosage ; Lipopolysaccharides/adverse effects ; *Toll-Like Receptor 4/genetics/metabolism/immunology ; *Gastrointestinal Microbiome/drug effects ; Signal Transduction/drug effects ; *AMP-Activated Protein Kinases/genetics/metabolism ; *Heme Oxygenase-1/genetics/metabolism ; Mice ; Humans ; Membrane Proteins/genetics/metabolism ; Bacteria/classification/isolation &amp; purification/genetics ; }, abstract = {The impairment of the blood-milk barrier (BMB) during mastitis severely compromises breastfeeding efficacy, highlighting an urgent need for effective nonantibiotic interventions. Natural anti-inflammatory and traditional Chinese medicine (TCM) compounds have thus garnered increasing attention as promising alternatives. Neohesperidin (Neo), a major bioactive flavonoid derived from the TCM herbs such as Citrus aurantium and its related species, has been historically associated with heat-clearing and detoxifying properties in TCM theory. However, its role in mastitis remains unclear. Herein, we investigated the protective effects of Neo on BMB integrity using an LPS-induced mastitis model. Our results demonstrate that Neo significantly alleviates mammary tissue damage and preserves BMB function. Further mechanistic studies indicate that Neo attenuates LPS-induced inflammatory responses and oxidative stress in mammary epithelial cells by inhibiting the TLR4/NF-κB pathway and concurrently activating the AMPK/Nrf2/HO-1 axis. Additionally, 16S rRNA sequencing and fecal microbiota transplantation (FMT) experiments demonstrated that Neo alleviates mastitis by modulating the gut microbiota (increasing beneficial bacteria and reducing harmful bacteria). In summary, this study confirms that Neo can mitigate mastitis and protect BMB function through its anti-inflammatory, antioxidant, and microbiota-regulating effects. The research not only elucidates the molecular mechanisms by which Neo exerts its mammary protective effects through inflammation-oxidative stress-gut microbiota but also provides new insights for the prevention and treatment of mastitis.}, }
@article {pmid41506765, year = {2026}, author = {Rognstad, &#xd8;B and Botteri, E and Hoff, G and Bretthauer, M and Nguyen, HD and Schult, AL and Holme, &#xd8; and Randel, KR}, title = {Use of claims data to identify adverse events after colonoscopy in a randomised colorectal cancer screening trial in Norway: a cross-sectional study.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e109883}, pmid = {41506765}, issn = {2044-6055}, mesh = {Humans ; Cross-Sectional Studies ; Norway/epidemiology ; Male ; Female ; Middle Aged ; *Colonoscopy/adverse effects ; *Colorectal Neoplasms/diagnosis ; Aged ; *Early Detection of Cancer/adverse effects/methods ; Retrospective Studies ; *Gastrointestinal Hemorrhage/etiology/epidemiology ; Intestinal Perforation/etiology/epidemiology ; *Insurance Claim Review ; Occult Blood ; }, abstract = {OBJECTIVES: Accurate identification of adverse events after colonoscopy is essential for quality assurance in colorectal cancer (CRC) screening. Review of medical records is labour intensive as adverse events are infrequent. The object of this study was to investigate the accuracy of claims data in identifying adverse events after colonoscopy in CRC screening.<br><br>DESIGN: Cross-sectional, retrospective.<br><br>SETTING AND PARTICIPANTS: Males and females aged 50-74 years were randomised to once-only sigmoidoscopy or biennial faecal immunochemical test in a CRC screening trial at two screening centres in Norway. Participants in the present study underwent follow-up colonoscopy from 2012 to April 2020 after initial positive screening test. We reviewed medical records for adverse events within 30 days following 11&#x2009;205 colonoscopies.<br><br>The primary outcome of the study was to assess the sensitivity of claims data from the Norwegian Patient Registry to identify lower gastrointestinal bleeding using emergency contact International Statistical Classification of Diseases and Related Health Problems 10th Revision diagnostic code sets under two definitions: a stringent definition (codes explicitly identifying bleeding) and a broad definition (including suggestive codes). Secondary outcome measures included the sensitivity to identify perforation using a stringent and a broad definition. Additionally, we assessed whether incorporating procedure codes and non-emergency contacts improved accuracy.<br><br>RESULTS: 87 cases of lower gastrointestinal bleeding and eight perforations were confirmed. Sensitivity for bleeding differed between the centres (p<0.001). At centre 1, sensitivity was 48.6% (95% CI 31.9% to 65.6%) using the stringent and 89.2% (95% CI 74.6% to 97.0%) using the broad definition. At centre 2, sensitivity was 36.0% (95% CI 22.9% to 50.8%) and 50.0% (95% CI 35.5% to 64.5%), respectively. Combined sensitivity for perforation was 37.5% (95% CI 8.5% to 75.5%) using the stringent and 62.5% (95% CI 24.5% to 91.5%) using the broad definition. Adding procedure codes and non-emergency contacts slightly increased sensitivity but increased false positives.<br><br>CONCLUSIONS: Use of claims data underestimated adverse event rates following colonoscopy. Difference in coding practice across hospitals underscores the need for standardised reporting in screening programmes.<br><br>TRIAL REGISTRATION NUMBER: NCT01538550.}, }
@article {pmid41507585, year = {2026}, author = {Hsu, CL and Shukla, S and Freund, L and Chou, AC and Yang, Y and Bruellman, R and Raya Tonetti, F and Cabré, N and Mayo, S and Lim, HG and Magallan, V and Cordell, BJ and Lang, S and Demir, M and Stärkel, P and Llorente, C and Palsson, BO and Mandyam, C and Boland, BS and Hohmann, E and Schnabl, B}, title = {Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort.}, journal = {Nature microbiology}, volume = {11}, number = {2}, pages = {415-428}, pmid = {41507585}, issn = {2058-5276}, support = {K99 AA031328/AA/NIAAA NIH HHS/United States ; R21 AA030654/AA/NIAAA NIH HHS/United States ; R01 AA020098/AA/NIAAA NIH HHS/United States ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; R01 AA029106, R21 AA030654, P30 AR073761//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; BX004594//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R00 AA031328/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Ethanol/metabolism ; Feces/microbiology/chemistry ; *Gastrointestinal Microbiome/genetics ; Cohort Studies ; Metabolic Networks and Pathways/genetics ; Male ; Fermentation ; Female ; Fecal Microbiota Transplantation ; Escherichia coli/metabolism/genetics/isolation &amp; purification ; Metagenomics ; Middle Aged ; Metabolomics ; Adult ; }, abstract = {Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS.}, }
@article {pmid41508463, year = {2026}, author = {Dong, Y and Xie, Y and Yao, R and Mai, Y and Zhang, L and Wang, H and Wang, H and Zhang, J}, title = {Lactobacillus fermentum ZNL16 attenuates ETEC-induced intestinal injury by regulating gut microbiota and short-chain fatty acid metabolism to suppress the IL-17/JAK2-STAT3 pathway.}, journal = {Food research international (Ottawa, Ont.)}, volume = {225}, number = {}, pages = {118038}, doi = {10.1016/j.foodres.2025.118038}, pmid = {41508463}, issn = {1873-7145}, mesh = {Animals ; *Limosilactobacillus fermentum/physiology ; STAT3 Transcription Factor/metabolism ; *Interleukin-17/metabolism ; *Fatty Acids, Volatile/metabolism ; Intestinal Barrier Function ; Signal Transduction ; Mice ; *Gastrointestinal Microbiome/physiology ; Janus Kinase 2/metabolism ; *Enterotoxigenic Escherichia coli ; *Probiotics/pharmacology ; *Escherichia coli Infections/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; Intestines/microbiology ; }, abstract = {Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea, threatening neonates, travelers, and livestock by disrupting the intestinal barrier and weakening immunity. Lactobacillus fermentum has been shown to enhance barrier integrity and modulate immune activity, while gut microbiota and their metabolites are critical regulators of intestinal health. Our findings demonstrate that Lactobacillus fermentum ZNL16 improved intestinal barrier function and reduced inflammation via the IL-17/JAK2-STAT3 signaling pathway, while also promoting microbial balance and short-chain fatty acid metabolism. Antibiotic-induced microbiota depletion confirmed that these protective effects are microbiota-dependent. Furthermore, fecal microbiota transplantation (FMT) from ZNL16-treated mice and sodium butyrate supplementation both alleviated ETEC-induced intestinal damage. Taken together, our findings demonstrate the capacity of L. fermentum ZNL16 to safeguard intestinal barrier integrity and modulate immune responses, supporting its promise as a candidate for probiotic development.}, }
@article {pmid41508489, year = {2026}, author = {Qu, Q and Zhou, Q and Peng, X and Li, Z and Jia, M and Zhang, Y and Yang, C and Dai, X and Sheng, M and Kang, J and Shi, X}, title = {Monascus fermentation enhances the lipid-lowering properties of ginseng in vivo and component assay.}, journal = {Food research international (Ottawa, Ont.)}, volume = {225}, number = {}, pages = {118067}, doi = {10.1016/j.foodres.2025.118067}, pmid = {41508489}, issn = {1873-7145}, mesh = {*Monascus/metabolism ; Animals ; *Fermentation ; *Panax/chemistry ; *Hyperlipidemias/drug therapy ; Mice ; Male ; Mice, Inbred C57BL ; *Hypolipidemic Agents/pharmacology ; Lovastatin/pharmacology ; Ginsenosides ; Liver/metabolism ; Gastrointestinal Microbiome/drug effects ; Lipids/blood ; }, abstract = {Hyperlipidemia is a global health concern characterized by elevated lipid levels and increased cardiovascular risk. Ginseng (Panax ginseng) has lipid-lowering properties, and Monascus fermentation can yield monacolin K, a natural statin. However, it remains unclear whether Monascus-fermented ginseng (MFG) offers synergistic benefits over ginseng or Monascus alone. This study aimed to compare the lipid-lowering efficacy of MFG versus unfermented ginseng, Monascus, and their non-fermented combination in hyperlipidemic mice. Multi-omics analyses (hepatic transcriptomics, serum/fecal metabolomics, and gut microbiota profiling) were integrated to elucidate underlying mechanisms, and fecal microbiota transplantation (FMT) assessed the causal role of MFG-altered microbiota. MFG supplementation markedly improved serum lipid profiles and attenuated hepatic steatosis, outperforming ginseng, Monascus, or their unfermented combination. Phytochemical analysis confirmed that fermentation introduced monacolin K into MFG and increased its rare ginsenoside content, distinguishing it from unfermented ginseng. Mechanistically, MFG increased hepatic p-AMPK and upregulated fatty acid oxidation while downregulating lipogenesis (SREBP-1c, FAS). Metabolomics revealed elevated short-chain fatty acid levels and enhanced bile acid biotransformation in MFG-treated mice. MFG reshaped gut microbiota composition and enriched beneficial taxa. Importantly, FMT from MFG-fed donors recapitulated the lipid-lowering effects in recipients, confirming a microbiota-mediated mechanism. In conclusion, MFG exerts superior lipid-lowering effects through complementary host metabolic and gut microbial modulation, highlighting fermented herbal products as promising interventions against hyperlipidemia.}, }
@article {pmid41511706, year = {2026}, author = {Shekar, P and Pradeep, S and Shivamallu, C and Prashant, A and Vishwanath, P}, title = {Immune-microbiota crosstalk in colorectal cancer: mechanistic pathways, biomarkers, and translational therapeutics.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {28}, number = {6}, pages = {1971-1985}, pmid = {41511706}, issn = {1699-3055}, mesh = {Humans ; *Colorectal Neoplasms/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; Biomarkers, Tumor ; Translational Research, Biomedical ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.}, }
@article {pmid41512666, year = {2026}, author = {Liu, JB and Li, S and Sun, GZ and Lin, ZX and Miao, ZM}, title = {Gut microbiota modulation by novel synbiotic improves production performance and ovarian function in aged laying hens via gut-ovary axis.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106394}, pmid = {41512666}, issn = {1525-3171}, mesh = {Animals ; Female ; *Chickens/physiology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Synbiotics/administration &amp; dosage ; *Ovary/physiology/drug effects ; *Inulin/administration &amp; dosage/pharmacology/metabolism ; Diet/veterinary ; Animal Feed/analysis ; *Bacillus amyloliquefaciens/chemistry ; Random Allocation ; *Reproduction/drug effects ; }, abstract = {The management of oxidative stress and ovarian dysfunction associated with aged laying hens, which is highly involved in gut microbiota, has been suggested as a feasible approach to improve production performance. Here, we investigated the effects of a novel synbiotic (Bacillus amyloliquefaciens + inulin, BAI), a gut microbiota regulator, on the improvement of production performance in aged laying hens, and dissected the underlying mechanisms using multi-omics analysis. Our findings showed that, compared to the control, high-dosage BAI supplementation significantly improved production performance; enhanced intestinal health, evidenced by the increase of villus height (p < 0.01), the expression of gut barrier-related genes (Claudin-1 and Claudin-2) (all p < 0.001), and immune levels (SIgA and IFN-γ) (all p < 0.01); meliorated ovarian function, confirmed by reduced oxidative stress (p < 0.001) and pathological lesions, as well as increased follicle numbers (p < 0.01 or p < 0.001), serum contents of reproductive hormone (estrogen, luteinizing hormone, and follicle-stimulating hormone) (p < 0.05 or p < 0.001), and the mRNA levels of yolk precursor synthesis-associated genes (APOVLDL-Ⅱ, VTG-Ⅱ, and VLDLR) (all p < 0.001). The 16S rRNA sequencing showed that BAI augmented the relative amount of Lactobacillus, Akkermansia, and Bacteroides and other short-chain fatty acids (SCFAs)-producers. Blood metabolome analysis demonstrated that the predominant metabolites changed by BAI were principally involved in SCFA metabolism, steroid hormone biosynthesis, steroid biosynthesis, and intestinal immune network for IgA production. Ovarian transcriptome analysis indicated that BAI significantly inhibited pathways of ferroptosis and peroxisome, confirmed by RT-qPCR. Furthermore, fecal microbiota transplantation (FMT) from BAI-treated aged hens improved production performance, ovarian function, and oxidative stress status in antibiotic-administrated hens. In sum, our study uncovers that BAI improves production performance and ovarian dysfunction via gut microbiota in aged laying hens. Thus, modulating gut microbiome is an effective approach to laying rate reduction of aged hens.}, }
@article {pmid41514614, year = {2025}, author = {Peddireddi, RSS and Kuchana, SK and Kode, R and Khammammettu, S and Koppanatham, A and Mattigiri, S and Gobburi, H and Alahari, SK}, title = {Role of Gut Microbiome in Oncogenesis and Oncotherapies.}, journal = {Cancers}, volume = {18}, number = {1}, pages = {}, pmid = {41514614}, issn = {2072-6694}, abstract = {The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care.}, }
@article {pmid41515997, year = {2025}, author = {Ahmed, I and Nijs, J and Vanroose, M and Vandeputte, D and Kindt, S and Elma, &#xd6; and Hendrix, J and Huysmans, E and Lahousse, A}, title = {Oral and Gut Health, (Neuro) Inflammation, and Central Sensitization in Chronic Pain: A Narrative Review of Mechanisms, Treatment Opportunities, and Research Agenda.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41515997}, issn = {1422-0067}, mesh = {Humans ; Animals ; *Chronic Pain/therapy/microbiology/etiology/metabolism ; *Gastrointestinal Microbiome ; *Neuroinflammatory Diseases/therapy ; *Central Nervous System Sensitization ; Dysbiosis ; }, abstract = {Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood-brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain.}, }
@article {pmid41516146, year = {2025}, author = {Barbu, AC and Stoleru, S and Zugravu, A and Poenaru, E and Dragomir, A and Costescu, M and Aurelian, SM and Shhab, Y and Stoleru, CM and Coman, OA and Fulga, I}, title = {Dopamine and the Gut Microbiota: Interactions Within the Microbiota-Gut-Brain Axis and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516146}, issn = {1422-0067}, mesh = {Humans ; *Dopamine/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Parkinson Disease/metabolism/microbiology/therapy ; *Brain/metabolism ; *Brain-Gut Axis ; Levodopa/metabolism/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The microbiota-gut-brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson's disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine-microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies.}, }
@article {pmid41516340, year = {2026}, author = {Liu, M and Wang, Y and Huang, H}, title = {Gut Microbiota-Derived Propionic Acid Mediates ApoA-I-Induced Amelioration of MASLD via Activation of GPR43-Ca[2+]-CAMKII-ATGL Hepatic Lipolysis.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516340}, issn = {1422-0067}, support = {5232004//Beijing Natural Science Foundation/ ; 32071130//National Natural Science Foundation of China/ ; }, mesh = {*Propionates/metabolism/pharmacology ; Animals ; *Lipolysis/drug effects ; *Receptors, G-Protein-Coupled/metabolism ; Liver/metabolism ; *Gastrointestinal Microbiome ; *Apolipoprotein A-I/metabolism/genetics ; Mice ; Calcium/metabolism ; Male ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Fatty Liver/metabolism ; Humans ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread hepatic condition characterised by hepatic lipid accumulation and inflammation. Emerging research highlights the contribution of the intestinal microbiota and its metabolic byproducts to the pathogenesis of MASLD through the gut-liver axis. Apolipoprotein A-I (apoA-I), the principal structural component of high-density lipoprotein (HDL), is linked to various metabolic disorders; however, its function in MASLD has not yet been clearly elucidated. This study sought to examine whether apoA-I protects against MASLD, with a focus on the possible role of the gut microbiota and propionic acid (PPA). The contribution of the gut microbiota was evaluated using faecal microbiota transplantation (FMT) and antibiotic cocktail (ABX)-mediated depletion. Microbial composition was assessed via 16S rRNA sequencing, and concentrations of short-chain fatty acids (SCFAs) were quantified. The effects of PPA on MASLD were examined using in vivo and in vitro models. The results showed that apoA-I overexpression alleviated MASLD in a gut microbiota-dependent manner, restored microbial homeostasis, and elevated PPA levels. PPA supplementation improved MASLD phenotypes. Mechanistically, PPA treatment was associated with the activation of the GPR43-Ca[2+]-CAMKII-ATGL pathway, suggesting that PPA plays a role in stimulating hepatic lipolysis and enhancing mitochondrial β-oxidation. These findings reveal a novel pathway through which apoA-I ameliorates MASLD by modulating the gut microbiota and increasing PPA levels, which activate a hepatic lipolysis cascade. The apoA-I-microbiota-PPA axis represents a promising therapeutic target for MASLD intervention.}, }
@article {pmid41517132, year = {2025}, author = {Lu, S and Gao, M and Kuttappan, D and Amalaradjou, MA}, title = {Low-Fat Cheddar Cheese Influences Gut Microbiota Composition and Diversity in Human Microbiota-Associated Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517132}, issn = {2304-8158}, support = {430855//Foundation for Food and Agriculture Research New Innovator Award/ ; }, abstract = {Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota-associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% w/w) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3-V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of Firmicutes and a reduction in Bacteroidetes (p < 0.001). At the genus level, Lactococcus and Streptococcus were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans.}, }
@article {pmid41518808, year = {2026}, author = {Qu, J and Jiang, X and Ma, Y and Sheng, X and Pi, C and Wang, Y and Xu, Q and Li, R and Wang, P and Qian, D and Wang, J and Yi, Z and Yi, J and Wen, L and Liu, S}, title = {Unveiling the gut-brain axis: How chronic exposure to arsenic-induced microglial pyroptosis drives Alzheimer's disease-like pathology.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141087}, doi = {10.1016/j.jhazmat.2026.141087}, pmid = {41518808}, issn = {1873-3336}, mesh = {Animals ; *Microglia/drug effects/pathology ; *Alzheimer Disease/chemically induced/pathology/metabolism ; Mice ; *Pyroptosis/drug effects ; *Arsenic/toxicity ; Male ; Gastrointestinal Microbiome/drug effects ; *Brain/drug effects/pathology/metabolism ; Cognitive Dysfunction/chemically induced ; Mice, Inbred C57BL ; *Brain-Gut Axis/drug effects ; Signal Transduction/drug effects ; }, abstract = {Arsenic, a pervasive environmental contaminant in groundwater, poses a severe global threat to public health. Chronic arsenic exposure has been linked to neurological impairment, however, its specific pathogenic mechanism and whether the gut-brain axis plays a key role remain unclear. This study investigated the role of gut microbiota and its metabolite indoxyl sulfate (IS) in mediating chronic exposure to arsenic-induced cognitive impairment and Alzheimer's disease (AD)-like pathology, with a specific focus on microglial pyroptosis. We found that chronic arsenic exposure induced cognitive dysfunction and intestinal barrier injury, disrupted gut microbiota composition, promoted IS accumulation in serum and brain, and activated the AhR/NF-κB/NLRP3 signaling pathway, triggering microglial pyroptosis and elevating AD-like pathological markers in mice. Meanwhile, fecal microbiota transplantation (FMT) from arsenic-exposed mice recapitulated cognitive impairment, elevated IS levels, and neuroinflammation in recipient mice. Furthermore, arsenic upregulated hepatic IS-synthesis genes (CYP2E1, Sult1d1) and downregulated renal IS-excretion gene (ABCG2). In vitro, arsenic and IS co-exposure promoted M1 polarization and enhanced pyroptosis by activating the AhR/NF-κB/NLRP3 signaling pathway, while suppressing phagocytosis-related proteins (TREM2, SYK and CD36). Furthermore, SiAhR treatment could alleviated microglial inflammatory injury and enhancing the microglia's phagocytic capacity induced by arsenic and IS co-exposure in BV2 cells through inhibiting the AhR/NF-κB/NLRP3-mediated pyroptosis signaling pathway. In conclusion, chronic arsenic exposure induced cognitive impairment and AD-like pathological via the gut microbiota-AhR-pyroptosis cascade, where in IS accumulation served a key mediator. These findings provide new insights into preventing arsenic-related cognitive damage.}, }
@article {pmid41519109, year = {2026}, author = {Hoedt, EC and Talley, NJ}, title = {Toward a personalized diet-microbiome strategy in inflammatory bowel disease: Matching donor, diet, and patient.}, journal = {Med (New York, N.Y.)}, volume = {7}, number = {1}, pages = {100918}, doi = {10.1016/j.medj.2025.100918}, pmid = {41519109}, issn = {2666-6340}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diet therapy ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Diet ; *Gastrointestinal Microbiome ; }, abstract = {Fecal microbiota transplant plus dietary change to restore the imbalance of an individual's microbiome to relieve disorders such as inflammatory bowel disease has not been established but has promise. In this commentary, we suggest the need to embrace a more nuanced, personalized approach, one that considers microbial functionality, dietary context, and host compatibility.}, }
@article {pmid41519323, year = {2026}, author = {Wang, L and Lu, C and Li, S and Wu, T and Ren, X and Song, S and Ai, C}, title = {Laminaria japonica fucoidan ameliorates D-galactose-induced cognitive impairment via the regulation of tryptophan metabolism along the gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {340}, number = {Pt 1}, pages = {150151}, doi = {10.1016/j.ijbiomac.2026.150151}, pmid = {41519323}, issn = {1879-0003}, mesh = {Animals ; *Polysaccharides/pharmacology/chemistry/therapeutic use ; *Laminaria/chemistry ; *Galactose/adverse effects ; Mice ; *Cognitive Dysfunction/drug therapy/chemically induced/metabolism ; *Tryptophan/metabolism ; Oxidative Stress/drug effects ; Gastrointestinal Microbiome/drug effects ; *Brain-Gut Axis/drug effects ; *Brain/metabolism/drug effects ; Neuroprotective Agents/pharmacology ; Male ; Aging/drug effects ; Edible Seaweeds ; }, abstract = {Aging is a multifactorial biological process in which chronic inflammation and oxidative stress are central to the development of age-related disorders, including neurodegenerative decline. Fucoidan, a sulfated polysaccharide extracted from brown algae, has well-documented anti-inflammatory and antioxidant effects, and therefore has the potential to be a neuroprotective agent against cognitive impairment associated with aging. In the present study, the major fucoidan fraction (LJF-2) isolated from Laminaria japonica was examined for its neuroprotective properties in a D-galactose induced aging mouse model. Oral administration of LJF-2 for 8 weeks significantly improved spatial learning and memory and suppressed neuroinflammatory responses and oxidative stress while significantly reducing the activation of astrocytes and microglia. These neuroprotective effects were linked to the regulation of key proteins involved in neuronal protection and synaptic function, such as neprilysin and synapsin, by cAMP response element-binding protein signaling. Furthermore, LJF-2 significantly remodeled the gut microbiota through a reduction in the abundance of the Bacteroidota, Proteobacteria, and several putative pathogenic genera, which enhanced the intestinal barrier integrity and modified the microbial metabolite profiles, especially those associated with tryptophan metabolism. Fecal microbiota transplantation experiments further confirmed the role of the gut microbiota modulated by LJF-2 in mediating its neuroprotective effects through reduction of oxidative stress and inflammation. Collectively, these findings suggest that LJF-2 may be a promising therapeutic approach to address the aging-related cognitive decline by modulating the gut-brain axis.}, }
@article {pmid41520280, year = {2026}, author = {van de Guchte, M and Mondot, S and Cadiou, J and Raghuvanshi, R and Rous, C and Doré, J}, title = {Improving ulcerative colitis prospects through fecal microbiota transfer: atypical donor microbiota can boost success rate.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609457}, pmid = {41520280}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/microbiology ; Rats ; Disease Models, Animal ; Humans ; *Feces/microbiology ; Treatment Outcome ; *Gastrointestinal Microbiome ; }, abstract = {Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.}, }
@article {pmid41520913, year = {2026}, author = {Liu, Y and Miao, K and Yang, X}, title = {Microbiome-modulated immunotherapy in oncology: Current applications and future prospects.}, journal = {Seminars in cancer biology}, volume = {119}, number = {}, pages = {38-53}, doi = {10.1016/j.semcancer.2026.01.001}, pmid = {41520913}, issn = {1096-3650}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Microbiota/immunology ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Cancer immunotherapy has transformed oncology, yet therapeutic efficacy remains heterogeneous and frequently limited by primary or acquired resistance. Increasing evidence demonstrates that both intra- and extratumoral microbiota critically modulate antitumor immunity, influencing clinical responses of immunotherapy and immune-related adverse events (irAEs). Microbial communities regulate the tumor immune microenvironment through multiple mechanisms, including microbe-associated molecular patterns, microbial metabolites, and outer membrane vesicles, acting on tumor or immune cells. These insights have fostered the development of microbiome-based applications in oncology, ranging from predictive biomarkers to therapeutic interventions such as engineered bacteria, fecal microbiota transplantation, probiotics, prebiotics, outer membrane vesicles, bacteriophages, and dietary modulation. Early-phase clinical studies indicate that microbiota-targeted strategies can enhance immunotherapy efficacy or mitigate irAEs, although strain specificity, interindividual variability, and safety remain significant challenges. Future progress will require mechanistic elucidation, integration of multi-omics analyses, standardization of methodologies, and personalized intervention frameworks to translate microbiome modulation into clinically actionable, precision immunotherapy.}, }
@article {pmid41521300, year = {2026}, author = {Deng, W and Chen, D and Wei, Y and Chen, W and Chen, K and Zhong, H and He, X}, title = {Washed microbiota transplantation relieves atopic dermatitis via gut-skin microbiome rebalancing.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41521300}, issn = {1471-2180}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 82300440//National Natural Science Foundation of China Youth Program/ ; }, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology ; Skin Microbiome ; Female ; Male ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Adolescent ; Adult ; Dysbiosis/therapy ; Child ; Skin/microbiology ; Treatment Outcome ; Young Adult ; Bacteria/classification/isolation &amp; purification/genetics ; Severity of Illness Index ; Feces/microbiology ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which dysbiosis of gut and skin microbiota contributes to pathogenesis and severity. Washed microbiota transplantation (WMT)-an improved form of fecal microbiota transplantation with enhanced safety and microbiota quality control-has shown efficacy in a single reported adolescent case. However, clinical data on WMT in AD and its effects on the skin and gut microbiota remain limited.<br><br>METHODS: Twenty-three patients with moderate-to-severe AD received at least two courses of WMT between January 2022 and December 2023. Disease activity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index, the Eczema Area and Severity Index (EASI), the Numeric Rating Scale (NRS) for itch, and the Dermatology Life Quality Index (DLQI). Peripheral blood counts, cytokine profiles, lymphocyte subsets, and gut and skin microbiota were assessed before and after treatment.<br><br>RESULTS: WMT was well tolerated (58 sessions; 5.2% mild adverse events) and significantly improved SCORAD, EASI, DLQI, and NRS scores, with greater EASI reductions in adults than in children. Absolute basophil counts decreased significantly after treatment, whereas other hematologic and cytokine parameters remained stable. Gut microbiota showed an increased Gut Microbiome Health Index, a decreased Microbial Dysbiosis Index, and enrichment of short-chain fatty acid-producing taxa, including the Eubacterium coprostanoligenes group, Lachnospiraceae, and Coprococcus. Skin microbiota shifted from Staphylococcus dominance to higher abundances of Acinetobacter, Perlucidibaca, and other potentially protective genera, inversely correlating with disease severity and systemic inflammation.<br><br>CONCLUSIONS: WMT appears safe and effective in alleviating clinical manifestations of AD while reshaping both gut and skin microbiota. These parallel microbial shifts support the gut-skin axis as a therapeutic target and highlight WMT as a promising microbiota-centered intervention for immune-mediated skin diseases.}, }
@article {pmid41522358, year = {2026}, author = {Jin, Y and Zhang, SJ and Zhuang, S and Li, P and Miao, H and Zhao, YY}, title = {Microbiota-gut-kidney axis in health and renal disease.}, journal = {International journal of biological sciences}, volume = {22}, number = {2}, pages = {750-770}, pmid = {41522358}, issn = {1449-2288}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Kidney/metabolism ; *Kidney Diseases/microbiology/metabolism ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Acute Kidney Injury/microbiology/metabolism ; Probiotics ; }, abstract = {Gut microbiota plays a central role in programming host metabolic function and immune modulation in both health and disease. Microbial dysbiosis leads to an increase in opportunistic pathogens and a reduction in beneficial bacteria, which collectively result in the excessive production of detrimental metabolites, particularly uremic toxins such as indoxyl sulfate and trimethylamine-N-oxide, while concurrently decreasing beneficial metabolites, such as short-chain fatty acids and tryptophan catabolites, including indole-3-aldehyde. The accumulation of harmful metabolites and depletion of protective metabolites contribute to fibrosis progression through various mediators, including the renin-angiotensin system, reactive oxygen species, Toll-like receptor 4, aryl hydrocarbon receptor, inhibitor of kappa B/nuclear factor kappa B, and Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways. This review highlights the pathogenic link between gut microbiota and kidney damage via the gut-kidney axis, encompassing acute kidney injury (AKI) and chronic kidney disease (CKD). Innovative therapeutic strategies, including microbial therapeutics (such as probiotics, prebiotics, and synbiotics), natural products (such as neohesperidin, isoquercitrin, and polysaccharides), and fecal microbiota transplantation, have been proposed to restore microbial balance and improve kidney function. Targeted modulation of the gut microbiota offers a promising strategy for developing novel treatments in AKI, CKD, and the transition from AKI-to-CKD. This approach has the potential to prevent or mitigate these conditions and their complications.}, }
@article {pmid41522487, year = {2026}, author = {Al Qassab, M and Chaarani, N and Hamou, A and Harb, R and Jradi, A and Zeineddine, M and Ghadieh, HE and Khattar, ZA and Azar, S and Kanaan, A and Harb, F}, title = {The Gut Microbiota-Insulin Resistance Axis: Mechanisms, Clinical Implications, and Therapeutic Potential.}, journal = {FASEB bioAdvances}, volume = {8}, number = {1}, pages = {e70080}, pmid = {41522487}, issn = {2573-9832}, abstract = {Emerging evidence highlights the pivotal role of the gut microbiota (GM) in regulating host metabolism and contributing to the development of insulin resistance (IR). Gut dysbiosis alters the production of critical metabolites, including short-chain fatty acids (SCFAs), bile acids, indole derivatives, and trimethylamine N-oxide (TMAO), which influence intestinal barrier integrity, inflammatory pathways, and glucose homeostasis. Recent clinical and translational studies indicate that SCFAs can improve fasting insulin and HOMA-IR, although the magnitude of benefit varies substantially across individuals, highlighting ongoing controversy surrounding their metabolic effects. Altered microbial regulation of bile-acid metabolism has also been implicated in impaired lipid and glucose signaling, reinforcing the relevance of FXR- and TGR5-mediated pathways in IR. Elevated TMAO levels have further been associated with adverse metabolic outcomes, though debate persists regarding its causal role versus its function as a diet-dependent biomarker. Microbiota-targeted strategies, including dietary fiber, probiotics, and fecal microbiota transplantation (FMT), show potential to modulate these metabolic pathways, yet clinical results remain inconsistent. This narrative review synthesizes recent mechanistic discoveries and clinical findings on microbiota-derived metabolites in IR, highlights key controversies, and outlines future priorities for translating microbiome science into effective and personalized interventions for metabolic disease prevention and management.}, }
@article {pmid41523687, year = {2026}, author = {Zhang, S and Cheng, X and Chen, L and Wang, Y}, title = {2'-Fucosyllactose (2'-FL) alleviates choline-deficient fat diet-induced nonalcoholic steatohepatitis (NASH) by remodeling intestinal flora.}, journal = {Food science and biotechnology}, volume = {35}, number = {1}, pages = {203-213}, pmid = {41523687}, issn = {2092-6456}, abstract = {UNLABELLED: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease lacking effective treatment. This study investigated 2'-Fucosyllactose (2'-FL) for its therapeutic potential. In vitro, 2'-FL reduced lipid accumulation, oxidative stress, and inflammation in Hepa1-6 cells. In a NASH mouse model, 2'-FL alleviated key disease features: hepatic steatosis, inflammation, and oxidative stress. Furthermore, 2'-FL intervention reversed NASH-associated gut microbiota dysbiosis, specifically by increasing Bacteroidota and decreasing Firmicutes at the phylum level. Fecal microbiota transplantation (FMT) validated the role of gut microbiota in these effects. The findings indicate that 2'-FL ameliorates NASH by remodeling the gut microbiota, thereby reducing endotoxemia and improving lipid metabolism. This suggests 2'-FL as a promising dietary intervention for metabolic liver diseases.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-02034-3.}, }
@article {pmid41523758, year = {2025}, author = {Khan, AS and Kamthan, M and Ali, A}, title = {Understanding the intricate interactions between microbiota and host.}, journal = {World journal of experimental medicine}, volume = {15}, number = {3}, pages = {101277}, pmid = {41523758}, issn = {2220-315X}, abstract = {The review examines the intricate relationship between the microbiota and its host, highlighting how these microbial communities influence various physiological functions beyond simple coexistence. The microbiota plays a crucial role in regulating the immune system, metabolism, and overall health. We explore the diverse microbial populations inhabiting different body regions and their essential contributions to maintaining balance within the host. Recent research has uncovered molecular mechanisms that govern microbiota-host interactions, offering new insights into how these microbes support health and, conversely, how imbalances known as dysbiosis can increase susceptibility to diseases. While much attention has been given to the gut microbiota, this review also explores the influence of microbes in other parts of the body, including their effects on various organs and tissues. Additionally, we discuss emerging evidence on the gut-brain axis, illustrating how the microbiota can impact brain function and behavior. Understanding this connection could open new possibilities for treating neurological and psychological disorders. Finally, we evaluate microbiota-based therapies such as probiotics and fecal microbiota transplantation, emphasizing the importance of personalized approaches. By integrating findings from multiple disciplines, this review provides a comprehensive perspective on the microbiota's vital role in human health and its potential as a therapeutic target.}, }
@article {pmid41525005, year = {2026}, author = {Mir, PA and Kumar, N and Bhutia, GT and Chaudhary, P and Kaur, G and Gupta, SK}, title = {The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.}, journal = {GeroScience}, volume = {48}, number = {2}, pages = {2201-2241}, pmid = {41525005}, issn = {2509-2723}, mesh = {*Alzheimer Disease/immunology/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; *Aging/immunology/physiology ; Probiotics/therapeutic use ; *Neuroglia/immunology/physiology ; *Neuroinflammatory Diseases/immunology ; Prebiotics ; Synbiotics ; Fecal Microbiota Transplantation ; Dysbiosis ; }, abstract = {Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.}, }
@article {pmid41525948, year = {2026}, author = {Valia, D and Karama, I and Ingelbeen, B and Garba, Z and van Kleef, E and Lompo, P and Tiendrebeogo, EW and Kaboré, B and Kiemdé, F and Yougbare, S and Tiendrebeogo, AL and Van Puyvelde, S and Prizzon, A and Vandenbroucke, AT and Argudín, MA and Kabamba, BM and Jacobs, J and Tinto, H and van der Sande, MAB and Robert, A and Rodriguez-Villalobos, H}, title = {Faecal colonization with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in rural Burkina Faso.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {32}, number = {7}, pages = {1125-1134}, doi = {10.1016/j.cmi.2026.01.001}, pmid = {41525948}, issn = {1469-0691}, mesh = {Humans ; Burkina Faso/epidemiology ; Cross-Sectional Studies ; *beta-Lactamases/genetics ; Rural Population ; *Klebsiella pneumoniae/isolation &amp; purification/genetics/enzymology/drug effects ; Female ; *Escherichia coli/genetics/isolation &amp; purification/enzymology/drug effects ; Male ; Adult ; *Escherichia coli Infections/epidemiology/microbiology ; *Feces/microbiology ; Prevalence ; Young Adult ; Adolescent ; Middle Aged ; *Klebsiella Infections/epidemiology/microbiology ; Child, Preschool ; Child ; Anti-Bacterial Agents/pharmacology ; Infant ; Aged ; Carrier State/epidemiology/microbiology ; Microbial Sensitivity Tests ; }, abstract = {OBJECTIVES: The burden of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is increasing globally and is often linked to community-acquisition in low-resource settings. In sub-Saharan Africa, occurrence of antimicrobial resistance (AMR) in rural areas remains understudied despite anticipated higher risks. We investigated the epidemiology and genetic characteristics of ESBL-E in rural Burkina Faso.<br><br>METHODS: In a community-based cross-sectional survey (May 2021 to May 2022), participants were randomly selected in two health catchment areas, and through face-to-face interviews, field workers collected data on hygiene, animal presence, household characteristics, and healthcare use. Stool samples were also collected for ESBL-E screening. Prevalence of extended-spectrum &#x3b2;-lactamase-producing Escherichia coli (ESBL-EC) and extended-spectrum &#x3b2;-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was estimated, and associated factors were assessed. Based on resistance profiles and PCR screening, selected isolates underwent whole genome sequencing.<br><br>RESULTS: Among 1482 participants, ESBL-E prevalence was 61.3% (58.8-63.7%); ESBL-EC prevalence was 53.0% (50.5-55.5%), and ESBL-KP prevalence was 22.3% (20.3-24.5%). Colonization was more common in the rainy season than in the dry season (70.2% vs. 53.6%, p < 0.001) and among individuals not washing hands with soap before meals (62.5% vs. 49.0%, p < 0.001). Ciprofloxacin resistance exceeded 65% in both species. The predominant extended-spectrum &#x3b2;-lactamase gene was blaCTX-M-15 (47.3% in ESBL-EC and 19.9% in ESBL-KP), with one ESBL-EC isolate carrying blaNDM-5. Incompatibility group F (IncF) plasmids predominated, and plasmid-mediated quinolone resistance genes (qnr, aac(6')-ib-cr and oqxAB) were frequently codetected with extended-spectrum &#x3b2;-lactamase genes.<br><br>CONCLUSIONS: ESBL-E prevalence was high and was associated with poor hygiene and seasonal variation. Higher rainy season prevalence was not explained by reported antibiotic use and may reflect increased environmental exposure risks, which requires further exploration. Improving hygiene standards and establishing community-level AMR surveillance can provide effective steps toward mitigating AMR burden in rural sub-Saharan Africa.}, }
@article {pmid41526816, year = {2026}, author = {Yang, Y and Wang, Y and Li, J and Gao, Y and Wu, Z and Tan, X and Feng, S and Cheng, W and Zhang, H and Gan, Q and Wei, H and Li, Q}, title = {Fecal microbiota transplantation from healthy piglets ameliorates intestinal inflammation in mice by modulating recipient metabolism.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {147}, pmid = {41526816}, issn = {1471-2180}, support = {2025J01556//Fujian Provincial Natural Science Foundation of China/ ; }, abstract = {Research in livestock indicates that the gut microbiota of healthy piglets plays a crucial role in regulating intestinal immune development. However, the potential of Fecal microbiota transplantation (FMT) derived from healthy piglets to alleviate intestinal inflammation in recipients and the underlying mechanisms remain unexplored. This study utilized FMT from healthy piglets to intervene in a dextran sulfate sodium (DSS)-induced intestinal inflammation model in germ-free Kunming mice, investigating its effects on intestinal barrier function and inflammatory levels. As anticipated, the results demonstrated that FMT significantly alleviated DSS-induced intestinal inflammation. This was evidenced by reduced weight loss and lower disease activity index scores. Furthermore, FMT improved intestinal barrier integrity, maintained homeostasis of host inflammatory cytokines, and markedly attenuated oxidative stress. Untargeted metabolomics analysis further revealed that FMT significantly increased the abundance of multiple metabolites, including 3-Methoxytyramine-betaxanthin and Sialorphin, downregulated several inflammation-related metabolites, including Cholic acid, and modulated host metabolic pathways (e.g., the betalain biosynthesis pathway). Correlation analysis revealed that the differential metabolites in the FMT group exhibited positive and negative associations with inflammatory markers. This study provides novel insights into the mechanism by which pig-derived gut microbiota alleviates host intestinal inflammation through modulation of host metabolism.}, }
@article {pmid41527019, year = {2026}, author = {Zhong, J and Zhu, B and Zou, Z and Li, Y and Feng, Y and Wu, K and Hou, X}, title = {Gut microbiota mediates the beneficial effects of exercise on autism-like behaviors.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {}, pmid = {41527019}, issn = {1471-2180}, support = {no. 2025A04J4356//the Guangzhou Municipal Science and Technology Bureau, Basic Research Program/ ; no. 2023B0303020001//the Key-Area Research and Development Program of Guangdong Province/ ; no. 2021ZDJS021//the Provincial Significant Scientific Research Projects for General Universities in Guangdong Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Rats ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism ; Female ; Feces/microbiology ; *Autism Spectrum Disorder/therapy/chemically induced/microbiology ; *Physical Conditioning, Animal ; Male ; RNA, Ribosomal, 16S/genetics ; Valproic Acid/adverse effects ; Rats, Sprague-Dawley ; Behavior, Animal ; Neurotransmitter Agents/metabolism ; Bacteria/classification/genetics/isolation &amp; purification ; Pregnancy ; *Autistic Disorder/therapy ; }, abstract = {BACKGROUND: The gut-brain axis plays a critical role in autism spectrum disorder (ASD), but the mechanisms through which exercise modulates gut microbiota, short-chain fatty acids (SCFAs), and central neurotransmitters to ameliorate ASD-like behaviors remain unclear. This study aimed to investigate the effects of exercise on ASD-like behaviors, gut microbiota, and metabolism in a valproic acid (VPA)-induced ASD rat model and to validate these findings via fecal microbiota transplantation (FMT).<br><br>METHODS: ASD rat models were established through prenatal exposure to VPA and divided into four groups: exercise (E_ASD), non-exercise (ASD), FMT, and sham FMT (sFMT). The E_ASD group underwent 6 weeks of voluntary wheel running, while the FMT group received fecal microbiota from the E_ASD group for 4 weeks. Behavioral assessments were conducted to evaluate cognitive and social functions. Fecal microbiota composition was analyzed via 16S rRNA sequencing, while SCFAs and neurotransmitters were measured using gas and liquid chromatography-mass spectrometry.<br><br>RESULTS: Six weeks of voluntary exercise significantly alleviated ASD-like behaviors, particularly improving social interactions. Exercise also altered gut microbiota composition, increasing Limosilactobacillus and Lactobacillus while decreasing Allobaculum. Additionally, SCFAs and neurotransmitter levels in the prefrontal cortex were modulated. Notably, FMT from the exercise group replicated these behavioral and metabolic improvements in ASD rats. Exercise improves ASD-like behaviors by modulating gut microbiota, SCFAs, and neurotransmitter levels, and FMT offers further validation of these effects.<br><br>CONCLUSION: These findings highlight exercise and FMT as promising strategies for alleviating ASD-related symptoms through gut-brain axis modulation.}, }
@article {pmid41527151, year = {2026}, author = {Li, JY and Huang, HB and Shi, CW and Pan, TX and Li, MH and Wang, N and Shan, JJ and Jiang, YL and Yang, WT and Cao, X and Wang, JZ and Guan, JY and Yu, SY and Wang, CF and Yang, GL}, title = {Increased caecal Intestinimonas abundance inhibits E. tenella gametogenesis via EtGFAT regulation and alleviates infection through immunity.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {62}, pmid = {41527151}, issn = {2049-2618}, support = {32072888, U21A20261, 32202819//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Eimeria tenella/growth &amp; development/physiology/pathogenicity/immunology/genetics ; *Cecum/microbiology/parasitology ; Chickens/parasitology ; *Poultry Diseases/parasitology/immunology/microbiology ; *Coccidiosis/veterinary/immunology/parasitology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Dysbiosis/veterinary ; }, abstract = {BACKGROUND: Chicken coccidiosis caused by Eimeria tenella (E. tenella) poses a major threat to global poultry production, with its tropism for the caecal microenvironment and dynamic interactions with the resident microbiota remaining incompletely understood. The caecal microbiota plays a critical role in host‒parasite interplay, yet the mechanisms through which microbial homeostasis influences E. tenella development and host resistance remain elusive. This study aimed to elucidate the causal relationship between caecal dysbiosis and E. tenella pathogenesis, with a focus on identifying microbiota-derived regulators of parasite development and host immunity.<br><br>RESULTS: Antibiotic-induced caecal dysbiosis (ABX) significantly impaired E. tenella macrogametogenesis, demonstrating microbiota-dependent regulation of parasitic development. Faecal microbiota transplantation (FMT) validated this causal link, revealing that microbial reconstitution restored parasite maturation. Notably, Intestinimonas spp. were identified as key inhibitors of E. tenella development through transcriptional regulation of the EtGFAT gene (Eimeria tenella glucosamine: fructose-6-phosphate aminotransferase), a critical mediator of macrogamete formation. Furthermore, the transplantation of Intestinimonas butyriciproducens (I. butyriciproducens) attenuated clinical manifestations of infection while increasing IFN-&#x3b3; secretion from CD8[+] T lymphocytes, thereby enhancing host resistance to E. tenella.<br><br>CONCLUSIONS: This study revealed that caecal microbiota homeostasis is indispensable for E. tenella developmental progression and highlights Intestinimonas as a pivotal microbial regulator of parasite biology. The dual role of I. butyriciproducens in suppressing parasitic virulence and potentiating adaptive immune responses underscores the therapeutic potential of microbiota-targeted strategies. These findings provide a foundation for the development of novel anticoccidial interventions through targeted manipulation of caecal microbial communities. Video Abstract.}, }
@article {pmid41529466, year = {2026}, author = {Wang, Z and Yu, Y and Shao, W and Zhao, Y and Li, Z and Han, J and Wen, J and Meng, Y and Lin, Y and Wang, S}, title = {Puerarin ameliorates alcoholic liver disease by regulating intestinal flora and MAPK/Nrf2 signalling pathways.}, journal = {Ecotoxicology and environmental safety}, volume = {309}, number = {}, pages = {119699}, doi = {10.1016/j.ecoenv.2026.119699}, pmid = {41529466}, issn = {1090-2414}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Isoflavones/pharmacology ; Male ; *Liver Diseases, Alcoholic/drug therapy/metabolism ; *NF-E2-Related Factor 2/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; *MAP Kinase Signaling System/drug effects ; Fecal Microbiota Transplantation ; Feces ; Oxidative Stress/drug effects ; }, abstract = {Puerarin is a natural flavonoid glycoside extracted from the traditional Chinese medicine Puerariae Lobatae Radix or Pueraria lobata (Willd), known for its hepatoprotective properties. While prior studies indicate that PR can mitigate ALD, the underlying mechanisms by which PR exerts its anti-ALD effects via intestinal flora remain poorly understood. This study aimed to investigate the metabolic differences of PR in normal and ALD model rats were analyzed using UHPLC-HRMS. Further validation of PR metabolic products in vivo through in vitro fecal fermentation. Additionally, the relationship between the anti-ALD properties of PR and intestinal flora was explored using 16S rRNA sequencing technology, with confirmation obtained from fecal microbiota transplantation (FMT) experiments and functional strain experiments. Finally, through non-targeted metabolomics and liver transcriptomics combined with in vitro cell pharmacological studies, the mechanism of action of PR and its in vitro fermentation metabolites against ALD was explored. In the PR metabolic test, 20 metabolites were identified in the serum, urine, and feces of normal and ALD model rats, primarily associated with reactions including deglycosylation, hydrogenation, aldehyde esterification, hydroxylation, and methylation. 6 metabolites were verified in vitro transformation system. Subsequently, we used FMT experiments and 16S rRNA sequencing to find that intestinal flora imbalance can lead to liver disease and PR can improve liver disease by regulating intestinal flora. Based on multi-omics analysis and in vitro pharmacological activity analysis, PR and its in vitro fermented metabolites inhibit MAPK and Nrf2 pathways, further reducing inflammation and oxidative stress. The results of this study show that PR can improve ALD, with its mechanism of action potentially involving regulation of the intestinal flora, suppression of inflammatory responses, and inhibition of oxidative stress.}, }
@article {pmid41530574, year = {2026}, author = {Deng, YH and Liu, Q and Luo, XQ}, title = {The gut-kidney axis in pediatric acute kidney injury: a review of pathophysiological mechanisms and therapeutic frontiers.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {41530574}, issn = {1432-198X}, support = {2024JJ6595//Natural Science Foundation of Hunan Province/ ; }, abstract = {Acute kidney injury (AKI) is a frequent and severe condition in hospitalized children, leading to significant morbidity, mortality, and long-term risk of chronic kidney disease. This review explores the gut-kidney axis, a concept describing the bidirectional relationship between the gut microbiome and kidney function, as a critical driver of pediatric AKI. In critically ill children, interventions such as broad-spectrum antibiotics and necessary nutritional support strategies (e.g., parenteral nutrition or fasting) can cause profound gut microbial imbalance (dysbiosis). This dysbiosis initiates a deleterious feedback loop, exacerbating kidney injury. Key mechanisms include the disruption of the intestinal barrier (leaky gut), which allows bacterial endotoxins to enter the bloodstream, triggering renal inflammation via Toll-like receptor 4 signaling. Concurrently, the dysbiotic gut increases production of directly nephrotoxic gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, while failing to produce protective anti-inflammatory metabolites like short-chain fatty acids. While therapies targeting the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, are theoretically promising, their clinical use in pediatric AKI is unsupported by evidence and carries substantial risks, particularly iatrogenic infection. A significant knowledge gap exists due to a relative lack of pediatric-specific clinical research. The conclusion emphasizes an urgent need for longitudinal, multi-omics studies in children to understand this axis, identify functional biomarkers, and develop safe, targeted therapies to improve outcomes.}, }
@article {pmid41530607, year = {2026}, author = {Miller, CB and Bader, GA and Kay, CL}, title = {Fecal Microbiota Transplantation in 2025: Two Steps Forward, One Step Back.}, journal = {Current gastroenterology reports}, volume = {28}, number = {1}, pages = {5}, pmid = {41530607}, issn = {1534-312X}, mesh = {*Fecal Microbiota Transplantation/trends/methods/history ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Irritable Bowel Syndrome/therapy ; *Clostridium Infections/therapy ; }, abstract = {PURPOSE OF REVIEW: This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT-highlighting major advances and minor setbacks that have led to the state of FMT in 2025.<br><br>RECENT FINDINGS: After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk-in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome's halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025. Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome's role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.}, }
@article {pmid41530748, year = {2026}, author = {Zhang, Y and Sun, C and Wang, Y and Zhang, H and Fan, Y and Zhao, H and Li, P}, title = {Targeting gut-liver-kidney axis: microbiota-derived metabolites and therapeutic implications.}, journal = {Cell communication and signaling : CCS}, volume = {24}, number = {1}, pages = {107}, pmid = {41530748}, issn = {1478-811X}, support = {82174296//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Liver/metabolism ; *Gastrointestinal Microbiome ; Animals ; *Kidney/metabolism ; }, abstract = {The gut-liver-kidney axis has emerged as a central regulatory network orchestrating metabolic, immune, and inflammatory homeostasis across organ systems. At its core lies the dynamic interplay between gut microbiota and host metabolism. Dysbiosis and impaired intestinal barrier integrity facilitate the systemic translocation of microbial metabolites-such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine-N-oxide (TMAO), and tryptophan derivatives-which profoundly influence hepatic lipid metabolism, renal immune responses, and overall metabolic balance. This review examines the molecular mechanisms through which gut-derived metabolites contribute to liver and kidney pathology, emphasizing inter-organ signaling and the pathological cascade of the "leaky gut-hepatic injury-renal dysfunction" loop. We critically evaluate emerging therapeutic strategies targeting this axis, including probiotic supplementation, fecal microbiota transplantation (FMT), dietary modulation (low-protein, high-fiber regimens), and pharmacological detoxification (e.g., AST‑120, molecular adsorbent recirculating systems [MARS]). Finally, we propose a conceptual "diet-microbiota-drug" triad to guide precision interventions, and discuss current challenges such as interindividual variability, the lack of standardized assessment tools, and the need for integrative multi‑omics and clinical validation. A deeper mechanistic understanding of gut-organ crosstalk may pave the way for innovative therapies to restore systemic metabolic homeostasis.}, }
@article {pmid41532069, year = {2026}, author = {Mu, S and Chang, M and Shen, Y and Wu, X and Han, Y and Xiang, H and Luo, Y and Chen, Y and Zheng, H and Song, Z and Tong, C}, title = {Gut microbiota metabolite butyric acid alleviated Klebsiella Pneumoniae induced lung injury by regulating CX3CR1[+]NK via PI3K/AKT pathway.}, journal = {Burns &amp; trauma}, volume = {14}, number = {}, pages = {tkaf069}, pmid = {41532069}, issn = {2321-3868}, abstract = {BACKGROUND: The expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. This study aims to explore the role of gut microbiota components in regulating CX3CR1 expression and its impact on pneumonia-induced lung injury during sepsis.<br><br>METHODS: Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved.<br><br>RESULTS: In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1[+] NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1[+] NK cells and interferon (IFN)-&#x3b3; secretion, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability.<br><br>CONCLUSIONS: We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1[+] NK cells via the PI3K/AKT pathway.}, }
@article {pmid41535289, year = {2026}, author = {Panah, FM and Støving, RK and Sjögren, M and Micali, N and Maschek, S and Reis, KD and Mirsepasi-Lauridsen, HC and Petersen, AM and Nielsen, DS and Helms, M and Rasmussen, MA and Barfod, KK}, title = {Impact of a single fecal microbiome transplantation in adult women with anorexia nervosa: an open-label feasibility pilot trial.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {1747}, pmid = {41535289}, issn = {2041-1723}, support = {R370-2021-863//Lundbeckfonden (Lundbeck Foundation)/ ; }, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation/methods ; *Anorexia Nervosa/therapy/microbiology/psychology ; Pilot Projects ; Adult ; Feasibility Studies ; Feces/microbiology ; Young Adult ; *Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Dysbiosis/therapy ; }, abstract = {Anorexia nervosa (AN) is a severe mental disorder characterized by restrictive eating and disturbance in the way one's body weight or shape is experienced, often accompanied by depression and anxiety. Current evidence-based treatments for AN have limited efficacy, with less than half of the patients achieving full recovery in long-term follow-up studies. Recent findings have identified gut microbiota (GM) dysbiosis as a potential contributor to AN pathology through the gut-brain axis. This open-label, non-randomized, feasibility trial (Clinicaltrials.gov Identifier: NCT05834010) evaluated the feasibility of utilizing fecal microbiota transplantation (FMT) to modify the GM and GM-associated signaling in females with AN and to examine biological effects following a single FMT procedure. Adult female participants diagnosed with AN were recruited. FMT was administered either orally via capsules or as rectal enema. Stool and blood samples were collected pre- and one week post-FMT to assess GM composition, hormonal changes, and biomarkers. Primary endpoints: Feasibility of FMT in individuals with AN and preferred route of FMT. Secondary endpoints: A single FMT treatment can alter GM composition in individuals with AN short term and relevant gut brain signaling in serum. 18/22 participants (81%) completed FMT and sampling and 19/22 participants chose oral capsules, with no serious adverse effects reported. GM analysis showed significant shifts toward donor composition 1-week post-FMT, with improved stool consistency. No significant changes were observed in psychopathology measures or appetite-related biomarkers. Oral FMT is a feasible intervention for adult women with AN, leading to changes in GM profile. Future studies should focus on placebo-controlled trials to assess the efficacy of repeated oral treatments and explore long-term effects on GM, appetite, body weight, sex hormones, disorder-specific symptoms, and overall well-being.}, }
@article {pmid41535300, year = {2026}, author = {Wong, OWH and Xu, Z and Chan, SSM and Mo, FYM and Shea, CKS and Su, Q and Wan, MYT and Cheung, CP and Ching, JYL and Tang, W and Tun, HM and Chan, FKL and Ng, SC}, title = {A novel synbiotic (SCM06) for anxiety and sensory hyperresponsiveness in children with autism spectrum disorder: an open-label pilot study.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {36}, pmid = {41535300}, issn = {2055-5008}, support = {NCI202346//New Cornerstone Science Foundation/ ; }, mesh = {Humans ; Pilot Projects ; *Autism Spectrum Disorder/microbiology/complications/psychology ; Male ; Child ; *Synbiotics/administration &amp; dosage ; *Anxiety/therapy ; Female ; Feces/microbiology ; Metagenomics ; Gastrointestinal Microbiome ; Child, Preschool ; Pentanoic Acids ; Treatment Outcome ; }, abstract = {Anxiety and sensory hyperresponsiveness are common in children with autism spectrum disorder (ASD), but effective treatments are lacking. Targeting the microbiota-gut-brain axis is a promising strategy. This open-label pilot study evaluated SCM06, a novel synbiotic designed to target anxiety and sensory hyperresponsiveness, in 30 children with ASD (mean age 8.2 years, 22 males). We assessed symptom improvement, compliance, and safety, and collected stool samples for metagenomics and metabolomic analysis over 12 weeks. SCM06 was safe and well-tolerated, and significant improvements were observed in anxiety, sensory hyperresponsiveness, and abdominal pain. Following SCM06 treatment, increase in Bifidobacterium pseudocatenulatum was associated with improved functional abdominal pain (p = 0.0011, p_adj = 0.054), while the abundances of valeric acid and butyric acid increased (p_adj = 0.004 and p_adj = 0.072). Key microbial species, Coprococcus comes and Veillonella dispar, were candidate mediators of symptom improvements. Further randomised controlled trials are warranted to confirm its clinical efficacy.}, }
@article {pmid41535683, year = {2026}, author = {Chen, S and Yuan, Y and Wang, Y and Peng, Y and Tun, HM and Jiang, Z and Miao, Y and Lee, S and Yin, X and Shen, X and DeLeon, O and Chang, EB and Chan, FKL and Sun, Y and Ng, SC and Su, Q}, title = {Identification of antimicrobial peptides from ancient gut microbiomes.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {1788}, pmid = {41535683}, issn = {2041-1723}, support = {2025 Youth Science and Technology Talent Development Program//China Association for Science and Technology (China Association for Science &amp; Technology)/ ; }, mesh = {Humans ; *Antimicrobial Peptides/pharmacology/isolation &amp; purification/chemistry ; Animals ; Feces/microbiology ; Metagenome ; *Gastrointestinal Microbiome ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Fecal coprolites preserve ancient microbiomes and are a potential source of extinct but highly efficacious antimicrobial peptides (AMPs). Here, we develop AMPLiT (AMP Lightweight Identification Tool), an efficient tool deployable to portable hardware for AMP screening in metagenomic datasets. AMPLiT demonstrates AUPRC performances of 0.9486 ± 0.0003 and reasonable overall training time of 3200 ± 53 s. By computationally utilizing AMPLiT, we analyze seven ancient human coprolite metagenomes, identifying 160 AMP candidates. Of 40 representative peptides synthesized, 36 (90%) peptides demonstrate measurable antimicrobial activity at 100 μM or less in vitro. Strikingly, approximately two-thirds of these peptides are sourced from Segatella copri, a dominant ancient gut commensal that is conspicuously underrepresented in modern populations, particularly those with Westernized lifestyles. Representative S. copri-derived AMPs exhibit disruptions against membranes of pathogenic bacteria, coupled with low cytotoxicity and hemolytic risk. In vivo, lead peptides demonstrate potent antibacterial and wound-healing efficacy comparable to traditional antibiotics, especially in combating gram-positive pathogens. Our findings highlight the ancient gut microbiomes as sources of novel AMPs, offering valuable insights into the historical role of S. copri in human health and its decline in contemporary populations.}, }
@article {pmid41535719, year = {2026}, author = {Almonte, AA and Thomas, S and Iebba, V and Kroemer, G and Derosa, L and Zitvogel, L}, title = {Gut dysbiosis in oncology: a risk factor for immunoresistance.}, journal = {Cell research}, volume = {36}, number = {2}, pages = {103-120}, pmid = {41535719}, issn = {1748-7838}, support = {INCA_16698//CNIB (INCA)/ ; 955575//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *Neoplasms/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; Risk Factors ; Animals ; }, abstract = {The gut microbiome is recognized as a determinant of response to immune checkpoint inhibitor (ICI) therapies in cancer. However, the clinical translation of microbiome science has been hampered by inconsistent definitions of dysbiosis, inadequate biomarker frameworks, and limited mechanistic understanding. In this review, we synthesize the current state of knowledge on how gut microbial composition and function influence ICI efficacy, highlighting both correlative and causal evidence. We discuss computational approaches based on α-diversity or taxonomic abundance and argue for more functionally and clinically informative models, such as the topological score (TOPOSCORE) and other dysbiosis indices derived from machine learning. Using retrospective analyses of metagenomic datasets from thousands of patients and healthy controls, we examine microbial patterns that distinguish responders from non-responders. We also explore how dysbiosis perturbs immunoregulatory pathways, including bile acid metabolism, gut permeability, and mucosal immunomodulation. Finally, we assess emerging therapeutic strategies aimed at correcting microbiome dysfunction - including dietary modification, bacterial consortia, and fecal microbiota transplantation - and describe how they are being deployed in multiple clinical trials. We conclude with a brief discussion of the ONCOBIOME initiative, which works with international partners to incorporate microbiome science into oncology workflows. By refining our understanding of gut-immune interactions and translating it into action, microbiome-informed oncology may unlock new therapeutic potential for patients previously resistant to immunotherapy.}, }
@article {pmid41536244, year = {2026}, author = {Girdhar, K and Dedrick, S and Rhodes, L and Kim, D and Powis, A and Mahon, C and Chapdelaine, H and Obaid, L and McNamara, M and Altindis, E}, title = {Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2614039}, pmid = {41536244}, issn = {1949-0984}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology/immunology ; Animals ; *Gastrointestinal Microbiome ; *Diet ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; }, abstract = {The incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.}, }
@article {pmid41538653, year = {2026}, author = {Zhang, H and Sun, J and Zheng, X and Yang, H and Xie, A and Ding, Y and Mei, Y and Li, J and Hu, Y and Ren, M and Liu, Y and Liang, Y}, title = {Fermented Lacticaseibacillus Paracasei Cultures Ameliorate Colitis by Modulating Microbiota-Derived Tryptophan Metabolism and Macrophage Polarization.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {13}, pages = {e13920}, pmid = {41538653}, issn = {2198-3844}, support = {HBNYHXGG2024-10//Hubei Provincial Agricultural Science and Technology Research Project/ ; 2024AFB698//Natural Science Foundation of Hubei Province, China/ ; 2022BCE006//Key Research and Development Program of Hubei Province/ ; 2662025SKPY011//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Colitis/metabolism/chemically induced/microbiology ; *Tryptophan/metabolism ; *Probiotics/pharmacology ; *Lacticaseibacillus paracasei/metabolism ; *Macrophages/metabolism ; *Gastrointestinal Microbiome/physiology/drug effects ; Mice ; Fermentation ; Dextran Sulfate ; Disease Models, Animal ; *Inflammatory Bowel Diseases/metabolism ; Mice, Inbred C57BL ; }, abstract = {High-density solid-state fermented probiotic products, combining live bacteria with microbial and substrate-derived bioactives, offer a potential solution to address dysregulation of gut microbiota-immune homeostasis associated with inflammatory bowel disease (IBD). However, their synergistic efficacy against IBD remains elusive. Here, we discuss our high-density solid-state fermented Lacticaseibacillus paracasei culture (PYW) and its effects on dextran sulfate sodium (DSS)-induced colitis. Comparison of the effects of PYW, enriched with viable cells and bioactive metabolites-obtained via fermentation with wheat bran-with those of its thermally inactivated postbiotic (SPYW) shows superior efficacy of PYW than SPYW, with a viable bacterial load of ≥ 5 × 10[10] CFU g[-1] being indispensable. PYW effectively restores microbiota structure, restructures the gut tryptophan metabolic network, enriching indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA), which activate the aryl hydrocarbon receptor (AhR) signaling pathway, suppress pro-inflammatory mediators, and strengthen mucosal barriers. Antibiotic depletion abolishes the effects of PYW, while fecal microbiota transplantation from PYW-treated donors and exogenous ILA/IAA supplementation replicate its anti-colitic benefits. These findings suggest that PYW alleviates colitis via microbiota-dependent enrichment of ILA/IAA and subsequent AhR pathway activation, highlighting its potential as a probiotic therapeutic targeting the microbiota-metabolism-immunity regulatory axis in IBD.}, }
@article {pmid41538937, year = {2026}, author = {Yan, H and Wang, C and Wang, H and Liu, J and Zhou, H and Zhong, W and Wang, X and Chen, Y and Ju, Z and Tong, H and Zhang, Y}, title = {Perfluorooctane sulfonates drives colitis via a gut microbiota-bile acid-endoplasmic reticulum stress axis in mice: Mechanistic validation and targeted interventions.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141122}, doi = {10.1016/j.jhazmat.2026.141122}, pmid = {41538937}, issn = {1873-3336}, mesh = {Animals ; *Fluorocarbons/toxicity ; *Alkanesulfonic Acids/toxicity ; *Colitis/chemically induced/microbiology/metabolism/pathology ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Endoplasmic Reticulum Stress/drug effects ; Mice ; *Environmental Pollutants/toxicity ; Male ; Mice, Inbred C57BL ; }, abstract = {Perfluorooctane sulfonate (PFOS), a widespread environmental pollutant, is implicated in systemic toxicity, yet its role in colitis remains unclear. This study aimed to investigate whether PFOS exacerbates colitis via the gut microbiota-bile acid-endoplasmic reticulum stress (ERS) axis and to explore potential interventions. Following 15-week oral PFOS exposure (0.1 or 0.3 mg/kg/d), mice developed dose-dependent colitis, featuring weight loss, colon shortening, barrier dysfunction, and elevated inflammation. High-dose PFOS disturbed bile acid homeostasis, depleting conjugated species like tauroursodeoxycholic acid (TUDCA) while accumulating deconjugated bile acids such as deoxycholic acid (DCA), thereby activating ERS pathways (PERK/eIF2α, IRE1/XBP1, ATF6). Gut microbiota analysis revealed reduced diversity, a lower Firmicutes/Bacteroidetes ratio, increased bacteria with bile salt hydrolase (BSH) activity (e.g., Lachnospira), and decreased potential bacteria (e.g., Akkermansia). Interventions with TUDCA, a BSH inhibitor, or fecal microbiota transplantation from healthy donors alleviated colitis, restored conjugated bile acids, and suppressed ERS. These findings demonstrate that PFOS triggers colitis via BSH-mediated bile acid deconjugation and ERS activation, highlighting the therapeutic potential of targeting this axis.}, }
@article {pmid41539089, year = {2026}, author = {Ou, G and Wu, J and Wang, S and Bi, W and Peng, R and Liu, P and Jiang, Y and Chen, Y and Xu, H and Deng, L and Zhao, H and Chen, X and Xu, L}, title = {Plantago asiatica L. extract alleviates hyperuricemia-associated renal injury by modulating gut microbiota to inhibit NLRP3 inflammasome activation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157771}, doi = {10.1016/j.phymed.2026.157771}, pmid = {41539089}, issn = {1618-095X}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Hyperuricemia/drug therapy/chemically induced/complications ; *Plantago/chemistry ; *Inflammasomes/metabolism/drug effects ; *Gastrointestinal Microbiome/drug effects ; Male ; *Plant Extracts/pharmacology ; Uric Acid/blood/metabolism ; Mice ; Kidney/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid.<br><br>METHODS: A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium.<br><br>RESULTS: In the HUA model, elevated sUA levels (p < 0.01), activation of the renal NLRP3 inflammasome (p < 0.05), renal edema, and impaired renal function were accompanied by gut microbiota dysbiosis. PTGA extract markedly reduced sUA levels by approximately 70 % compared to the model group (p&#x2009;<&#x2009;0.01), regulated uric acid transporter expression in both the intestine and kidney (p < 0.05), and reshaped gut microbiota composition. Moreover, PTGA enhanced intestinal uric acid catabolism of uric acid in the intestine. FMT and Lachnospiraceae bacterium supplementation experiments further confirmed the regulation of the gut microbiota is a key mediator of PTGA's therapeutic efficacy.<br><br>CONCLUSION: This study demonstrates that PTGA exerts hypouricemic and renoprotective effects through modulation of the gut-kidney axis by enriching Lachnospiraceae, promoting intestinal uric acid catabolism, and suppressing renal NLRP3 inflammasome activation. These findings provide novel mechanistic insights into the gut microbiota-dependent therapeutic action of herbal medicine, distinguishing this work from previous studies focused solely on direct organ-level effects.}, }
@article {pmid41539094, year = {2026}, author = {Wang, L and Xiong, Z and Chen, J and Liu, J and Liu, M and Yan, X and Fang, Z}, title = {Synergistic gut microbiome-host lipid axis underlies the antihypertensive effect of Qianyang Yuyin formula.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157804}, doi = {10.1016/j.phymed.2026.157804}, pmid = {41539094}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; *Antihypertensive Agents/pharmacology ; Male ; Rats ; *Lipid Metabolism/drug effects ; Rats, Inbred SHR ; Blood Pressure/drug effects ; *Prehypertension/drug therapy/microbiology ; Fecal Microbiota Transplantation ; Dysbiosis ; Hypertension/drug therapy ; Disease Models, Animal ; }, abstract = {BACKGROUND: Prehypertension (Pre-HTN) is highly prevalent and substantially increases the risk of developing hypertension and cardiovascular disease. Gut microbiota (GM) dysbiosis and altered lipid metabolism are increasingly recognized as critical regulators of blood pressure (BP). Traditional Chinese Medicine (TCM) formulas, such as Qianyang Yuyin Granules (QYYY), offer multi-target interventions, yet their preventive mechanisms in Pre-HTN remain unclear.<br><br>PURPOSE: This study aimed to investigate the antihypertensive effects of QYYY and elucidate its underlying mechanisms in a prehypertensive rat model.<br><br>METHODS: Prehypertensive spontaneously hypertensive rats (SHRs) were treated with QYYY for four weeks. Multi-omics analyses, including metagenomics, plasma metabolomics, and transcriptomics, were conducted. Causal involvement of GM was tested using antibiotic-induced pseudo-germ-free SHRs with fecal microbiota transplantation (FMT) from QYYY-treated donors, administered alone or in combination with QYYY. Gut barrier integrity, systemic inflammation, and vascular function were evaluated by histology, immunofluorescence, transmission electron microscopy, and ELISA.<br><br>RESULTS: QYYY significantly lowered SBP and DBP, reversed GM dysbiosis, normalized the Firmicutes/Bacteroidetes ratio, and modulated differential bacteria including Frisingicoccus and Blautia. These microbial shifts correlated with restoration of lysophosphatidylethanolamines (LPEs), inversely associated with BP, revealing a GM-lipid-BP axis. FMT alone was insufficient, whereas the combination of FMT+QYYY produced the strongest antihypertensive effect, restoring intestinal barrier integrity, enhancing ZO-1 expression, and normalizing Ang-II and NO levels. Transcriptomic analyses suggested PPAR and ROS signaling pathways as potential mechanisms mediating the antihypertensive effect of QYYY.<br><br>CONCLUSION: QYYY prevents BP elevation in Pre-HTN via synergistic microbiota-dependent and independent mechanisms, offering a comprehensive strategy for early hypertension prevention.}, }
@article {pmid41539104, year = {2026}, author = {Gong, Z and Xia, Y and Jiang, Y and Zhang, Y and Xu, C and Zhao, L and Zhang, R and Cai, W and Wen, Y and Ma, J and Yang, S and Gao, S}, title = {Xin-Ji-Er-Kang alleviates heart failure induced by myocardial ischemia-reperfusion injury through reshaping gut microbiota and metabolites.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157800}, doi = {10.1016/j.phymed.2026.157800}, pmid = {41539104}, issn = {1618-095X}, mesh = {Animals ; *Heart Failure/drug therapy/etiology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Mice ; Male ; Fecal Microbiota Transplantation ; *Myocardial Reperfusion Injury/complications/drug therapy ; Disease Models, Animal ; Mice, Inbred C57BL ; Feces/microbiology ; Myocardium/pathology ; }, abstract = {BACKGROUND: The relationship between the gut-heart axis and heart failure has attracted growing interest, making the gut microbiota a potential target for new treatments. Previously, we have reported the beneficial effects of the traditional Chinese medicine Xin-Ji-Er-Kang (XJEK) on heart failure (HF), but the influence of the intestinal microbiota on XJEK's protection of the heart remains to be confirmed.<br><br>PURPOSE: This study investigates the role of gut microbiota in XJEK's therapeutic impact on HF and elucidates its potential mechanism.<br><br>STUDY DESIGN: MIR-induced HF model mice were established and different concentrations of XJEK were administered by gavage. The pharmacological effects of XJEK were evaluated by multiple pharmacodynamic methods. Subsequently, fecal microbiota transplantation (FMT) and antibiotic-induced microbiota inhibition were used to explore the effect of XJEK on HF. We next employed 16S rRNA sequencing combined with fecal metabolomics to investigate alterations in gut microbiota and metabolic profiles, and further investigated the effects of mono-colonization with D. piger in mice.<br><br>RESULTS: XJEK administration dose-dependently enhanced cardiac function and reduced myocardial damage in MIR-induced HF mice, as evidenced by reduced cardiomyocyte hypertrophy, diminished myocardial fibrosis, and a decline in serum levels of NT-proBNP and cTnI. FMT from XJEK-treated mice to recipient mice revealed that the therapeutic effects of XJEK on heart failure partially depend on the gut microbiota. XJEK reshaped the gut microbiota, leading to elevated abundance of probiotics Faecalibacterium, Limosilactobacillus and Bifidobacterium, while pathogenic bacteria Staphylococcus was depleted. Additionally, XJEK elevated the levels of beneficial metabolites, including deoxycholic acid and &#x3b2;-MCA. Notably, XJEK led to a rise in the relative abundance of D. fairfieldensis, and through the study of D. piger of the same genus, it was found that Desulfovibrio may produce beneficial effects in HF mice.<br><br>CONCLUSION: XJEK effectively improved cardiac function, mitigated myocardial injury, and suppressed the progression of heart failure. XJEK improved gut microbiota composition and related metabolism, alleviating heart failure.}, }
@article {pmid41539110, year = {2026}, author = {Shrivastav, K and Pandey, M and Gor, H and Nema, V}, title = {Gut virome plays an extended role with bacteriome in neurological health and disease.}, journal = {Journal of the neurological sciences}, volume = {481}, number = {}, pages = {125754}, doi = {10.1016/j.jns.2026.125754}, pmid = {41539110}, issn = {1878-5883}, mesh = {Humans ; *Nervous System Diseases/microbiology/virology/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis ; *Virome/physiology ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; }, abstract = {The gut-brain axis (GBA) is a complex two-way communication system that links the gastrointestinal tract and the central nervous system (CNS) through neural, immune, hormonal, and microbial pathways. The microbiota-gut-brain axis (MGBA), a more specific concept, focuses on how gut microorganisms, including bacteria, viruses, and other microbes, modulate this communication and influence neurological health. This comprehensive review examines the intricate mechanisms through which gut microorganisms modulate neural function and contribute to neurological health and disease pathogenesis. The gut microbiota, comprising bacteria, viruses, fungi, and bacteriophages, produces essential neuroactive compounds including neurotransmitters- Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), short-chain fatty acids (SCFAs), and metabolites that directly influence brain physiology through vagal, hormonal, and immunological pathways. Dysbiosis of the gut microbiota has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorders, and schizophrenia. In healthy conditions, beneficial bacterial strains such as Lactobacillus species synthesize GABA and regulate mood, while SCFA-producing bacteria like Fecalibacterium prausnitzii maintain blood-brain barrier integrity and exert neuroprotective effects. Conversely, pathological states demonstrate altered microbial compositions, reduced bacterial diversity, and compromised production of beneficial metabolites. Emerging evidence highlights the previously underexplored role of the gut virome, particularly bacteriophages, in regulating bacterial populations and influencing neurodevelopment. Viral dysbiosis correlates with cognitive impairment and neurodegenerative processes through modulation of bacterial metabolism and inflammatory responses. Understanding these complex host-microbiome-virome interactions provides novel therapeutic opportunities for neurological disorders through targeted interventions including probiotics, fecal microbiota transplantation, and phage-based therapies, representing a paradigm shift toward microbiome-centered approaches in neurological medicine.}, }
@article {pmid41539609, year = {2026}, author = {Yang, D and Ren, D and Zhang, Y and Hao, Y and Yue, Y and Li, Q and Fan, Q and Sun, C and Cui, M and Zhang, M}, title = {The gut microbiota dysbiosis in geriatric multimorbidity: Pharmacotherapeutic implications, pathophysiological mechanisms, and precision modulation strategies.}, journal = {Ageing research reviews}, volume = {115}, number = {}, pages = {103023}, doi = {10.1016/j.arr.2026.103023}, pmid = {41539609}, issn = {1872-9649}, mesh = {Humans ; *Dysbiosis/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology/drug effects ; *Multimorbidity ; Precision Medicine ; *Aging/physiology ; Polypharmacy ; Aged ; }, abstract = {Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these reasons, the gut microbiota is becoming an important therapeutic target for optimizing precision medicine strategies in treating patients with geriatric multimorbidities. In this narrative review, we systematically synthesize the evidence regarding how gut dysbiosis leads to decreased efficacy of multi-drug regimens through the interplay between metabolism, immune response, and barrier function in aging patients with multimorbidities, and we evaluate targeted interventions. Furthermore, we demonstrate that current interventions (e.g., probiotics, prebiotics, fecal microbiota transplants (FMT), phage therapy, and dietary modulation) have unique benefits but are limited by inter-individual variability, safety concerns, and a lack of proven long-term efficacy. Thus, many areas of microbiota-drug interactions in older adults with multimorbidity should be explored through future research. Key areas to address are: the establishment of large, multicenter longitudinal cohorts of older adults with multimorbidity that would allow for repeated collection of microbiota profiles, medication use, and health outcomes to identify the evolving interaction between multimorbidity, microbiota, and polypharmacy; the urgent need for standardized and integrated databases of microbiome-drug interactions that harmonize data formats, provide metabolic annotations and medication identifiers in order to support reproducible cross-study validation; and the further validation and application of artificial intelligence (AI) and machine learning (ML) in clinical trials. High-dimensional data collected from cohorts and databases will enable the development of predictive algorithms to identify individual drug responses and how effective microbiota-targeted interventions will be; these algorithms must then be prospectively validated. Ultimately, these initiatives are necessary to move toward the personalized management of microbiota-drug interactions in older adults with multimorbidity, providing greater safety of polypharmacy and promoting healthy aging.}, }
@article {pmid41539758, year = {2026}, author = {Zhang, T and Liu, H and Yuan, J and Xie, B}, title = {Auricularia auricula polysaccharides intervention in vivo: inhibition of endogenous malodorous gas compounds through gut regulation and enhanced liver metabolism.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118122}, doi = {10.1016/j.foodres.2025.118122}, pmid = {41539758}, issn = {1873-7145}, mesh = {Animals ; *Liver/metabolism/drug effects ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; *Prebiotics ; Rats ; *Auricularia/chemistry ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Fermentation ; Feces/microbiology/chemistry ; Diet, High-Protein/adverse effects ; *Gases/metabolism ; }, abstract = {High-fat and high-protein diets increase susceptibility to endogenous malodorous gas compounds (EMGCs), particularly in long-term enclosed environments with limited nutrients. Auricularia auricula polysaccharides (AAP) are proposed to mitigate protein residues fermentation by gut microbiota, thereby reducing EMGCs accumulation and benefiting both health and environmental quality. This study elucidated the prebiotic mechanisms of AAP via rat interventions, fecal microbiota transplantation in pseudo-sterile rats, and in vitro fermentation with AAP-derived functional components and specific bacterial strains. Results demonstrated that AAP intervention effectively reduced EMGCs levels in feces and adipose tissue induced by high-fat and high-protein diets. The degradation products of AAP, including mannitol, lactose, and lyxose, along with reshaped gut microbiota, especially the functional strain Bacteroides xylanisolvens, all exhibited independent EMGCs-inhibiting activities. Mechanistically, AAP or its degradation products enhanced hepatic CYP450 expression through bile acid-mediated enterohepatic circulation, forming a gut-liver axis for EMGCs suppression. Additionally, gut metabolites lactose and maltose promoted colonic carbohydrate absorption, hepatic Col5a3 and Col1a1 enhanced hepatic protein absorption. Upregulated gut metabolites (histidine, choline bitartrate, lactose, maltose) and hepatic genes (Abcg8, Abcb9) enriched the ABC transporter pathway, expediting hepatic EMGCs excretion. This study supports AAP as a dietary supplement to inhibit EMGCs, ensuring environmental livability and health.}, }
@article {pmid41539785, year = {2026}, author = {Huang, F and Guo, A and Liu, S and Liu, H and Zhang, Z and Lin, T and Xiao, S and Luo, K and Kong, J and Wu, L and Yan, H}, title = {Gut microbiota-derived propionate alleviate traumatic painful neuroma through inhibiting the RIG-I-NF-κB-mediated neuroinflammation.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118087}, doi = {10.1016/j.foodres.2025.118087}, pmid = {41539785}, issn = {1873-7145}, mesh = {Animals ; *NF-kappa B/metabolism ; *Propionates/pharmacology/metabolism ; Mice ; Male ; *Gastrointestinal Microbiome/drug effects/physiology ; Signal Transduction/drug effects ; *Neuroma/drug therapy/metabolism ; *DEAD Box Protein 58/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Neuroinflammatory Diseases/metabolism ; Sciatic Nerve/injuries ; }, abstract = {Traumatic painful neuroma (TPN) is a debilitating condition that frequently develops after peripheral nerve injury, yet its pathogenesis remains poorly elucidated. Growing evidence implicates the gut microbiota in the regulation of pain and inflammatory processes, but its specific role in TPN has not been investigated. This study examines the contribution of the gut microbiota and its metabolite propionate to TPN development via modulation of the RIG-I-NF-κB signaling pathway. In a murine model of sciatic nerve transection, we identified distinct gut microbial communities between TPN-susceptible and non-susceptible mice, characterized by a reduction in beneficial bacteria and decreased fecal propionate levels in TPN-prone mice. Depletion of gut microbiota through antibiotic treatment aggravated neuroma formation and pain-like behaviors, effects that were reversible by fecal microbiota transplantation (FMT). Administration of propionate dose-dependently ameliorated neuroinflammation, fibrotic progression, and pain responses. Mechanistic studies revealed that propionate suppressed the RIG-I-NF-κB pathway activation, downregulated pro-inflammatory cytokines, and enhanced intestinal barrier integrity. Notably, FMT from propionate-treated mice replicated these protective outcomes. Our results indicate that gut microbiota-derived propionate mitigates TPN by inhibiting RIG-I-NF-κB-driven neuroinflammation and preserving gut barrier function, underscoring the gut-brain-nerve axis as a promising target for TPN therapy.}, }
@article {pmid41539854, year = {2026}, author = {Choi, S and Kwon, H and Kim, WK and Ko, G}, title = {Attenuation of Clostridioides difficile Infection by Clostridium hylemonae.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2510017}, pmid = {41539854}, issn = {1738-8872}, mesh = {Animals ; *Clostridium Infections/microbiology/therapy/prevention &amp; control ; *Clostridioides difficile ; *Clostridium/physiology/genetics ; Gastrointestinal Microbiome ; Mice ; Disease Models, Animal ; Feces/microbiology ; Bile Acids and Salts/metabolism ; }, abstract = {Clostridioides difficile infection (CDI) is a bacterial infection of the colon that can cause diarrhea and colitis. The use of antimicrobials disrupts the intestinal microbiota, weakening colonization resistance and creating an environment in which C. difficile can establish infection. It is, therefore, necessary to identify specific bacteria that are helpful for the recovery of the intestinal microbiota in individuals with CDI. Previous studies have identified several strains that showed a negative correlation with C. difficile. Among these strains, C. hylemonae DSM 15053, which possesses the bai operon similar to Clostridium scindens, was selected. To test this hypothesis, we utilized a CDI mouse model and evaluated the inhibitory effect of C. hylemonae DSM 15053. Furthermore, to gain insights into the underlying mechanisms, we performed gut microbiota analysis. Contrary to our expectations, C. hylemonae DSM 15053 did not significantly produce SBAs. Interestingly, however, microbial diversity and richness were significantly higher in the C. hylemonae DSM 15053-treated group compared with the PBS control group. In addition, we observed a higher abundance of the genera Phocaeicola, Akkermansia, and Parabacteroides in the C. hylemonae DSM 15053 group. Moreover, metagenomic and metabolomic analyses revealed that C. hylemonae DSM 15053 mitigates CDI through a mechanism distinct from that of C. scindens KCTC 5591, which primarily functions as a regulator of bile acid metabolism.}, }
@article {pmid41540689, year = {2026}, author = {Zhang, Y and Duan, Y and Zhang, C and Yu, L and Liu, Y and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Wang, Y}, title = {[Poria cocos polysaccharide alleviates cyclophosphamide-induced intestinal barrier dysfunction and inflammation in mice by modulating gut flora].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {46}, number = {1}, pages = {34-46}, pmid = {41540689}, issn = {1673-4254}, support = {82505171 and 82204748//Natural Science Foundation for the Youth (NSFY) of China/ ; }, mesh = {Animals ; *Cyclophosphamide/adverse effects ; Mice ; Mice, Inbred BALB C ; *Gastrointestinal Microbiome/drug effects ; Intestinal Barrier Function/drug effects ; *Polysaccharides/pharmacology ; *Intestinal Mucosa/drug effects ; Inflammation ; Fatty Acids, Volatile/metabolism ; Occludin/metabolism ; Male ; *Poria/chemistry ; }, abstract = {OBJECTIVES: To investigate the protective effects of Poria cocos polysaccharide (PCP) against cyclophosphamide (CTX)-induced intestinal mucosal injury and its impact on gut flora and their metabolites in mice.<br><br>METHODS: Adult BALB/C mice were randomized into normal control group, CTX model group, glutamine (positive control) group, and low-, medium- and high-dose PCP treatment groups. In all but the normal control group, the mice were subjected to modeling of CTX-induced intestinal mucosal injury by intraperitoneal CTX injections for 3 days, followed by treatment with gavage of normal saline, glutamine (300 mg/kg), or PCP at 75, 150, or 300 mg/kg for 7 consecutive days. The colonic expressions of tight junction proteins (occludin and ZO-1), serum endotoxin, D-lactate, and DAO levels, intestinal permeability, colon injury, and colonic cytokine levels (IL-4, IL-22, IL-17A, and IFN-&#x3b3; mRNA) were assessed. Gut microbiota, short-chain fatty acids (SCFAs; mainly acetates and propionates) and colonic GPR41 expression were analyzed using 16S rRNA sequencing, GC-MS, and Western blotting, respectively. Fecal microbiota transplantation (FMT) experiment was conducted to validate the role of gut microbes in PCP-mediated repair of intestinal injuries.<br><br>RESULTS: Compared with those in the model group, the mice treated with PCP showed significantly increased colonic occludin and ZO-1 expressions, reduced serum endotoxin, D-lactate and DAO levels, and lowered intestinal permeability with increased colonic expressions of IL-4, IL-22, IL-17A, and IFN-&#x3b3; mRNA. PCP treatment obviously increased the abundance of Muribaculaceae, decreased Lactobacillus and Bacteroides, increased the contents of acetate and propionate in the colon, and upregulated colonic GPR41 expression. The results of FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinal injuries in mice.<br><br>CONCLUSIONS: PCP can protect against CTX-induced intestinal mucosal injury in mice possibly by modulating gut flora and SCFAs metabolism to enhance intestinal defense capacity.}, }
@article {pmid41541603, year = {2026}, author = {Cheung, SLY and Kenway, LC}, title = {Pathophysiological Mechanisms and Nonpharmacological Interventions in Irritable Bowel Syndrome: Current Insights and Future Directions.}, journal = {Journal of nutrition and metabolism}, volume = {2026}, number = {}, pages = {4520019}, pmid = {41541603}, issn = {2090-0724}, abstract = {Irritable bowel syndrome, diagnosed using the ROME IV diagnostic criteria, is one of the most common dysfunctional disorders of the gastrointestinal system with a high global prevalence. Although symptom presentation is diverse, symptoms primarily manifest as abdominal pain, bloating, and alterations to bowel habits, negatively impacting quality of life but without an associated increase in mortality risk. Disruptions to the gut-brain axis, the bidirectional communication system between the central nervous system and the enteric nervous system, are hypothesised to be at the core of irritable bowel syndrome. Dysfunction may also be associated with stress and anxiety, as well as dietary factors, among other aspects related to physical and social environment, genetic predisposition and medical history. Patients with irritable bowel syndrome have also demonstrated increased vulnerability to neurotransmitter imbalances, with abnormalities associated with changes in gastrointestinal motility, low-grade inflammation and visceral pain. Moreover, chronic stress and anxiety may significantly exacerbate symptoms through the upregulation of cortisol secretion, disrupting the gut microbiome and elevating visceral sensitivity. While the gut microbiome maintains the integrity of the gut-brain axis and intestinal barrier, decreases in its diversity heighten susceptibility to intestinal inflammation. Although there is currently no known cure for irritable bowel syndrome, research supports stress management and behavioural therapies, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and probiotic supplementation as key interventions to alleviate symptoms. Additionally, faecal microbiota transplantation emerges as a promising intervention that addresses some of the limitations in current interventions. This literature review explores the pathophysiological mechanisms relating to irritable bowel syndrome, with insight into current interventions and future directions to directly address the underlying factors driving symptomology.}, }
@article {pmid41543263, year = {2026}, author = {Baral, B and Parajuli, M and Pinilla, J and Muniz, J and Baral, B and Cançado, GGL}, title = {Safety and efficacy of oral microbiome therapy for the treatment of recurrent Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Scandinavian journal of gastroenterology}, volume = {61}, number = {3}, pages = {308-316}, doi = {10.1080/00365521.2026.2616310}, pmid = {41543263}, issn = {1502-7708}, mesh = {Humans ; *Clostridium Infections/therapy ; Randomized Controlled Trials as Topic ; Recurrence ; *Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; Clostridioides difficile ; Administration, Oral ; *Microbiota ; Vancomycin/therapeutic use ; }, abstract = {INTRODUCTION: This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI).<br><br>METHODS: A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software.<br><br>RESULTS: Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33-0.99; p&#x2009;=&#x2009;0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03-4.01; p&#x2009;=&#x2009;0.40) or vancomycin use (RR 0.68; 95% CI 0.30-1.55; p&#x2009;=&#x2009;0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI -10.55 to 94.11; p&#x2009;=&#x2009;0.12) and week 8 (MD 34.06; 95% CI -2.49 to 70.61; p&#x2009;=&#x2009;0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo.<br><br>CONCLUSION: OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings.<br><br>REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.}, }
@article {pmid41543761, year = {2026}, author = {Munira, MS and Stevens, JE and Shahin, W and Wang, K and Franks, AE and Perez, ARJ and Scott, JW and Hill-Yardin, EL}, title = {Towards treatments targeting the gut to improve behavioural outcomes in autism spectrum disorder.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {41543761}, issn = {1435-1463}, support = {APP2003848//National Health and Medical Research Council/ ; }, abstract = {Autism spectrum disorder (ASD; autism) is a prevalent and heterogeneous neurodevelopmental disorder characterised by social communication difficulties, repetitive behaviour, and restricted interests. For individuals with autism, in particular those who require substantial care-giver support, irritability, heightened sensitivity and aggressive behaviours in response to sensory, social, or environmental triggers can limit access to health, education and community services and impact quality of life. Although gastrointestinal (GI) symptom severity is associated with irritable behaviours in autism, there are few approved medications to address challenging behaviour or comorbid psychiatric disorders, or gut dysfunction in autism. Here, we review the mode of action of drugs undergoing clinical trials for treating irritable behaviour and improving social communication as well as potentially gastrointestinal symptoms in individuals with autism. Repurposed medications such as pimavanserin (an atypical antipsychotic) and the antiparasitic suramin are being trialled for treating irritable behaviours and impaired social interaction, respectively, in autism. NTI164 is a medicinal cannabis-derived biopharmaceutical undergoing clinical safety and efficacy trials for improving social communication and similarly, ML-004 is an investigational drug being assessed for treating social communication deficits. Two other repurposed medications previously utilised for schizophrenia; brexpiprazole and lumateperone, as well as AB-2004, a microbial metabolite sequestering agent (with proposed actions on gut function), are undergoing clinical trials to assess impacts on irritability associated with autism. We also outline emerging findings from clinical studies on the use of gut-targeted small molecules and bacteriophage therapy, prebiotics, probiotic supplementation and faecal microbiota transplantation (FMT), and their potential impact on behavioural symptoms in autism.}, }
@article {pmid41544875, year = {2026}, author = {Zuo, G and Chang, F and Yuan, X and Shen, Y and Guo, X and Tang, B and Huang, JA and Liu, Z and Lin, Y}, title = {Differential toll-like receptor 2 activation by Akkermansia muciniphila and Bacteroides thetaiotaomicron mediates the beneficial effects of Fu brick tea polysaccharide against colitis.}, journal = {Pharmacological research}, volume = {224}, number = {}, pages = {108100}, doi = {10.1016/j.phrs.2026.108100}, pmid = {41544875}, issn = {1096-1186}, mesh = {Animals ; *Toll-Like Receptor 2/metabolism/genetics/immunology ; *Colitis/drug therapy/microbiology/metabolism/chemically induced/immunology ; *Polysaccharides/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Bacteroides thetaiotaomicron ; *Tea/chemistry ; Male ; Mice ; Dextran Sulfate ; Colon/drug effects/metabolism/pathology/immunology/microbiology ; Gastrointestinal Microbiome/drug effects ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Signal Transduction ; Akkermansia ; Fecal Microbiota Transplantation ; }, abstract = {Fu Brick Tea Polysaccharide (FBTP) ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the key intestinal bacterial strains and downstream molecular mechanisms mediating these protective effects remain unclear. In this study, FBTP ameliorated colitis and concurrent liver injury in a microbiota-dependent manner, primarily by enriching Akkermansia muciniphila (A. muciniphila) and depleting Bacteroides thetaiotaomicron (B. thetaiotaomicron). The essential role of the microbiota was confirmed through fecal microbiota transplantation. Mechanistically, A. muciniphila synergistically employed both its microbe-associated molecular patterns (MAMPs) and metabolic activity to activate the toll-like receptor 2 (TLR2)-Akt anti-inflammatory signaling pathway, favorably modulating Treg/Th17 immune homeostasis. However, challenging its established status as a beneficial commensal, B. thetaiotaomicron was found to activate the TLR2-NF-κB pro-inflammatory pathway driven primarily by its MAMPs, significantly exacerbating colitis, bacterial translocation, and liver injury. The pivotal role of TLR2 in mediating these divergent bacterial outcomes was confirmed through gene knockdown experiments. In conclusion, this study reveals that FBTP restores immune homeostasis by orchestrating a complex, TLR2-dependent interplay between beneficial (A. muciniphila) and pathobiontic (B. thetaiotaomicron) bacteria. This discovery not only clarifies the therapeutic mechanism of FBTP but also highlights the context-dependent risk of key commensals, offering critical insights for developing more precise microbiota-targeted interventions.}, }
@article {pmid41545303, year = {2026}, author = {Huang, JJ and YousefiAsl, M and Singh, N and Grivas, P and Bhatia, S}, title = {Steroid-sparing strategies for managing immune-related adverse events.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {1}, pages = {}, pmid = {41545303}, issn = {2051-1426}, support = {K23 AR079588/AR/NIAMS NIH HHS/United States ; R03 AG082857/AG/NIA NIH HHS/United States ; T32 CA009515/CA/NCI NIH HHS/United States ; T32 GM145449/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Immune Checkpoint Inhibitors/adverse effects ; *Neoplasms/drug therapy/immunology ; *Immunotherapy/adverse effects/methods ; *Steroids/therapeutic use ; *Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology ; Animals ; }, abstract = {Although immune checkpoint inhibitors (ICI) have greatly improved outcomes in several cancer types, their use is also associated with immune-related adverse events (irAEs) that can impact any organ system and lead to significant morbidity and even mortality. Current approaches to treatment of irAEs largely rely on the use of systemic corticosteroids, which can compromise antitumor immune responses and oncologic outcomes. Prolonged use of systemic corticosteroids is also associated with its own set of toxicities. Thus, there is a critical need for steroid-sparing treatment approaches for irAEs.In this article, we review the literature for alternative therapeutic approaches for irAEs, which include targeted delivery (alternate routes of administration) of steroids (eg, budesonide) as well as systemic non-steroidal strategies using other mechanisms of action, such as integrin/cytokine blockade, antibody depletion, disease-modifying antirheumatic drugs and fecal microbiota transplant, among others. Many of these approaches have shown significant promise in their ability to induce a clinical response and improve symptoms, even in the setting of steroid-refractory or steroid-dependent irAEs. These approaches are being increasingly used as primary and secondary prophylaxis in patients at high risk of irAEs. Importantly, these strategies may mitigate steroid-associated toxicities, preserve antitumor immune responses and allow continuation of ICI after development of irAEs, hence enabling the full potential of ICI against cancer.}, }
@article {pmid41545905, year = {2026}, author = {Ma, J and Liu, M and Xu, J and Liu, B and Cui, Y and Shi, Y}, title = {Fecal microbiota transplantation mitigates lipopolysaccharide-induced oxidative stress in weaned piglets by modulating gut microbiota and enhancing riboflavin metabolism.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {9}, pmid = {41545905}, issn = {1674-9782}, support = {CARS-34//Modern Agro-industry Technology Research System of China/ ; No. 244200510010//the Science and Technology Innovation Leading Talent in Central Plains/ ; No.30500636//the Outstanding Talents of Henan Agricultural University/ ; }, abstract = {BACKGROUND: During the weaning phase, piglets are exposed to significant physiological and environmental stressors, which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea. Previous studies have demonstrated that alfalfa fiber, derived from the stems and leaves of alfalfa, can effectively alleviate diarrhea in piglets. Additionally, multiple studies have highlighted the potential of fecal microbiota transplantation (FMT) in mitigating diarrhea in various models of intestinal diseases in young animals. However, the specific mechanisms by which FMT from targeted sources alleviates diarrhea in weaned piglets remain to be fully elucidated.<br><br>RESULTS: In this study, FMT from donor piglets fed an alfalfa fiber-supplemented diet effectively alleviated diarrhea, improved intestinal morphology, and enhanced gut barrier function in weaned piglets. FMT further promoted the colonization of beneficial bacterial genera (including UCG-005, unclassified Lachnospiraceae, Lachnospiraceae AC2044 group, UCG-002, Candidatus Saccharimonas, and Lachnospiraceae ND3007 group) while inhibiting the detrimental genus Tyzzerella, consequently enhancing the production of short-chain fatty acids (SCFAs). Additionally, FMT upregulated riboflavin metabolism, leading to elevated flavin adenine dinucleotide (FAD) levels and increased glutathione reductase activity, thereby collectively attenuating lipopolysaccharide (LPS)-induced oxidative stress and contributing to intestinal health.<br><br>CONCLUSIONS: We found that FMT modulates the structure of the gut microbiota, enhances microbial diversity and composition, increases the production of SCFAs, and upregulates riboflavin metabolism to elevate FAD levels. These changes collectively enhance immune and antioxidant capacities, thereby alleviating diarrhea.}, }
@article {pmid41546540, year = {2026}, author = {Thelen, AC and Korten, NM and Blischke, L and Voelz, C and Beyer, C and Seitz, J and Trinh, S}, title = {Faecal Microbiota Transplantation in Anorexia Nervosa: A Systematic Review of Methodologies, Outcomes, and Challenges With Recommendations for Future Studies.}, journal = {European eating disorders review : the journal of the Eating Disorders Association}, volume = {34}, number = {4}, pages = {926-945}, doi = {10.1002/erv.70080}, pmid = {41546540}, issn = {1099-0968}, support = {//Doktor Robert Pfleger-Stiftung/ ; START (101/23)//RWTH Aachen University/ ; START (16/22)//RWTH Aachen University/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; *Anorexia Nervosa/therapy/microbiology ; Humans ; Animals ; Treatment Outcome ; *Gastrointestinal Microbiome ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric disorder displaying an altered gut microbiome. Faecal microbiome transplantation (FMT) has emerged as a powerful research tool and potential treatment option in AN due to the microbiome-gut-brain axis. Current studies are limited and reveal variable FMT protocols. This leads to heterogeneous outcomes and complicates drawing definitive conclusions from existing literature. This review aims to compile and assess the different protocols and develop recommendations on ideal donors, handling of faeces, recipients, duration/frequency of FMT, and measuring transfer success for future FMT studies regarding AN.<br><br>METHODS: We systematically screened three databases (Pubmed, Embase, Web of Science), identifying 13 studies, including two human case reports, one human study protocol, and 10 animal studies.<br><br>RESULTS: While all studies demonstrated microbial alterations in the recipients, not all animal studies successfully induced an AN/underweight phenotype, suggesting that precise coordination of study protocol components to allow further refinement is essential.<br><br>CONCLUSION: Researchers should prioritise clear, comprehensive, and transparent documentation to ensure the interpretability and reproducibility of FMT procedures. Detailed reporting will enable more meaningful comparisons across studies, deepen our understanding of the microbiome's role in AN, and help identify methodological factors that influence outcomes. Ultimately, completeness of documentation in FMT studies in AN has substantial potential to support future clinical applications and improve patient care.}, }
@article {pmid41547071, year = {2026}, author = {Xu, X and Fang, H and Liu, F and Zhou, Y and Wen, Y and Wang, X and Du, D and Lu, L and Yin, J and Sun, T and He, F and He, J and Zhou, M}, title = {Akebia saponin D attenuates ulcerative colitis via targeting EGFR and remodeling gut microbiota homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157829}, doi = {10.1016/j.phymed.2026.157829}, pmid = {41547071}, issn = {1618-095X}, mesh = {Animals ; *Saponins/pharmacology ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology ; *Gastrointestinal Microbiome/drug effects ; ErbB Receptors/metabolism ; Male ; Humans ; Mice ; Dextran Sulfate ; Homeostasis/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Colon/drug effects ; Anti-Inflammatory Agents/pharmacology ; Fecal Microbiota Transplantation ; HT29 Cells ; }, abstract = {BACKGROUND: Ulcerative colitis (UC), a refractory subtype of inflammatory bowel disease (IBD), is clinically characterized by chronic abdominal pain and bloody hematochezia. Although therapeutic interventions have advanced significantly in recent years, existing treatment modalities remain limited. Akebia saponin D (ASD), a bioactive triterpenoid saponin extracted from the traditional medicinal herb Dipsacus asper, has been demonstrated potent multimodal bioactivity.<br><br>PURPOSE: This study systematically evaluates the therapeutic potential of ASD in UC treatment and elucidates its underlying molecular mechanisms.<br><br>METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was established, and ASD treatment was administered to observe its effects on colitis and organ toxicity. Inflammation was induced in NCM460 and HT29 cells using lipopolysaccharide (LPS), and ASD treatment was applied to evaluate its anti-inflammatory effects. To assess the involvement of the gut microbiota and metabolite landscape, fecal microbiota transplantation (FMT), 16S rRNA sequencing, and untargeted metabolomics were conducted. Single-cell RNA sequencing (scRNA-seq) was performed using the MGISEQ-2000 platform to characterize the ASD-induced cellular landscape of the colon. Additionally, network pharmacology approaches were employed to predict and validate potential molecular targets of ASD.<br><br>RESULTS: ASD demonstrated significant therapeutic efficacy in UC, as evidenced by attenuated body weight loss, restored colonic length, and improved mucosal barrier integrity. Treatment with ASD substantially remodeled the gut microbiota composition and metabolic profiles, notably elevating the abundance of Akkermansia muciniphila (A. muciniphila) and levels of indole-3-carbinol (I3C). Single-cell resolution analysis revealed that ASD promoted the expansion of Hmgb2[+] transit-amplifying cells (TACs) and Muc2[+] goblet cells (GCs) in colonic tissues. Mechanistically, we demonstrated that EGFR is a key molecular target of ASD upstream of the MEK/ERK/AP-1 signaling cascade.<br><br>CONCLUSION: Our study demonstrates that ASD, as a microbiota-modulating therapeutic agent, alleviates intestinal inflammation by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.}, }
@article {pmid41547302, year = {2026}, author = {Zhang, W and Zhang, K and Xu, W and Sun, X and Xue, Y}, title = {Microbiota-targeted modulation of the gut-kidney axis in diabetic kidney disease: Therapeutic advances and future perspectives.}, journal = {Biochemical and biophysical research communications}, volume = {800}, number = {}, pages = {153294}, doi = {10.1016/j.bbrc.2026.153294}, pmid = {41547302}, issn = {1090-2104}, mesh = {Humans ; *Diabetic Nephropathies/microbiology/therapy/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Kidney/pathology/metabolism/microbiology ; Fecal Microbiota Transplantation ; Dysbiosis ; Probiotics/therapeutic use ; }, abstract = {Diabetic kidney disease (DKD) is increasingly recognized as a systemic disorder driven by immune-metabolic dysfunction, in which the gut microbiota plays a pivotal role. Dysbiosis of the intestinal microbiota disrupts epithelial barrier integrity, promotes endotoxemia, and triggers chronic low-grade inflammation, contributing to renal injury and fibrosis. Conversely, declining kidney function exacerbates gut microbial imbalance and uremic toxin accumulation, forming a bidirectional pathological loop. Beyond the classical gut-kidney axis, recent findings highlight the existence of a multi-organ signaling network-encompassing immune, metabolic, and hematopoietic pathways-that mediates cross-talk between the gut and kidneys. Microbial metabolites such as short-chain fatty acids, indoxyl sulfate, and bile acids act as endocrine-like regulators modulating renal inflammation, fibrosis, and metabolic stress. This review outlines the mechanistic underpinnings of gut-derived renal injury, including gut-immune-kidney, gut-metabolism-kidney, and gut-bone marrow-kidney axes. We also discuss emerging microbiota-targeted therapies, including probiotics, engineered bacteria, fecal microbiota transplantation, and AI-based personalized interventions. Together, these insights support a systems-level redefinition of DKD and underscore the therapeutic potential of restoring gut microbial homeostasis.}, }
@article {pmid41547475, year = {2026}, author = {Aràjol, C and González Suárez, B and Bonilla Moreno, M and Puig-Asensio, M and Robles-Alonso, V and Surís, G and Solé, C and Santos, JR and Rodríguez-Alonso, L}, title = {Clostridioides difficile infection: Position paper of the Catalan Society of Gastroenterology.}, journal = {Gastroenterologia y hepatologia}, volume = {49}, number = {5}, pages = {502634}, doi = {10.1016/j.gastrohep.2025.502634}, pmid = {41547475}, issn = {0210-5705}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Cross Infection/diagnosis/therapy/microbiology ; Algorithms ; Diarrhea/microbiology ; Recurrence ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea and is associated with significant morbidity and mortality, primarily due to its high recurrence rate. For this reason, the Catalan Society of Gastroenterology commissioned the development of a position paper aimed at providing practical recommendations, grounded in scientific evidence and expert consensus, on the diagnosis and management of CDI.<br><br>METHODS: This position paper was developed by specialists in Gastroenterology, Infectious Diseases and Microbiology. It was based on a non-systematic review of the scientific evidence. Recommendations were formulated through expert consensus.<br><br>RESULTS: The document presents a structured approach to the diagnosis and treatment of CDI, emphasizing individualized management and strategies to reduce recurrence rates. Key components include the role of fecal microbiota transplantation and a therapeutic algorithm informed by disease severity and by whether the episode is initial or recurrent.<br><br>CONCLUSIONS: This position paper aims to serve as a practical, evidence-based guide for healthcare professionals involved in the clinical management of CDI, promoting the implementation of optimal therapeutic strategies and addressing the main challenges associated with this infection.}, }
@article {pmid41548987, year = {2026}, author = {Wang, A and Miao, Z and Huang, B and Zeng, J and Yuan, M and Yan, D}, title = {Baicalin Restores the Hypoglycemic Effect of Metformin by Regulating the Microbial Imidazole Propionate and Short-Chain Fatty Acids.}, journal = {Phytotherapy research : PTR}, volume = {40}, number = {3}, pages = {1060-1073}, pmid = {41548987}, issn = {1099-1573}, support = {82204699//National Natural Science Foundation of China/ ; 82130112//National Natural Science Foundation of China/ ; U24A20789//National Natural Science Foundation of China/ ; 2022-4-20218//Capital's Funds for Health Improvement and Research/ ; 2022-051//Youth Beijing Scholar/ ; 320.6750.2023-03-16//Clinical Research Project of Wu Jieping Medical Foundation/ ; }, mesh = {*Metformin/pharmacology ; Animals ; *Flavonoids/pharmacology ; *Hypoglycemic Agents/pharmacology ; *Imidazoles/metabolism/blood ; Mice ; *Fatty Acids, Volatile/metabolism ; *Propionates/metabolism/blood ; Male ; *Gastrointestinal Microbiome/drug effects ; Insulin Resistance ; Mice, Inbred C57BL ; }, abstract = {Gut microbiota dysbiosis is implicated in metformin non-response. This study aimed to investigate whether baicalin, a microbiota-modulating flavonoid derived from Radix Scutellariae, could restore metformin sensitivity and explored the underlying mechanisms. Fecal samples from metformin-treated responders and non-responders were collected and used to establish mouse models via fecal microbiota transplantation (FMT). The hypoglycemic efficacy of baicalin in combination with metformin was then evaluated. Serum levels of imidazole propionate (ImP) and the expression of downstream signaling proteins were assessed. Gut microbiota analysis identified ImP-producing bacteria modulated by baicalin, which was further validated in vitro. The roles of these bacteria and short-chain fatty acids (SCFAs) in metformin responsiveness were also examined. In vitro experiments were conducted to investigate the mechanism of SCFAs affect the production of ImP. Metformin responder and non-responder mouse models were successfully established. Baicalin co-administration significantly ameliorated insulin resistance in non-responder mice, reduced serum ImP levels, suppressed p38γ/Akt/AMPK (S485) signaling, and restored AMPK (T172) phosphorylation. Baicalin markedly suppressed key ImP-producing bacteria- Staphylococcus epidermidis and Streptococcus mutans . Notably, colonization with S. epidermidis induced metformin non-response in previously responsive mice. Furthermore, baicalin increased the abundance of SCFA-producing bacteria and elevated colonic SCFAs levels. SCFAs reduced ImP production by inhibiting the growth of ImP-producing bacteria, thereby enhancing metformin responsiveness. These findings indicate that baicalin restores metformin sensitivity by enriching SCFAs, suppressing ImP-producing bacteria, and lowering serum ImP, thereby reinstating metformin's hypoglycemic action. This study supports the potential of baicalin as an adjunct therapy for overcoming metformin non-response.}, }
@article {pmid41550945, year = {2025}, author = {Bibbò, S and De Maio, F and Capone, F and Quaranta, G and Rondinella, D and Rosato, R and Minelli, M and De Lorenzis, D and Sanguinetti, M and Cammarota, G and Di Lazzaro, V and Masucci, L}, title = {Correction: Case Report: Fecal microbiota transplantation via capsules ameliorated clinical outcomes in a patient with multiple sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1768227}, doi = {10.3389/fimmu.2025.1768227}, pmid = {41550945}, issn = {1664-3224}, abstract = {[This corrects the article DOI: 10.3389/fimmu.2025.1678759.].}, }
@article {pmid41553256, year = {2026}, author = {Linn, A and Boton, N and Beekmann, SE and Kociolek, L and Sandora, TJ and Polgreen, PM and Lee, MSL and Mehrotra, P}, title = {Pediatric Infectious Diseases Physicians' Preferences for Management of Clostridioides difficile Infection: An Emerging Infections Network Survey.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {15}, number = {1}, pages = {}, doi = {10.1093/jpids/piag004}, pmid = {41553256}, issn = {2048-7207}, support = {NU50CK000574/CC/CDC HHS/United States ; }, mesh = {Humans ; *Clostridium Infections/therapy/drug therapy ; *Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; Clostridioides difficile ; *Practice Patterns, Physicians'/statistics &amp; numerical data ; Antibodies, Monoclonal/therapeutic use ; Child ; Surveys and Questionnaires ; *Communicable Diseases, Emerging/therapy ; Broadly Neutralizing Antibodies ; }, abstract = {We queried pediatric infectious diseases physicians via the Emerging Infections Network regarding management preferences for Clostridioides difficile infection (CDI). We explored use of vancomycin, fidaxomicin, bezlotoxumab, and fecal microbiota transplantation and found that physicians are increasingly considering newer and adjunctive therapies for pediatric CDI, highlighting the need for updated guidelines.}, }
@article {pmid41554400, year = {2026}, author = {Chen, N and Ai, R and Wen, Q and Wu, J and Zhang, F and Cui, B and Ji, G}, title = {Washed microbiota transplantation as salvage therapy for antibiotic-resistant Salmonella infection in two pediatric patients.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {164}, number = {}, pages = {108408}, doi = {10.1016/j.ijid.2026.108408}, pmid = {41554400}, issn = {1878-3511}, mesh = {Humans ; *Salmonella Infections/therapy/microbiology ; *Salvage Therapy/methods ; Anti-Bacterial Agents/therapeutic use ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Drug Resistance, Bacterial ; Child ; Salmonella/drug effects ; Treatment Outcome ; Child, Preschool ; *Microbiota ; }, abstract = {OBJECTIVES: As antibiotic-resistant Salmonella infections pose a serious therapeutic challenge in children, this case report aims to introduce washed microbiota transplantation (WMT) as a novel salvage therapy.<br><br>DESIGN OR METHODS: Two pediatric patients with Salmonella infection received WMT as salvage therapy after failing antibiotic treatment.<br><br>RESULTS: Both patients achieved sustained clinical and microbiological remission.<br><br>CONCLUSION: WMT is a promising option for refractory pediatric salmonellosis.}, }
@article {pmid41554975, year = {2026}, author = {Garzón, E and Galindo, V and Harary, Y and Teman, A and Yavits, L}, title = {Integrated BSI bacteria identifier-on-chip using approximate k-mer matching.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {5722}, pmid = {41554975}, issn = {2045-2322}, mesh = {Humans ; *Bacteria/genetics/isolation &amp; purification/classification ; Genome, Bacterial ; DNA, Bacterial/genetics ; }, abstract = {Acute graft-versus-host (GVHD) is a deadly disease that can be treated through fecal microbiota transplantation. However, such treatment is often followed by life-threatening bloodstream infections (BSI). Rapid detection of BSI-causing bacteria is critical in preventing BSI-related deaths. PC-CAM is a pathogen identification system-on-chip designed to assist in avoiding BSI by real-time detection of pathogen bacterial genomes using k-mer matching. The core of PC-CAM is an Approximate search-capable (Hamming distance tolerant) Content Addressable Memory (ACAM). PC-CAM was designed and manufactured in a commercial 65nm process. We use PC-CAM for real-time detection of bacteria in blood and stool samples of GVHD patients and evaluate PC-CAM bacteria identification efficiency, performance, silicon area, and power consumption based on silicon measurements. PC-CAM is capable of classifying 960K short DNA reads/sec within a silicon area of 2.38mm[Formula: see text] consuming about 1.27mW. We envision PC-CAM as a platform deployed at points of care to provide real-time, accurate, privacy-preserving, easy-to-operate, and energy-efficient pathogen classification.}, }
@article {pmid41555353, year = {2026}, author = {Yu, C and Qian, Y and Zhou, Y and Sang, Y and Huang, W and Yang, L and Lu, L and Rong, X and Wu, H and Shi, Y and Kong, X}, title = {Deficiency of osteopontin in gut epithelial cells enhances intestinal integrity by promoting gut renewal through the JAK3/STAT4 pathway in acetaminophen (APAP)-induced acute liver injury.}, journal = {Cell communication and signaling : CCS}, volume = {24}, number = {1}, pages = {112}, pmid = {41555353}, issn = {1478-811X}, support = {82405136//National Natural Science Foundation of China/ ; 82370582//National Natural Science Foundation of China/ ; PKJ2022-Y42//Shanghai Pudong New Area Science and Technology Development Fund Institutional Public Welfare Research Special Program Healthcare Project/ ; 201940352//The Scientific Program of Shanghai Municipal Health Commission/ ; 22ZR1428100//the Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Animals ; *Osteopontin/deficiency/metabolism/genetics ; *Acetaminophen/adverse effects ; *Signal Transduction ; Mice ; *Intestinal Mucosa/metabolism/pathology ; *Epithelial Cells/metabolism ; *Chemical and Drug Induced Liver Injury/metabolism/pathology ; *Janus Kinase 3/metabolism ; Intestinal Barrier Function ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; STAT Transcription Factors/metabolism ; }, abstract = {Gut barrier dysfunction is a key feature of acute liver injury (ALI) and leads to systemic immune responses (SIRS). Our previous studies have demonstrated that knockout of osteopontin (OPN) modulates antimicrobial peptide expression and reduces intestinal flora, thereby ameliorating sepsis. In this study, we employed an acetaminophen (APAP)-induced hepatotoxicity model, the leading cause of acute liver failure (ALF) worldwide, to investigate the role of intestinal epithelial-derived OPN in gut barrier integrity during ALF. We found that intestinal epithelial-specific OPN knockout mice (Opn[△][IEC]) exhibited significant protection against APAP-induced liver injury and reduced gut barrier leakage. Fecal transplantation experiments revealed that mice receiving feces from Opn[△][IEC] mice showed increased resistance to APAP-induced liver injury and enhanced immune defense. Mechanistically, transcriptome analysis of the gut barrier indicated that OPN exacerbated gut barrier damage by inhibiting gut self-renewal via the JAK3/STAT4 signaling pathway. Epithelial-derived OPN may play a critical role in compromising gut barrier integrity and may be a target for suppressing inflammation and ameliorating ALI.}, }
@article {pmid41555858, year = {2026}, author = {Wu, Z and Yang, Z and Lyu, C and Sun, B and Zhang, R and Li, H and Chen, J}, title = {Gut microbiota and neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a review of current evidence and emerging insights.}, journal = {Therapeutic advances in medical oncology}, volume = {18}, number = {}, pages = {17588359251413948}, pmid = {41555858}, issn = {1758-8340}, abstract = {Locally advanced rectal cancer (LARC) presents a significant burden on lower gastrointestinal diseases, with current treatment strategies primarily involving neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. However, patient responses to nCRT exhibit significant variability, highlighting the need for personalized therapeutic approaches. Emerging evidence suggests that the gut microbiota plays a critical role in influencing both treatment outcomes and toxicity in LARC patients. Intestinal dysbiosis has been linked to LARC progression and may affect the efficacy and adverse effects of nCRT. This narrative review critically evaluates the current literature on the relationship between gut microbiota and nCRT in LARC. Certain microbial taxa, such as Alistipes spp., Akkermansia muciniphila, and Faecalibacterium prausnitzii, have been associated with enhanced therapeutic responses, while others, such as Fusobacterium nucleatum and Enterotoxigenic Bacteroides fragilis, may contribute to treatment resistance and exacerbate adverse effects. We also discuss novel mechanisms by which specific gut microbiota and their metabolites modulate nCRT response distinct from conventional immune regulation, alongside emerging strategies for microbiota modulation, including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation. Despite challenges in standardizing microbiota analysis and fully understanding the precise mechanisms, microbiota-targeted interventions offer a promising avenue for personalized treatment in LARC, with the potential to improve patient outcomes and quality of life.}, }
@article {pmid41556761, year = {2026}, author = {Xu, J and Han, Z and Xue, Q and Wang, H and Song, J and Li, Y and Zhang, Y and Wang, D and Hu, M}, title = {Limosilactobacillus mucosae attenuates hyperlipidemic periodontitis via the gut-oral axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2617699}, pmid = {41556761}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Periodontitis/microbiology/therapy/metabolism ; *Hyperlipidemias/microbiology/complications ; *Gastrointestinal Microbiome ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology ; Male ; Fecal Microbiota Transplantation ; Claudin-1/metabolism/genetics ; }, abstract = {The link between hyperlipidemia and periodontitis is well-established, but the underlying mechanisms remain incompletely understood. Here, we reveal a critical role for a 'gut-oral' axis in mediating this interaction. Integrating multi-omics analyses of clinical samples and mouse models, we identified that a significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis (HPD). Fecal microbiota transplantation established a causal link between this gut dysbiosis and exacerbated periodontitis. Mechanistically, oral administration of live L. mucosae ameliorates HPD by restoring intestinal levels of the key metabolite, glycerophosphocholine (α-GPC). Notably, supplementation with α-GPC alone recapitulated this protective effect by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue. This reinforcement of the epithelial barrier curtailed inflammatory infiltration and restored bone homeostasis. Our findings uncover a protective ' L. mucosae-α-GPC-CLDN1' axis, providing mechanistic insight into how gut microbiota mediates metabolism-associated inflammation and proposing a potential therapeutic strategy for HPD.}, }
@article {pmid41557025, year = {2026}, author = {Alnaggar, M and Chen, Y and Wang, C and Wang, S and Zhu, F and Lin, Y and Abdu, FA and Gong, L}, title = {Synergistic Effect of Fecal Microbiota Transplantation, γδT Cell Immunotherapy, and Pembrolizumab in Refractory Advanced Pancreatic Cancer: A Case Report.}, journal = {Journal of gastrointestinal cancer}, volume = {57}, number = {1}, pages = {23}, pmid = {41557025}, issn = {1941-6636}, support = {KJZD20230923115110020//Shenzhen Major Scientific and Technological Project./ ; }, mesh = {Humans ; Male ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; *Pancreatic Neoplasms/therapy/pathology/immunology ; Aged ; *Fecal Microbiota Transplantation/methods ; Combined Modality Therapy/methods ; Immunotherapy/methods ; *Antineoplastic Agents, Immunological/therapeutic use ; }, abstract = {BACKGROUND: Pancreatic cancer (PC) remains one of the most lethal malignancies with limited treatment options, particularly in advanced stages. Emerging immunotherapeutic strategies, such as Gamma Delta (γδ) T cell therapy paired with microbiota management, have demonstrated promise.<br><br>CASE PRESENTATION: We report a case of a 75-year-old male diagnosed with advanced-stage and poorly differentiated PC who demonstrated significant clinical improvement following a novel therapeutic approach combining fecal microbiota transplantation (FMT), &#x3b3;&#x3b4; T cell therapy, and pembrolizumab. Initial chemotherapy and radiotherapy were discontinued due to adverse effects. Pre-treatment the CA19-9 (1206 U/mL), tumor markers were significantly elevated with CEA, CA15-3 and CA125 all within normal limits. No pathogenic mutations (e.g., BRCA1/2, PALB2) were identified. A comprehensive assessment revealed tumor progression, immunosuppression, and gut microbiota dysbiosis, resulting in FMT and &#x3b3;&#x3b4; T cell therapy being introduced alongside pembrolizumab.<br><br>OUTCOMES: The combination therapy resulted in the clearance of circulating tumor cells (CTCs), normalization of CA19-9 to 72 U/mL, improved clinical symptoms, and a marked reduction in tumor size, as confirmed by CT. Tolerability was excellent with no serious adverse events occurred.<br><br>CONCLUSION: This case suggests that FMT combined with &#x3b3;&#x3b4; T cell therapy may be a promising immunotherapeutic strategy for advanced PC. Further studies are needed to validate these findings.}, }
@article {pmid41557194, year = {2026}, author = {Hayashi, A and Okamoto, T and Takahashi, T and Sato, Y and Ueda, Y}, title = {Pitfalls in the differential diagnosis of diarrhea after kidney transplantation: challenges in identifying Yersinia enterocolitica infection.}, journal = {CEN case reports}, volume = {15}, number = {1}, pages = {25}, pmid = {41557194}, issn = {2192-4449}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; Male ; *Yersinia enterocolitica/isolation &amp; purification ; *Yersinia Infections/diagnosis/drug therapy/microbiology ; *Diarrhea/microbiology/diagnosis/etiology ; Diagnosis, Differential ; Adolescent ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Immunocompromised Host ; Abdominal Pain/etiology ; Colonoscopy/methods ; Graft Rejection ; }, abstract = {We present the case of a 14-year-old boy with a history of kidney transplantation due to focal segmental glomerulosclerosis who developed severe diarrhea and abdominal pain following an episode of antibody-mediated rejection. Despite stable kidney function, the patient required increased immunosuppressive therapy, raising concerns regarding possible drug-induced enteritis or infections. Initial investigations, including stool tests for common pathogens and imaging, failed to identify the causative agent. Colonoscopy revealed thickening of the terminal ileum and aphthae in the colon; however, common infections, such as cytomegalovirus and Epstein-Barr virus, were excluded. Given the persistence of symptoms and worsening ultrasound findings showing enlarged lymph nodes and mucosal thickening, Yersinia enterocolitica infection was suspected. Special stool culture media for Yersinia spp. confirmed the infection, and the patient responded well to antibiotic therapy. Our case highlights several challenges in diagnosing gastrointestinal infections in kidney transplant recipients, including the non-specific nature of symptoms and the difficulty in distinguishing between drug-induced enteritis, viral or bacterial infections, and other transplant-related complications. This underscores the importance of considering rare pathogens, such as Yersinia, in the differential diagnosis of gastrointestinal symptoms in immunocompromised transplant patients, including pediatric patients, and emphasizes the need for specialized diagnostic techniques, such as stool culture on selective media, to confirm the diagnosis.}, }
@article {pmid41558030, year = {2026}, author = {Fan, C and Hayase, T and Chang, CC and Glover, IK and Flores, II and McDaniel, LK and Ortega, MR and Sanchez, CA and El-Himri, RK and Brown, AN and Karmouch, JL and Jamal, MA and Ahmed, SS and Halsey, TM and Jin, Y and Tsai, WB and Prasad, R and Enkhbayar, A and Mohammed, A and Schmiester, M and Damania, A and Ajami, NJ and Wargo, JA and Peterson, CB and Rondon, G and Al-Juhaishi, T and Alousi, AM and Molldrem, JJ and Champlin, RE and Shpall, EJ and Martens, E and Arias, CA and Jenq, RR and Hayase, E}, title = {Fecal carbohydrate-degrading bacteria are associated with reduced incidence of lower gastrointestinal GVHD.}, journal = {Blood advances}, volume = {10}, number = {6}, pages = {1979-1991}, pmid = {41558030}, issn = {2473-9537}, mesh = {Humans ; *Feces/microbiology ; *Graft vs Host Disease/etiology/epidemiology/microbiology ; *Carbohydrate Metabolism ; *Bacteria/metabolism ; Hematopoietic Stem Cell Transplantation/adverse effects ; Incidence ; *Gastrointestinal Diseases/etiology/microbiology/epidemiology ; *Gastrointestinal Microbiome ; }, abstract = {Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop LGI-GVHD compared with those who did. The specific gene abundances of xylosidase, which contribute to the degradation of xylose-containing polysaccharides, were significantly associated with a reduced risk of LGI-GVHD. All these findings show the importance of the carbohydrate-degrading functionality of putative beneficial bacteria in mediating risk of LGI-GVHD.}, }
@article {pmid41560360, year = {2026}, author = {Zhang, J and Wang, Z and Li, S and Luo, C and Li, H and Ma, S and Wang, P and Liu, H and Sun, L and Yin, Y and Zhang, W and Wang, Q}, title = {Phocaeicola coprophilus-Derived 6-Methyluracil Attenuates Radiation-Induced Intestinal Fibrosis by Suppressing the IDO1-Kynurenine-AHR Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {18}, pages = {e18502}, pmid = {41560360}, issn = {2198-3844}, support = {JDYY15202429//Youth Development Fund of the First Hospital of Jilin University/ ; JDYY-DEP-2022006//Doctor of Excellence Program (DEP), The First Hospital of Jilin University/ ; YDZJ202402012CXJD//Department of Science and Technology of Jilin Province/ ; 82330017//National Natural Science Foundation of China/ ; 82270610//National Natural Science Foundation of China/ ; 20240484505//Beijing Nova Program/ ; 2024ZD0530100//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, mesh = {Animals ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism/genetics ; *Kynurenine/metabolism ; *Fibrosis/metabolism ; Mice ; *Receptors, Aryl Hydrocarbon/metabolism ; *Uracil/analogs &amp; derivatives/metabolism/pharmacology ; *Intestines/pathology/drug effects ; Gastrointestinal Microbiome ; Humans ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; }, abstract = {Therapeutic options for radiation-induced intestinal fibrosis (RIF) remain limited. This study reveals that intestinal kynurenine (Kyn) is persistently elevated after radiation and correlates with fibrosis severity in both murine models and human rectal cancer samples. Exogenous Kyn exacerbated RIF, whereas inhibition of indoleamine 2,3-dioxygenase 1 (IDO1) attenuated fibrotic progression. Mechanistically, Kyn activates the aryl hydrocarbon receptor (AHR) to promote fibroblast activation and fibrosis. Antibiotic depletion of gut microbiota abrogates radiation-induced IDO1-Kyn upregulation and protects against RIF. Conversely, fecal microbiota transplantation from irradiated mice recapitulates the elevated IDO1-Kyn phenotype. Metagenomic analysis identify radiation-induced depletion of Phocaeicola coprophilus (P. coprophilus), whose abundance inversely correlates with Kyn levels. Supplementation with live P. coprophilus suppresses IDO1-Kyn signaling and ameliorates RIF. Untargeted metabolomics further show that radiation reduces 6-methyluracil, a metabolite derived from P. coprophilus. Exogenous 6-methyluracil replenishment inhibits repression of the IDO1-Kyn axis and mitigates fibrosis. Together, these findings define a microbiota-metabolite-host pathway in which radiation depletes P. coprophilus, leading to loss of 6-methyluracil and derepression of the IDO1-Kyn-AHR axis, thereby driving fibrogenesis. Restoration of either P. coprophilus or its metabolite 6-methyluracil represents a promising therapeutic strategy against RIF.}, }
@article {pmid41560593, year = {2026}, author = {Reddy, N and Lau, K and Naman, J and Lu, K and McGillivary, E and Salmasi, A and Liss, M and Stewart, T}, title = {Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.}, journal = {Oncoimmunology}, volume = {15}, number = {1}, pages = {2611458}, pmid = {41560593}, issn = {2162-402X}, mesh = {Humans ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology/drug effects ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Immune Checkpoint Inhibitors/therapeutic use ; *Carcinoma, Transitional Cell/therapy/immunology/microbiology ; *Urinary Bladder Neoplasms/therapy/immunology/microbiology ; }, abstract = {Urothelial carcinoma (UC) remains a common cancer with significant morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have helped revolutionize the treatment of UC, and there is growing evidence suggesting the crucial role of the gut microbiome in immune system function influences immunotherapy outcomes in this disease. Herein, we review the preclinical basis for how manipulation of the gut microbiome may alter the efficacy of immunotherapy for patients with cancer, highlight interventions optimizing gut microbiome diversity currently in use, review recent and ongoing clinical trials supporting the role of the gut microbiome in improving immunotherapy outcomes, and discuss clinical implications to improve outcomes for UC patients with immunotherapy in the real world. There is growing evidence that suggests that specific gut microbiome compositions significantly modulate the host immune system and response to ICIs. Early studies have shown that certain microbial taxa enhance antitumor immunity by influencing T cell priming, dendritic cell activation, and cytokine production. Fecal microbiota transplantation (FMT), probiotic supplementation, and dietary modulation have emerged as promising methods to alter microbiomes to improve immunotherapy outcomes. Taxa from positive immunotherapy responders across a variety of cancers demonstrate beneficial effects when transplanted into both treatment-naive or prior nonresponders. Increasing evidence suggests that the gut microbiome plays a crucial role in cancer care, particularly when patients are treated with immunotherapy. Future studies are needed to better understand the underlying mechanisms. While some studies are currently underway to explore gut manipulation for patients with UC, more studies are needed to investigate the potential to convert nonresponders into responders through microbiome manipulation.}, }
@article {pmid41561048, year = {2025}, author = {Wang, L and Chen, S and Cai, X and Zheng, Y and Zheng, C and Yao, Y}, title = {The influence of immune regulation mediated by intestinal microbiota on postmenopausal osteoporosis and intervention strategies.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1720484}, pmid = {41561048}, issn = {1664-2392}, mesh = {Humans ; Female ; *Osteoporosis, Postmenopausal/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; }, abstract = {Postmenopausal osteoporosis (PMO) is a common metabolic bone disease characterized by reduced bone mass and deteriorated bone microarchitecture, leading to an increased risk of fractures. In recent years, growing evidence has highlighted the role of gut microbiota and its immune-mediated regulation in the pathogenesis and progression of PMO. The gut microbiota modulates host immune responses, influencing the balance between bone resorption and bone formation. Estrogen deficiency after menopause disrupts gut microbiota composition, induces systemic inflammation, and promotes osteoclast activation, accelerating bone loss. Moreover, specific microbial communities and their metabolites, such as short-chain fatty acids (SCFAs), regulate bone metabolism by modulating immune cells, including T cells, B cells, and macrophages. Various microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), have shown potential in improving bone health. However, several challenges remain, including individual variability in microbiota composition, the long-term effects of interventions, and their clinical applicability. Further investigations into the gut microbiota-mediated immune regulation of PMO may provide novel insights and therapeutic strategies for osteoporosis prevention and treatment.}, }
@article {pmid41561085, year = {2025}, author = {Bu, W and Chen, Z and Liu, B and Jia, X}, title = {Gut microbiota and its metabolism in autism spectrum disorder: from pathogenesis to therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1687691}, pmid = {41561085}, issn = {2235-2988}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology/metabolism/etiology ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Animals ; Brain-Gut Axis ; Prebiotics ; Probiotics ; Dysbiosis ; Brain ; }, abstract = {Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Studies show that nearly half of ASD patients have gastrointestinal symptoms such as abdominal pain and diarrhea, indicating the important role of gut microbiota in its pathogenesis. This review finds that ASD patients exhibit reduced gut microbiota diversity and imbalanced Bacteroidetes/Firmicutes ratio, with abnormal microbial structure affecting neurobehavior through the gut-brain axis. Abnormalities in gut microbiota metabolites (short-chain fatty acids, phenolic compounds, bile acids, amino acids, etc.) are key mediators, which can exacerbate symptoms by affecting BBB permeability, neuroinflammation, and neurotransmitter balance. The gut-brain axis regulates ASD through mechanisms including the HPA axis, vagus nerve, immune pathways, and barrier functions. Gut microbiota-targeted interventions (exercise, dietary intervention, fecal microbiota transplantation, prebiotics/probiotics, etc.) can alleviate gastrointestinal and behavioral symptoms of ASD by regulating microbiota balance and improving metabolic environment. However, there are still issues such as unclear metabolite regulation mechanisms and significant individual differences in interventions. Future studies should combine multi-omics and artificial intelligence to identify core targets, develop personalized plans, and promote clinical translation.}, }
@article {pmid41561086, year = {2025}, author = {Zhang, MY and Chen, SY and Lin, YH and Yuan, XX}, title = {Gut microbiota modulation in gastrointestinal disorders: current evidence and therapeutic perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1740322}, pmid = {41561086}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Diseases/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/microbiology ; Dysbiosis/therapy ; }, abstract = {Gut microbiome medicine is a promising field in functional medicine, offering personalized treatment strategies for gastrointestinal disorders. Advanced metagenomic and metabolomic technologies have revealed the gut microbiome's systemic influence, extending to distant organs like the brain and lungs. While small molecules and genes facilitate these effects, the gut microbiota's greatest abundance and activity are concentrated in the gastrointestinal tract, particularly in the distal regions. The balance of microbial communities in the small and large intestines is crucial for gastrointestinal health. However, the dominance of pathogenic bacteria can disrupt this balance, leading to tissue damage and contributing to gastrointestinal disorders. Emerging interventions, such as probiotics, fecal microbiota transplantation, and dietary enrichment with short-chain fatty acids, show potential in restoring microbial balance, enhancing immune function, and potentially protecting against carcinogenesis. Current evidence from clinical trials and animal models supports the therapeutic role of gut microbiome modulation in reversing gastrointestinal disorders. However, variability in study outcomes highlights the need for further research to standardize these approaches for clinical practice. This review underscores the gut microbiome's pivotal role in gastrointestinal health and the therapeutic promise of functional medicine in addressing these disorders. This review also explores emerging interventions, such as phage therapy and engineered microbes, and provides comparative analyses of microbiota signatures and therapeutic approaches across different gastrointestinal disorders.}, }
@article {pmid41562083, year = {2025}, author = {Liu, J and Hong, W and Sun, Z and Zhang, S and Xue, C and Dong, N}, title = {The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1693964}, pmid = {41562083}, issn = {1664-3224}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/immunology ; *Lung/immunology/metabolism/microbiology ; *Lung Diseases/microbiology/immunology/metabolism/therapy/etiology ; Dysbiosis/immunology/microbiology ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; Probiotics/therapeutic use ; Polyamines/metabolism ; }, abstract = {The proposal of the gut-lung axis has profoundly reshaped our understanding of the mechanisms underlying respiratory diseases. As a crucial component of this axis, the gut microbiota plays a central role in pulmonary immune regulation through inter-organ communication mediated by metabolic products. However, a systematic integration of mechanisms explaining how gut microbes achieve precise cross-organ immune regulation remains elusive. Existing research predominantly focuses on descriptive observations, such as the association between early-life microbiota dysbiosis and an increased risk of asthma and chronic obstructive pulmonary disease (COPD), as well as the frequent occurrence of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), often accompanied by gut microbiome disruption. This paper focuses on three key gut microbial metabolites-short-chain fatty acids (SCFAs), tryptophan metabolites, and polyamines (PAs)-to examine their roles in immune regulation, maintenance of barrier function, and modulation of metabolic signaling networks. Based on the latest experimental and clinical evidence, this study systematically elucidates how dysbiosis of the gut microbiota, a key component of the gut-lung axis, crosses physiological barriers to exacerbate pulmonary inflammation. Regarding intervention strategies, probiotics, fecal microbiota transplantation (FMT), and CRISPR-Cas systems have demonstrated significant therapeutic potential in restoring gut microbial balance. Finally, this paper outlines future research directions, emphasizing the need to further explore non-invasive microbial sampling techniques, molecular interaction mechanisms of the gut-lung axis, and personalized microbiome-based diagnostic and therapeutic strategies to provide new insights for the prevention and treatment of respiratory diseases involving gut microbiota.}, }
@article {pmid41564102, year = {2026}, author = {Pu, X and Liu, B and Dong, L and Yuan, M and Jin, S and Jiang, X}, title = {Fecal microbiota transplantation ameliorates radiation-induced lung injury by reshaping gut metabolic homeostasis to activate FAM134B-mediated ER-phagy.}, journal = {PLoS pathogens}, volume = {22}, number = {1}, pages = {e1013786}, pmid = {41564102}, issn = {1553-7374}, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; *Endoplasmic Reticulum/metabolism ; Homeostasis ; *Lung Injury/metabolism/etiology/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; *Membrane Proteins/metabolism ; Male ; Mice, Inbred C57BL ; *Intracellular Signaling Peptides and Proteins/metabolism ; *Radiation Injuries/metabolism/therapy ; *Radiation Injuries, Experimental/therapy/metabolism ; }, abstract = {Radiation-induced lung injury (RILI) is a serious complication of thoracic radiotherapy, with limited effective treatment options. This study demonstrates that fecal microbiota transplantation (FMT) confers protection against RILI through modulation of the gut-lung axis. In a total lung irradiation (TLI) mouse model, FMT significantly alleviated pulmonary histopathological injury, inflammatory responses, oxidative stress, and collagen deposition during fibrogenesis. Concurrently, FMT improved intestinal motility, enhanced mucosal barrier integrity, and restored TLI-induced dysbiosis in gut microbiota diversity and community structure. Metabolomic analysis revealed that TLI significantly disrupted the metabolism of unsaturated fatty acids and arachidonic acid (AA), whereas FMT partially restored these metabolic networks. Transcriptomic and ultrastructural analyses indicated that RILI suppressed endoplasmic reticulum (ER) protein processing and induced ER swelling, while FMT promoted protective ER-phagy and facilitated restoration of ER morphology. Integrated multi-omics analysis further identified the AA metabolism as a key component of FMT-mediated protection, with its alterations closely associated with pulmonary tissue repair. Further in vivo and in vitro experiments demonstrated that AA binds to and activates the nuclear receptor PPARγ, leading to transcriptional upregulation of FAM134B, promoting protective ER-phagy and ameliorating RILI. In summary, this study highlights the bidirectional gut-lung axis as a therapeutic target in RILI progression and intervention, and reveals that FMT confers protection through metabolic remodeling and activation of the PPARγ-FAM134B-mediated ER-phagy pathway, providing a mechanistic basis for potential clinical translation.}, }
@article {pmid41566359, year = {2026}, author = {Ko, H and Kim, CJ and Choi, S and Noh, J and Kim, SW and Lee, J and Byun, S and Lee, H and Park, JC and Park, HE and Sharma, A and Park, M and Park, J and Lee, CG and Cha, KH and Im, SH}, title = {Commensal microbe-derived butyrate enhances T follicular helper cell function to boost mucosal vaccine efficacy.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {37}, pmid = {41566359}, issn = {2049-2618}, support = {RS-2024-00414820//Ministry of Education, Science and Technology/ ; 2Z07251//Korea Institute of Science and Technology/ ; RS-2024-00345575//Ministry of Science and ICT, South Korea/ ; }, mesh = {Animals ; *Butyrates/metabolism ; Mice ; *Immunity, Mucosal ; Peyer's Patches/immunology/cytology ; *T Follicular Helper Cells/immunology ; *Gastrointestinal Microbiome/immunology ; Immunoglobulin A/immunology ; Mice, Inbred C57BL ; B-Lymphocytes/immunology ; Immunoglobulin A, Secretory/immunology ; Spleen/immunology ; *Vaccines/immunology ; Cell Differentiation ; Female ; Symbiosis ; *T-Lymphocytes, Helper-Inducer/immunology ; }, abstract = {BACKGROUND: The gut microbiota plays an essential role in mucosal immunity, with secretory immunoglobulin A (IgA) acting as a key effector in neutralizing pathogens and maintaining host-microbiota homeostasis. IgA production occurs via T cell-dependent (TD) and -independent pathways, with T follicular helper (Tfh) cells driving high-affinity, antigen-specific IgA responses. However, the specific microbial taxa and metabolites that regulate Tfh-mediated IgA responses under steady-state conditions remain poorly understood. This study investigated how gut microbiota-derived signals shape Tfh responses and IgA production, with implications for enhancing mucosal vaccine efficacy.<br><br>RESULTS: We demonstrate that Peyer's patches (PP)-derived Tfh cells exhibit superior IgA-inducing capacity compared to splenic Tfh cells. RNA sequencing revealed distinct transcriptional profiles in PP-Tfh cells, including upregulation of the genes associated with Tfh differentiation and activation (Bcl6, Cd40lg, Maf), T-B cell interactions (Il21, Sh2d1a, Fyn), and migration (Ccr6, Cxcr5). Functionally, PP-Tfh cells formed larger T-B cell contact areas and induced significantly higher IgA secretion in co-culture than their splenic counterparts. Microbiota depletion experiments revealed that eliminating neomycin-depleted bacteria reduced fecal IgA levels and diminished PP-Tfh cell frequencies. Fecal microbiota transplantation from neomycin-treated mice restored both IgA production and Tfh responses in germ-free (GF) mice. Bioinformatic analysis (PICRUSt2 and LEfSe) identified butyrate-producing Lachnospiraceae and Ruminococcaceae as key drivers of the Tfh-IgA axis. Butyrate supplementation enhanced Tfh differentiation and IgA&#x207a; germinal center B cell development in vitro and increased fecal IgA levels in vivo. Mechanistically, butyrate promoted IgA production via GPR43 signaling, as its effect was lost in co-cultures with Gpr43[&#x207b;/&#x207b;] Tfh cells. Moreover, treatment with tributyrin, a butyrate prodrug, enhanced vaccine-induced IgA and protected mice against Salmonella Typhimurium infection, reducing bacterial burden and tissue damage. These findings define a functional microbiota-Tfh-IgA axis sustained by neomycin-depleted, butyrate-producing bacteria.<br><br>CONCLUSIONS: Our study underscores the crucial role of the gut microbiota, particularly neomycin-depleted butyrate producing taxa, in regulating PP-Tfh cell function and IgA production. Butyrate emerges as a metabolite linking microbial metabolism to Tfh differentiation and IgA class switching. Together, these findings establish a microbiota-metabolite-Tfh cell axis essential for mucosal immune homeostasis and suggest novel strategies for enhancing vaccine efficacy and protection against enteric infections. Video Abstract.}, }
@article {pmid41567684, year = {2025}, author = {Lanas, A and Alvarez-Mercado, AI}, title = {Editorial: Improving the gut microbiome: applications of fecal transplantation in disease, volume II.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1758943}, doi = {10.3389/fmed.2025.1758943}, pmid = {41567684}, issn = {2296-858X}, }
@article {pmid41568166, year = {2026}, author = {Lu, M and Guo, S and Nie, Z and Ji, J and Wang, Y and Jiang, X and Zhang, L and Xiang, B and Wu, W and Ji, J and Zou, J and Ding, X and Yu, X}, title = {Differences in gut microbiota composition are an important reason for lower serum p-cresol sulfate levels in anuric peritoneal dialysis patients compared to hemodialysis patients.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100548}, pmid = {41568166}, issn = {2666-5174}, abstract = {BACKGROUND: Patients with end-stage kidney disease (ESKD) accumulate toxic metabolites that contribute to severe clinical complications. Peritoneal dialysis (PD) and hemodialysis (HD) exhibit distinct capacites for toxin clearance. Furthermore, the gut microbiota plays a significant role in toxin generation and is modulated by dialysis modality. This study aimed to compare gut microbiota composition and serum metabolite profiles between PD and HD patients, and to investigate their association with uremic toxin production.<br><br>METHODS: This single-center, cross-sectional study included 100 anuric ESKD patients (50 PD and 50 HD) matched for age, gender, and dialysis duration. Fecal and serum samples were collected and analyzed using 16S rRNA gene sequencing and non-targeted metabolomics. To validate the gut microbiota-serum metabolite relationship, fecal microbiota transplantation (FMT) was performed in germ-free CKD mice.<br><br>RESULTS: No significant differences in alpha diversity were observed between PD and HD groups (all indices P > 0.05), but beta diversity analysis revealed distinct gut microbial compositions (ANOSIM R = 0.093, P = 0.001), with PD patients showing higher abundance of opportunistic pathogens and lower abundance of beneficial bacteria. Non-targeted metabolomics identified 314 significantly different metabolites between the two groups, including significantly lower levels of p-cresyl sulfate (PCS) in PD patients (PD:19.16(7.24,53.83), HD:70.21(26.75,96.79), P < 0.001), with altered metabolic pathways such as tyrosine, tryptophan, and phenylalanine metabolism. FMT experiments in CKD germ-free mice confirmed higher serum PCS levels in HD recipients than in PD recipients (PD:30,456.02&#xb1;4598.39, HD:45,025.00&#xb1;4513.59, P < 0.05), supporting the role of gut microbiota in toxin production.<br><br>CONCLUSION: PD and HD patients show distinct gut microbiota and serum metabolite profiles, with notably lower PCS levels in PD patients. These differences are associated with variations in gut microbiota. Animal experiments provide additional evidence suggesting a potential causal relationship. Modulating gut microbiota may represent a promising therapeutic approach to decrease uremic toxin production in dialysis patients.}, }
@article {pmid41568320, year = {2025}, author = {Perry, S and Pillarisetti, L and Gelfman, T and Agrawal, DK}, title = {Gut-Brain Axis in Inflammatory Bowel Disease: Pathogenesis and Therapeutics.}, journal = {Archives of internal medicine research}, volume = {8}, number = {4}, pages = {339-345}, pmid = {41568320}, issn = {2688-5654}, support = {R25 AI179582/AI/NIAID NIH HHS/United States ; }, abstract = {Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract driven by complex interactions between genetic susceptibility, environmental triggers, microbial dysbiosis, and immune dysregulation. The gut microbiome, composed primarily of Firmicutes and Bacteroidetes, plays a crucial role in maintaining intestinal barrier integrity, immune balance, and neuroimmune signaling. Disruption of this microbial ecosystem is characterized by loss of beneficial short chain fatty acid producing bacteria and expansion of pathogenic species which promotes mucosal inflammation, cytokine release, and neuroimmune signaling that can disrupt mental health through the gut-brain axis. Emerging evidence links microbial metabolites, vagal tone, and the hypothalamic-pituitary-adrenal axis in a feedback loop that perpetuates inflammation and alters mood regulation. Current therapeutic approaches include diet modification, osteopathic manipulative treatments, fecal microbiota transplantation and phage therapy. This article focuses on understanding mechanisms linking dysbiosis, immune activation, and neuroinflammation to guide future interventions. A holistic model addressing the gut-brain axis holds the greatest promise for improving outcomes and personalizing care for IBD.}, }
@article {pmid41568321, year = {2026}, author = {Yahyapour, A and Najafi, A and Ahmadi, A and Salarizadeh, N}, title = {Immunoprotective and neuroprotective properties of gut microbiome in psoriasis.}, journal = {Journal of translational autoimmunity}, volume = {12}, number = {}, pages = {100348}, pmid = {41568321}, issn = {2589-9090}, abstract = {Psoriasis impacts nearly 100 million people globally and is associated with neuropsychiatric comorbidities such as depression and anxiety. With gut microbiome dysbiosis serving as a primary pathophysiological factor, the gut-brain-skin axis provides a crucial framework for understanding this relationship. This review evaluates the mechanisms of the gut-brain-skin axis in psoriasis pathophysiology and assesses the therapeutic potential of microbiome-based treatments, combining preclinical, clinical, and multi-omics data. Patients with psoriasis show specific gut dysbiosis patterns, including reduced microbial diversity, lower SCFA-producing bacteria (especially Faecalibacterium and Akkermansia), and increased pro-inflammatory bacteria. This microbial imbalance damages intestinal barrier integrity, triggers systemic inflammation, activates cutaneous Th17 pathways, and induces neuroinflammation through blood-brain barrier disruption. Axis communication occurs through immune-inflammatory mechanisms mediated by SCFAs and neuroendocrine pathways involving microbially-derived neurotransmitters (GABA, serotonin, dopamine). Metagenomic research indicates functional deficiencies in neurotransmitter and SCFA synthesis pathways are more significant than taxonomic alterations. Machine learning models can utilize these functional features to identify patients at risk for neuropsychiatric comorbidities and predict treatment response. Recent randomized controlled trials demonstrate that targeted interventions (probiotics, prebiotics, postbiotics, fecal microbiota transplantation) significantly improve Psoriasis Area and Severity Index scores, inflammatory markers, and microbiota composition. The evidence supports a shift toward integrated microbiome strategies, emphasizing functional approaches including mitochondrial therapies, psychobiotics, precision nutrition, and multi-omics-guided therapies.}, }
@article {pmid41568946, year = {2026}, author = {Huang, P and Cao, L and Cao, T and Wang, X and Cui, S and Jiang, S and Chen, H and Di, L and Li, S and Huang, L}, title = {Intermittent Fasting Alleviates Anesthesia/Surgery-Induced Delirium-Like Behavior in Aged Mice by Remodeling Gut Microbiota.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {32}, number = {1}, pages = {e70748}, pmid = {41568946}, issn = {1755-5949}, support = {//Hebei Medical University Postdoctoral Fund/ ; PD2025007//Postdoctoral Research Support Program for Clinical Medicine of Hebei Medical University/ ; H2022206586//the S&amp;T Program of Hebei/ ; }, mesh = {Animals ; *Intermittent Fasting ; Mice ; *Gastrointestinal Microbiome/physiology ; Male ; *Delirium/prevention &amp; control/etiology ; Mice, Inbred C57BL ; Aging ; Hippocampus/ultrastructure ; Fecal Microbiota Transplantation ; *Fasting ; *Postoperative Complications/prevention &amp; control ; Mitochondria/metabolism ; Sevoflurane ; }, abstract = {BACKGROUND: Postoperative delirium (POD) is a serious complication in elderly patients, associated with prolonged recovery and adverse outcomes. Recent evidence links POD to mitochondrial dysfunction. While intermittent fasting (IF) has been shown to enhance mitochondrial function and exert neuroprotective effects, potentially through gut microbiota modulation, its ability to prevent POD and the underlying mechanisms remain unclear.<br><br>METHODS: We examined the effects of preoperative IF on delirium-like behavior in aged mice following anesthesia/surgery. Assessments included neurobehavioral tests, gut microbiota composition, fecal shortchain fatty acids (SCFAs), hippocampal synaptic and mitochondrial ultrastructure via transmission electron microscopy, mitochondrial function, and related molecular markers. To establish causality, fecal microbiota transplantation and SCFA supplementation experiments were conducted.<br><br>RESULTS: Preoperative IF significantly attenuated anesthesia/surgery-induced delirium-like behaviors. Mechanistically, IF reshaped the gut microbiota and preserved SCFA levels, which collectively maintained hippocampal mitochondrial homeostasis. Both fecal microbiota transplantation and SCFA supplementation replicated the protective effects of IF, confirming the causal role of gut microbiota and its metabolites.<br><br>CONCLUSION: These findings demonstrate that preoperative intermittent fasting mitigates delirium-like behavior by modulating the gut microbiota-SCFA-mitochondrial axis, highlighting its potential as a non-pharmacological strategy to enhance neurocognitive resilience and prevent POD in elderly surgical patients.}, }
@article {pmid41569045, year = {2026}, author = {Yao, G and Zhang, T and Qin, Z and Wang, Y and Gu, J and He, C and Jin, J}, title = {Corn silk extract as a prebiotic exerts antihypertensive effects via gut microbiota modulation in hypertensive rats.}, journal = {Microbiology spectrum}, volume = {14}, number = {3}, pages = {e0144225}, pmid = {41569045}, issn = {2165-0497}, support = {AHWJ2023c049//Anhui Province Health and Wellness Research Project/ ; AHWJ2024BAc20018//Anhui Province Health and Wellness Research Project/ ; 2308085QH260//Youth Project of Anhui Provincial Natural Science Foundation/ ; 2023yf126, WK2023ZQNZ61//Wuhu Science and Technology Bureau Research Project and Wannan Medical College Scientific Research Fund/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Antihypertensive Agents/administration &amp; dosage/pharmacology ; *Zea mays/chemistry ; *Hypertension/drug therapy/microbiology ; *Prebiotics/administration &amp; dosage/analysis ; Male ; *Plant Extracts/administration &amp; dosage/pharmacology ; Blood Pressure/drug effects ; Rats, Inbred SHR ; Bacteria/classification/genetics/isolation &amp; purification/drug effects ; Fecal Microbiota Transplantation ; Nitric Oxide/metabolism ; Cytokines ; }, abstract = {UNLABELLED: Corn silk extract (CSE), a traditional medicinal food rich in polysaccharides, flavonoids, and saponins, has been used as a natural antihypertensive agent, but its mechanism remains unclear. This study aimed to evaluate whether CSE can lower blood pressure through gut microbiota modulation. Spontaneously hypertensive rats received oral CSE for 4 weeks, followed by a 4-week drug-free observation. The treatment significantly reduced blood pressure, increased microbial diversity, decreased the Firmicutes/Bacteroidetes ratio, and enriched beneficial genera, such as Akkermansia and Lactobacillus. These changes were accompanied by reduced serum lipopolysaccharide and pro-inflammatory cytokines, elevated nitric oxide (NO) levels, and restored endothelial function. Permutational multivariate analysis of variance (PERMANOVA) and correlation analyses showed that microbiota and inflammatory markers were more strongly associated with blood pressure improvements than urinary indices. Structural equation modeling suggested a potential mechanistic pathway involving gut microbiota-inflammation-NO regulation. Importantly, fecal microbiota transplantation using post-treatment donor samples reproduced the antihypertensive and anti-inflammatory effects, confirming the microbiota's critical mediating role. These findings provide the first experimental evidence that CSE functions as a prebiotic to improve gut microbial balance and vascular health, offering a promising natural strategy for microbiota-targeted blood pressure control.<br><br>IMPORTANCE: This study identifies corn silk extract (CSE) as a novel plant-derived prebiotic with antihypertensive effects mediated through gut microbiota modulation. Using a spontaneously hypertensive rat model, we demonstrated that CSE reshapes gut microbial composition, enhances microbial diversity, and promotes beneficial genera while reducing systemic inflammation and restoring nitric oxide (NO)-mediated vascular function. Importantly, fecal microbiota transplantation confirmed the causal role of gut microbiota in mediating these effects. These findings highlight a gut microbiota-inflammation-NO axis as a key pathway through which CSE regulates blood pressure. As a safe, accessible, and food-compatible intervention, CSE represents a promising strategy for non-pharmacological blood pressure management and broadens the application scope of prebiotics in cardiovascular health.}, }
@article {pmid41569851, year = {2026}, author = {Kabil, AK and Cait, A and Reynolds, LA and Chopra, S and Bilenky, M and Moksa, M and Li, Y and Cait, J and Hernaez, DC and Scott, RW and Fogarty, E and Finlay, BB and Mohn, WW and Hirst, M and Hughes, MR and McNagny, KM}, title = {Early-life microbiota skews long-term gene expression and chromatin states of bone marrow hematopoietic precursors.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116871}, doi = {10.1016/j.celrep.2025.116871}, pmid = {41569851}, issn = {2211-1247}, mesh = {Animals ; *Hematopoietic Stem Cells/metabolism ; *Chromatin/metabolism ; Mice ; Histones/metabolism ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Epigenesis, Genetic ; Immunoglobulin E/blood ; *Microbiota ; *Gastrointestinal Microbiome ; Bone Marrow Transplantation ; }, abstract = {Early life is a critical window during which the gut microbiota sculpts immunity and long-term susceptibility to allergic disease. Using neonatal antibiotic administration and bone marrow transplantation assays, we show that depletion of short-chain fatty acid (SCFA)-producing bacteria alters gene expression in hematopoietic stem and progenitor cells (HSPCs) and imprints a persistent, transplantable atopic immune phenotype. Bone marrow transplants from exposed mice generate recipients with elevated serum immunoglobulin E (IgE), downstream increased IgE bound to basophils, and exacerbated allergic lung inflammation following papain challenge. Depletion of SCFA-producing bacteria also impairs recovery from chemotherapy-induced myelosuppression and increases DNA damage in long-term HSPCs in an antibiotic-specific manner. Histone 3 lysine 27 (H3K27) chromatin immunoprecipitation sequencing (ChIP-seq) analyses further reveal differential histone acetylation in HSPCs, consistent with an SCFA-mediated epigenetic regulatory mechanism. Collectively, these findings establish a link between gut microbiota composition, hematopoiesis, and long-term immune function, offering a mechanistic explanation for microbiota-driven susceptibility to atopic disease and hematopoietic dysfunction.}, }
@article {pmid41570783, year = {2026}, author = {Ding, J and Xu, F and Chen, D and Xi, J and Gao, F and Chen, L and Wang, B and Dou, X and Qiu, J and He, G}, title = {Qing Hua Yu Du formula ameliorates alcoholic hepatic fibrosis by regulating MAPK/TLR4-MyD88 inflammatory pathways, restoring hepatic metabolism and modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {152}, number = {}, pages = {157830}, doi = {10.1016/j.phymed.2026.157830}, pmid = {41570783}, issn = {1618-095X}, mesh = {Animals ; Toll-Like Receptor 4/metabolism ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Myeloid Differentiation Factor 88/metabolism ; Mice ; Liver/metabolism/drug effects ; Mice, Inbred C57BL ; *Liver Cirrhosis, Alcoholic/drug therapy/metabolism ; Signal Transduction/drug effects ; Disease Models, Animal ; Histidine/metabolism ; Humans ; }, abstract = {BACKGROUND: Alcohol-induced liver injury (ALI) and subsequent hepatic fibrosis pose significant global health burdens, with limited effective therapeutic options. Traditional Chinese Medicine (TCM) formulas, such as Qing Hua Yu Du (QHYD) formula, have shown potential in treating alcoholic hepatic fibrosis in clinical, but their therapeutic effects, and underlying mechanisms remain incompletely characterized. Additionally, the interplay between hepatic inflammation, metabolic disorders, and gut-liver axis dysregulation in ALI-related fibrosis necessitates comprehens