@article {pmid42790831,
year = {2026},
author = {Xie, J and Ren, Y and Lai, M and Liang, J and Liang, J and Zheng, Y and Wang, H and Zhang, J and Zhao, B and Song, W and Yin, J},
title = {Gut microbiota rescues vascular cognitive impairment by improving glymphatic function via the ILA-AHR-AQP4 pathway.},
journal = {Pharmacological research},
volume = {233},
number = {},
pages = {109646},
doi = {10.1016/j.phrs.2026.109646},
pmid = {42790831},
issn = {1096-1186},
abstract = {Microbial tryptophan metabolites regulate cognitive function, but their role in vascular cognitive impairment (VCI) induced by chronic cerebral hypoperfusion (CCH) remains poorly understood. In the CCH cohort, we observed gut microbiota dysbiosis and reduced levels of microbial tryptophan metabolites, including indole-3-lactic acid (ILA), in cognitively impaired CCH patients, with these metabolites serving as protective factors. In mice with bilateral carotid artery stenosis, gut microbiota dysbiosis and ILA reduction preceded cognitive decline and were accompanied by astrocytic aryl hydrocarbon receptor (AHR) inactivation, aquaporin-4 (AQP4) depolarization, and glymphatic dysfunction. Fecal microbiota transplantation (FMT) reconstituted the gut microbiota and salvaged cognition. The cognitive improvement following FMT depended on the restoration of the glymphatic system. Tryptophan supplementation increased cerebral ILA concentrations, activated astrocytic AHR, and polarized AQP4, thereby rescuing glymphatic function and enabling cognitive recovery. Notably, ILA supplementation alone was sufficient to restore AQP4 polarization and cognitive function. Mechanistically, we identified dioxin-responsive elements within the promoters of the AQP4 polarization-associated genes alpha-syntrophin (Snta1) and dystroglycan 1 (Dag1). ILA supplementation activated AHR in astrocytes and upregulated the expression of these genes, whereas AHR-specific antagonist pretreatment inhibited the upregulation of Snta1 and Dag1 induced by ILA. These findings demonstrate an ILA-AHR-AQP4 axis linking microbial tryptophan metabolism to the glymphatic system, which is important for cognitive restoration and indicates a novel therapeutic insight for VCI associated with CCH. Given the exploratory nature of the clinical cohorts, the findings warrant validation in larger independent cohorts. (Trial registration: ClinicalTrials. gov. ID number: NCT04688138).},
}

@article {pmid42791458,
year = {2026},
author = {Belhout, C and Freire, S and Aldeia, C and Endimiani, A},
title = {Humanizing Zophobas morio larvae microbiota for rapid screening of emerging decolonization strategies against multidrug-resistant bacteria.},
journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology},
volume = {},
number = {},
pages = {},
pmid = {42791458},
issn = {1435-4373},
abstract = {PURPOSE: Designing efficient strategies against the gut colonization due to multidrug-resistant (MDR) bacteria is an important task. However, scalable and reliable in vivo models that possess a human-like gut microbiota are not yet available. Here, we tested whether Zophobas morio larvae (ZmL) could be used as a humanized microbiota model.

METHODS: A pooled fecal transplant material from 7 human donors was administered via contaminated food to a group of ZmL every 48-h for 28 days (T28), followed by a 28-day washout phase. A control group received the standard diet. Gut microbiota composition was assessed at 9 timepoints (from T0 to T56) by 16S rRNA gene amplicon sequencing across 3 independent runs.

RESULTS: Fecal microbiota transplants (FMTs) increased the richness of the larval gut bacterial population, with 8 of 10 top human-associated genera increasing during this phase. The experimental group exhibited higher observed richness than the control across T7-T56 (median 116 vs. 62 amplicon sequence variants; p < 0.001). A humanization score, calculated as the sum of the 10 top human genera detected in the transplanted ZmL, peaked at T14, and declined to near zero by the end of the washout phase (T56). Community composition differed significantly between groups, with the variable diet accounting for more variation than the run (PERMANOVA, R2 = 13.3%; p = 0.001).

CONCLUSIONS: Under repeated FMTs, ZmL underwent a humanization of their microbiota making this model a promising tool to study novel decolonization strategies against MDR bacteria. Future efforts should focus on the stabilization of the human-like microbiota without repeated FMTs.},
}

@article {pmid42791513,
year = {2026},
author = {Si, J and Wang, P and Li, Z and Hao, J and Wang, J and Zhang, L},
title = {Short-chain fatty acids as key mediators of the microbiota-gut-brain axis in chronic cerebral hypoperfusion: mechanisms and therapeutics.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {32},
number = {1},
pages = {},
pmid = {42791513},
issn = {1528-3658},
mesh = {Humans ; *Fatty Acids, Volatile/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Brain Ischemia/metabolism/etiology/therapy ; *Brain/metabolism ; *Brain-Gut Axis ; Blood-Brain Barrier/metabolism ; Dysbiosis ; Chronic Disease ; },
abstract = {Chronic cerebral hypoperfusion (CCH) is an important contributor to vascular cognitive impairment and neurodegenerative disorders, characterized by neuronal injury, blood-brain barrier (BBB) disruption, neuroinflammation, mitochondrial dysfunction, and synaptic impairment. Increasing evidence suggests that the microbiota-gut-brain axis plays a crucial role in ischemic brain injury. CCH is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, and reduced production of microbiota-derived short-chain fatty acids (SCFAs), which may be linked to cognitive decline through bidirectional gut-brain communication. This review summarizes the mechanisms potentially involved in CCH-related neurological damage and highlights the potential neuroprotective effects of SCFAs, including regulation of neuroinflammation, BBB integrity, mitochondrial homeostasis, neuronal apoptosis, and synaptic plasticity. Furthermore, potential microbiota-targeted therapeutic strategies, such as fecal microbiota transplantation, probiotics/prebiotics, and SCFA supplementation, are discussed. Targeting gut microbiota-derived SCFAs may represents a promising approach for improving CCH-associated cognitive impairment, although further clinical validation is required.},
}

Humans
*Fatty Acids, Volatile/metabolism
Animals
*Gastrointestinal Microbiome
*Brain Ischemia/metabolism/etiology/therapy
*Brain/metabolism
*Brain-Gut Axis
Blood-Brain Barrier/metabolism
Dysbiosis
Chronic Disease

@article {pmid42792717,
year = {2026},
author = {Bhatia, M and Mishra, SP and Mishra, RK and Jain, S and Yadav, H and Tomar, RS},
title = {Gut Microbiota and Brain Aging: Identifying Keystone Biomarkers for Cognitive Health.},
journal = {Biomedicines},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/biomedicines14091975},
pmid = {42792717},
issn = {2227-9059},
abstract = {The fact that the population is getting older has greatly increased the occurrence of cognitive decline and neurodegenerative diseases, underlining the importance of having reliable biomarkers that can measure biological aging before irreversible neurological damage takes place. New evidence shows that brain aging is not just the result of changes within neurons themselves but is also greatly affected by the gut microbiota via immune, metabolic, endocrine, and neurovascular signaling. This review brings together the existing knowledge about biomarkers of biological aging-such as telomere shortening, epigenetic clocks, oxidative stress, inflammation, cellular senescence, and metabolic dysfunction-as well as established cognitive biomarkers obtained from neuroimaging, cerebrospinal fluid, blood, genetic evaluations, and neuropsychological tests. We also point out that changes associated with age in the composition of the gut microbiota and the metabolites it produces are becoming more and more involved in the mechanisms connecting intestinal dysbiosis, dysfunction of the blood-brain barrier (BBB), neuroinflammation, and age-related cognitive decline. Through this approach of combined and complementary biomarker systems, we hypothesize that the gut microbiota has emerged as a central regulator of biological and cognitive aging and may provide a useful source for development of biomarkers of cognitive resilience and risk of neurodegenerative diseases. Lastly, we consider microbiome-based interventions, including probiotics, prebiotics, dietary changes, fecal microbial transplant, and new treatment modalities derived from molecular studies, as possible approaches to the prevention and management of age-related cognitive decline. Collectively, this review provides a comprehensive framework linking aging biology, microbiome science, and cognitive biomarkers to advance biomarker-driven precision medicine for healthy brain aging.},
}

@article {pmid42792816,
year = {2026},
author = {Țîrlea, LG and Lipan, L and Tănase, AD},
title = {Microbiota-Inflammation Crosstalk in Myeloproliferative Neoplasms: MPN-Specific Human Data, Mechanistic Plausibility and Translational Priorities.},
journal = {Biomedicines},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/biomedicines14092074},
pmid = {42792816},
issn = {2227-9059},
abstract = {Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders driven mainly by somatic mutations in JAK2, CALR or MPL, but their clinical phenotype is also shaped by chronic inflammation, immune dysregulation, vascular complications and microenvironmental remodeling. Emerging evidence suggests that the gut microbiota may contribute to this inflammatory and immunometabolic landscape; however, the current literature remains heterogeneous and its translational relevance is still insufficiently defined. This critical narrative review maps the available evidence linking the gut microbiota, microbial metabolites and systemic microbial signatures to MPN biology. We distinguish direct human MPN data from indirect mechanistic evidence derived from studies of intestinal barrier dysfunction, thrombo-inflammation, hematopoietic regulation, allogeneic hematopoietic cell transplantation and infection risk. Across human MPN cohorts, the most consistent findings are not uniform changes in global microbial diversity, but rather alterations in specific immunoregulatory taxa, particularly reduced Firmicutes/Faecalibacterium-related communities and dysbiotic signatures associated with JAK2V617F status. Mechanistically, dysbiosis and impaired intestinal barrier integrity may facilitate low-grade endotoxemia, TLR4/NF-κB activation, cytokine amplification, endothelial activation and platelet priming. In parallel, microbial metabolites may influence hematopoietic stem cell programs, the bone marrow niche, megakaryopoiesis and thrombopoiesis. Treatment exposure and diet are relevant modifiers of the microbiota-inflammation axis, although available interventional data remain preliminary. Mendelian randomization and multi-omics studies provide hypothesis-generating evidence for microbiota-metabolome-MPN interactions, but require longitudinal validation, functional studies and contamination-aware analytical pipelines, especially for low-biomass blood and bone marrow samples. Microbiota-targeted strategies, including nutritional interventions and fecal or washed microbiota transplantation, represent promising but still investigational approaches, particularly in immunocompromised or post-transplant settings. Future studies should integrate microbiome, metabolome, genome, proteome, inflammatory biomarkers and clinical outcomes while controlling for diet, antibiotics, treatment exposure and driver mutation status. Such an approach may clarify whether the microbiota is a biomarker, mediator or therapeutic target in MPNs.},
}

@article {pmid42793152,
year = {2026},
author = {Kong, W and Qiu, H and Jiang, Y and Ge, H and Wu, W and Huang, L and Chu, L and Ge, L},
title = {Research Progress on Bidirectional Regulation of the Microbiota-Gut-Brain Axis in Autism Spectrum Disorder Based on the Immune-Metabolic-Endocrine Interactive Network.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091321},
pmid = {42793152},
issn = {2218-273X},
support = {771200F0012//National Natural Science Foundation of China/ ; 025-54//Zhejiang Provincial Health Commission/ ; 2026JKZDZC07//Zhejiang Chinese Medical University/ ; },
mesh = {Humans ; *Autism Spectrum Disorder/microbiology/metabolism/immunology ; *Gastrointestinal Microbiome ; Animals ; *Brain/metabolism ; *Brain-Gut Axis ; },
abstract = {Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of ASD. The microbiota-gut-brain axis (MGBA), a critical pathway mediating crosstalk between the gut microbiota and the brain, has been extensively documented to be deeply involved in the pathological progression of ASD in recent years. However, prior studies have predominantly focused on the unidirectional regulation of the brain by gut microbiota, lacking an integrated account of the bidirectional regulation across immune, metabolic, and endocrine systems. Centered on the immune-metabolic-endocrine interactive network, this review systematically delineates the bidirectional regulatory mechanisms of the MGBA in ASD by integrating recent evidence from microbiota sequencing, animal models, and clinical intervention studies, with the aim of clarifying the bidirectional causal controversy between intestinal microecological disturbance and ASD behavioral abnormalities. This review proposes that in children with ASD, decreased abundance of beneficial intestinal bacteria and disrupted metabolic profiles of short-chain fatty acids synergistically impair intestinal barrier integrity, triggering peripheral chronic inflammation that further drives excessive microglial activation-mediated central neuroinflammation. Subsequently, disturbances in the homeostasis of multiple neurotransmitters including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), histamine, and dopamine occur via the vagus nerve and hypothalamic-pituitary-adrenal (HPA) axis, ultimately driving ASD behavioral abnormalities. Conversely, chronic stress and behavioral characteristics associated with ASD reshape the intestinal microecology through neuroendocrine pathways, forming a vicious cycle of "microbiota dysbiosis-immune inflammation-HPA axis hyperactivity-further intestinal microecological imbalance". This review summarizes the therapeutic efficacy and translational bottlenecks of three types of microecological interventions: fecal microbiota transplantation (FMT), probiotics, and ketogenic diet, and analyzes the current limitations in the field, including pronounced population heterogeneity, unclear cross-talk mechanisms among multiple pathways, and the scarcity of large-sample clinical evidence. Collectively, this review preliminarily elucidates the complete multi-system interactive framework of MGBA regulation in ASD, providing theoretical support for mechanistic research and gut-targeted individualized interventions for ASD.},
}

Humans
*Autism Spectrum Disorder/microbiology/metabolism/immunology
*Gastrointestinal Microbiome
Animals
*Brain/metabolism
*Brain-Gut Axis

@article {pmid42795509,
year = {2026},
author = {Ge, Y and Li, Z and Yu, C and Guo, W and Fan, G and Lin, G and Yu, H and Wang, Y},
title = {Gut Microbiota-Elicited Aberrant Phosphorylation Induces Protein Structural Anomalies: A Non-Negligible Pathogenic Driver of Autism Spectrum Disorder.},
journal = {Microorganisms},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/microorganisms14091925},
pmid = {42795509},
issn = {2076-2607},
support = {82301341//National Natural Science Foundation of China/ ; 202328016//R&D Program of Jinan City, Shandong, China/ ; },
abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by impaired social interaction and repetitive stereotyped behaviors, with pathogenic mechanisms that remain incompletely understood. The gut microbiota has emerged as a key regulator of ASD; however, its impact on hippocampal proteomic and phosphoproteomic signatures has not been fully characterized. In this study, we performed fecal microbiota transplantation (FMT) by transferring fecal samples from children with ASD and typically developing controls into antibiotic-treated mice. Gut microbiota from children with ASD induced several ASD-like behaviors in recipient mice, accompanied by aberrant activation of microglia, astrocytes, and neurons, as well as impaired neurogenesis. Phosphoproteomic profiling combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that differentially phosphorylated proteins were predominantly enriched in synapse-related pathways. ASD-derived microbiota markedly reduced synaptic density, downregulated the synaptic proteins SYP and PSD-95, and inhibited the expression of blood-brain barrier (BBB) tight junction proteins. In silico structural simulations using AlphaFold3 (AF3) and HADDOCK further supported that ASD-FMT may promote abnormal phosphorylation, potentially remodeling SHANK3 and SRRM2 conformations and weakening the binding affinity of SHANK3. Integrative proteomic and phosphoproteomic screening identified FNDC3A as a potential susceptibility-associated protein upregulated by gut microbiota from children with ASD, which was verified in mouse hippocampal tissues and plasma samples from children with ASD using Western blotting and ELISA, respectively. Mechanistically, ASD pathogenesis may be attributable not only to the dysregulation of classical ASD susceptibility genes but also to gut microbiota-driven post-translational phosphorylation remodeling of multiple protein structures. Importantly, this study established an innovative research framework that integrates in silico analyses with wet-lab experiments, yielding novel insights into ASD pathogenesis from the perspective of gut microbiota-induced alterations in the hippocampal phosphoproteome and revealing a plausible molecular mechanism underlying ASD.},
}

@article {pmid42795547,
year = {2026},
author = {Yuan, L and Zhang, C and Li, W and Yi, J and Liu, C and Jin, W and Li, G and Wang, B and Li, S and Wang, H},
title = {Intestinal Microbiota Structure of Xichuan Black-Bone Chickens and Preliminary Evaluation of a Probiotic-Based Fecal Microbiota Substitute.},
journal = {Microorganisms},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/microorganisms14091966},
pmid = {42795547},
issn = {2076-2607},
support = {2026ZC75//Henan Academy of Agricultural Sciences/ ; 2026BX54//Henan Academy of Agricultural Sciences/ ; 2025XMYG04//Henan Academy of Agricultural Sciences/ ; },
abstract = {In this study, we aimed to explore the intestinal microbiota structure of Xichuan black-bone chickens (XBCs) and evaluate the effect of fecal microbiota substitute transplantation (FMST) by comparing it with traditional fecal microbiota transplantation (FMT). Metagenomic sequencing was used to analyze the microbiota composition and diversity of different intestinal segments (duodenum, jejunum, ileum, cecum, and rectum) of adult XBCs. Probiotic strains were subsequently isolated and screened from the cecal contents under anaerobic conditions to prepare FMST preparations. In total, 90 1-day-old XBCs were randomly divided into the FMT group, FMST group and control group (CK) for the transplantation experiment. The results revealed that the cecum had the highest species richness among all intestinal segments, with a mean species number of 7593.2. Three probiotic strains, namely, Lactobacillus crispatus, Weissella paramesenteroides and Bacillus amyloliquefaciens, were successfully screened and identified. In the transplantation experiment, the FMT group exhibited optimal α diversity of the cecal microbiota, while compared with the FMT group, the FMST group had significantly reduced expression of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) and increased expression of intestinal tight junction proteins (claudin-1 and ZO-1). In conclusion, the cecum of XBCs has the most abundant microbial resources. Under the short-term intervention model tested herein, the custom FMST formulation delivers superior intestinal protective effects and shows promising potential as a standardized alternative to conventional FMT, which is highly important for the standardized application of fecal microbiota transplantation in poultry production.},
}

@article {pmid42796959,
year = {2026},
author = {Zhou, H and Shen, Q and Wu, L and Ma, Z and Ren, X and Wang, J and Hao, Z and Zhao, Q},
title = {Adzuki Bean Peptide Prevents DSS-Induced Colitis by Modulating the Gut Microbiota.},
journal = {Nutrients},
volume = {18},
number = {18},
pages = {},
doi = {10.3390/nu18182975},
pmid = {42796959},
issn = {2072-6643},
support = {32301983//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Dextran Sulfate ; *Gastrointestinal Microbiome/drug effects ; Bioactive Peptides, Dietary ; Mice ; Male ; *Vigna/chemistry ; *Colitis/chemically induced/prevention & control/microbiology ; Fatty Acids, Volatile/metabolism ; Feces/microbiology/chemistry ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/prevention & control/chemically induced ; Colon/pathology/drug effects/microbiology ; Cytokines/metabolism ; Disease Models, Animal ; },
abstract = {Background: The incidence of ulcerative colitis (UC) continues to rise, and food-derived bioactive peptides have attracted increasing attention as potential nutritional interventions for intestinal inflammation. This study investigated the preventive effects of the adzuki bean-derived peptide IFNNDPNNHP (IP10 peptide) on dextran sulfate sodium (DSS)-induced acute colitis in mice and explored the involvement of the gut microbiota. Methods: Mice received prophylactic IP10 peptide at 100 or 200 mg·kg[-1]. Colitis severity was assessed based on body weight, disease activity index, colon length, histopathology, and inflammatory cytokine levels. Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to further evaluate the role of the gut microbiota. Results: Prophylactic IP10 peptide administration attenuated DSS-induced colitis, with the 200 mg·kg[-1] dose more effectively attenuating body weight loss and colon shortening, reducing disease activity index scores, and modulating inflammatory cytokine levels. IP10 peptide increased microbial richness and diversity, decreased the relative abundance of Escherichia-Shigella, and increased the relative abundances of SCFA-associated taxa, including norank_f__Muribaculaceae and Lachnospiraceae_NK4A136_group. It also increased fecal SCFA levels, particularly acetate and butyrate; the high dose additionally restored propionate and valerate. When the gut microbiota was depleted using antibiotics, the protective effects of the IP10 peptide were no longer detectable, whereas FMT using fecal microbiota from donors receiving the high dose of IP10 peptide attenuated colitis and increased fecal SCFA levels in recipient mice. Conclusions: IP10 peptide alleviates DSS-induced acute colitis, and this effect may be partly associated with alterations in the gut microbiota, including the enrichment of SCFA-associated taxa and increased fecal SCFA levels. These findings support its potential as a functional food ingredient for intestinal health.},
}

Animals
Dextran Sulfate
*Gastrointestinal Microbiome/drug effects
Bioactive Peptides, Dietary
Mice
Male
*Vigna/chemistry
*Colitis/chemically induced/prevention & control/microbiology
Fatty Acids, Volatile/metabolism
Feces/microbiology/chemistry
Mice, Inbred C57BL
Fecal Microbiota Transplantation
*Colitis, Ulcerative/prevention & control/chemically induced
Colon/pathology/drug effects/microbiology
Cytokines/metabolism
Disease Models, Animal

@article {pmid42797045,
year = {2026},
author = {Wu, L and Bai, Y and Su, E and Cao, F and Fang, X and Zhao, L},
title = {Dietary Isorhamnetin Alleviates Alcoholic Liver Injury in Mice by Regulating Gut Microbiota via the Gut-Liver Axis.},
journal = {Nutrients},
volume = {18},
number = {18},
pages = {},
doi = {10.3390/nu18183062},
pmid = {42797045},
issn = {2072-6643},
support = {2022YFD2200605//the National Key R & D Program of China/ ; LYKJ[2024]01//the Jiangsu Forestry Science and Technology Innovation and Extension Project/ ; },
mesh = {Animals ; *Quercetin/analogs & derivatives/pharmacology/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; *Liver/drug effects/metabolism ; *Liver Diseases, Alcoholic/drug therapy/microbiology ; Mice ; Male ; Oxidative Stress/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Background: Alcoholic liver disease (ALD) refers to a progressive liver injury syndrome induced by chronic excessive alcohol intake. Current treatment options are mainly limited to symptom management, and there are safety risks associated with long-term use. Hence, there is an urgent demand to discover new therapeutic targets and investigate natural active substances. Isorhamnetin (IS) is an O-methylated flavonoid, and its specific structure confers unique biological activities and relatively good oral bioavailability, making it a potential natural candidate for the prevention of metabolic liver diseases. However, few studies have explored the application and action mechanism of IS in the intervention of alcoholic liver injury and intestinal flora imbalance. Methods: This work established a mouse model of chronic alcoholic liver injury to evaluate the beneficial effects of IS on hepatic injury, oxidative stress, and intestinal flora disturbance. Results: The results showed that IS intervention therapy can alleviate the symptoms of increased liver index, ALT, AST, TC, and TG levels due to alcohol intake. Furthermore, IS can alleviate liver oxidative stress caused by alcohol consumption, thereby protecting the liver of mice. Intestinal analysis in mice revealed that IS elevated the expression of tight junction proteins ZO-1 and Claudin-1, thereby attenuating alcohol-induced intestinal hyperpermeability and LPS translocation. This further suppressed the activation of the hepatic LPS/TLR4 signaling pathway and decreased the production of TNF-α and IL-1β. Meanwhile, IS significantly improved the intestinal flora disorder induced by alcohol in a dose-dependent manner. Compared with the EtOH group, IS treatment, particularly at the high dose (EISH), significantly increased the Ace, Chao1, Shannon, and Simpson indices. Conclusions: Consistently, NMDS analysis based on the OTU level showed that the IS-treated groups clustered away from the EtOH group and shifted toward the Control group, indicating a partial restoration of the overall microbial community structure toward that of healthy controls. In terms of species composition, IS treatment enriched beneficial microbial communities and inhibited the proliferation of pathogenic bacteria, efficiently restoring intestinal flora homeostasis. Collectively, these findings suggested that the hepatoprotective effects of IS were closely associated with the amelioration of gut microbiota dysbiosis and intestinal barrier function, pointing to a potential involvement of the gut-liver axis, although its causal contribution remains to be confirmed by further mechanistic studies (e.g., microbiota depletion or fecal microbiota transplantation). The findings not only provide new scientific evidence for the hepatoprotective effects of isorhamnetin but also offer a preliminary theoretical basis for the development of natural products potentially targeting the gut-liver axis.},
}

Animals
*Quercetin/analogs & derivatives/pharmacology/administration & dosage
*Gastrointestinal Microbiome/drug effects
*Liver/drug effects/metabolism
*Liver Diseases, Alcoholic/drug therapy/microbiology
Mice
Male
Oxidative Stress/drug effects
Disease Models, Animal
Mice, Inbred C57BL

@article {pmid42797073,
year = {2026},
author = {David, DE and Paraschiv, CM and Checherita, LE and Chiriac, SA and Grigorasi, GR and Lupu, VV and Lupu, A and Pertea, LI and Paduraru, G and Adam Raileanu, A and Tataranu, E and Temneanu, OR and Dramba, T and Casapu, AM and Esanu, IM},
title = {Targeting the Gut Microbiome in Cardiovascular Disease: Current Therapeutic Strategies and Future Perspectives.},
journal = {Nutrients},
volume = {18},
number = {18},
pages = {},
doi = {10.3390/nu18183091},
pmid = {42797073},
issn = {2072-6643},
support = {351058//Health Programme (PS) 2021-2027/ ; },
mesh = {Humans ; *Cardiovascular Diseases/microbiology/therapy/prevention & control ; *Gastrointestinal Microbiome/physiology/drug effects ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Animals ; Intestinal Barrier Function ; },
abstract = {The gut microbiota is increasingly recognized as an important modulator of cardiovascular health, demonstrating complicated interactions among diet, metabolism, immunology and host physiology. Evidence is accumulating that changes in the composition and function of the gut microbiome may contribute to the pathogenesis of atherosclerosis, hypertension, heart failure, thrombosis and other cardiovascular phenotypes through mechanisms involving microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation. In this context, the key question of this narrative review is: how far can modulation of the gut microbiome and its metabolic functions be a clinically meaningful approach in the prevention and treatment of cardiovascular disease, and which of the currently available microbiome-targeted approaches have sufficient mechanistic and clinical evidence to justify translation into cardiovascular practice? To answer this question, we review the evidence linking the gut microbiome to major cardiovascular phenotypes, such as atherosclerosis, hypertension, heart failure, thrombosis and atrial fibrillation, with particular focus on the mechanisms through which microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation may affect cardiovascular risk. We then review current and emerging strategies for microbiome modulation, including dietary interventions, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation and targeted inhibition of microbial metabolic pathways such as trimethylamine (TMA)/trimethylamine N-oxide (TMAO) production. We also examine bidirectional interactions between cardiovascular drugs and gut microbiome and the role of these interactions in the development of precision methods to cardiovascular prevention and treatment. Finally, we outline the major limitations of the current evidence and highlight goals for future mechanistic, translational and clinical research.},
}

Humans
*Cardiovascular Diseases/microbiology/therapy/prevention & control
*Gastrointestinal Microbiome/physiology/drug effects
Probiotics/administration & dosage
Prebiotics/administration & dosage
Fecal Microbiota Transplantation
Animals
Intestinal Barrier Function

@article {pmid42797532,
year = {2026},
author = {Wang, X and Huang, M and Xu, X},
title = {Associations Between Gut Microbiota and Tissue Exposure of Gastrodia elata-Derived Bioactive Components: Observations from Fecal Microbiota Transplantation in SHRs and Wistar Rats.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {9},
pages = {},
doi = {10.3390/ph19091487},
pmid = {42797532},
issn = {1424-8247},
support = {2682026ZTPY038//the Fundamental Research Funds for the Central Universities/ ; },
abstract = {Background/Objectives: This study aimed to explore potential associations between gut microbiota and the in vivo tissue exposure profiles of bioactive constituents derived from Gastrodia elata in spontaneously hypertensive rats (SHRs). Methods: Fecal microbiota transplantation (FMT), high-performance liquid chromatography (HPLC) tissue quantification, and 16S rRNA gene sequencing were applied in the present work. Results: Distinct tissue exposure patterns of Gastrodia elata-derived gastrodin (GAS) and gastrodigenin (HBA) were observed following gut microbiota remodeling. Noticeable shifts in the relative abundance of specific intestinal bacterial taxa were detected between hypertensive SHRs and normotensive Wistar rats, and these taxonomic alterations showed correlation with tissue levels of the target herbal components. Conclusions: It should be noted that the FMT experimental design in this study cannot fully decouple microbiota-related effects from drug treatment confounders; hence, our findings represent preliminary correlative observations rather than definitive causal evidence. This work provides experimental clues for understanding host-microbe-herb interplay under hypertensive conditions and may offer reference information for optimizing administration strategies of natural hypotensive compounds.},
}

@article {pmid42798011,
year = {2026},
author = {Wang, J and Zhang, X and Song, X and He, Y and Lang, W and Zhang, X},
title = {Gram-Negative Bacterial Overgrowth Predominated by: Potential Association with Intestinal Barrier Impairment and Inflammatory Diarrhea in Cats.},
journal = {Veterinary sciences},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/vetsci13090976},
pmid = {42798011},
issn = {2306-7381},
support = {24JK0425//Education Department of Shaanxi Province/ ; },
abstract = {BACKGROUND: Feline diarrhea is one of the most common gastrointestinal disorders encountered in veterinary clinics. Dysbiosis of Gram-negative bacteria is widely presumed to be a key cause of this disease, yet adequate in vivo evidence demonstrating its roles in provoking inflammation and impairing intestinal barrier integrity is still lacking. In this study, we investigated the effects of bacterial flora in cats with diarrhea on gut health in mice.

RESULTS: The results show the following: (1) Microorganisms in feces of diarrheal cats can cause weight loss in antibiotic-treated mice; the histopathological section of the colon showed that neutrophil aggregation occurred in the colon of mice in the fecal bacteria transplantation group; this indicates that gavage using fecal microbes from diarrheic cats could impair intestinal barrier integrity in antibiotic-treated recipient mice. (2) In addition, microbes in cats with diarrhea can induce inflammation in the colon and aggregation of macrophages, which may be caused by some Gram-negative bacteria in feces of cats with diarrhea. (3) The composition of the intestinal microbial community was analyzed by 16S rRNA gene sequencing, and it was found that the relative abundance of Escherichia-Shigella in feces of cats with diarrhea was significantly higher than that of normal cats. (4) Quantitative analysis of fecal samples revealed that diarrheic cats exhibited a significantly higher load of fecal Gram-negative bacteria compared with healthy cats, verifying that excessive colonization of Gram-negative bacteria may be highly correlated with feline diarrhea.

CONCLUSION: In summary, fecal microbes from diarrheic cats are capable of triggering intestinal inflammation and barrier damage in antibiotic-treated mice. Excessive proliferation of Gram-negative bacteria, mainly Escherichia-Shigella species, may be highly associated with feline diarrhea.},
}

@article {pmid42798402,
year = {2026},
author = {Ahn, J and Kim, M and Min, SH and Bae, HG and Bae, JY and Kwon, J and Yi, H and Park, DH},
title = {Fecal microbiota transplantation from duodenal light stimulation-conditioned donors is associated with improved glucose tolerance and intestinal incretin-related remodeling in diabetic Goto-Kakizaki rats.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1900693},
pmid = {42798402},
issn = {2235-2988},
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats ; *Diabetes Mellitus, Type 2/therapy/metabolism ; *Incretins/metabolism ; *Gastrointestinal Microbiome ; *Duodenum/microbiology ; Male ; Glucose Tolerance Test ; Disease Models, Animal ; Blood Glucose ; Feces/microbiology ; },
abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by impaired glucose homeostasis and β-cell dysfunction. Emerging evidence suggests that the gut microbiota-incretin axis may contribute to metabolic regulation. However, whether microbiota from duodenal light stimulation (DLS)-conditioned donors can influence metabolic phenotypes via fecal microbiota transplantation (FMT) remains unclear.

METHODS: We evaluated whether FMT from DLS-conditioned donors was associated with metabolic and intestinal changes in diabetic GK (Goto-Kakizaki) rats. Recipients received FMT from week -2 to week 0 and were then followed for 7 weeks after the final FMT dose. Metabolic phenotyping, intestinal histology, short-chain fatty acid (SCFA) profiling, and shotgun metagenomic profiling of bacterial and viral communities were performed.

RESULTS: FMT recipients showed within-group improvement in OGTT glucose profiles, without significant changes in fasting glucose levels. Total glucose AUC0-120 was significantly reduced within the FMT group in the within-group (period) comparison; however, the group × period interaction was not significant, indicating no statistically significant longitudinal between-group treatment effect. Early GLP-1 responses showed a modest increasing trend in FMT recipients, whereas total GLP-1 AUC0-120 was not significantly changed. HOMA-β (homeostatic model assessment of β-cell function) increased within the FMT group, and pancreatic insulin-positive area was greater in FMT recipients than in controls at the study endpoint. Intestinal remodeling was evident, including an increased villus:crypt ratio and increased colonic GLP-1-positive cells. FMT was associated with fecal bacteriome differences, including one FDR-significant taxon and several nominally associated taxa, such as Akkermansia muciniphila and Xylanibacter rodentium. No significant global shift in fecal virome composition was observed, although selected viral taxa showed nominal group-associated differences that did not remain significant after FDR correction. Exploratory network analysis suggested group-specific bacteriome-virome association patterns after FMT.

CONCLUSION: FMT from DLS-conditioned donors was associated with improved glucose tolerance, intestinal incretin-related remodeling, increased pancreatic insulin-positive area, and fecal bacteriome differences in diabetic GK rats based on within-group longitudinal changes for the glucose- and β-cell-related outcomes, for which the group × period interactions were not significant, whereas the histological and microbiome differences reflect cross-sectional between-group comparisons at the study endpoint. These findings support a hypothesis-generating link between donor-conditioned FMT, intestinal remodeling, and microbiome-associated metabolic regulation, while further studies are required to define DLS-specific and donor-derived effects.},
}

Animals
*Fecal Microbiota Transplantation/methods
Rats
*Diabetes Mellitus, Type 2/therapy/metabolism
*Incretins/metabolism
*Gastrointestinal Microbiome
*Duodenum/microbiology
Male
Glucose Tolerance Test
Disease Models, Animal
Blood Glucose
Feces/microbiology

@article {pmid42798820,
year = {2026},
author = {Zhou, R and Wang, S},
title = {Gut-placenta axis: gut microbiota metabolites may play a role in regulating maternal-fetal immune tolerance and the pathogenesis of adverse pregnancy outcomes.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1960306},
doi = {10.3389/fimmu.2026.1960306},
pmid = {42798820},
issn = {1664-3224},
mesh = {Humans ; Female ; Pregnancy ; *Gastrointestinal Microbiome/immunology ; *Placenta/immunology/metabolism ; Pregnancy Outcome ; *Immune Tolerance ; Animals ; *Maternal-Fetal Exchange/immunology ; *Pregnancy Complications/immunology/metabolism/microbiology ; Dysbiosis/immunology ; },
abstract = {Pregnancy is a unique physiological stage characterized by the coordinated remodeling of maternal metabolism, immunity, and endocrine systems. Previous studies have primarily focused on the local uterine microenvironment, neglecting the role of the maternal gut microbiota in mediating distal, cross-organ regulation via the gut-placental axis. The concept of the gut-placental axis was formally proposed in 2018 and has attracted widespread research attention in recent years. Studies using germ-free animals, fecal microbiota transplantation (FMT), and in vitro experiments with human multi-omics cohorts suggest that live gut bacteria generally cannot colonize the placenta, and that soluble microbial metabolites mediate bidirectional signaling between the gut and the placenta. Pregnancy-related factors such as a high-sugar, high-fat diet, antibiotic use, and obesity can induce gut microbiota dysbiosis and intestinal barrier dysfunction, leading to decreased levels of potentially protective metabolites such as short-chain fatty acids (SCFAs) and tryptophan derivatives, while pro-inflammatory molecules such as lipopolysaccharide (LPS), and trimethylamine N-oxide (TMAO) to accumulate in the bloodstream. These substances cross the placental barrier, disrupting maternal-fetal immune homeostasis, inhibiting trophoblast function and spiral artery remodeling, and are statistically associated with adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and spontaneous preterm birth. This article is a narrative review that systematically elucidates the - placental axis for substance transport and the potential molecular mechanisms by which metabolites regulate maternal-fetal immune balance; it maps out the pathological pathways through which microbiota dysbiosis mediates various adverse pregnancy outcomes; it objectively analyzes controversies and gaps in areas such as placental microbial colonization, bidirectional feedback loops, and evidence for clinical interventions; and it proposes a future research framework centered on multi-omics candidate biomarkers and stratified microbiome interventions. Microbial metabolites are promising candidates for non-invasive biomarkers; stratified microbiome interventions are merely potential prevention and control strategies suggested by laboratory and small-scale clinical studies. There is still a lack of unified, standardized clinical protocols, and large-scale, long-term, randomized controlled trials (RCTs) are needed to validate their safety and efficacy, thereby providing a theoretical foundation for subsequent mechanistic and translational research on maternal-fetal microbiome interactions.},
}

Humans
Female
Pregnancy
*Gastrointestinal Microbiome/immunology
*Placenta/immunology/metabolism
Pregnancy Outcome
*Immune Tolerance
Animals
*Maternal-Fetal Exchange/immunology
*Pregnancy Complications/immunology/metabolism/microbiology
Dysbiosis/immunology

@article {pmid42799756,
year = {2026},
author = {Westerbeke, FHM and Warmbrunn, MV and Rios-Morales, M and Li, XS and Tian, MY and Novak, MA and Williams, AM and Hazen, SL and Attaye, I and Nieuwdorp, M},
title = {Plasma indole-3-propionic acid is a gut-derived metabolite and is associated with type 2 diabetes and cardiometabolic outcomes: Evidence from a human antibiotic intervention.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2736321},
doi = {10.1080/19490976.2026.2736321},
pmid = {42799756},
issn = {1949-0984},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/blood/metabolism/drug therapy ; *Indoles/blood ; *Gastrointestinal Microbiome/drug effects ; *Anti-Bacterial Agents/administration & dosage/therapeutic use ; Male ; Female ; Middle Aged ; Feces/microbiology ; Bacteria/classification/genetics/isolation & purification/metabolism/drug effects ; Adult ; Propionates ; },
abstract = {The gut microbiota influences host metabolism through diverse metabolites, many of which have been linked to glucose homeostasis and type 2 diabetes (T2D). Understanding microbial contributions to metabolite biosynthesis is essential for developing dietary and microbiota-targeted T2D prevention and treatment strategies. We performed targeted plasma metabolomics in individuals with T2D and healthy controls, all receiving histidine supplementation, before and after gut microbiota suppression using 7-day broad-spectrum antibiotic treatment. Associations between pre-antibiotic metabolite levels and fecal metagenomics-derived gut microbiota composition were examined using co-abundance network analysis and Random Forest modeling. Indole-3-propionic acid (IPA) was the only gut-derived metabolite differing between groups before antibiotics, with lower levels in T2D and higher levels associated with reduced T2D odds. Antibiotic treatment reduced IPA to near-undetectable levels in both groups, confirming its predominantly microbial origin. Beyond established inverse associations with BMI and glycemic markers, we found a novel inverse correlation between IPA and glycemic variability, consistent with a protective association with T2D. Plasma IPA was associated with gut microbiota beta diversity. IPA-associated species clustered within a single co-abundance module, but did not include known IPA producers, suggesting plasma IPA is influenced by broader microbial community composition rather than IPA-producing capacity of individual taxa alone. This study provides direct human evidence that plasma IPA is virtually exclusively gut microbiota-derived in individuals with T2D, extending prior findings in healthy populations. It highlights IPA's relevance to metabolic health and T2D, and guides future research on dietary and microbiota-targeted strategies to modulate IPA, advancing T2D prevention and treatment.},
}

Humans
*Diabetes Mellitus, Type 2/microbiology/blood/metabolism/drug therapy
*Indoles/blood
*Gastrointestinal Microbiome/drug effects
*Anti-Bacterial Agents/administration & dosage/therapeutic use
Male
Female
Middle Aged
Feces/microbiology
Bacteria/classification/genetics/isolation & purification/metabolism/drug effects
Adult
Propionates

@article {pmid42800367,
year = {2026},
author = {Shen, S and Zhou, Y and Qian, J and Li, T and Hu, X and Ji, X and Zhang, X and Zhou, D},
title = {An intestine-centric view of neurodegeneration: How intestine-derived signals mediate the intestine-brain axis to impact Alzheimer's disease.},
journal = {Journal of neuroimmunology},
volume = {421},
number = {},
pages = {579102},
doi = {10.1016/j.jneuroim.2026.579102},
pmid = {42800367},
issn = {1872-8421},
abstract = {Alzheimer's disease (AD) has emerged as an increasingly prevalent and burdensome public health challenge with global aging, underscoring the urgent need to clarify the key factors involved in its pathogenesis for effective prevention and management. Mounting evidence suggests that disrupted crosstalk between the intestine and brain may contribute to aging-related neurodegeneration, including AD. Acting as a peripheral modulatory hub of the intestine-brain axis, the intestine releases a variety of bioactive substances that regulate brain function. This narrative review synthesizes current evidence on intestine-derived signaling molecules and immune mediators implicated in AD pathogenesis, with a focus on two primary communication routes: the vagus nerve and systemic circulation. In addition, intestine-targeted interventions-including dietary modification, probiotic supplementation, and fecal microbiota transplantation-are summarized. Notably, metagenomics-based intestinal microbiota aging clocks represent an emerging non-invasive strategy for AD risk prediction. Although preclinical findings are encouraging, the translational limitations and heterogeneity of current intestine-brain research remain noteworthy. In summary, this narrative review integrates substantial evidence on the correlation between intestine-derived mediators and AD and provides potential insights for the development of intestine-targeted preventive strategies.},
}

@article {pmid42785880,
year = {2026},
author = {Liu, W and Li, Y and Sun, Y and Liu, X and Bai, Y and Du, L and Lan, X and Yang, J and Guan, L},
title = {Purified polysaccharides from safflower (Carthamus tinctorius L.) post-extraction residues alleviate immunosuppression in mice by modulating gut microbiome.},
journal = {Carbohydrate polymers},
volume = {391},
number = {},
pages = {125841},
doi = {10.1016/j.carbpol.2026.125841},
pmid = {42785880},
issn = {1879-1344},
mesh = {Animals ; *Carthamus tinctorius/chemistry ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Polysaccharides/pharmacology/chemistry/isolation & purification ; Cyclophosphamide ; Immunosuppression Therapy ; Male ; Fecal Microbiota Transplantation ; },
abstract = {A novel polysaccharide AES-S was extracted from safflower post-extraction residues using response surface methodology (RSM) and artificial neural network (ANN) optimization techniques, and was purified to obtain a homogeneous polysaccharide. Structural analysis revealed that AES-S is an RG-I-type pectic polysaccharide with a backbone of →4)-α-GalpA-(1 → 2)-α-Rhap-(1 → and a molecular weight (Mw) of 16.27 kDa. AES-S restored the immune homeostasis of cyclophosphamide (CTX)-induced immunosuppressed mice by promoting cytokine secretion, recovering T cell proliferation, increasing immunoglobulins and maintaining intestinal barrier integrity. Based on a pseudo-sterility mouse model and fecal microbiota transplantation (FMT), a crucial role of the gut microbiome and its associated metabolites in protective effects of AES-S against intestinal injury was confirmed. 16S ribosomal RNA (rRNA) and internal transcribed spacer (ITS) sequencing showed that AES-S remodeled the gut microbiome, enriching beneficial bacteriota (Corynebacterium) and mycobiota (Rhodotorula). Metabolomics further revealed key changes in immunomodulatory metabolites, including 5-methylthio-d-ribose and D-galactose 6-sulfate, as well as a marked increase in short-chain fatty acids (SCFAs). Correlation analyses linked these microbial shifts to metabolic recovery. These findings demonstrate that AES-S exerts immunomodulatory effects via the gut microbiome-metabolism axis, positioning it as a promising natural immunomodulatory agent.},
}

Animals
*Carthamus tinctorius/chemistry
*Gastrointestinal Microbiome/drug effects
Mice
*Polysaccharides/pharmacology/chemistry/isolation & purification
Cyclophosphamide
Immunosuppression Therapy
Male
Fecal Microbiota Transplantation

@article {pmid42786564,
year = {2026},
author = {Jacobs, I and Ceulemans, M and Lenfant, M and Cremer, J and De Hertogh, G and Ferrante, M and Sabino, J and Vermeire, S and Breynaert, C and Vanuytsel, T and Verstockt, B},
title = {Distinct intestinal eosinophil subsets in ulcerative colitis and their modulation by advanced inflammatory bowel disease therapies.},
journal = {Journal of Crohn's & colitis},
volume = {20},
number = {9},
pages = {},
doi = {10.1093/ecco-jcc/jjag141},
pmid = {42786564},
issn = {1876-4479},
support = {//Clinical Research Fund/ ; //Research Council at the KU Leuven/ ; },
mesh = {Humans ; *Colitis, Ulcerative/drug therapy/immunology/pathology ; *Eosinophils/metabolism/immunology ; Female ; Male ; Retrospective Studies ; Eosinophil-Derived Neurotoxin/analysis ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Middle Aged ; Flow Cytometry ; Feces/chemistry ; *Colon/pathology/immunology ; *Gastrointestinal Agents/therapeutic use ; Leukocyte L1 Antigen Complex/analysis ; B7-1 Antigen/metabolism ; },
abstract = {BACKGROUND AND AIMS: Despite the importance of eosinophils in histologic scoring systems of ulcerative colitis (UC), the impact of advanced therapies on eosinophils is poorly understood. Additionally, data regarding distinct eosinophil subsets in UC are scarce.

METHODS: Colonic immune cells from 20 patients were analyzed by flow cytometry, alongside matched stool samples measuring fecal calprotectin and eosinophil-derived neurotoxin. In a separate cohort of 29 UC patients starting advanced therapy, immune cells from blood and colon were profiled at baseline and post-induction. Treatment response was defined as a Mayo endoscopic subscore of 0-1. A retrospective cohort (n = 21) was used to validate our findings.

RESULTS: Inflamed colonic tissue was characterized by an increased abundance of total eosinophils (P = .007), with an enrichment of B-Eos (CD80- PD-L1-) and depletion of A-Eos (CD80+ PD-L1+ active eosinophils) (both P < .0001) compared with unaffected tissue (correlated with histological activity RHI, P = .003). Endoscopic response to advanced therapy was associated with a reduction in total eosinophils (P = .0008) and various other immune cells, whereas nonresponse showed significant immune remodeling. Exploratory analyses in patients treated with vedolizumab (n = 11) demonstrated reductions in colonic total eosinophils (P = .07) and B-Eos (P = .008), together with an increase in A-Eos (P = .0003), resulting in an increased A-Eos/B-Eos ratio irrespective of endoscopic outcome.

CONCLUSION: We confirmed enrichment of total eosinophils in inflamed colonic tissue, characterized by an increase in B-Eos and a reduction in A-Eos, resulting in a decreased A-Eos/B-Eos ratio. Exploratory analyses suggest that vedolizumab is associated with reduced B-Eos, increased A-Eos, and restoration of the A-Eos/B-Eos ratio, raising the hypothesis that this therapy may differentially modulate mucosal eosinophil biology. These findings identify distinct eosinophil subsets as potential biomarkers and therapeutic targets in UC and provide a biological framework for future mechanistic studies.},
}

Humans
*Colitis, Ulcerative/drug therapy/immunology/pathology
*Eosinophils/metabolism/immunology
Female
Male
Retrospective Studies
Eosinophil-Derived Neurotoxin/analysis
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use
Middle Aged
Flow Cytometry
Feces/chemistry
*Colon/pathology/immunology
*Gastrointestinal Agents/therapeutic use
Leukocyte L1 Antigen Complex/analysis
B7-1 Antigen/metabolism

@article {pmid42786851,
year = {2026},
author = {Hu, C and Li, H and Li, Y and Huang, S and Wang, W and Zhang, F and Zhao, Y and Hao, Y},
title = {The Interaction Between Gut Microbiota and Neuroinflammation in the Gut-Brain Axis of Autism Spectrum Disorder.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X478343260906114952},
pmid = {42786851},
issn = {1875-6190},
abstract = {Autism Spectrum Disorder (ASD) is characterized primarily by social deficits and repetitive behaviors, often accompanied by gastrointestinal dysfunction. Its etiology involves interactions among genetic, environmental, and biological factors. Current studies indicate that neuroinflammation and gut microbiota imbalance are key factors in the development of ASD. Neuroinflammation is characterized by elevated levels of pro-inflammatory factors and abnormal glial cell activation, whereas gut microbiota imbalance is evidenced by dysbiosis and compromised intestinal barrier function. The gut-brain axis regulates neuroinflammation and synaptic function through pathways such as short-chain fatty acids (SCFAs), tryptophan metabolism, γ-aminobutyric acid (GABA) metabolism, and the hypothalamic-pituitary-adrenal (HPA) axis. Although modulation of the microbiota, for example, fecal microbiota transplantation (FMT) and probiotics, could improve ASD symptoms by repairing the intestinal barrier and alleviating neuroinflammation, the molecular mechanisms underlying these effects remain to be elucidated. This article reviews the interaction between gut microbiota and neuroinflammation in ASD, aiming to provide insights for treatment and research.},
}

@article {pmid42786856,
year = {2026},
author = {Dong, S and Cui, Q and Zong, L and Xue, Y and Zhao, L and Li, Y},
title = {Resveratrol's Therapeutic Role in Sepsis-Associated Encephalopathy.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273502075260910113533},
pmid = {42786856},
issn = {1996-3181},
abstract = {INTRODUCTION/OBJECTIVE: Sepsis-Associated Encephalopathy (SAE) represents a lifethreatening complication of sepsis, whose pathogenesis is driven by intestinal dysbiosis through bidirectional gut-brain axis signaling. Resveratrol, a neuroprotective natural polyphenol, exerts anti-SAE effects in a microbiota-dependent manner; nevertheless, existing mechanistic evidence has not been systematically integrated. This review comprehensively summarizes its multitiered protective signaling cascades centered on gut-brain crosstalk.

METHODS: We systematically retrieved relevant literature published between January 2006 and July 2026 from mainstream databases in accordance with the PRISMA-S reporting standard. We integrated CLP/LPS septic animal and cellular data, and compared auxiliary evidence from non-septic models without direct extrapolation.

RESULTS: Preclinical septic animal studies confirmed four core protective axes of resveratrol centered on gut microbiota remodeling: (1) reshaping intestinal flora to limit LPS translocation; (2) stabilizing intestinal and cerebral tight junctions via SIRT1/NF-κB signaling; (3) elevating gut-derived shortchain fatty acids to inhibit glial pro-inflammatory activation; (4) activating Nrf2/HO-1 to relieve cerebral mitochondrial oxidative injury. Reciprocal fecal microbiota transplantation, germ-free and antibiotic depletion assays verified gut flora as an indispensable intermediate mediator linking oral resveratrol to neurological recovery. Non-septic model data provided auxiliary molecular references but cannot be extrapolated to SAE without septic-specific validation. Major translational obstacles include low oral bioavailability, narrow therapeutic window, and conflicting efficacy under combined ICU routine medications.

DISCUSSION: All cerebral pathological lesions (neuroinflammation, glial polarization, oxidative stress, BBB damage) originate from gut dysbiosis and endotoxin translocation in SAE, which establishes the gut-brain axis as the core therapeutic target of resveratrol. Repeated redundant mechanistic descriptions across pathways were condensed and overlapping glial sections merged in this revised minireview to meet journal word limits. Indirect non-septic evidence lacks the systemic endotoxin storm characteristic of SAE, thus only serves as supplementary reference. Novel microbiota-targeted delivery formulations are promising solutions to overcome resveratrol's pharmacokinetic defects.

CONCLUSION: Resveratrol alleviates SAE through multi-modal gut-brain axis regulation. Novel microbiota- targeted delivery carriers and standardized clinical trials focusing on delayed intervention are urgently needed to overcome translational limitations and facilitate the clinical application of resveratrol as an adjuvant therapy for SAE.},
}

@article {pmid42787156,
year = {2026},
author = {Vanous, K and Rojas, CA and Pomeroy, C and Ganz, HH},
title = {Gut microbiota variation in captive tortoises is associated with host species, trophic category, and growth rate.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1861012},
pmid = {42787156},
issn = {1664-302X},
abstract = {Despite the ecological and conservation importance of tortoises, their gut bacterial microbiotas remain poorly characterized, particularly across species in captivity. Associations between gut microbiota composition and tortoise age, sex, and growth rate are also poorly understood. Here, we use full-length 16S rRNA gene sequencing to characterize the gut microbiotas of 55 captive tortoises, representing seven species: red-footed tortoise (Chelonoidis carbonarius), yellow-footed tortoise (Chelonoidis denticulatus), Mojave desert tortoise (Gopherus agassizii), Texas tortoise (Gopherus berlandieri), leopard tortoise (Stigmochelys pardalis), African spurred tortoise (Centrochelys sulcata), and Russian tortoise (Testudo horsfieldii). By examining individuals maintained under consistent environmental conditions, we reduced large-scale environmental variation and evaluated associations with host characteristics. Across species, we identified a core set of 18 bacterial taxa, including cellulose degraders (Cellulosilyticum ruminicola and Ruminococcus champanellensis) and fatty-acid producers (Clostridium butyricum, and members of the families Lachnospiraceae and Christensenellaceae). Despite this shared bacterial core, microbiota composition differed by host species, age, and trophic category (herbivore vs. omnivore). Additionally, the relative abundances of two taxa-R. champanellensis, an important fiber degrader, and Anaerocella delicata, a propionate and acetate producer-were associated with variation in tortoise growth rate. Collectively, our findings suggest that although captive tortoises share a common microbial core, host species and digestive physiology shape microbiota structure, while specific bacterial taxa are associated with variation in growth rate.},
}

@article {pmid42787367,
year = {2026},
author = {Sun, Y and Zheng, F and Long, Q and Cheng, J and Ji, Q and Wang, R and Li, W},
title = {FMT and Bifidobacterium quadruple viable tablets supplementation modulate gut microbiota to ameliorate high-altitude exposure induced colonic injury.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1856635},
pmid = {42787367},
issn = {1664-302X},
abstract = {High-altitude hypoxic environments can induce significant gut microbiota dysbiosis, which in turn triggers colonic inflammation and intestinal barrier injury. This study aims to elucidate the core driving role of the gut microbiota in high-altitude induced colonic injury and to verify the protective effects of Bifidobacterium quadruple viable tablets (BQT). Here, we exposed C57BL/6 mice to acute and subacute exposure in high-altitude environment. High-altitude hypoxia led to colonic tissue damage, including epithelial cell shedding and inflammatory cell infiltration, and significantly reduced gut microbiota diversity in mice, manifested as a decreased Firmicutes/Bacteroidota ratio and increased abundances of Proteobacteria and Verrucomicrobiota. Fecal microbiota transplantation (FMT) improved colonic tissue morphology, reduced inflammatory cytokine levels, and enhanced intestinal barrier function. BQT intervention effectively alleviated colonic inflammation and reversed the down-regulation of tight junction proteins (ZO-1, Occludin, and Claudin-1) induced by hypoxia. In conclusion, gut microbiota dysbiosis is a key factor in high-altitude induced colonic inflammatory injury. FMT and BQT ameliorate high-altitude induced intestinal damage by restoring gut microbiota homeostasis and repairing the intestinal barrier. These findings suggest that supplementation with BQT may serve as a candidate microecological strategy for the prevention and treatment of intestinal injury in high-altitude populations.},
}

@article {pmid42787414,
year = {2026},
author = {Zhu, Y and Wan, JY and Sawadogo, R and Zhong, JM and Yao, HQ and Zhang, QH and Wang, CZ and Xu, M and Yuan, CS},
title = {Morphine-induced dysbiosis and metabolic remodeling of the gut microbiota is transmissible via fecal microbiota transplantation in mice.},
journal = {American journal of clinical and experimental immunology},
volume = {15},
number = {4},
pages = {277-289},
pmid = {42787414},
issn = {2164-7712},
abstract = {OBJECTIVE: Opioids such as morphine are widely used analgesics but are highly addictive. Emerging evidence implicates the gut microbiota in modulating opioid-associated pathophysiology. However, the global metabolic impact of morphine on gut microbial function and the causal transmissibility of morphine-induced dysbiosis remain to be fully elucidated.

METHODS: Adult C57BL/6 mice received repeated morphine administration for four consecutive days. Fecal metabolomic profiling was performed using integrated gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) platforms. Gut microbial composition was analyzed by 16S rRNA gene sequencing and terminal restriction fragment length polymorphism (T-RFLP) profiling. To determine causality and transmissibility, fecal microbiota transplantation (FMT) was conducted from morphine-treated donor mice into antibiotic-depleted recipient mice.

RESULTS: Repeated morphine administration induced a profound global reprogramming of fecal metabolic profiles, with clear separation between morphine-treated and control mice. A total of 179 fecal metabolites were annotated. Morphine significantly increased diethylene glycol, N-acetyl-L-glutamic acid, and urea, while decreasing 3-aminoisobutyric acid, 2-aminobutyric acid, and pseudouridine. Pathway enrichment analysis revealed that amino acid-centered metabolic pathways, including branched-chain amino acid biosynthesis, arginine biosynthesis, and aminoacyl-tRNA biosynthesis, were the most prominently disrupted. Morphine exposure also induced a distinct dysbiotic microbial signature characterized by expansion of Enterococcus faecalis and Alistipes indistinctus, and depletion of Prevotella melaninogenica. Importantly, FMT from morphine-treated donors into microbiota-depleted recipients successfully transferred both the dysbiotic microbial structure and metabolic phenotype. Post-transplant recipient mice exhibited microbial profiles closely resembling morphine-treated donors, demonstrating that the morphine-induced dysbiosis is transmissible in the short term in the absence of direct drug exposure.

CONCLUSION: Repeated acute morphine exposure alters fecal amino acid and nitrogen metabolism and drives a transmissible dysbiotic state in the short term. These findings highlight a potential association between morphine exposure, metabolic remodeling, and gut dysbiosis, suggesting the gut microbiota may be a relevant factor in opioid-associated intestinal interactions.},
}

@article {pmid42787448,
year = {2026},
author = {Gao, Y and Fan, L and Ma, R and Wu, L},
title = {The role of intestinal microbial metabolites in polycystic ovary syndrome: mechanistic insights and intervention prospects.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1886749},
pmid = {42787448},
issn = {1664-2392},
mesh = {Humans ; *Polycystic Ovary Syndrome/metabolism/microbiology/therapy ; Female ; *Gastrointestinal Microbiome/physiology ; Animals ; Insulin Resistance ; },
abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder among women of reproductive age, defined by the core features of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is frequently complicated by insulin resistance, obesity, dyslipidemia, and chronic low-grade inflammation, which substantially impair patients' reproductive health, metabolic homeostasis, and quality of life. Although the etiology of PCOS remains incompletely elucidated, accumulating evidence indicates that gut microbiota and their metabolites participate in the pathogenesis and progression of PCOS via metabolic, immune, and neuroendocrine pathways. Focusing on the gut-ovary axis, this review systematically summarizes the molecular mechanisms by which gut microbial metabolites mediate PCOS-related pathological processes, as well as potential intervention strategies.

METHODS: This article is a narrative review. To ensure comprehensive literature coverage, we searched the PubMed, Embase, Web of Science, and Cochrane Library databases from their inception to June 30, 2026. Search terms included polycystic ovary syndrome, PCOS, gut microbiota, gastrointestinal microbiota, microbial metabolites, short-chain fatty acids, bile acids, lipopolysaccharide, branched-chain amino acids, tryptophan metabolism, gut-ovary axis, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Original basic research, clinical observational studies, randomized controlled trials, systematic reviews, meta-analyses, and clinical guidelines related to PCOS and gut microbiota were prioritized for inclusion. Content lacking clear support from primary literature, with evidence limited to other disease models, or involving excessive mechanistic extrapolation was either excluded or interpreted conservatively.},
}

Humans
*Polycystic Ovary Syndrome/metabolism/microbiology/therapy
Female
*Gastrointestinal Microbiome/physiology
Animals
Insulin Resistance

@article {pmid42787543,
year = {2026},
author = {Zeng, Z and Xu, L and Yang, M and Wang, W},
title = {Gut microbiota dysbiosis aggravates liver injury in acute-on-chronic liver failure through D-lactate accumulation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1851153},
pmid = {42787543},
issn = {1664-302X},
abstract = {INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a life-threatening condition arising from the abrupt worsening of pre-existing chronic liver disease, typically accompanied by multi-organ failure and markedly elevated short-term mortality. Gut microbiota dysbiosis is frequently observed in patients with ACLF, yet the mechanisms by which microbial alterations contribute to disease progression remain unclear. Here, we investigated whether gut microbiota dysbiosis could exacerbate liver injury in ACLF and explored the underlying mechanisms.

METHODS: The correlation between serum lactic acid levels and liver injury in patients with ACLF was analyzed. ACLF model in SD rats was established to investigate the effects of lactate transporter inhibitor on liver injury. 16S rRNA sequencing was performed to characterize alterations in the gut microbiota of ACLF rats, and correlations between serum lactate levels, fecal lactate levels and liver injury-related indicators were evaluated. A pseudo-germ-free ACLF rat model was established to determine whether gut microbiota dysbiosis could aggravate liver injury in ACLF rats.

RESULTS: Serum L-lactate and D-lactate levels were significantly positively correlated with ALT levels in patients with ACLF. Moreover, inhibiting lactic acid transport exacerbated liver injury in ACLF rats. The abundance of lactate-producing bacteria, particularly Lactobacillus and Ligilactobacillus, was significantly increased in the gut of ACLF rats, accompanied by elevated lactate levels in serum, liver tissues and feces. Correlation analysis revealed strong positive associations between serum lactic acid levels, fecal lactate levels and biochemical markers of liver injury, and between D-lactate levels and the abundance of lactate-producing taxa. Moreover, transplantation of fecal microbiota from conventional ACLF rats into pseudo-germ-free ACLF rats reduced microbial diversity, enriched lactate-producing genera, increased lactic acid levels in serum, liver tissues and feces, and exacerbated liver injury.

CONCLUSION: Our results suggested that gut microbiota dysbiosis may contribute to ACLF progression, potentially through expansion of lactate-producing bacteria and subsequent D-lactic acid accumulation. Our results provided a conceptual basis for targeting microbial lactic acid metabolism as a therapeutic strategy for ACLF.},
}

@article {pmid42788000,
year = {2026},
author = {Zhu, L and Wang, F and Dai, Y and Yang, X and Wang, X},
title = {The microbiota-gut-brain axis in postpartum depression: a review of microbial mechanisms and therapeutic potential.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1812091},
pmid = {42788000},
issn = {1664-0640},
abstract = {Postpartum depression (PPD), a common but mechanistically uncertain mood disorder, occurs in 10-15% of mothers and seriously affects maternal and infant health. Recent evidence suggests that alteration of gut microbiota could dysregulate gut-brain axis functioning, which is potentially linked to the pathogenesis of PPD. This review innovatively synthesizes up-to-date preclinical and clinical evidence to illustrate relevant mechanisms, including microbial metabolite signaling, immune-inflammatory pathways, and neuroendocrine disruptors. Furthermore, the therapeutic potential of microbial-targeting approaches, including probiotics, dietary changes, and fecal microbiota transplant, to remedy PPD by restoring microbial health is discussed. Nevertheless, several notable limitations, translational uncertainties and major knowledge gaps still exist in this field. Most current evidence derives from cross-sectional observations, and well-designed longitudinal human studies are urgently needed to confirm causal relationships. In addition, available microbiota-related interventions have not yet developed into mature precision microbiome therapeutics. Against this background, this study proposes a microbiome framework connecting basic science and clinical applications that may help unravel the etiology and treatment of PPD.},
}

@article {pmid42790240,
year = {2026},
author = {Duan, L and Liang, J and Zhang, W and Liu, Z and He, Z and Jiang, G and Li, X and Gao, A},
title = {Gut microbiota dysbiosis is associated with the synaptic deficits and cognitive impairment induced by LCM mixtures within a proposed mechanistic framework consistent with the AOP concept.},
journal = {Environment international},
volume = {216},
number = {},
pages = {110542},
doi = {10.1016/j.envint.2026.110542},
pmid = {42790240},
issn = {1873-6750},
abstract = {Liquid crystal monomers (LCMs), as emerging environmental contaminants, have poorly understood cognitive effects under realistic mixture exposure scenarios. This study integrated ecological and human exposure data to characterize LCM mixtures and assessed their neurotoxicity using in vitro and in vivo models. We found that long-term exposure to LCM mixtures at environmental levels more strongly inhibited viability in hippocampal HT22 cells and microglial BV2 cells than individual compounds, and was associated with memory deficits in mice accompanied by neuroinflammation and reduced hippocampal synaptic plasticity. Within an AOP-based mechanistic framework, LCM binding to Zonula occludens-1 (ZO-1) is proposed as a hypothesized molecular initiating event (MIE), which may contribute to gut barrier injury, colonic inflammation, and gut microbiota dysbiosis. Altered microbiota composition showed significant correlations with cognitive index. Fecal microbiota transplantation provided suggestive evidence for the role of gut dysbiosis in cognitive impairment, while probiotic supplementation administered concurrently with LCM exposure showed protective effects against the deficits by restoring microbial balance and suppressing inflammation. This study systematically outlines a putative mechanistic framework consistent with the AOP concept for LCM mixtures: an initial gut barrier injury, hypothesized to be triggered by ZO‑1 binding, may disturb the gut‑brain axis, thereby contributing to neuroinflammation, synaptic dysfunction, and cognitive decline. Our findings provide mechanistic insights into how environmental-level LCM mixtures impair cognitive health and suggest probiotics as a potential prevention strategy.},
}

@article {pmid42790639,
year = {2026},
author = {Huai, Q and Li, X and Wang, H and Yin, S},
title = {The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease and Associated Hepatocellular Carcinoma: Pathogenesis and Therapeutic Interventions.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.09.004},
pmid = {42790639},
issn = {1525-2191},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases from simple steatosis to metabolic dysfunction-associated steatohepatitis and its associated fibrosis, cirrhosis, and MASLD-associated hepatocellular carcinoma (MASLD-HCC). MASLD affects over one-third of the global adult population and is closely associated with insulin resistance, obesity, genetic factors, and increasingly recognized, gut microbiome dysbiosis. The gut-liver axis, referring to the communication network between the intestinal microbiota and liver, is critical to the progression of MASLD. The gut microbiota composition and/or functions are disrupted, leading to intestinal barrier destruction, systemic inflammation and modulation of hepatic metabolism and immune responses. The review aims to summarize the effects of gut microbiota on MASLD and its malignant transition to associated HCC based on their roles of microbial metabolites, immune regulation and their associated genetic factors, and to discuss the potential application of microbiome-targeted therapeutic strategies, including probiotics and prebiotics, synbiotics and postbiotics, fecal microbiota transplantation, engineered bacteria and bacteriophage therapy, small molecule inhibitors, microbiota-derived metabolites, with the aim of providing a new vision in the treatment of MASLD and MASLD-HCC. Finally, we discuss current challenges in basic and clinical research of the role of microbiome in MASLD and propose future directions to drive progress in this field.},
}

@article {pmid42778117,
year = {2026},
author = {Li, Y and Wen, J and Huang, D and Wang, Z and Peng, Y and Xu, Y and Jenis, J and Sun, S and Luo, M and Zeng, L and Ni, L and Hao, Z and Huang, T and Jiang, C and Shen, C and Liu, L and Zhu, H and Li, Q and Liu, Q},
title = {IDO1 integrates gut microbiota-derived SCFAs signals and host WNT/TGF-β pathways to mediate the anti-colorectal cancer effects of licorice flavonoids.},
journal = {Pharmacological research},
volume = {233},
number = {},
pages = {108474},
doi = {10.1016/j.phrs.2026.108474},
pmid = {42778117},
issn = {1096-1186},
abstract = {Licorice flavonoids (LF), bioactive components of Glycyrrhiza uralensis Fisch, exhibit promising anti-colorectal cancer (CRC) potential. However, the mechanism by which LF inhibits CRC remains unclear. In this study, we attempt to elucidate how indoleamine 2,3-dioxygenase 1 (IDO1) functions as a convergent downstream effector of both microbiota-derived signals and host oncogenic pathways in order to mediate the chemopreventive effects of LF on CRC. Using AOM/DSS and Apc[min/+] CRC mice models and colonic epithelial cells, we combined 16S rRNA sequencing, metabolomics, transcriptomics, and functional assays including IDO1 knockout, fecal microbiota transplantation, and antibiotic treatment. LF markedly inhibited colorectal tumorigenesis and restored intestinal barrier integrity. Mechanistically, LF remodeled the gut microbiota to enrich SCFAs‑producing genera, including Parabacteroides, Paramuribaculum, and Parasutterella, thereby increasing the levels of SCFAs such as butyric acid, isobutyric acid, valeric acid, and isovaleric acid in feces. These SCFAs downregulated IDO1 in CRC cells, and genetic ablation of IDO1 largely abolished SCFAs‑induced anti‑proliferative effects, establishing IDO1 as a critical downstream mediator. This regulation rewired tryptophan metabolism, reducing kynurenine metabolites and elevating microbiota-related indoles. Notably, the protective effect of LF against CRC was substantially diminished in IDO1‑knockout mice, underscoring IDO1 as a critical mediator. Additionally, LF treatment was associated with suppression of WNT/TGF‑β signaling. Collectively, these results identify IDO1 as a critical downstream effector that responds to the regulation of gut microbiota-SCFAs signaling and host WNT/TGF‑β pathways by LF, suggesting that LF‑induced IDO1 inhibition may represent a promising translational strategy for CRC prevention through concurrent modulation of microbial and host pathways.},
}

@article {pmid42780227,
year = {2026},
author = {Damiani, F and Ashtiani, KC and Tognozzi, A and Abdelkarim, SS and Cornuti, S and Caldarelli, M and Baldi, P and Tognini, P},
title = {The Critical Period Microbiota Shape Brain Plasticity.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-10931343/v1},
pmid = {42780227},
issn = {2693-5015},
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 {pmid42780516,
year = {2026},
author = {Jiang, X and Shi, S and Li, M and Zhang, Y and Xing, G and Yan, Q and Li, S and Sun, W and Li, H},
title = {Fecal microbiota transplantation in adolescents with obesity induces limited and donor-dependent remodeling of the gut microbiome.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1927870},
doi = {10.3389/fendo.2026.1927870},
pmid = {42780516},
issn = {1664-2392},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adolescent ; *Gastrointestinal Microbiome/physiology ; Female ; Male ; *Pediatric Obesity/therapy/microbiology ; Longitudinal Studies ; Metagenome ; },
abstract = {INTRODUCTION: Obesity is a global health challenge, and fecal microbiota transplantation (FMT) is considered a potential intervention; however, its long-term ecological impact remains unclear.

METHODS: In this 182-day longitudinal cohort of adolescents with obesity (378 samples), metagenomic sequencing was used to assess FMT-induced remodeling of the multi-kingdom gut ecosystem through species composition, diversity, microbial networks, and machine learning analyses.

RESULTS: FMT induced only transient shifts in community structure, with limited donor strain engraftment and strong resilience of recipient core taxa. Bacteria were the primary responders, the virome showed short-term perturbation, and network restoration was partial and donor-dependent.

DISCUSSION: FMT exerts limited, donor-dependent ecological effects in obese adolescents. Optimizing donor selection and personalized matching may be essential for improving long-term efficacy.},
}

Humans
*Fecal Microbiota Transplantation/methods
Adolescent
*Gastrointestinal Microbiome/physiology
Female
Male
*Pediatric Obesity/therapy/microbiology
Longitudinal Studies
Metagenome

@article {pmid42780996,
year = {2026},
author = {Sun, M and Dong, J and Su, M and Liu, H and Sun, Q and Lin, K and Yu, R and Yang, H and Lin, J and Chen, J and Shen, J and Ye, H},
title = {Circadian rhythm disruption aggravates high-fat diet-induced NAFLD through gut microbiota alterations in mice.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1916861},
pmid = {42780996},
issn = {1664-302X},
abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota dysbiosis, and circadian rhythm disruption (CRD) has been reported to aggravate metabolic disorders. However, the contribution of gut microbiota alterations to CRD-associated deterioration of NAFLD remains incompletely understood.

OBJECTIVE: This study aimed to investigate the effects of CRD on gut microbiota alterations and hepatic metabolic abnormalities in high-fat diet (HFD)-induced NAFLD mice, and to explore whether microbiota modulation could influence CRD-associated disease progression.

METHODS: Male C57BL/6J mice were divided into three groups: normal diet with normal light-dark cycle (ND-LD), HFD with normal light-dark cycle (HFD-LD), and HFD with disrupted light-dark cycle (HFD-CRD). Food intake, locomotor activity, and body weight were monitored. After 14 weeks, samples were collected following euthanasia. The remaining HFD-LD mice were further divided into two groups: fecal microbiota donor and normal light-dark cycle with saline gavage (LD-NS). The remaining HFD-CRD mice were assigned to either disrupted light-dark cycle with saline gavage (CRD-NS) or disrupted light-dark cycle with fecal microbiota transplantation (CRD-FMT). After another 14 weeks, samples were again collected following euthanasia. Serum biochemical parameters, liver histology, inflammatory markers, and gut microbiota composition based on 16S rRNA sequencing were analyzed.

RESULTS: HFD induced NAFLD, while CRD exacerbated metabolic dysfunction, liver injury, and gut microbiota alterations. Over time, the impact of CRD on glucose metabolism and liver injury diminished. CRD further altered gut microbiota in NAFLD mice, reducing microbial diversity and increasing pro-inflammatory taxa. FMT from HFD-LD donors partially reshaped gut microbiota composition of CRD mice and attenuated several CRD-associated metabolic and hepatic abnormalities, although its effects on body weight and glucose metabolism were limited.

CONCLUSION: These findings suggest that gut microbiota alterations contribute to CRD-associated aggravation of HFD-induced NAFLD, although further studies are required to identify specific microbial mediators.},
}

@article {pmid42781335,
year = {2026},
author = {Zhang, Z and Wen, J and Zhang, P and Zou, Y and Wu, J and Yao, R},
title = {Heat stress-induced gut dysbiosis and multi-organ injury: mechanisms and therapeutic modulation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1930660},
doi = {10.3389/fcimb.2026.1930660},
pmid = {42781335},
issn = {2235-2988},
mesh = {Animals ; *Dysbiosis/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; Heat Stroke ; *Heat-Shock Response ; *Multiple Organ Failure/etiology/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {Heat stress (HS) is an increasingly prevalent environmental and exertional challenge. In severe cases, HS may progress to heatstroke, a life-threatening clinical syndrome characterized by severe hyperthermia, systemic inflammation, and multi-organ dysfunction. This review synthesizes evidence from laboratory rodent models and suggests that gut microbiota dysbiosis may act as a mediator and amplifier of HS-induced pathology. Across diverse rodent models, HS remodels the gut microbiota by reducing microbial diversity. These compositional changes are accompanied by decreased short-chain fatty acids, altered bile acid profiles, and increased lipopolysaccharide burden, although the specific metabolites affected vary across models. Causal evidence from fecal microbiota transplantation and gnotobiotic experiments supports microbiota-dependent amplification of intestinal barrier failure, hepatic inflammation, and neuroinflammation. In contrast, evidence for the gut-reproductive, gut-kidney, gut-heart, gut-muscle, and gut-adipose axes remains predominantly associative or derived from interventional correlations without formal causality testing. Targeting the gut-organ axis through probiotics, prebiotics, antioxidants, or functional amino acids offers promising but largely preclinical adjunctive strategies, with rapid cooling and supportive care remaining the foundation of heatstroke management. Future research should prioritize temporally resolved human studies, multi-omics integration, and causal validation to define the translational potential of microbiome-directed interventions.},
}

Animals
*Dysbiosis/therapy/microbiology
Humans
*Gastrointestinal Microbiome/physiology
Disease Models, Animal
Heat Stroke
*Heat-Shock Response
*Multiple Organ Failure/etiology/therapy
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid42781477,
year = {2026},
author = {Gospodarik, AV and Khromykh, NI and Prokhorova, ND and Shansky, YD and Balazs, I and Bespyatykh, JA},
title = {A multi-step screening algorithm for fecal microbiota transplantation donors: integrating metagenomic and metabolomic profiling for improved safety and donor quality assessment.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1927788},
doi = {10.3389/fmicb.2026.1927788},
pmid = {42781477},
issn = {1664-302X},
abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) has emerged as a highly effective treatment for recurrent Clostridioides difficile infection. It is also a promising therapeutic approach for other microbiome-related disorders. However, the safety and efficacy of FMT depend critically on rigorous donor screening and selection protocols. In this study, we developed and evaluated an optimized donor screening and selection workflow that integrates multistep pathogen detection, metagenomic and metabolomic profiling, and clinical compatibility assessment to enhance FMT safety and donor quality assessment.

METHODS: In this prospective cross-sectional study we evaluated 178 stool donor candidates using a novel screening algorithm, which combined extended medical history, blood and urine testing, stool metagenomics (16S rRNA gene sequencing) and metabolomics (short-chain fatty acids), and microbiological stool tests to exclude the stool samples with pathogens and ensure their microbial diversity.

RESULTS: The FMT donor screening and selection workflow was developed and included four main steps: 1. Potential donors (n = 178) had to meet all the study inclusion criteria (47.8% of donors passed this screening step); 2. Potential donors (n = 85) underwent microbiological and microscopic stool examination (23% of initially enrolled donors passed this screening step). Most of the healthy donors were excluded at this selection step due to the abnormal values of Enterococcus spp. (47.1% of healthy donors had abnormal values), total number of Enterobacteriaceae and Bifidobacterium spp. (for both parameters 41.2% of healthy donors had abnormal values) abundance; 3. Potential donors (n = 41) underwent blood (total blood cell count, biochemical blood analysis) and urine (urinalysis) tests. Only 13 donors (7.3% of the initial cohort) proceeded to the final metabolomic analysis, resulting in the selection of 3 FMT donors (1.7% eligibility rate).

CONCLUSIONS: This study establishes a data-driven, high-stringency donor selection framework that provides a rational basis for improving FMT safety and donor quality. Our findings advocate for the standardized implementation of advanced screening technologies, particularly SCFA metabolomics, as a critical quality control step in stool banking. While clinical validation of the efficacy-enhancing potential of this protocol requires prospective studies, the strong association between butyrate-producing microbiota and favorable FMT outcomes, combined with our previous clinical observations, supports the utility of our approach.},
}

@article {pmid42782450,
year = {2026},
author = {Li, Y and Yu, W and Liu, R and Xiao, P and Li, X and Zhang, T},
title = {Acute Tolerability and Long-Term Surveillance of Fecal Microbiota Transplantation in Children with Autism: A Real-World Study of 604 Procedures.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {42782450},
issn = {1865-8652},
support = {20244Y0090//Shanghai Municipal Health Commission/ ; },
abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is a promising adjunctive therapy for autism spectrum disorder (ASD), yet comprehensive, real-world safety data in pediatric populations remain limited. This study aimed to systematically evaluate the safety profile, temporal kinetics, and risk factors for adverse events (AEs) following FMT in children with ASD.

METHODS: We conducted a longitudinal observational study of 224 children with ASD (aged 2-17 years) who underwent a total of 604 FMT procedures. Interventions were administered via oral capsules (Caps), nasojejunal tube (NJT), or transendoscopic enteral tube (TET). AEs were systematically graded using common terminology criteria for AEs (CTCAE) criteria, and a multivariate generalized estimating equations (GEE) model was used to identify independent risk factors.

RESULTS: In our study, the overall incidence of AEs across 604 procedures was low at 2.5% (15/604 procedures). All documented AEs had an acute onset (< 48 h post-procedure), were strictly Grade 1 (mild) in severity, and spontaneously resolved (median duration 28.0 h). The most frequent symptoms were vomiting and irritability, with no severe or long-term AEs observed. Delivery route significantly impacted safety, and TET exhibited the highest AE rate (26.3%), whereas Caps (1.7%) and NJT (1.8%) demonstrated favorable tolerability. Multivariate analysis identified TET as the independent risk factor for AEs (adjusted odds ratio 21.90, P < 0.001).

CONCLUSION: FMT demonstrates favorable acute tolerability in children with ASD, with long-term longitudinal surveillance showing no delayed adverse outcomes. Oral capsules are associated with a low AE rate and represent a preferred delivery route.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, http://www.chictr.org.cn .},
}

@article {pmid42783727,
year = {2026},
author = {Araújo, G and Domingues, S and da Silva, GJ and Lima, T},
title = {Pharmacomicrobiomics: From Host-Microbiome-Drug Interactions to Clinical Translation in Precision Medicine.},
journal = {Metabolites},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/metabo16090602},
pmid = {42783727},
issn = {2218-1989},
abstract = {Marked interindividual variability in drug response remains a major challenge in clinical pharmacology and cannot be fully explained by host genetics alone. Increasing evidence indicates that the gut microbiota constitutes an additional determinant of drug efficacy and toxicity through bidirectional interactions with pharmacological therapies. This recognition has led to the emergence of pharmacomicrobiomics, a field that investigates how microbial communities influence drug disposition and response, and how drugs, in turn, alter the microbiome. Microbiome-mediated effects on drug efficacy and toxicity have been described across several therapeutic areas, including oncology, multiple sclerosis, and type 2 diabetes mellitus. Although these findings are promising, most mechanistic evidence derives from preclinical and animal studies, with relatively limited validation in controlled clinical trials. Strategies to modulate the gut microbiota, including prebiotics, probiotics, and faecal microbiota transplantation, have shown preliminary promise in optimising drug efficacy and reducing adverse effects, although methodological heterogeneity and incomplete mechanistic understanding limit their current clinical application. The identification of robust microbiome-derived biomarkers and the integration of multi-omics approaches, particularly metabolomics, are expected to accelerate the translation of pharmacomicrobiomics into precision medicine. This review summarises current evidence regarding microbiome-drug interactions, the mechanisms underlying microbiome-mediated modulation of pharmacokinetics and pharmacodynamics, emerging therapeutic strategies, and the challenges that remain before pharmacomicrobiomics can be implemented in clinical practice.},
}

@article {pmid42783785,
year = {2026},
author = {Qiu, Z and Zhang, H and Ma, M and Pan, B and Cao, C},
title = {Gut Microbiota and Their Metabolites in Acute Kidney Injury: Classification, Mechanisms, and Therapeutic Potential.},
journal = {Metabolites},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/metabo16090660},
pmid = {42783785},
issn = {2218-1989},
support = {82170698//National Natural Science Foundation of China/ ; BE2023830//Jiangsu Provincial Key Research and Development Program/ ; },
abstract = {Acute kidney injury (AKI) is a common critical syndrome with high morbidity and mortality, and a subset of patients may progress to chronic kidney disease. Recent studies have revealed that gut microbiota and their metabolites play pivotal roles in the pathogenesis of AKI. Under AKI conditions, the gut microbiota composition undergoes significant alterations, characterized by decreased beneficial bacteria and expansion of opportunistic pathogens, accompanied by impaired intestinal barrier and disordered microbial metabolism. Gut microbiota metabolites can be classified into protective metabolites (short-chain fatty acids, secondary bile acids, tryptophan metabolites, D-amino acids, and polyamines) and toxic metabolites (indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and endotoxin). The former exert renoprotective effects through anti-inflammatory, antioxidant, and barrier-maintaining mechanisms, while the latter aggravate kidney injury via oxidative stress, inflammation activation, and hemodynamic disturbance. Based on the gut-kidney axis theory, interventions targeting gut microbiota (probiotics, prebiotics, fecal microbiota transplantation) and those targeting metabolites (supplementation of protective metabolites, removal of toxic metabolites) have shown promising prospects. This narrative review summarizes the characteristics of gut microbiota changes, classification and function of key metabolites, core mechanisms driving AKI, and microbiota-based intervention strategies, aiming to provide novel insights for early recognition and precision prevention of AKI.},
}

@article {pmid42785337,
year = {2026},
author = {Liu, J and Shin, A},
title = {Healthy donor faecal microbiota transplantation in irritable bowel syndrome: interpreting negative findings.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(26)01815-5},
pmid = {42785337},
issn = {1474-547X},
}

@article {pmid42785338,
year = {2026},
author = {Johnsen, PH and Juul, FE and Hoff, DAL and Hillestad, ER and Holme, Ø and Skjevling, LK and Hansen, HM and Rasmus, MH and Barnett, L and Barry, SJE and Hjerde, E and Lindstedt, K and Buczek, DJ and Hatlebakk, JG and Steinsvik, EK and Berentsen, B and Garborg, KK and Valeur, J and Valle, PC and Løberg, M and Kalager, M and Bretthauer, M and Goll, R},
title = {Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(26)01424-8},
pmid = {42785338},
issn = {1474-547X},
abstract = {BACKGROUND: Gut microbiota composition might have a role in the pathogenesis of irritable bowel syndrome (IBS), and faecal microbiota transplantation has been proposed as a means of restoring healthy gut microbiota for individuals with this condition. We aimed to investigate the efficacy and safety of faecal microbiota transplantation in patients with IBS.

METHODS: In this parallel-group, randomised, double-blind, placebo-controlled, phase 3 trial, conducted at five hospitals in Norway, we enrolled men and women aged 18-65 years with moderate-to-severe IBS. IBS diagnosis was defined by the Rome IV criteria and an IBS-Severity Scoring System (IBS-SSS) score of 175 points or higher. A colonoscopy within 5 years before study enrolment was required for all participants aged 50 years or older to rule out colorectal cancer, and participants with IBS with predominantly diarrhoea required negative biopsies to exclude microscopic colitis. Participants were randomly assigned 2:1 to faecal microbiota transplantation with faeces samples from either healthy donors (intervention) or the participants themselves (placebo group). All investigators, participants, and study personnel involved in treatment administration, patient care, and outcome assessment were masked to treatment allocation throughout the study. Treatments were delivered as a once-only rectal enema. The primary endpoint was the proportion of participants with a reduction of 75 points or more in IBS-SSS score at 90 days after treatment compared with baseline, assessed in all patients who received their allocated treatment. All participants were advised to report any adverse event during follow-up to their study contact, preferably by telephone. A patient representative was involved in the planning of the trial. The trial was registered at ClinicalTrials.gov (NCT04691544).

FINDINGS: Between May 5, 2021, and July 14, 2022, we assessed 2304 individuals for eligibility, and 450 participants were enrolled and randomly assigned to the intervention group (299) or placebo group (151); two randomly assigned participants were excluded from analyses because their allocated treatments were switched. 293 (65%) of 448 participants were women, 155 (35%) were men, and the median age was 36 years (IQR 29-44). 119 (40%) participants in the donor faecal microbiota transplantation group and 57 (38%) in the placebo group showed an improvement of at least 75 points on the IBS-SSS at 90 days after treatment. The absolute difference was 1·9 percentage points (95% CI -8·1 to 12·0; p=0·76). The proportion of participants with adverse events was similar in the two study groups.

INTERPRETATION: The trial did not show a clinical benefit of faecal microbiota transplantation in patients with IBS. These findings suggest that microbiota modulation alone might be insufficient for symptom improvement in IBS.

FUNDING: KLINBEFORSK.},
}

@article {pmid42586481,
year = {2026},
author = {Alwali, A and Thingholm, LB and Bang, C and Beckmann, JH and Sebens, S and Rühlemann, M and Laudes, M and Schafmayer, C and Franke, A and Philipp, M and von Schönfels, W},
title = {Oral and gut microbiota features associated with weight-loss outcomes after metabolic and bariatric surgery: A pilot study.},
journal = {Clinical nutrition ESPEN},
volume = {75},
number = {},
pages = {105025},
doi = {10.1016/j.clnesp.2026.105025},
pmid = {42586481},
issn = {2405-4577},
mesh = {Humans ; Pilot Projects ; *Bariatric Surgery ; *Weight Loss ; Female ; Male ; Adult ; Middle Aged ; *Mouth/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Treatment Outcome ; RNA, Ribosomal, 16S/genetics ; *Obesity, Morbid/surgery/microbiology ; *Obesity/surgery/microbiology ; Bacteria/classification/genetics ; *Microbiota ; Adipose Tissue/microbiology ; },
abstract = {BACKGROUND: Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, yet postoperative weight loss outcomes vary considerably between patients. With the relevance of the gut microbiome for obesity, it is of interest to understand the potential role of the oral and gut microbiota for the outcome of MBS. This pilot, hypothesis-generating study aimed to investigate associations between microbiota features and postoperative weight loss outcomes after MBS, assessed by percentage excess weight loss (EWL).

METHODS: In this pilot study, microbiota profiles from multiple body sites were analyzed in 33 patients undergoing MBS. Stool, oral swab, serum, and adipose tissue samples were collected at the time of surgery; stool and oral samples were collected again six months postoperatively. Microbiota diversity and composition were assessed using 16S rRNA gene sequencing and related to EWL and metabolic outcomes. Bacterial DNA in adipose tissue and serum was explored as an indirect marker of microbial translocation.

RESULTS: Higher diversity of the oral microbiota before surgery was associated with greater postoperative EWL. Stool microbiota diversity increased after surgery and was positively associated with EWL, suggesting postoperative recovery of the gut microbiota in patients with better weight loss outcomes. At the taxonomic level, higher postoperative abundance of Alistipes was observed in stool of patients achieving the greatest EWL, while for the oral cavity at time of operation, Veillonella, a bacteria considered largely beneficial in the oral cavity, was found to be positively associated with response. Community-level analyses of bacterial profiles in subcutaneous fat samples taken at time of MBS showed associations with both EWL (R[2] = 0.097, p = 0.006) and BMI (R[2] = 0.055, p = 0.017), whereas no associations were observed for visceral fat or serum. Findings related to individual bacterial taxa and extraintestinal compartments should be interpreted cautiously due to the exploratory nature of the analyses.

CONCLUSIONS: This exploratory pilot study suggests that oral and gut microbiota features may be associated with weight loss outcomes after metabolic and bariatric surgery. Future studies are required for validation in larger, procedure-specific cohorts with adjustment for clinical confounders.},
}

Humans
Pilot Projects
*Bariatric Surgery
*Weight Loss
Female
Male
Adult
Middle Aged
*Mouth/microbiology
Feces/microbiology
*Gastrointestinal Microbiome
Treatment Outcome
RNA, Ribosomal, 16S/genetics
*Obesity, Morbid/surgery/microbiology
*Obesity/surgery/microbiology
Bacteria/classification/genetics
*Microbiota
Adipose Tissue/microbiology

@article {pmid42772323,
year = {2026},
author = {Li, SS and Niu, YH and Yu, HJ},
title = {A retrospective metagenomic analysis of fecal microbiota transplantation donors from five countries: Safety considerations for donor screening and core microbiome profiles of qualified donors.},
journal = {Journal of microbiology (Seoul, Korea)},
volume = {64},
number = {9},
pages = {e2604010},
doi = {10.71150/jm.2604010},
pmid = {42772323},
issn = {1976-3794},
support = {//Shanghai Engineering Research Center of Innovative Probiotic Drugs/ ; },
mesh = {Humans ; Retrospective Studies ; *Fecal Microbiota Transplantation/adverse effects ; *Metagenomics ; *Feces/microbiology ; *Bacteria/genetics/classification/isolation & purification ; Canada ; New Zealand ; Netherlands ; China ; United States ; *Tissue Donors ; *Donor Selection ; Virulence Factors/genetics ; *Metagenome ; *Gastrointestinal Microbiome/genetics ; *Microbiota/genetics ; },
abstract = {Fecal microbiota transplantation (FMT) has been successfully applied on clinical aspects, but its clinical outcomes remain unpredictable due to inconsistent donor screening protocols across hospitals, institutions, and countries. Hence, a retrospective analysis of metagenomic data from published studies on FMT donors via a unified bioinformatics workflow might contribute to the understanding of the safety considerations for donor screening and the fecal microbial profiles of qualified donors. In this study, we reanalyzed metagenomic data of 475 screened donor fecal samples from 24 studies spanning China, the USA, Canada, New Zealand, and the Netherlands. The genomic safety risks were evaluated by profiling antibiotic resistance genes (ARGs) and virulence factors (VFs), the results of which showed that no major toxin-associated virulence genes, such as Shiga toxin, Shiga-like toxin, or botulinum neurotoxin (BoNTs) genes harbored in the detected Escherichia coli, Clostridium butyricum, and Streptococcus pneumoniae, but several high-risk ARGs remained insufficiently addressed. The distribution of ARG-harboring bacteria in eligible FMT donors was country-specific. The alpha-diversity and microbial community structure were comparable between donor fecal samples from China and the USA. Interestingly, the core microbiome in fecal samples from Canada, the Netherlands, and New Zealand formed a single guild, while that from China and the USA formed two guilds, with predominantly positive intra-guild and negative inter-guild correlations, indicating that the co-abundance patterns of the core microbiome were conserved among certain countries. Furthermore, an exploratory retrospective classifier was developed based on core microbiome profiles to distinguish eligible FMT donors from general healthy individuals. These results provide evidence for integrating metagenomic sequencing into future FMT donor screening strategies.},
}

Humans
Retrospective Studies
*Fecal Microbiota Transplantation/adverse effects
*Metagenomics
*Feces/microbiology
*Bacteria/genetics/classification/isolation & purification
Canada
New Zealand
Netherlands
China
United States
*Tissue Donors
*Donor Selection
Virulence Factors/genetics
*Metagenome
*Gastrointestinal Microbiome/genetics
*Microbiota/genetics

@article {pmid42774065,
year = {2026},
author = {Shen, Y and Chen, Q and Yang, H},
title = {Case report end-stage cystic fibrosis with fatal outcome in two siblings from a Chinese family: a 15-year diagnostic odyssey.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1894322},
pmid = {42774065},
issn = {1663-9812},
abstract = {BACKGROUND: Cystic fibrosis (CF) remains severely underdiagnosed in China due to the absence of newborn screening, limited sweat chloride testing capacity, and low clinical awareness. Diagnostic delay results in irreversible lung damage and precludes timely genotype-directed therapy.

CASE PRESENTATION: A 16-year-old Chinese boy presented with end-stage CF lung disease after a 15-year diagnostic odyssey. He had recurrent lower respiratory tract infections since infancy, progressive bronchiectasis, CF-associated liver disease with portal hypertension, and chronic Pseudomonas aeruginosa/Burkholderia cepacia co-infection. Sweat chloride was 102 mmol/L. Whole-exome sequencing identified compound heterozygous CFTR variants: c.579 + 1_579+2insACAT (a canonical splice-site insertion, predicted null) inherited from the father, and c.1766 + 5G>T (CF-causing in CFTR2, near-complete exon 13 skipping) inherited from the mother. Fecal elastase was preserved (525 μg/g), confirming pancreatic sufficiency; this finding is consistent with but does not prove residual CFTR function. CFTR modulator therapy was unavailable. He died of cardiopulmonary failure approximately 1 year after diagnosis while awaiting lung transplantation. Cascade testing confirmed the same genotype in his 11-year-old sister (sweat chloride 111 mmol/L), who also died of cardiopulmonary failure within months. Their eldest brother had died at age two of severe pneumonia without CF being suspected.

CONCLUSION: This family illustrates the convergence of three pharmacologically relevant barriers in underserved CF populations: prolonged diagnostic delay precluding specialized care, uncharacterized population-specific variants lacking theratyping data, and inaccessibility of CFTR modulators. The preserved pancreatic function despite end-stage lung disease is compatible with residual CFTR activity, but the contribution of either allele and potential responsiveness to CFTR modulators require transcript, protein, and functional characterization. This underscores the urgent need for systematic theratyping of under-characterized CFTR variants reported in East Asian populations. Expansion of sweat chloride testing, clinician education, and international collaborative theratyping efforts are needed to break this cycle.},
}

@article {pmid42774166,
year = {2026},
author = {Zhao, Y and Wang, L and Zhang, K and Zhang, J and Guo, Z and Lu, X and Li, J},
title = {Multi-dimensional dynamic assessment revealed the antibiotic-induced pseudo-germ-free model in SD rats stabilized within 4 days.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1930662},
pmid = {42774166},
issn = {1664-302X},
abstract = {Pseudo-germ-free (PGF) animal models are typically established after 7 days of antibiotic treatment, mostly validated using 16S rRNA sequencing. However, this method cannot distinguish live from dead bacteria and may overestimate the required depletion time. We investigated whether PGF model establishment in Sprague-Dawley (SD) rats could be completed in shorter than 7 days using an antibiotic cocktail. Gut microbiota was dynamically monitored with antibiotic cocktail treatment on days 0 to 7 by aerobic/anaerobic bacterial culture, Gram staining, and 16S rRNA sequencing, alongside body weight, food intake, and water intake. Body weight continued to increase in the Test group, while feed and water intake decreased only transiently during the first 2 days and returned to normal from day 3. No visible aerobic or anaerobic bacterial growth after 4 days and persisting through day 7. 16S rRNA sequencing showed that shared amplicon sequence variants (ASVs) with the Control group dropped from 379 on day 0 to 27 on day 4, stabilizing at 19-31 ASVs thereafter. Alpha diversity indices showed no significant changes after day 3 (p > 0.05). Beta diversity showed the peak period of microbiota restructuring on days 2-3 (R [2] = 0.558, p = 0.001), while the effect size between adjacent time points dropped to an extremely low level after day 4 (R [2] ≤ 0.025). LEfSe identified Escherichia-Shigella as the dominant genus. The multi-dimensional data demonstrated that 4 days of antibiotic cocktail treatment were sufficient to establish a stable PGF state in SD rats, aligning with 3R principles.},
}

@article {pmid42775139,
year = {2026},
author = {Wang, K and Tang, Q and Fan, W and Su, Q},
title = {Gut-prostate axis in prostate cancer: microbiome signatures, mechanistic insights, and therapeutic opportunities.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1882172},
pmid = {42775139},
issn = {2235-2988},
mesh = {Humans ; Male ; *Prostatic Neoplasms/therapy/microbiology/metabolism/pathology ; *Gastrointestinal Microbiome/physiology ; *Prostate/microbiology/pathology/metabolism ; Signal Transduction ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Androgens/metabolism ; },
abstract = {Prostate cancer (PCa) is one of the most common malignant tumors in men, and its onset and progression may be closely associated with an imbalance in the gut microbiota. Existing studies indicate that PCa patients exhibit reduced fecal microbiota diversity and altered microbiota composition, with the abundance of certain bacterial genera correlated with disease risk and progression. Mechanistically, the gut microbiota may regulate signaling pathways such as IGF-1, MAPK/PI3K, and NF-κB through metabolites including short-chain fatty acids, bile acids, and microbiota-derived androgens, thereby potentially contributing to tumor proliferation, inflammatory responses, and immune evasion. Androgen deprivation therapy (ADT) can also reshape the gut microbiota; certain bacterial populations may contribute to the development of castration resistance through androgen metabolism, while changes in bacteria such as Akkermansia muciniphila are associated with treatment response. Currently, strategies such as dietary interventions, probiotics, and fecal microbiota transplantation have shown some promise; however, most existing studies are small-sample or cross-sectional in nature, and causal relationships remain unclear. Future studies should combine multicenter longitudinal cohorts with multi-omics technologies to further elucidate the translational value of the gut microbiota in PCa screening, risk stratification, prognostic assessment, treatment-response prediction, toxicity monitoring, and personalized microbiome-targeted interventions.},
}

Humans
Male
*Prostatic Neoplasms/therapy/microbiology/metabolism/pathology
*Gastrointestinal Microbiome/physiology
*Prostate/microbiology/pathology/metabolism
Signal Transduction
Fecal Microbiota Transplantation
Animals
Probiotics/therapeutic use
Androgens/metabolism

@article {pmid42775698,
year = {2026},
author = {Wang, J and Li, L and Mei, L and Tang, Z and Liao, B and Zhao, Q and Wang, Y and Fu, Q and Ren, L and Zhai, Z and Xu, Y and Yang, A and Duan, S and Zhai, Z and Hao, Y and Zhou, Y and Xu, Y and Yang, Y and Wu, Z and Ji, Y},
title = {Transplantation of Elderly Human Gut Microbiota Into Pigs Reprograms Intestinal Barrier Function, Plasma Metabolome, and Gut Mucosal Transcriptomic Landscape.},
journal = {Aging cell},
volume = {25},
number = {10},
pages = {e70725},
doi = {10.1111/acel.70725},
pmid = {42775698},
issn = {1474-9726},
support = {2022YFF1100104//National Key Research and Development Program of China/ ; 2022YFD1300501//National Key Research and Development Program of China/ ; 2022YFF1100102//National Key Research and Development Program of China/ ; },
mesh = {Animals ; Swine ; Intestinal Barrier Function ; Humans ; *Gastrointestinal Microbiome/physiology ; *Metabolome ; *Intestinal Mucosa/metabolism ; *Transcriptome/genetics ; *Fecal Microbiota Transplantation/methods ; Aging ; },
abstract = {The gut microbiota plays a pivotal role in maintaining intestinal homeostasis and regulating host metabolism, yet its composition and function undergo substantial alterations with aging. However, the relationship between age-associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or elderly human donors on gut structure, barrier integrity, plasma metabolites, and intestinal mucosal transcriptomics. FMT resulted in distinct gut microbial profiles, with elderly-donor FMT reducing ileal villus height and tight junction proteins (ZO-1, claudin-1, and occludin) across multiple intestinal segments. At the species level, Phocea massiliensis predominated in young-donor pigs, while Blautia obeum was enriched in elderly-donor pigs. Plasma metabolomic analysis revealed increased 3-methyloxindole, prostaglandin E3, and 2-hydroxybutanoic acid but reduced Tyr-Phe and 2-hydroxyoctadecanoic acid in the elderly group. Among B. obeum-associated metabolites, Tyr-Phe and 2-hydroxyoctadecanoic acid exhibited a positive correlation with certain intestinal tight junction protein levels, whereas prostaglandin E3 showed an inverse correlation. Further validation performed in IPEC-1 cells demonstrated that Tyr-Phe elevated transepithelial electrical resistance (TEER), while prostaglandin E3 lowered this parameter. Transcriptomic profiling identified seven hub genes (MX2, ISG15, IFI6, IFIT1, OAS1, DHX58, ISG12(A)) that were consistently downregulated in the ileal mucosa of pigs receiving elderly-donor microbiota. These findings link age-associated microbiota alterations to coordinated changes in intestinal architecture, barrier integrity, and host metabolic and transcriptional profiles, providing insights into microbial and metabolic features associated with age-related intestinal decline.},
}

Animals
Swine
Intestinal Barrier Function
Humans
*Gastrointestinal Microbiome/physiology
*Metabolome
*Intestinal Mucosa/metabolism
*Transcriptome/genetics
*Fecal Microbiota Transplantation/methods
Aging

@article {pmid42776479,
year = {2026},
author = {Granata, G and Petrosillo, N and Taglietti, F},
title = {Novel options for the management of C. difficile: a look into the future.},
journal = {Expert review of anti-infective therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14787210.2026.2739273},
pmid = {42776479},
issn = {1744-8336},
abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) remains one of the leading causes of healthcare-associated diarrhea; additionally, evidence suggests a growing incidence of community-acquired CDI worldwide. CDI is characterized by substantial morbidity, mortality, and risk of recurrence. CDI underdiagnosis and recurrent CDI represent a major unmet clinical need, highlighting the need for innovative diagnostic, preventive and therapeutic strategies.

AREAS COVERED: This perspective article summarizes emerging approaches that may shape the future management of CDI, including novel microbiome-sparing antimicrobials, fecal microbiota transplantation (FMT), live biotherapeutic products, C. difficile vaccines, bacteriophage-derived therapies, CRISPR-Cas technology and artificial intelligence (AI) applications.

EXPERT OPINION: Future CDI management is expected to evolve toward precision medicine focused on microbiome preservation, prevention of recurrence, and individualized patient care. Novel antimicrobials such as ibezapolstat and CRS3123, phage-derived approaches, and CRISPR-guided antimicrobials may provide highly targeted alternatives to conventional treatments. Microbiota-based therapies will evolve to assume an increasingly central role in reducing microbiota disruption. Simultaneously, advances in diagnostics, vaccine development, and AI-driven predictive tools may improve risk stratification, therapeutic selection, and infection prevention and control. All these innovative strategies have the potential to redefine CDI prevention and treatment, although robust clinical validation and long-term safety data remain essential.},
}

@article {pmid42777154,
year = {2026},
author = {Zare, N and Burden, SJ and Beach, M and Jones, A},
title = {Microbiome-Targeted Interventions for Early Cardiometabolic Prevention: A Systematic Review and Meta-Analysis in Children and Adolescents.},
journal = {European journal of preventive cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/eurjpc/zwag500},
pmid = {42777154},
issn = {2047-4881},
abstract = {BACKGROUND: Cardiometabolic disease develops across the life course, making childhood critical for cardiovascular prevention. Although microbiome-targeted interventions improve some cardiometabolic outcomes in adults, whether similar interventions influence cardiometabolic risk during childhood remains uncertain. This systematic review and meta-analysis evaluated microbiome-targeted interventions for cardiometabolic outcomes in children and adolescents.

METHODS: A systematic search of PubMed, MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and CINAHL was conducted. Randomised controlled trials assessing dietary interventions, fecal microbiome transfer, prebiotics, probiotics, or synbiotics in participants aged 1 month-19 years were included. Cardiometabolic outcomes were grouped as: adiposity, lipids, liver function, inflammation, glycaemic regulation, and blood pressure. Inverse-variance weighted random-effects meta-analysis with restricted maximum likelihood produced pooled estimates. Sources of heterogeneity (age, sex, and intervention duration) were assessed by meta-regression (PROSPERO CRD42022321814).

RESULTS: Twenty-one of 28 included studies were meta-analysed. Compared with placebo, body mass index z-score (Hedges' g=-0.36, 95% CI -0.64 to -0.08) and C-reactive protein (g=-0.68, -1.27 to -0.09) decreased following microbiome-targeted interventions, with a borderline reduction of alanine aminotransferase (g=-0.33, -0.66 to 0.00); body fat percentage, lipid outcomes, insulin resistance, and blood pressure did not change significantly. In a multivariate analysis across pre-specified cardiometabolic markers, a small overall reduction was observed (g=-0.21, -0.33 to -0.10).

CONCLUSIONS: The pattern of responses to microbiome-targeted interventions was consistent with greater effects on early biological components of paediatric cardiometabolic disease, including adiposity, hepatic dysfunction and systemic inflammation. Evidence for downstream cardiometabolic risk factor modification was limited. Longer, targeted trials are needed to confirm clinical relevance.},
}

@article {pmid42777374,
year = {2026},
author = {Wu, L and Lin, T and Wang, Z and Zhan, S and Sun, X and Yu, D and Liu, B},
title = {Age-related succession of the gut microbiome drives ovarian function decline in laying hens.},
journal = {Poultry science},
volume = {105},
number = {12},
pages = {107689},
doi = {10.1016/j.psj.2026.107689},
pmid = {42777374},
issn = {1525-3171},
abstract = {The precipitous decline in egg production and the deterioration of egg quality induced by aging in laying hens pose significant challenges to the poultry industry; however, the underlying systemic mechanisms remain incompletely elucidated. This study aimed to comprehensively delineate the trajectory of ovarian function decline during the aging of laying hens and to explore the underlying mechanisms involving age-related intestinal injury and the succession of the intestinal microbiome. Laying hens at the peak, mid, and late laying periods were utilized as the experimental models. The results showed that with the increase of age, the production performance of laying hens decreased significantly, the follicle reserve was exhausted, and the secretion of reproductive hormones was significantly reduced, and the expression of key steroid synthases and hormone receptors was significantly down-regulated. Furthermore, severe oxidative stress and inflammatory responses were observed in the ovaries during the late laying period, which subsequently triggered ovarian cell apoptosis. Concurrently, the normal intestinal architecture and physical barrier function were compromised in aging hens, evidenced by a significant downregulation of tight junction proteins and accompanied by marked intestinal dysbiosis. Moreover, aging induced profound alterations in the intestinal microbial community. The late laying period was characterized by a reduced abundance of beneficial bacteria, including Parabacteroides and Lactobacillus, alongside a substantial enrichment of pathogenic taxa such as Helicobacter. In order to verify whether intestinal microbes are involved in regulating ovarian function, a fecal microbiota transplantation (FMT) experiment was conducted in this study. The FMT results indicated that receiving fecal microbiota from peak-laying donors effectively ameliorated the ovarian condition and alleviated ovarian functional decline in aged recipient hens, thereby confirming the regulatory role of the gut microbiota. In conclusion, by delineating ovarian functional degradation, systematically evaluating age-related intestinal tissue damage and microbiota succession, and revealing the potential link between age-associated gut microbes and core indicators of reproductive decline, this study provides comprehensive insights into hen aging. Importantly, the FMT trial substantiates the regulatory effect of the gut microbiota on ovarian aging, offering a crucial theoretical basis for targeting gut microecology to delay reproductive senescence and prolong the laying cycle in poultry.},
}

@article {pmid42778035,
year = {2026},
author = {Qaid, EYA and Long, I},
title = {The Gut-Lung Axis in Respiratory Diseases: Mechanisms, Microbiome Dysbiosis, and Therapeutic Implications. A Comprehensive Review.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {109167},
doi = {10.1016/j.rmed.2026.109167},
pmid = {42778035},
issn = {1532-3064},
abstract = {The gut and lung, though anatomically distinct, are connected through a dynamic, bidirectional communication network known as the gut-lung axis, whereby intestinal microbiota, immune cells, and microbial metabolites regulate pulmonary immunity and homeostasis, while pulmonary perturbations reciprocally alter gut microbial composition and barrier integrity. This narrative review synthesises current evidence on the mechanisms underlying this crosstalk, including immune cell trafficking, short-chain fatty acid and other microbial metabolite signalling, vagal neuroimmune communication, and epigenetic regulation of gut and lung tissues. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library from inception to March 2025, supplemented by manual reference screening, yielding 146 included studies. We examine disease-specific patterns of gut dysbiosis and altered gut-lung signalling across asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, respiratory infections, COVID-19 and post-COVID sequelae, obstructive sleep apnoea, and lung cancer, alongside the reverse pathway by which pulmonary disease and critical illness disrupt intestinal homeostasis. We further review microbiome-targeted therapeutic strategies, including probiotics, prebiotics, dietary interventions, faecal microbiota transplantation, and vagus nerve stimulation, and discuss their current evidentiary limitations. Persistent challenges include predominantly observational study designs, inconsistent methodology, limited multi-omics integration, and a paucity of human mechanistic data. We conclude that the gut-lung axis represents a central, bidirectional framework for understanding respiratory disease pathogenesis, and that future progress will depend on longitudinal, multi-omics, and microbiome-stratified interventional studies to enable precision, microbiome-informed respiratory therapeutics.},
}

@article {pmid42766561,
year = {2026},
author = {Chen, X and Lei, M and Tang, J and Wang, H and Chen, J and Liu, Y and Li, S and Liu, F and Wang, Y and Li, Z and Dai, Z},
title = {Efficacy, safety, and feasibility of youth-derived fecal microbiota transplantation among adults with type 1 diabetes mellitus: A protocol of Pilot Randomized Controlled Trial.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0343078},
pmid = {42766561},
issn = {1932-6203},
mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Pilot Projects ; Adult ; Double-Blind Method ; Female ; Glycated Hemoglobin/metabolism/analysis ; Male ; Feasibility Studies ; Young Adult ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Blood Glucose ; Adolescent ; Continuous Glucose Monitoring ; Gastrointestinal Microbiome ; Insulin/therapeutic use ; },
abstract = {BACKGROUND: Dysbiosis of gut microbiota plays a key role in type 1 diabetes mellitus (T1DM). Fecal microbiota transplantation represents a novel therapeutic avenue. We hypothesize that youth-derived fecal microbiota transplantation (yFMT) can remodel the gut microecosystem and improve clinical outcomes. This pilot trial aims to assess the feasibility, safety, and preliminary efficacy of yFMT in adults with T1DM.

METHODS AND ANALYSIS: This single-center, randomized, double-blind, placebo-controlled pilot study will enroll adults with T1DM who have suboptimal glycemic outcomes (glycated hemoglobin [HbA1c] of 7.0-14.0% or time in range [TIR] <70%). Following a 17-day run-in period for insulin optimization, continuous glucose monitoring (CGM) wearing, baseline assessments and bowel preparation, participants will be randomly allocated (1:1) to take yFMT or placebo capsules for 6 consecutive days, alongside their standard insulin therapy, and then complete a 12-week follow-up. The primary efficacy endpoint is the change from baseline in the rate of achieving the composite target of TIR > 70% and time below range <4% at 12 weeks post-randomization. Secondary efficacy endpoints include: (1) the change from baseline in the same composite achievement rate at 4 weeks post-intervention; (2) changes from baseline at Weeks 4 and 12 in other glycemic metrics (including HbA1c, fasting plasma glucose, 2-hour postprandial glucose, and additional CGM metrics), C-peptide, immune responses, infection markers, and gut microbiota composition; and (3) changes from baseline at Week 12 in serum metabolomic profiles (bile acids, short-chain fatty acids, and other related metabolites). Feasibility will be assessed through recruitment rate, retention rate, intervention adherence, and acceptability. Safety endpoints include the incidence of adverse events and serious adverse events.

DISCUSSION: Our findings will offer new insight into the feasibility and effects of oral yFMT capsules in adults with T1DM and provide the necessary evidence to power a subsequent multicenter large-scale study. Exploratory biomarker analyses conducted within this study may further pave the way for future individualized microbiome‑based therapeutics.

TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2500111955 (November 7, 2025).},
}

Humans
*Diabetes Mellitus, Type 1/therapy/microbiology
*Fecal Microbiota Transplantation/methods/adverse effects
Pilot Projects
Adult
Double-Blind Method
Female
Glycated Hemoglobin/metabolism/analysis
Male
Feasibility Studies
Young Adult
Randomized Controlled Trials as Topic
Treatment Outcome
Blood Glucose
Adolescent
Continuous Glucose Monitoring
Gastrointestinal Microbiome
Insulin/therapeutic use

@article {pmid42768289,
year = {2026},
author = {DeVito, A and Kimm-Drapeau, AL and Higgins, WJ and Montecillo, M and Bernstein, MN and Wright, S and Li, C and Bal, I and Dadhania, DM and Selbach, F and Lee, JR},
title = {Serial Blood Microbiome Profiles in Kidney Transplant Recipients Reveal Evidence of Circulating Gut and Non-Gut Derived Microbial DNA.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70323},
doi = {10.1111/tid.70323},
pmid = {42768289},
issn = {1399-3062},
support = {R21 AI 173849/NH/NIH HHS/United States ; R01DK139249/NH/NIH HHS/United States ; R01AI184528/NH/NIH HHS/United States ; UL1TR002384//National Center for Advancing Translational Sciences of the National Institutes of Health/ ; 539291308//German Research Foundation/ ; },
abstract = {BACKGROUND: In this study, we sought to investigate the utility of 16S rRNA gene sequencing of whole blood in kidney transplant recipients and to assess a link between the gut microbiota and the blood microbiota.

METHODS: We recruited 63 kidney transplant recipients who provided 163 whole blood specimens over the first 140 days after transplantation. We profiled the blood microbiome using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We additionally evaluated the gut microbiota via metagenomic sequencing in a subset of kidney transplant recipients who had matched blood specimens.

RESULTS: We generated a median of 19 959 sequences per blood specimen. We discovered that most whole blood microbiome profiles consisted of mitochondrial DNA (mean relative blood abundance greater than 99%) with minimal microbial DNA detected. Out of the 163 blood specimens, 83 (51%) had detectable microbial 16S rRNA sequences and there were 92 distinct taxa detected at the genus level. Among the 51 kidney transplant recipients, blood microbial 16S sequences were persistently detected in 10 kidney transplant recipients over time, intermittently detected in 29 kidney transplant recipients over time, and not detected in 12 kidney transplant recipients over time. Among 76 matched blood-fecal specimens, 9 blood specimens had detectable gut microbial 16S sequences, which were also detected in 3 of the 9 fecal specimens.

CONCLUSION: Our study finds minimal detection of bacterial DNA in the blood microbiome in kidney transplant recipients and evidence of gut bacterial DNA in the bloodstream of kidney transplant recipients.},
}

@article {pmid42768926,
year = {2026},
author = {Spencer, EA and Cohen, S 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 D'Orsi, M and Schneider, AM and Pujol-Muncunill, G and Gotesdyner, L and Kang, B and Gasparetto, M and Rungø, C and Romano, C and Miele, E and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Magen Rimon, R and Granot, M and Scarallo, L and Trindade, E and Velasco Rodríguez-Belvís, M and Turner, D and Yerushalmy-Feler, A},
title = {Upadacitinib treatment in pediatric Crohn's disease: 52-week outcomes of an international multicenter retrospective cohort study from the pediatric IBD Porto Group of ESPGHAN.},
journal = {Journal of Crohn's & colitis},
volume = {20},
number = {9},
pages = {},
doi = {10.1093/ecco-jcc/jjag125},
pmid = {42768926},
issn = {1876-4479},
mesh = {Humans ; *Crohn Disease/drug therapy ; Retrospective Studies ; Female ; Adolescent ; Male ; *Heterocyclic Compounds, 3-Ring/therapeutic use/administration & dosage/adverse effects ; Treatment Outcome ; Remission Induction ; Child ; Maintenance Chemotherapy/methods ; },
abstract = {BACKGROUND AND AIMS: Data on upadacitinib maintenance therapy in pediatric Crohn's disease (CD) are scarce. We aimed to evaluate the effectiveness, safety, and dosing of upadacitinib as maintenance therapy in pediatric CD.

METHODS: Children treated with upadacitinib for maintenance of remission of active CD from 35 centers affiliated with the Porto Group of ESPGHAN were included in this retrospective cohort study. Data on demographic, clinical, laboratory, endoscopic, and imaging findings and on adverse events (AEs) were recorded over 52 weeks of follow-up.

RESULTS: A total of 120 children were included (91 receiving upadacitinib as monotherapy and 29 as combination advanced therapy, mean age 15.4 ± 2.5 years). Prior to upadacitinib induction, 119/120 (99%) children had been treated with biologic therapies, 104 (87%) with two or more biologics and 98 (82%) had failed both vedolizumab and ustekinumab. Clinical remission and corticosteroid-free clinical remission (CFR) were observed after upadacitinib induction in 77 (64%) and 72 (60%) children, respectively. By week 52, 74 (62%) children achieved both clinical remission and CFR, and CFR was sustained in 66 (55%) children. CFR with normal C-reactive protein levels was achieved in 50% of children and CFR with fecal calprotectin levels <150 µg/g was achieved in 33% of children by week 52. Fifty-three (44%) children sustained AEs, two of which were serious (severe acne and intestinal perforation). The most frequent AEs were acne (n = 23), hyperlipidemia (n = 18), and infections (n = 14).

CONCLUSION: Upadacitinib is an effective maintenance therapy for refractory pediatric CD. Effectiveness should be weighed against the potential risks of AEs.},
}

Humans
*Crohn Disease/drug therapy
Retrospective Studies
Female
Adolescent
Male
*Heterocyclic Compounds, 3-Ring/therapeutic use/administration & dosage/adverse effects
Treatment Outcome
Remission Induction
Child
Maintenance Chemotherapy/methods

@article {pmid42768978,
year = {2026},
author = {Boettcher, SR and Kenney, RM and Everson, NA and Kashat, I and Soyad, A and Tengler, G and Ramesh, M and Veve, MP},
title = {Clinical Experience with Oral Fecal Microbiota Spores (Vowst®) in a Health System Specialty Pharmacy.},
journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajhp/zxag293},
pmid = {42768978},
issn = {1535-2900},
abstract = {PURPOSE: To describe clinical experience and patient outcomes with orally administered fecal microbiota spore (FMS) capsules, live-brpk, for prevention of recurrent Clostridioides difficile infection (rCDI) after workflow implementation into a local health-system specialty pharmacy (HSSP) model.

SUMMARY: rCDI carries substantial morbidity, and the approval of orally administered FMS capsules introduced a novel prevention option with new challenges in medication access, prior authorization, and cost. To meet this need, an HSSP workflow was adapted to support acquisition of FMS for adults receiving a prescription order. Over the period from June 1, 2023, through December 31, 2024, a total of 72 FMS prescriptions were generated for 50 patients, of which 29 (58%) ultimately obtained the medication. Patients reflected a real-world population, the median (IQR) age was 70 (55-79) years, 55% were men, the median (IQR) number of previous CDI episodes (including the proximal episode) was 2 (1-3), and 25% were immunocompromised. Among patients who received FMS, rCDI occurred in 2 (7%) patients at eight weeks. Of the 21 prescriptions obtained through the HSSP, 62% required a single prior authorization (PA) attempt, and the median (IQR) time to dispensing from prescription generation was 16 (12-20) days. Copayments ranged from $0 to >$2,500, with most patients (18, 86%) receiving FMS for less than $6.

CONCLUSION: Implementation of an adapted HSSP FMS medication workflow resulted in medication access for more than half of patients and offers a practical, adaptable model for integrating high-cost microbiome therapies into specialty pharmacy practice.},
}

@article {pmid42770722,
year = {2026},
author = {Choudhary, N and Mittal, A and Yadav, K and Maras, JS and Sarin, SK and Sharma, S},
title = {Fecal filtrate transplantation attenuates liver and gut injury in experimental alcohol-associated liver disease.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0037726},
doi = {10.1128/spectrum.00377-26},
pmid = {42770722},
issn = {2165-0497},
abstract = {Fecal microbiota transplantation (FMT) carries a risk of infection. Cell-free fecal filtrate transplantation (FFT) represents a potentially safer alternative. The benefit of FFT has not been explored in alcohol-associated liver disease (ALD). We evaluated the therapeutic potential of FFT in a murine model of ALD. C57BL/6N mice were pair-fed control or ethanol Lieber-DeCarli diets with thioacetamide for 12 weeks to induce ALD. FFT (0.22-µm-filtered stool slurry) from healthy mice was administered three times per week to ALD animals. Post-FFT day 7, hepatic and intestinal injury and inflammation were assessed. Fecal microbiota was assessed by 16S rRNA sequencing, and the hepatic/stool metabolome was assessed by mass spectrometry. FFT was significantly better than abstinence, with reduced hepatic pro-inflammatory markers at the protein level, including IL-6 (1.6 fold change [FC], P < 0.001), TNF-α (1.2 FC, P < 0.001), and also decreased collagen deposition (2.97 FC, P = 0.003) and TGF-β expression (2 FC, P < 0.001). FFT improved intestinal barrier integrity by upregulation of ZO-1 protein (1.5-fold, P = 0.002) and Muc2 mRNA (3.28 FC, P = 0.007), with concomitant reduction of plasma-endotoxin (2.5 FC, P < 0.001). FFT suppressed pathogenic taxa like Escherichia-Shigella (log2 FC = -9.5, padj = 3.42E-13), Proteus (log2 FC = -5.6, padj = 0.004), Desulfovibrio (log2 FC = -1.5, padj = 0.004), and increased Prevotellaceae NK3B31 group (log2 FC = 2.7, padj = 0.018), and Acinetobacter (log2 FC = 4.9, padj = 9.41E-16) in the gut. Metabolomic profiling of stool revealed significant increases (P < 0.05) in butyric, valeric, isobutyric, and ursodeoxycholic acids. These metabolites enriched pathways like butyrate metabolism (P = 0.04), mitochondrial β-oxidation (P = 0.008), and PPARα signaling (P = 0.01), indicating intestinal and hepatic repair. FFT confers hepatoprotection in ALD by attenuating inflammation and fibrosis, and restoring the intestinal barrier, gut microbiota composition, and beneficial SCFA and bile acid metabolism. These findings support FFT as a promising preclinical strategy for gut-liver axis modulation in ALD.IMPORTANCEAlcohol-associated liver disease (ALD) involves disrupted gut-liver communication, contributing to inflammation, impaired intestinal barrier function, and metabolic disturbances that exacerbate liver injury. This study demonstrates that fecal filtrate transplantation (FFT) attenuates alcohol-induced liver injury while modulating intestinal barrier-related markers, gut microbial communities, and microbial metabolites. These findings highlight the potential of cell-free microbial components as modulators of the gut-liver axis and provide a basis for developing alternative approaches to gut-based intervention in ALD.},
}

@article {pmid42771339,
year = {2026},
author = {Zhang, Y and Mo, Z and Yang, Q and Jiang, B and Han, R and Wang, J and Liu, H and Zhou, S and Zhao, J},
title = {Near-infrared-II fluorescent quantum dots for in vivo tracking of colonization dynamics of transplanted gut microbiota.},
journal = {Biomaterials science},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6bm01047d},
pmid = {42771339},
issn = {2047-4849},
abstract = {Faecal microbiota transplantation (FMT) represents a critical therapeutic strategy for diseases associated with gut microbiota dysbiosis, but effective real-time monitoring methods for the dynamic behaviour of transplanted microbiota in the recipient gut are lacking. This study constructed a bacterial labelling probe based on near-infrared-II (NIR-II) fluorescent quantum dots (QDs). Using Ag2Te QDs as the fluorescent core, a PLGA-PEG coating was applied to improve their water dispersibility and biocompatibility, while heparin functionalization endowed them with bacterial labelling capabilities. This probe exhibits excellent in vivo and in vitro biosafety and stable NIR-II fluorescence performance, enabling efficient fluorescent labelling of bacteria within the transplanted microbiota. Based on NIR-II in vivo fluorescence imaging technology, real-time dynamic monitoring of FMT transplanted microbiota in the mouse intestine was achieved, and it was revealed that it has a long-term retention characteristic only in the intestine of CDI mice. This study establishes an NIR-II fluorescence imaging strategy for dynamic tracking of the transplanted microbiota during FMT, with potential for investigating its in vivo dynamics.},
}

@article {pmid42764262,
year = {2026},
author = {Yang, R and Yang, J and Su, Z and Su, R and Wu, L and Zhao, W and Ren, R and Xu, J},
title = {Mechanism of soluble dietary fiber from foxtail millet alleviating chronic colitis by reshaping intestinal fungi.},
journal = {Journal of the science of food and agriculture},
volume = {},
number = {},
pages = {},
doi = {10.1002/jsfa.71097},
pmid = {42764262},
issn = {1097-0010},
support = {202203021211118//Shanxi Province Fund Project/ ; 202510119002//Shanxi Province Higher Education University Student Innovation and Entrepreneurship Training Program Projec/ ; 20251273//Shanxi Province Higher Education University Student Innovation and Entrepreneurship Training Program Projec/ ; CXCY25094//Taiyuan Normal University Education Innovation Project/ ; },
abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a type of persistent chronic inflammation in the colon and can cause malignant transformation of colonic mucosa through various mechanisms. The dysbiosis of gut microbiota is closely related to the development and maintenance of IBD. Studies have shown that a proper intake of dietary fiber serves to maintain intestinal homeostasis by modulating commensal microbiomes. The present study aims to reveal the effect of soluble dietary fiber from foxtail millet bran (FMB-SDF) on chronic colitis and gut fungal community.

RESULTS: C57BL/6J mice were orally given dextran sulfate sodium (DSS) water to construct a chronic colitis model and FMB-SDF was gavage administered to investigate its ameliorative effects on colitis. Our findings demonstrated that FMB-SDF alleviated chronic colitis symptoms including weight loss, colonic shortening and inflammatory infiltration as well as reshaping the fungal community diversity and overall structure. At the phylum level, FMB-SDF significantly modulates the relative abundances of Ascomycota, Basidiomycota and Malassezia. Furthermore, fecal microbiota transplantation (FMT) confirmed that the relieved effects of FMB-SDF on colitis were microbiota-mediated, resulting in suppression of the expression of Ki-67 and enhanced intestinal barrier tight junction proteins ZO-1.

CONCLUSION: Our results proved that FMB-SDF alleviated chronic colitis by regulating the commensal fungal community. The present study highlights that FMB-SDF may be a promising functional food and therapeutic candidate for colitis. © 2026 Society of Chemical Industry.},
}

@article {pmid42764315,
year = {2026},
author = {Shao, Y and Zhang, RF and Wang, Z and Gan, J and Jiang, XJ and Yang, L},
title = {From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42764315},
issn = {1559-1182},
mesh = {Humans ; *Blood-Brain Barrier/metabolism/pathology ; Animals ; *Alzheimer Disease/metabolism/pathology/microbiology ; *Dysbiosis/metabolism ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; },
abstract = {Alzheimer's disease (AD) is not merely a central nervous system disorder; rather, it is a systemic condition profoundly influenced by the peripheral internal environment. Recent research has revealed that imbalances in the gut microbiota (GM) and metabolite disturbances contribute to AD onset and progression. Clinical and animal studies have indicated that AD patients commonly exhibit reduced GM diversity, decreased populations of short-chain fatty acid (SCFA)-producing and indole-producing bacteria, disrupted bile acid (BA) profiles, and elevated levels of trimethylamine N-oxide (TMAO) and kynurenine pathway (KP) activity. These alterations not only reflect gut dysbiosis, but also impair blood-brain barrier (BBB) integrity and amplify neuroinflammation by modulating tight junction proteins and inflammatory signaling through their effects on receptors and transporters such as G protein-coupled receptors(GPR41/43), aryl hydrocarbon receptor(AhR), Farnesoid X receptor(FXR)/ Takeda G protein-coupled receptor 5(TGR5), L-type amino acid transporter 1(LAT1), and Major Facilitator Superfamily Domain containing 2A(MFSD2A). From an integrative perspective, these changes -including short-Chain Fatty Acids (SCFAs) deficiency, elevated TMAO and toxic BA levels, overactivation of the KP, and Lipopolysaccharides (LPS) leakage-often act synergistically, collectively forming key pathological nodes in the "metabolic network-BBB-AD" axis. GM-targeted strategies such as dietary interventions, probiotics and fecal microbiota transplantation (FMT) have demonstrated potential in improving metabolite profiles and BBB homeostasis. Future research should utilize induced pluripotent stem cell-derived organoids and multi-omics integration approaches to elucidate the spatiotemporal dynamics of metabolites within the gut-brain axis (GBA), thereby laying the foundation for precise microbiome-based interventions in AD.},
}

Humans
*Blood-Brain Barrier/metabolism/pathology
Animals
*Alzheimer Disease/metabolism/pathology/microbiology
*Dysbiosis/metabolism
*Gastrointestinal Microbiome/physiology
*Brain-Gut Axis/physiology
*Brain/metabolism

@article {pmid42764910,
year = {2026},
author = {Zhai, Z and Yang, F and Feng, R and Zhang, H and Wang, J and Zuo, H and Yang, X and Ye, M and Xu, H and Hu, J and Lu, J and Zhao, Y and Song, J and Zhang, Y and Wang, Y and Xing, N},
title = {Quercetin's antitumor effect in bladder cancer: Synergistic regulation of gut microbiota and l-serine metabolic pathway.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {9},
pages = {5961-5979},
pmid = {42764910},
issn = {2211-3835},
abstract = {Quercetin is a bioflavonoid that is abundant and easy to extract, and has beneficial effects such as anti-cancer, anti-inflammatory, and antioxidant properties. We have demonstrated that oral administration of quercetin in an animal model inhibits bladder cancer (BCa), with inhibition rates of 48.5% (100 mg/kg) and 51.41% (200 mg/kg), respectively. Additionally, quercetin treatment reverses gut microbiota dysbiosis in the model mice. Metabolomics results showed that l-serine had the highest correlation coefficient with tumor weight in model mice (r = 0.935), and oral quercetin reduced l-serine levels by modulating the abundance of Escherichia-Shigella in the gut microbiota. Transcriptomic sequencing results revealed that quercetin treatment downregulates the expression of phosphoserine phosphatase (PSPH), inhibiting the serine synthesis pathway (SSP) and reducing l-serine levels in the body, thus exerting anti-tumor effects. Fecal microbiota transplantation (FMT) experiments reproduced the pharmacological results of oral quercetin treatment for BCa and identified Escherichia coli Nissle 1917 as capable of inhibiting BCa growth by metabolizing l-serine. In conclusion, quercetin effectively inhibits the progression of BCa by comprehensively regulating l-serine levels in the body at both endogenous and exogenous levels.},
}

@article {pmid42765011,
year = {2026},
author = {Leung, EL},
title = {A novel intervention strategy for bladder cancer targeting dual metabolic pathways-Unraveling the pleiotropic mechanisms of quercetin.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {9},
pages = {6299-6300},
pmid = {42765011},
issn = {2211-3835},
}

@article {pmid42765047,
year = {2026},
author = {Guo, Q and Liang, F and Chen, P and Zhang, Y and Xie, M and Wan, X and Mao, J and Chen, H and Wu, W and Jiang, D and Wu, S},
title = {Microbiota-Host Interactions in Perimenopausal Syndrome: Mechanisms and Therapeutic Strategies (Review).},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {631942},
pmid = {42765047},
issn = {1179-1411},
abstract = {BACKGROUND: Perimenopausal syndrome (PMS) is common, with more than 70% of perimenopausal women experiencing symptoms such as hot flashes and anxiety. As a key regulator of host physiology, the gut microbiota may play an important role in the pathogenesis of PMS.

OBJECTIVE: This review aimed to synthesize clinical and preclinical evidence on alterations in the gut microbiota during perimenopause, elucidate the potential mechanisms underlying host-microbiota interactions, and summarize and critically evaluate current therapeutic strategies targeting the gut microbiota.

METHODS: A targeted literature search of PubMed and Web of Science was conducted for relevant studies published through July 15, 2026. Search terms covered perimenopause, menopause, gut microbiota, estrobolome, gut-brain axis, metabolomics, female microbiome, ovarian function, probiotics, and fecal microbiota transplantation. Human studies were prioritized, with high-quality animal and mechanistic studies included when clinical evidence was limited.

RESULTS: Few studies have directly examined women with PMS. Findings on gut microbial diversity and changes in specific taxa have been inconsistent across studies, and no reproducible pattern of gut dysbiosis specific to PMS has been established. Current evidence suggests that ovarian aging and fluctuations in sex hormones may reshape the gut microbial ecosystem. In turn, microbial enzymes and metabolites may interact bidirectionally with host endocrine changes by influencing the enterohepatic circulation of estrogens, immune and inflammatory responses, ovarian function, and gut-brain communication. Lifestyle interventions are supported by a relatively substantial body of evidence for symptom improvement, although whether their effects are mediated by the gut microbiota remains unclear. Certain strain-specific probiotics have shown preliminary clinical promise. However, evidence supporting prebiotics, synbiotics, traditional Chinese medicine, acupuncture, plant-derived products, and fecal microbiota transplantation is derived mainly from small clinical studies or preclinical experiments. By distinguishing direct clinical evidence from PMS populations from indirect evidence derived from other populations and experimental studies, this review reveals a central paradox in current research that strong biological plausibility coexists with insufficient clinical causal evidence.

CONCLUSION: The gut microbiota may contribute to the pathogenesis and progression of PMS through the "gut microbiota-estrogen-ovary-immune-brain axis". However, current evidence primarily supports bidirectional associations and biological plausibility. Although microbiota-targeted interventions have potential therapeutic value, the available evidence remains insufficient to support their routine clinical use. Future research should include longitudinal cohort studies using standardized menopausal staging and multicenter randomized controlled trials. Confounding factors such as age, diet, medication use, and hormone therapy should be adequately controlled. Integrated analyses of multiple omics datasets should also be combined with mechanistic studies to establish the causal role and clinical translational potential of the gut microbiota.},
}

@article {pmid42761811,
year = {2026},
author = {Le, Q},
title = {Restructuring the gut microbiota in obesity: molecular mechanisms linking dysbiosis to systemic inflammation and therapeutic opportunities.},
journal = {Frontiers in physiology},
volume = {17},
number = {},
pages = {1902756},
pmid = {42761811},
issn = {1664-042X},
abstract = {Obesity is characterized by a chronic low-grade inflammatory state that contributes to insulin resistance, type 2 diabetes, and metabolic syndrome. The gut microbiota has emerged as a critical mediator of this inflammatory process through multiple interconnected mechanisms including metabolic endotoxemia, short-chain fatty acid dysregulation, and intestinal barrier dysfunction. This review synthesizes current evidence on the structural and functional alterations of the gut microbiome in obesity, examines the mechanistic pathways linking dysbiosis to systemic inflammation, and critically evaluates therapeutic strategies aimed at restructuring the obese gut microbial community. We focus on three major intervention approaches: fecal microbiota transplantation, probiotic and prebiotic supplementation, and next-generation targeted microbial therapies. Analysis of clinical and preclinical studies reveals that successful microbial restructuring requires not only compositional shifts but also functional restoration of microbial metabolite production, particularly short-chain fatty acids. The evidence supports a model wherein obesity-associated dysbiosis perpetuates chronic inflammation through increased lipopolysaccharide translocation, reduced butyrate production, and compromised intestinal barrier integrity. Restoring microbial eubiosis through targeted interventions offers a promising avenue for resolving chronic low-grade inflammation and improving metabolic health outcomes in obese individuals.},
}

@article {pmid42761444,
year = {2026},
author = {Zou, Z and Liu, H and Hu, Y and Ge, X and Zhang, J and Li, X},
title = {Gut microbiota and microbiota-derived metabolites in radiation-induced injury: mechanisms and therapeutic opportunities.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1923929},
doi = {10.3389/fmicb.2026.1923929},
pmid = {42761444},
issn = {1664-302X},
abstract = {Radiation-induced injury is a complex pathological process involving DNA damage, oxidative stress, inflammatory amplification, epithelial barrier disruption, immune dysregulation, metabolic remodeling, and impaired tissue repair. Accumulating evidence indicates that the gut microbiota is not merely altered by irradiation but may also modify host radiation responses and tissue recovery; however, direct causal support remains confined to selected microbes, metabolites, and pathways, predominantly in preclinical models. Irradiation is frequently associated with reduced microbial diversity, depletion of selected commensals, expansion of opportunistic pathobionts, and altered microbial metabolic output; selected experimental studies further indicate that these changes can modify intestinal injury and host recovery. Conversely, defined microbes and metabolites have improved radiation outcomes in preclinical intervention models by supporting epithelial, immune, and metabolic homeostasis. In this review, we summarize current advances in understanding the gut microbiota-metabolite axis in radiation-induced injury. We first discuss radiation-induced gut dysbiosis and the major microbial metabolites involved, including short-chain fatty acids, tryptophan-derived metabolites, bile acids, lipid metabolites, polyamines, and other bioactive molecules. We then highlight the key mechanisms by which gut microbiota and microbial metabolites mitigate radiation injury, including suppression of oxidative stress, inhibition of inflammatory signaling, restoration of epithelial barrier integrity, promotion of intestinal stem cell-mediated regeneration, regulation of immune homeostasis, and modulation of lipid peroxidation-associated ferroptosis. Finally, we evaluate microbiota-targeted intervention strategies, including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, antibiotic modulation, natural products, engineered probiotics, and nanomedicine-assisted delivery systems. Overall, the gut microbiota-metabolite axis represents a biologically plausible and increasingly testable target for radioprotection and mitigation, although its clinical utility remains to be established. Future studies should move beyond descriptive microbiome profiling toward causal, function-oriented, and multi-omics-driven investigations, with particular emphasis on the microbiota-lipid metabolism-ferroptosis axis and precision microbiome therapeutics. Carefully validated microbiota-targeted approaches may provide future opportunities to reduce normal-tissue toxicity and improve recovery without compromising tumor control.},
}

@article {pmid42761446,
year = {2026},
author = {Li, S and Wan, J and Liang, Z and Li, J and Jiang, H and Luo, L and Li, Y and Luo, S and Huang, H},
title = {Gypenosides ameliorate polycystic ovary syndrome via gut microbiota modulation: An integrated gut microbiome and ovarian transcriptome study.},
journal = {iScience},
volume = {29},
number = {10},
pages = {117478},
doi = {10.1016/j.isci.2026.117478},
pmid = {42761446},
issn = {2589-0042},
abstract = {Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with complex metabolic and reproductive manifestations. Gut microbiota dysbiosis has emerged as a key factor in PCOS, yet the causal role of microbiota-targeted interventions remains to be fully defined. In a letrozole-induced rat model, we show that gypenosides (GPs)-bioactive saponins from Gynostemma pentaphyllum-alleviate weight gain, hormonal imbalance, and estrous cycle disruption, alongside reducing systemic oxidative stress and inflammation. Integrated ovarian transcriptomics and gut microbiome 16S rRNA sequencing reveal that GPs modulate ovarian gene expression related to inflammation and cellular function while reshaping gut microbiota by enriching beneficial genera including Lactobacillus and Romboutsia. Fecal microbiota transplantation (FMT) establishes causality: PCOS-derived microbiota transfers disease traits to normal recipients, whereas GPs-conditioned microbiota alleviates PCOS phenotypes in recipients. These findings demonstrate that GPs act through a "gut microbiota-oxidative stress-ovary" axis, supporting GPs as a promising microbiota-targeted intervention for PCOS management.},
}

@article {pmid42755036,
year = {2026},
author = {Romanchuk, A and Bramuzzo, M and Labriola, F and Aloi, M and Banzato, C and Bosa, L and Colucci, A and Corpino, M and Сozzali, R and D'Arcangelo, G and Dargenio, VN and Difrancisca, E and Nardo, GD and Toma, MD and Gatti, S and Gianolio, L and Graziano, F and Illiceto, MT and Iuliano, S and Mainetti, M and Marseglia, A and Martinelli, M and Motta, M and Musto, F and Opramolla, A and Scarallo, L and Sgaramella, P and Zuin, G and D'Antiga, L and Sansotta, N and , },
title = {Current practices and unmet needs in the management of Clostridioides difficile infection in pediatric inflammatory bowel disease: A national survey.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70575},
pmid = {42755036},
issn = {1536-4801},
support = {//None/ ; },
abstract = {OBJECTIVES: Children with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection (CDI), which is associated with worse clinical outcomes. We aimed to assess current diagnostic and therapeutic practices for CDI among Italian pediatric IBD centers.

METHODS: A nationwide survey was conducted in 2025 using a structured 28-item questionnaire distributed to all pediatric IBD centers in Italy. Items addressed diagnostic strategies, treatment approaches, recurrence management, and immunosuppressive therapy handling in children with IBD and CDI.

RESULTS: Twenty-seven centers responded (response rate, 90%). Diagnostic approaches varied: toxin enzyme immunoassays (EIA) were indicated by 21/27 centers (78%), glutamate dehydrogenase (GDH) testing by 19/27 (70%), and nucleic acid amplification tests (NAAT) by 13/27 (48%). Routine CDI testing at IBD diagnosis was indicated by 12/27 centers (44%), whereas 23/27 (85%) reported testing during IBD flares. For a first non-severe episode, vancomycin and metronidazole were equally identified as preferred first-line options (18/27; 66% each). Oral vancomycin was the preferred treatment for recurrent CDI (26/27; 96%). Third or subsequent recurrences prompted consideration of fidaxomicin (19/27; 70%), fecal microbiota transplantation (6/27; 22%), and bezlotoxumab (2/27; 7%). In fulminant CDI, 7/27 centers (26%) indicated adding fidaxomicin to standard therapy. In acute severe colitis with concomitant CDI at diagnosis, 18/27 centers (67%) described a cautious approach to biologic initiation.

CONCLUSIONS: This nationwide survey highlights substantial unmet needs in CDI management in pediatric IBD, including variability in diagnostic strategies, lack of consensus on first-line therapy, and uncertainty regarding immunosuppressive management, supporting the need for evidence-based pediatric-specific guidelines.},
}

@article {pmid42755623,
year = {2026},
author = {Xu, Z and Wang, Y and Zhang, X and Guo, F and Chen, J and Geng, H and Li, Y and Gao, Y},
title = {Application of metagenomic next-generation sequencing in gastrointestinal infections in children after allogeneic hematopoietic stem cell transplantation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1868295},
pmid = {42755623},
issn = {2235-2988},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *High-Throughput Nucleotide Sequencing/methods ; *Metagenomics/methods ; Female ; Child, Preschool ; Male ; Child ; Feces/microbiology/virology ; Infant ; Bacteria/classification/isolation & purification/genetics ; Viruses/classification/isolation & purification/genetics ; Transplantation, Homologous/adverse effects ; *Gastrointestinal Diseases/microbiology/diagnosis/etiology/virology ; Diarrhea/microbiology ; Adolescent ; Bacterial Infections/microbiology/diagnosis ; },
abstract = {BACKGROUND: Gastrointestinal infections are the leading cause of death for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Conventional microbiological testing (CMT) often fails to identify the pathogens, resulting in delayed diagnosis and poor treatment outcomes. Metagenomic next-generation sequencing (mNGS) offers a promising method that does not require cultivation, but its application in this specific situation has not been fully studied.

METHODS: 185 fecal samples were collected from 96 children who underwent HSCT and suffered from diarrhea. All samples were simultaneously subjected to mNGS and CMT testing. The diagnostic performance, pathogen spectrum and prevalence of gastrointestinal infection pathogens were systematically analyzed and compared.

RESULTS: Compared with CMT, mNGS detected significantly more bacteria, viruses and atypical pathogens. Among the pathogens detected by mNGS in the 185 fecal samples, the predominant bacteria were Pseudomonas spp. (28 cases), Clostridioides spp. (28 cases), Campylobacter spp. (25 cases), Acinetobacter spp. (16 cases), and Staphylococcus aureus (13 cases). Clostridioides spp. exhibited a significantly higher detection rate in fecal samples from patients receiving CsA-based combination therapy (p=0.01099) and those with bone marrow from unrelated donors (p=0.03188). Pseudomonas aeruginosa (p = 0.03038) and Campylobacter spp.(p = 0.00549) were detected significantly more frequently in patients within the early phase (1-30 days). The detection rate of Adenovirus was markedly decreased during the intermediate phase (31-100 days) (p = 0.01458). Furthermore, Polyomavirus showed a significantly increased detection rate in patients with short-term diarrhea (1-3 days) (p=0.03451).

CONCLUSION: Our findings highlight the substantial superiority of mNGS over CMT in pathogen detection, with a broader coverage encompassing bacteria, viruses, and atypical organisms. It uncovers complex polymicrobial and viral-bacterial co-infections, delineates infection dynamics linked to immune reconstitution. Integrating mNGS into the diagnostic workflow holds great potential for enabling precision antimicrobial therapy and improving outcomes in this high-risk population.},
}

Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
*High-Throughput Nucleotide Sequencing/methods
*Metagenomics/methods
Female
Child, Preschool
Male
Child
Feces/microbiology/virology
Infant
Bacteria/classification/isolation & purification/genetics
Viruses/classification/isolation & purification/genetics
Transplantation, Homologous/adverse effects
*Gastrointestinal Diseases/microbiology/diagnosis/etiology/virology
Diarrhea/microbiology
Adolescent
Bacterial Infections/microbiology/diagnosis

@article {pmid42755803,
year = {2026},
author = {Marjanović, M and Maletin, N and Kukić, B and Nikolić, I and Petrović, N and Radić, J and Đurić, A and Knezević, M and Dejanović, B and Ćalić, V},
title = {Gut microbiome-mediated primary and acquired resistance to immune checkpoint inhibitors in MSI-H/dMMR colorectal cancer: mechanisms, biomarkers, and therapeutic implications-a narrative review.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1907957},
pmid = {42755803},
issn = {2235-2988},
mesh = {Humans ; *Colorectal Neoplasms/drug therapy/genetics/immunology/microbiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/immunology ; *Drug Resistance, Neoplasm ; Microsatellite Instability ; Tumor Microenvironment/immunology ; DNA Mismatch Repair ; Animals ; Biomarkers, Tumor ; },
abstract = {INTRODUCTION: Immune checkpoint inhibitors (ICIs) have transformed the management of microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC). However, a substantial proportion of patients exhibit primary resistance or eventually develop acquired resistance, highlighting the need for a better understanding of the biological mechanisms influencing therapeutic response. Increasing evidence suggests that the gut microbiome-immune axis is an important regulator of antitumor immunity through complex interactions among microbial communities, microbial metabolites, host immunity, and the tumor microenvironment.

MAIN BODY: This narrative review summarizes current evidence regarding the role of the gut microbiome-immune axis in mediating primary and acquired resistance to immune checkpoint inhibition in MSI-H/dMMR CRC. We discuss the physiological interactions that maintain immune homeostasis and review the functional mechanisms through which alterations in microbial metabolic pathways, including short-chain fatty acids, bile acids, tryptophan-derived metabolites, inosine, and polyamines, may influence antitumor immune responses. We further examine microbial composition and functional biomarkers associated with immune checkpoint inhibitor response, together with emerging therapeutic strategies aimed at modulating the gut microbiome-immune axis, including dietary interventions, prebiotics, probiotics, selective antimicrobial approaches, fecal microbiota transplantation, live biotherapeutic products, and next-generation precision microbiome engineering. Finally, we discuss current translational challenges and future research priorities required for successful clinical implementation.

CONCLUSION: The gut microbiome-immune axis represents a promising area of investigation for understanding resistance to immune checkpoint inhibition in MSI-H/dMMR CRC. While growing evidence supports its biological relevance, much of the current knowledge remains preclinical or is derived from early-phase clinical studies. Future progress will depend on mechanistic investigation, longitudinal multi-omic microbiome profiling, standardized methodologies, prospective biomarker validation, and the rational development of microbiome-directed therapeutic strategies to support precision immuno-oncology.},
}

Humans
*Colorectal Neoplasms/drug therapy/genetics/immunology/microbiology
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Gastrointestinal Microbiome/immunology
*Drug Resistance, Neoplasm
Microsatellite Instability
Tumor Microenvironment/immunology
DNA Mismatch Repair
Animals
Biomarkers, Tumor

@article {pmid42756370,
year = {2026},
author = {Jiao, Y and Zhao, Y and Zhang, Z and Sun, H and Wang, Y and Bai, X and Piao, C and Lei, X and Zhang, N and Xu, H},
title = {Sishen wan modulates gut microbial and short-chain fatty-acid imbalances and ameliorates behavioral and inflammatory abnormalities in mice with chronic sleep deprivation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1944977},
pmid = {42756370},
issn = {1664-302X},
abstract = {BACKGROUND: Chronic sleep deprivation (CSD) disrupts mood-related behavior, gut microbial ecology, and inflammatory homeostasis. Sishen Wan (SSW), a medicinal plant formula used clinically for chronic diarrhea, has shown microbiota- and inflammation-modulating effects in colitis models, but its protective effects under sleep-deprivation conditions remain unclear.

METHODS: The chemical profile of SSW was characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Male C57BL/6 J mice underwent CSD using a modified multiple-platform method and received three doses of SSW or fluoxetine. Behavioral performance, histopathology, gut microbiota composition, and short-chain fatty acid (SCFA) concentrations in feces, serum, and hippocampal tissue were assessed. Fecal material from Control, Model, and high-dose SSW (SSW-H) donors was transplanted into antibiotic-pretreated recipients. Serum untargeted metabolomics, hippocampal transcriptomics, RT-qPCR, and resting-state functional magnetic resonance imaging were used to characterize metabolic, transcriptional, and brain-function changes.

RESULTS: CSD reduced sucrose preference and open-field activity, prolonged immobility in the tail-suspension and forced-swim tests, aggravated colonic and hippocampal injury, and increased pro-inflammatory cytokines. SSW-H produced the most consistent improvements. CSD also reduced gut microbial richness and diversity, altered community composition, and lowered fecal acetate, propionate, and butyrate and serum acetate. SSW-H shifted the community toward the Control profile, increased Akkermansia, reduced several Model-enriched taxa, and increased major fecal SCFAs and serum acetate. Recipients of Model-donor feces developed reduced sucrose preference and activity, prolonged immobility, and colonic and hippocampal abnormalities. In contrast, recipients of SSW-H-donor feces showed milder behavioral and histological changes and a microbial profile distinct from that of FMT-Model recipients. SSW-H was also associated with partial normalization of lipid-, amino-acid-, and one-carbon-metabolism-related serum features, modulation of hippocampal immune pathways involving chemokines, cytokines, and NF-κB signaling, and attenuation of several CSD-associated regional brain abnormalities.

CONCLUSION: SSW alleviated CSD-associated behavioral abnormalities, tissue injury, and inflammation, with the high dose showing the most consistent effects. These improvements were accompanied by changes in gut microbial composition and SCFA profiles.},
}

@article {pmid42756774,
year = {2026},
author = {Huang, Z and Dai, Z and Liu, Q},
title = {Efficacy and safety of fecal microbiota transplantation for chronic constipation: a systematic review and meta-analysis integrating pre-post and single-arm evidence.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1900353},
pmid = {42756774},
issn = {1664-302X},
abstract = {BACKGROUND: Chronic constipation is a common functional gastrointestinal disorder with a global prevalence of 12%-17%. Conventional treatments have limited efficacy for refractory cases, with high recurrence and side effects. Fecal microbiota transplantation (FMT) offers a novel strategy by restoring gut microecological balance, yet its efficacy requires systematic evaluation. This meta-analysis evaluated FMT efficacy and safety through an innovative "three-in-one" framework.

METHODS: We systematically searched CENTRAL, PubMed, Embase, and CNKI for RCTs, single-arm studies, and cohort studies. The framework comprised: (1) RCT random-effects meta-analysis; (2) single-arm proportional meta-analysis with Freeman-Tukey transformation; (3) pre-post paired sensitivity analysis (r = 0.5, with sensitivity tests at r = 0.3, 0.7, 0.9). Publication bias was assessed via Egger, Harbord, trim-and-fill, and fail-safe N tests.

RESULTS: 12 RCTs (n = 1040), 16 single-arm studies (n = 403), and 4 cohort studies (n = 422) were included. After trim-and-fill adjustment for publication bias, FMT was associated with a clinical total response rate of RR = 1.21 (95% CI: 1.10-1.33). The unadjusted pooled estimate was RR = 1.36 (95% CI: 1.21-1.52, P < 0.001); however, the Harbord test indicated potential publication bias (P = 0.003), necessitating this correction. Wexner score improved (MD = -2.08, 95% CI: -3.35 to -0.81, P = 0.003). Among the 16 single-arm studies, 8 (n = 249) reported remission/improvement rates, showing a remission rate of 51.7% (95% CI: 40.3%-62.9%) and paired pre-post improvements in BSFS, Wexner, and PAC-QOL; these within-group changes cannot establish causal efficacy. During follow-up periods of up to 24 weeks, no serious adverse events were reported; long-term safety data are lacking.

CONCLUSION: Current evidence suggests FMT is a promising therapeutic option for chronic constipation, with an adjusted clinical total response rate of RR = 1.21 (95% CI: 1.10-1.33) after correction for publication bias. While FMT was associated with improvements in symptom scores, quality of life, and intestinal function, the evidence quality is limited by publication bias, high heterogeneity, and high risk of bias in all included RCTs. More high-quality, sham-controlled RCTs are needed to validate these findings.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261394673, identifier: CRD420261394673.},
}

@article {pmid42756900,
year = {2026},
author = {Cheng, Y and Zhao, H and Lin, L and Chen, Y and Lin, H},
title = {Gut microbiota-host adaptive immune interactions in type 2 diabetes mellitus: mechanisms, disease progression, and microbiota-based therapeutic strategies.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1934029},
pmid = {42756900},
issn = {1664-302X},
abstract = {Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder whose development and progression are influenced not only by genetic susceptibility, obesity, and lifestyle-related factors but also by gut microbiota dysbiosis, chronic low-grade inflammation, and disruption of immunometabolic homeostasis. The gut microbiota regulates adaptive immune responses through diverse signals, including microbial structural components, metabolites, extracellular vesicles, and other secreted molecules. These microbial-derived signals modulate antigen presentation, T-cell differentiation, B-cell function, and IgA-mediated mucosal immunity, thereby influencing adaptive immune populations such as Th1 cells, Th17 cells, CD8[+] T cells, and regulatory T cells (Tregs). Conversely, the adaptive immune system can reshape microbial composition and functional outputs by regulating intestinal barrier integrity, mucosal immune homeostasis, and ecological niche stability, forming a dynamic and bidirectional gut microbiota-adaptive immunity interaction network. This reciprocal interaction persists throughout the progression from metabolic risk accumulation and insulin resistance to T2DM onset and diabetic complications, contributing to chronic low-grade inflammation, impaired insulin signaling, and pancreatic β-cell dysfunction. Unlike previous reviews that have primarily focused on gut microbiota dysbiosis, microbial metabolites, or innate immune regulation, this review highlights the bidirectional interactions between the gut microbiota and adaptive immunity as a central framework. We systematically summarize the underlying molecular mechanisms, dynamic disease evolution, and advances in microbiota-targeted therapeutic strategies. In recent years, dietary modulation, probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineered microbiome-based therapies have emerged as potential approaches targeting the microbiota-immune axis. Among these strategies, dietary interventions and certain microbiota-based supplements have obtained preliminary clinical support, whereas fecal microbiota transplantation, engineered bacteria, and phage-based therapies remain under active investigation. However, clinical translation of microbiome-targeted therapies is still challenged by interindividual microbiota heterogeneity, insufficient standardization of interventions, uncertain long-term safety, and limited causal evidence. Future efforts should integrate microbial composition, functional metabolic profiles, adaptive immune signatures, and host metabolic states to achieve precise patient stratification and facilitate the development of personalized microbiome-based interventions. This review provides a conceptual framework for understanding immunometabolic mechanisms in T2DM and offers new perspectives for precision therapeutic strategies.},
}

@article {pmid42757275,
year = {2026},
author = {Li, S and Wang, S and Ren, Y and Yan, J},
title = {Chemotherapy-Induced Remodeling of the Gut Microbiota-Inflammation Axis: Implications for the Course of Bipolar Disorder.},
journal = {Journal of multidisciplinary healthcare},
volume = {19},
number = {},
pages = {637471},
pmid = {42757275},
issn = {1178-2390},
abstract = {There is growing evidence that bipolar disorder, BD and cancer share several biological features, including immune dysregulation, gut microbiota alterations, and chronic inflammation. Chemotherapy remains a mainstay of cancer treatment but can substantially alter the gut microbial ecosystem, impair intestinal barrier integrity, and contribute to systemic inflammation. However, little research has been done on whether these changes brought on by chemotherapy affect how BD develops clinically. This review summarizes the mechanisms through which chemotherapy may modify the gut microbiota-inflammation axis, along with how these changes may impact BD via the microbiota-gut-brain axis. We discuss how intestinal barrier failure, microbial metabolite production, microbial composition, and inflammatory signaling pathways-such as the LPS-TLR4/NF-κB axis and NLRP3 inflammasome activation-are affected by chemotherapeutic drugs. We also investigate the role of gut-derived inflammatory responses in neuroinflammation, dysregulation of the hypothalamic-pituitary-adrenal,HPA axis, impaired neuroplasticity, neurotransmitter imbalance, and cognitive dysfunction, all of which may contribute to mood instability, treatment resistance, and neuroprogression in BD. We also evaluate developing microbiome-targeted therapies, such as probiotics, fecal microbiota transplantation, and dietary modification, and explore the possible therapeutic consequences of chemotherapy-induced microbiota remodeling for patients with concomitant cancer and BD. Taken together, the available evidence supports the possibility that chemotherapy-induced modification of the gut microbiota-inflammation axis may contribute to the clinical course of BD. This integrated mechanistic paradigm offers a potential platform for future translational research and the creation of tailored treatment approaches for patients with comorbid cancer and BD, despite the lack of direct clinical proof. This narrative review summarizes the current evidence linking chemotherapy-induced gut dysbiosis and inflammatory responses to the clinical course of bipolar disorder and discusses their potential implications for integrated therapeutic strategies.},
}

@article {pmid42758081,
year = {2026},
author = {Wang, J and Zhao, L and Zhao, S and Zhang, XH and Chen, X and Tian, HD and Zhang, X and Zhang, X and Liu, SL and Pang, D and Wu, H},
title = {Gut microbiota-mediated dietary lignans metabolism drives accumulation of N,N-dimethylsphingosine and sensitizes triple-negative breast cancer to paclitaxel.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo01787h},
pmid = {42758081},
issn = {2042-650X},
abstract = {For triple-negative breast cancer (TNBC), which lacks specific therapeutic targets, paclitaxel (PTX) chemotherapy remains the first-line clinical treatment. However, the widespread issue of treatment resistance severely limits its effectiveness, making it urgent to explore safer and more effective chemosensitization strategies. Dietary lignans (DL), bioactive compounds abundant in plants, require transformation by the gut microbiota to exert many of their effects and have shown potential antitumor activity. However, their impact on paclitaxel chemotherapy remains insufficiently understood. In this study, we show that DL enhance PTX efficacy in TNBC while attenuating PTX-induced gut microbial dysbiosis. Using antibiotic-induced microbiota depletion and fecal microbiota transplantation, we establish that the gut microbiota is essential for DL-mediated sensitization to PTX. Metabolomic profiling reveals that DL treatment markedly elevates the levels of the metabolite N,N-dimethylsphingosine (DMS). Importantly, DMS suppresses breast cancer cell proliferation and enhances PTX sensitivity even in the absence of gut microbiota, identifying DMS as a key functional metabolite of DL. Mechanistically, DMS downregulates PDGFRA and thereby modulates the PI3K-AKT signaling pathway. Together, these results indicate that DL potentiate PTX efficacy in TNBC, at least in part, through microbiota-dependent accumulation of DMS, offering a rationale for microbiota-informed strategies to optimize chemotherapy in TNBC.},
}

@article {pmid42759821,
year = {2026},
author = {Ma, L and Guo, Z and Li, Y and Wang, C and Yang, C and Wang, X and Li, T and Wang, Y and Li, Y and Bai, L and Li, R and Lv, M and Li, W and Yang, H and Li, J and Cai, Z and Yan, Z and Chang, R and Xie, S and Zhao, B and Yang, J and Wang, T and Dang, L and Lan, J and Liu, Z and Han, T and Xia, W and Wang, L and Ma, L and Li, H and Wang, Y},
title = {Faecalibacterium prausnitzii and its metabolite butyrate ameliorate psychological stress-induced obesity.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {107020},
doi = {10.1016/j.bbi.2026.107020},
pmid = {42759821},
issn = {1090-2139},
abstract = {OBJECTIVE: Although evidence indicates that modulating gut microbiota may mitigate psychological stress-induced obesity, the specific gut microbes and their mechanistic pathways remain unclear.

DESIGN: This study first examined the relationships between gut microbes, particularly Faecalibacterium prausnitzii (F.prausnitzii), psychological stress, and indicators of adiposity in adolescents, utilizing both cross-sectional (n = 124) and prospective cohort (n = 51) data. Second, fecal microbiota transplantation (FMT) was performed to investigate whether psychological stress induces obesity through alterations in gut microbiota. Third, using a chronic corticosterone administration mouse model to simulate psychological stress-induced obesity, we evaluated the therapeutic potential of F.prausnitzii and its primary metabolite butyrate in reversing corticosterone-induced obesity. The underlying mechanisms were further elucidated in vitro using mouse 3 T3-L1 adipocytes.

RESULTS: Cross-sectional data indicated inverse associations between the abundance of Faecalibacterium and both psychological stress and indicators of adiposity. Additionally, prospective cohort data demonstrated that baseline psychological stress inversely predicted follow-up abundance of F. prausnitzii. The abundance of F. prausnitzii was also inversely correlated with adiposity indicators. FMT from corticosterone-induced obese mice to antibiotic-treated recipients successfully recapitulated the obese phenotype. Supplementation with either F. prausnitzii or butyrate in corticosterone-induced obese mice significantly alleviated body fat accumulation, subcutaneous white adipose tissue (sWAT) weight gain, and lean mass reduction. Mechanistically, transcriptome and RT-qPCR analyses revealed that F. prausnitzii exerts its anti-obesity effects by upregulating the expression of genes related to fatty acid metabolism in sWAT. An in vitro model further confirmed that fatty acid metabolism contributes to butyrate-mediated protection against chronic stress-induced obesity.

CONCLUSION: These findings suggest that F.prausnitzii and butyrate may prevent obesity related to psychological stress through mechanisms involving fatty acid metabolism.},
}

@article {pmid42750261,
year = {2026},
author = {Franklin, S and Sahasrabhojane, P and Ivanov, I and Hayase, T and Hayase, E and Chang, CC and Senapati, J and Desikan, SP and Kadia, T and Lorenzi, P and Jenq, RR and Shelburne, S and Galloway-Peña, J},
title = {Inclusion of Multi-Omic Biomarkers Improves Prediction Accuracy of Response, Relapse, and Overall Survival in Acute Myeloid Leukemia Patients Receiving High-Intensity Induction Chemotherapy.},
journal = {Cancer medicine},
volume = {15},
number = {9},
pages = {e72281},
doi = {10.1002/cam4.72281},
pmid = {42750261},
issn = {2045-7634},
support = {K01AI143881//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Leukemia, Myeloid, Acute/drug therapy/mortality/genetics/microbiology ; Multiomics ; Female ; *Biomarkers, Tumor ; *Induction Chemotherapy/methods ; Male ; Neoplasm Recurrence, Local ; Middle Aged ; Prognosis ; Machine Learning ; Feces/microbiology ; Predictive Learning Models ; Adult ; Boosting Machine Learning Algorithms ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Recurrence ; Aged ; Risk Assessment ; },
abstract = {BACKGROUND: Despite advancements in genetic markers for acute myeloid leukemia (AML) risk stratification, outcome prediction remains challenging due to disease heterogeneity and dynamic genetic changes, highlighting the need for reliable biomarkers to improve AML treatment strategies and patient outcomes. To refine outcome predictions, we investigated the use of microbial-derived biomarkers to predict composite complete remission (CRc), relapse, and survival for patients on high- and low-intensity regimens, and to integrate those variables into the widely clinically utilized European Leukemia Network (ELN-2022) genetic risk classification model for high-intensity-treated patients.

METHODS: We first developed machine learning models that integrate baseline fecal metabolomics, 16S rRNA-based stool microbiome features, and clinical metadata (sex, antibiotic administration, AML somatic mutations, and cytogenetics) from two cohorts of AML patients (n = 83) undergoing remission induction chemotherapy. Univariate tests and sparse canonical correlation analysis were employed for variable selection and to explore fecal metabolite-microbe relationships. A robust machine learning approach using XGBoost was employed, with 100 stratified data splits (80% training, 20% testing) and coarse-to-fine hyperparameter optimization. Variable importance was aggregated across all models to select key predictors.

RESULTS: For high-intensity-treated patients, XGBoost models achieved aggregated AUROC scores of 0.719, 0.729, and 0.65 for CRc, relapse, and overall survival, respectively. For low-intensity-treated patients, these models achieved aggregate AUROC scores of 0.945, 0.724, and 0.768 for these same outcomes, respectively. Integrating the biomarkers identified in the high-intensity machine-learning models with the current ELN-2022 AML risk stratification system effectively stratified patients into risk categories, which obtained higher concordance indices and likelihood ratios, demonstrating improved prognostic accuracy for each outcome compared to ELN-2022 alone.

CONCLUSIONS: The inclusion of microbial-derived biomarkers serves as a robust prognostic tool to improve outcome prediction in AML patients, highlighting the potential of its integration into AML risk assessment and paving the way for personalized treatment strategies and improved patient outcomes.},
}

Humans
*Leukemia, Myeloid, Acute/drug therapy/mortality/genetics/microbiology
Multiomics
Female
*Biomarkers, Tumor
*Induction Chemotherapy/methods
Male
Neoplasm Recurrence, Local
Middle Aged
Prognosis
Machine Learning
Feces/microbiology
Predictive Learning Models
Adult
Boosting Machine Learning Algorithms
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Recurrence
Aged
Risk Assessment

@article {pmid42750798,
year = {2026},
author = {Bhandari, P and Sideeg, A and Elfeki, M and Xie, C and Singal, AK},
title = {Therapeutic modulation of the gut-brain axis in alcohol use disorder: A systematic review.},
journal = {Metabolism open},
volume = {32},
number = {},
pages = {100495},
pmid = {42750798},
issn = {2589-9368},
abstract = {BACKGROUND: Alcohol Use Disorder (AUD) involves gut-brain axis dysfunction. Modulating microbiota offers a promising therapeutic strategy.

METHODS: Clinical trials on fecal microbiota transplant (FMT), prebiotics (inulin), probiotics, and neurohormonal agents like glucagon-like peptide-1 (GLP-1) and ghrelin receptor antagonists) were identified through PubMed, Google Scholar, Scopus, and ClinicalTrials.gov (until 07/31/2026). Of the eleven included studies, five identified gut dysbiosis as a common feature in individuals with AUD.

RESULTS: Gut dysbiosis-directed interventions were associated with benefits on behavioral (alcohol craving, consumption, relapse), psychological (anxiety, sociability), and physiological (MELD score, AST/ALT ratio, systemic inflammation) outcomes. However, the magnitude and consistency of these effects varied among studies. Three studies specifically involved AUD patients with alcohol-associated liver disease (ALD), while the others focused on AUD. In another study, Ghrelin, which was investigated as a neurohormonal target, emerged as a potential anti-inflammatory agent. However, ghrelin receptor antagonism in the presence of alcohol did not alter systemic inflammation. Of five trials using GLP-1 receptor agonists, three showed a reduction in alcohol use, but the other two, although directionally consistent, did not reach statistically significant effects. The current evidence supports the gut-brain axis as a dual therapeutic target, offering potential benefits for both AUD and ALD. Microbial therapies (FMT, probiotics, prebiotics) show some benefits in AUD, albeit studies are small. Hormonal targets such as ghrelin and GLP-1 receptors are mechanistically relevant. Data on ghrelin are limited. Data on GLP-1 receptor agonists are directionally consistent but not statistically robust. Large-scale, controlled trials are needed to validate and optimize the integration of this approach into AUD treatment strategies.},
}

@article {pmid42750861,
year = {2026},
author = {Chai, Y and Lan, J and Li, K and Mei, X and Chen, Y and Zhou, N and Liu, X and Gong, W and Lei, H},
title = {Gut microbiota dysbiosis and the gut-lung axis in COPD: mechanisms, clinical relevance, and microbiota-targeted interventions.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1915007},
pmid = {42750861},
issn = {2296-634X},
abstract = {Chronic obstructive pulmonary disease (COPD), which is characterised by persistent inflammation and airflow limitation, has increasingly been linked to the gut-lung axis. Patients with COPD commonly exhibit reduced diversity of gut microbiota, decreased levels of bacteria that produce short-chain fatty acids (SCFAs), increased levels of opportunistic pathogens, and compromised intestinal barrier function. These alterations are driven by factors such as smoking, hypoxia, oxidative stress, medication use and ageing, and promote bacterial translocation and systemic inflammation, thereby exacerbating lung injury. Gut microbiota metabolites, including SCFAs, bile acids, tryptophan metabolites and trimetlylamine N-oxide (TMAO), further modulate immune responses and metabolic pathways, thereby influencing disease progression. Intervention strategies targeting the microbiome, including dietary fibre, probiotics, prebiotics, faecal microbiota transplantation (FMT) and phage therapy, have demonstrated potential therapeutic value, though clinical evidence remains limited. Elucidating the mechanisms linking gut dysbiosis and COPD will provide novel targets for precision interventions and disease management.},
}

@article {pmid42751519,
year = {2026},
author = {Yao, WC and Cui, JQ and He, R and Tian, HL and Chen, QY},
title = {[Research progress on the mechanisms and clinical interventions of gut microbiota in radiation-induced intestinal injury].},
journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery},
volume = {29},
number = {9},
pages = {1102-1109},
doi = {10.3760/cma.j.cn441530-20260720-00292},
pmid = {42751519},
issn = {1671-0274},
support = {2022YFA1304100//National Key Research and Development Program of China/ ; 82470701//National Natural Science Foundation of China/ ; 202240177//General Project of Shanghai Municipal Health Commission/ ; },
mesh = {Humans ; *Radiation Injuries/microbiology/therapy ; *Gastrointestinal Microbiome ; Probiotics ; Fecal Microbiota Transplantation ; *Intestines/radiation effects ; Animals ; },
abstract = {Radiotherapy is a critical treatment modality for abdominal and pelvic malignancies; however, it is associated with a high incidence of radiation-induced intestinal injury, which severely limits therapeutic efficacy and impairs patients' quality of life. In recent years, the bidirectional regulatory role of the gut microbiota in the development and progression of radiation-induced intestinal injury has garnered significant attention. Radiotherapy can induce a reduction in gut microbial diversity, disrupt the metabolism of short-chain fatty acids and tryptophan, and promote the expansion of opportunistic pathogens. Conversely, specific probiotics and their metabolites can alleviate intestinal injury through multiple targets. Based on these findings, gut microbiota-based interventions-such as probiotics and fecal microbiota transplantation-have demonstrated clear radioprotective and tissue-repairing effects. Perioperative modulation of the gut microbiota can also accelerate postoperative recovery of gastrointestinal function and improve nutritional status. Nonetheless, individual variability, standardization of donor screening, and long-term safety remain major challenges. Future efforts should leverage multi-omics and artificial intelligence technologies to advance precision intervention strategies tailored to individual microbiota profiles.},
}

Humans
*Radiation Injuries/microbiology/therapy
*Gastrointestinal Microbiome
Probiotics
Fecal Microbiota Transplantation
*Intestines/radiation effects
Animals

@article {pmid42752278,
year = {2026},
author = {Xia, J and Pan, D and Wu, T and Feng, Z and Tian, Y and He, Z and Zhang, Z and Shao, Y and Yu, J and Yan, W and Wang, J and Yin, S and Jin, X and Chen, Y and Wang, Y and Sun, G},
title = {Phytosterol-induced modulation of gut microbial bile salt hydrolases ameliorates hyperlipidemia via taurohyodeoxycholic acid-mediated FXR antagonism.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2731687},
doi = {10.1080/19490976.2026.2731687},
pmid = {42752278},
issn = {1949-0984},
mesh = {Animals ; Receptor, Farnesoid X-Activated ; Humans ; *Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/metabolism/genetics ; *Phytosterols/administration & dosage/metabolism/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Amidohydrolases/metabolism/genetics ; *Hyperlipidemias/metabolism/drug therapy/microbiology ; Rats ; Bile Acids and Salts/metabolism ; Male ; Liver/metabolism ; Rats, Sprague-Dawley ; Bacteria/classification/genetics/enzymology/isolation & purification/metabolism ; Signal Transduction/drug effects ; Ileum/metabolism ; Cholesterol 7-alpha-Hydroxylase/metabolism ; },
abstract = {Dyslipidemia remains a major cardiovascular risk factor. Although dietary phytosterols have established lipid-lowering effects, their interactions with the gut-liver metabolic axis remain incompletely understood. Here, we integrated human observational and intervention studies with mechanistic experiments in hyperlipidemic rats, fecal microbiota transplantation (FMT), and in vitro cellular models to investigate how phytosterols influence lipid homeostasis through gut microbiota-bile acid signaling. Human analyses identified associations between phytosterol exposure, lipid phenotypes, gut microbial features, and circulating bile acid profiles. In rats, phytosterol treatment altered gut microbial composition and the relative abundance of putative bile salt hydrolase (BSH)-producing taxa, accompanied by reduced ileal luminal BSH activity. These changes coincided with bile acid remodeling, including increased concentrations of taurohyodeoxycholic acid (THDCA) in liver tissue and ileal contents. In vitro cellular assays indicated that THDCA antagonized intestinal farnesoid X receptor (FXR) signaling. Consistent with this, phytosterol treatment in vivo attenuated ileal FXR-fibroblast growth factor 15 (FGF15) signaling and decreased hepatic CYP7A1 while increasing CYP7B1 protein expression, a pattern consistent with a shift from the classical toward the alternative bile acid synthesis pathway. Complementary FMT experiments further supported a contributory role of the gut microbiota in the lipid-modulating effects of phytosterols. Collectively, these findings suggest that dietary phytosterols may ameliorate dyslipidemia partly through modulation of the gut microbiota-bile acid-FXR axis, with microbiota-associated BSH-THDCA-FXR signaling representing one plausible contributing pathway. This study provides convergent preclinical mechanistic and exploratory human evidence for a diet-microbe-host pathway relevant to dyslipidemia.},
}

Animals
Receptor, Farnesoid X-Activated
Humans
*Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/metabolism/genetics
*Phytosterols/administration & dosage/metabolism/pharmacology
*Gastrointestinal Microbiome/drug effects
*Amidohydrolases/metabolism/genetics
*Hyperlipidemias/metabolism/drug therapy/microbiology
Rats
Bile Acids and Salts/metabolism
Male
Liver/metabolism
Rats, Sprague-Dawley
Bacteria/classification/genetics/enzymology/isolation & purification/metabolism
Signal Transduction/drug effects
Ileum/metabolism
Cholesterol 7-alpha-Hydroxylase/metabolism

@article {pmid42753368,
year = {2026},
author = {Zhou, H and Chen, M and Wang, X and Pan, Y and Liu, X and An, J and Liu, Z and Ma, B and Peng, S},
title = {Probiotics alleviate heat stress-induced uterine inflammation, reproductive hormone disruption and fetal growth restriction in mice.},
journal = {Theriogenology},
volume = {267},
number = {},
pages = {118192},
doi = {10.1016/j.theriogenology.2026.118192},
pmid = {42753368},
issn = {1879-3231},
abstract = {With rising global temperatures, the detrimental effects of heat stress on the reproductive performance of female animals have received increasing attention. In this study, we investigated the effects of heat stress on reproductive function in female mice and explored the therapeutic potential of probiotics in alleviating uterine damage through repair of the intestinal barrier. Seven-week-old female ICR mice were used to establish a systemic heat stress model. Mice in the treatment groups received Enterococcus faecium or Clostridium butyricum during heat stress. The results showed that heat stress induced systemic inflammation, oxidative stress, and elevated endotoxin (LPS) levels, leading to downregulation of tight junction proteins (ZO-1, occludin, and claudin-1) in the colon and uterine tissues. Systemic inflammation increased the levels of the pro-inflammatory cytokines IL-1β and IL-2 while decreasing the levels of the anti-inflammatory cytokines IL-4 and IL-10 in uterine tissue, resulting in uterine inflammatory damage and reproductive hormone dysregulation, thereby exacerbating placental injury and increasing the risk of fetal growth restriction. Treatment with E. faecium or C. butyricum repaired the intestinal barrier and inhibited the TLR4-MyD88 signaling pathway, thereby protecting the uterus from heat stress-induced injury and effectively alleviating uterine inflammation and fetal growth restriction. The 16S rRNA sequencing results demonstrate the regulatory effects of Enterococcus faecium and Clostridium butyricum on intestinal microbiota. Fecal microbiota transplantation (FMT) experiments further demonstrated that oxidative stress and uterine inflammatory damage in heat-stressed mice were alleviated following transplantation of intestinal microbiota from mice treated with E. faecium or C. butyricum. These findings suggest that E. faecium and C. butyricum have potential applications in reducing heat stress-induced reproductive damage in female animals.},
}

@article {pmid42753987,
year = {2026},
author = {Benech, N and Guarino-Vignon, P and McLellan, P and Campidelli, C and Sergeant, M and Joubert, F and Truong, S and Barbier, P and Sandoz, E and Ruffié, P and Sedda, D and Delmeule, A and Pradat, P and Landman, C and Bourrier, A and Marchand, L and Alric, L and Scanzi, J and Cassir, N and Dureault, A and Piet, E and Gallet, S and Botelho-Nevers, E and Roussel-Gaillard, T and Cuerq, C and Ader, F and Guillet, M and Rolhion, N and Grill, JP and Lamaziere, A and Chatel, JM and Pechine, S and Langella, P and Sokol, H},
title = {Faecalibacterium prausnitzii EXL01 Strain for the prevention of multiple-recurrent Clostridioides difficile Infection.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.09.002},
pmid = {42753987},
issn = {1528-0012},
abstract = {BACKGROUND AND AIMS: Recurrent Clostridioides difficile infection (rCDI) results from persistent microbiome dysfunction and impaired colonization resistance. Although fecal microbiota transplantation (FMT) is effective, defined and scalable alternatives are needed. We evaluated whether a single commensal strain could restore key microbiome functions and prevent recurrence.

METHODS: We assessed Faecalibacterium prausnitzii EXL01 in a murine CDI model and a multicenter, open-label single-arm phase I trial including adults with ≥3 CDI episodes. Following vancomycin preconditioning, patients received oral EXL01 for 8 weeks with 8-week follow-up. Primary endpoint was safety. Secondary endpoints included recurrence at week 8. Longitudinal stool samples underwent shotgun metagenomics and metabolomics. Outcomes were benchmarked against matched FMT cohorts. Additional in vitro and murine studies of EXL01 were performed.

RESULTS: In mice, EXL01 reduced C. difficile burden and intestinal inflammation in an antibiotic-disrupted murine model. Six patients were treated; no treatment-related serious adverse events occurred. Five of six patients (83.3%) remained recurrence-free at week 8, comparable to matched FMT cohorts. EXL01 was detectable in stool up to 8 weeks post-treatment. Multi-omics analyses showed that EXL01 engraftment was correlated with restoration of bile acid metabolism, including reduced primary bile acids and increased secondary bile acids, and increased short-chain fatty acid production, particularly butyrate, despite limited taxonomic recovery. EXL01 selectively deconjugated bile acids in vitro.

CONCLUSIONS: A single, well-characterized bacterial strain was associated with restoration of key microbiome functions and low recurrence rates in high-risk rCDI. These findings support precision microbiome therapeutics targeting ecosystem function rather than taxonomic complexity. Controlled trials are ongoing. (clinicaltrials.gov; NCT06306014).},
}

@article {pmid42744991,
year = {2026},
author = {Singh, K and Julka, JM},
title = {Microbial diversity: the essential foundation for life on our planet.},
journal = {Biologia futura},
volume = {},
number = {},
pages = {},
pmid = {42744991},
issn = {2676-8607},
abstract = {The biological basis of life on Earth is microbial diversity that ensures human health, agricultural productivity, ecological balance, and ecosystem functioning. Microorganisms enable ecosystem restoration through bioremediation, maintain soil fertility, support plant growth, manage vital biogeochemical cycles, and contribute to climate resilience. Precision probiotics, postbiotics, faecal microbiota transplantation, and personalized microbiome medicine are the examples of emerging microbiome-based therapies that offer promising therapeutic opportunities. In humans, the gut microbial community is essential for immune regulation, metabolism, and disease prevention. In terrestrial ecological systems, interactions between plants, fungi, bacteria, and other soil microorganisms improve carbon sequestration, nutrient cycling, stress resilience, and sustainable agricultural productivity in the given effects of climate change. Emerging uses in agriculture, environmental restoration, and medicine are made possible by advancements in multi-omic techniques, synthetic microbial genomes, microbiome engineering, and artificial intelligence. Considering these developments, issues with ecological complexity, long-term validation, standardization, and field scale application still exist. Therefore, preserving microbial diversity is important for conserving ecological resilience and strengthening the One Health framework, which highlights the mutual dependance of health of animal, human, plant, and environment. This review summarizes what has been discovered about ecological and biomedical relevance of microbiome, identifies important research gaps, highlighting emerging technologies, and evaluates potential future directions for using microbiome to support planetary sustainability.},
}

@article {pmid42745024,
year = {2026},
author = {Faggiani, I and Tuttle, C and Danese, S and Peyrin-Biroulet, L and Jairath, V and Sedano, R and Dotan, I and Panaccione, R and Ma, C},
title = {Antibiotic-Refractory Chronic Pouchitis After Ileal Pouch-Anal Anastomosis: Current and Emerging Therapeutic Strategies.},
journal = {Drugs},
volume = {},
number = {},
pages = {},
pmid = {42745024},
issn = {1179-1950},
abstract = {Chronic inflammatory pouch disorders may affect up to 20% of patients within 5 years after ileal pouch-anal anastomosis and remains a major therapeutic challenge. Within this spectrum, chronic antibiotic-refractory pouchitis is associated with impaired quality of life, long-term pouch-related complications, and potential risk for pouch failure and excision. Current recommendations support the use of probiotics for primary and secondary prevention in selected patients. Increasingly, targeted advanced therapies, including biologics and small molecules approved for the treatment of ulcerative colitis and Crohn's disease, are being used to reduce antibiotic dependence and maintain disease control in patients with pouch inflammation. Vedolizumab is the only advanced therapy approved in Europe for chronic pouchitis, whereas evidence for tumor necrosis factor (TNF) antagonists, ustekinumab, and newer agents, such as interleukin (IL)-23p19 antagonists and Janus kinase (JAK) inhibitors is largely based on observational data from clinical practice and real-world experience. Fecal microbiota transplantation is biologically attractive but remains investigational, with early studies showing inconsistent efficacy. Dietary patterns may modify pouch inflammation; however, most evidence is observational. Overall, current management strategies for chronic pouchitis are limited by incomplete understanding of disease pathogenesis, and by persistent methodological gaps, including poorly standardized treatment outcomes and the lack of validated treat-to-target strategies for this population. Well designed prospective and controlled studies are needed to define appropriate antibiotic-sparing strategies, optimal treatment positioning, and long-term durability of response.},
}

@article {pmid42745194,
year = {2026},
author = {Han, YL and Shang, DF and Tang, J and Yu, DD and Zhang, LY and Zhou, J and Wang, QB},
title = {Postelectroacupuncture Fecal Microbiota Transplantation (post-EA FMT) Regulates Gastrointestinal Hormones in Functional Dyspepsia Rats Is Associated With Modulation of the Intestinal Microbiota-Bile Acid Metabolic Pathway.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70744},
pmid = {42745194},
issn = {1440-1746},
support = {2024M750840//China Postdoctoral Science Foundation/ ; 2024ZXZX1169//2024 National Center for Traditional Chinese Medicine Inheritance and Innovation of Henan Health Commission Jointly Constructed Research Project/ ; SBGJ202403039//Medical Science and Technology Research Plan Project of Henan Province in 2024 (Provincial and Ministerial Co-construction Youth Project)/ ; 252300421388//General Project of Natural Science Foundation of Henan Province in 2025/ ; 2024YLZDJH072//Zhengzhou Medical and Health Science and Technology Innovation Guidance Plan Project/ ; 25A360025//Key Scientific Research Projects of Henan Universities in 2025/ ; CACMS-KY-2025005//Scientific Research Project of China Association of Chinese Medicine (Moxibustion Direction)/ ; 252300423792//Natural Science Foundation of Henan Province Youth Project in 2025/ ; },
abstract = {BACKGROUND: Electroacupuncture (EA) reshapes intestinal flora; whether post-EA fecal microbiota transplantation (post-EA FMT) regulates gastrointestinal hormones via the gut microbiota-bile acid (BA) pathway remains unclear.

METHODS: Sham EA (SEA) served as control. Gastrointestinal hormones/motility were assessed post-EA. Fecal microbiota from EA/SEA-treated rats were transplanted into pseudo-germ-free (PGF) rats. Gut microbiota and BA profiles were analyzed.

RESULTS: EA downregulated Ghrelin, PYY, GLP-1, upregulated CCK, and enhanced motility in FD rats. Post-EA FMT increased Firmicutes/Bacteroidetes (phylum); upregulated Lactobacillus, Prevotella, [Prevotella] (genus); decreased Blautia, Proteobacteria, Bacteroides; reduced multiple BAs (including TUDCA/TCDCA). TUDCA/TCDCA showed strong positive correlation.

CONCLUSIONS: The gut microbiota-BA pathway associates with post-EA FMT's beneficial regulation of gastrointestinal hormones. The gut microbiota-BA pathway is associated with post-EA FMT's beneficial regulation of gastrointestinal hormones. The gut microbiota-BA pathway is associated with post-EA FMT's beneficial regulation of gastrointestinal hormones. The Lactobacillus/TUDCA/TCDCA axis represents a candidate pathway that may contribute to this process (validation pending). Current findings indicate strong correlations, not causality.},
}

@article {pmid42745748,
year = {2026},
author = {Li, L and Pang, B and Wang, Z and Zhao, D and Wei, J and Wang, Q},
title = {The gut microbiota in Graves' disease: mechanistic insights and clinical implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1859658},
pmid = {42745748},
issn = {2235-2988},
mesh = {Humans ; *Graves Disease/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Dysbiosis ; Thyroid Gland/immunology ; Animals ; Probiotics ; Intestinal Barrier Function ; Autoimmunity ; },
abstract = {Graves' disease (GD) is an autoimmune form of hyperthyroidism characterized by loss of immune tolerance to the thyrotropin receptor and sustained thyroid hormone excess. Interest in the gut-thyroid axis has expanded rapidly, placing the gut microbiota within current models of GD pathophysiology. This review summarizes current evidence on gut microbial alterations in GD and discusses how these changes may intersect with thyroid autoimmunity. Available studies broadly support disruption of the intestinal microbial ecosystem in GD, although findings for individual taxa and diversity indices vary across cohorts. Proposed links between dysbiosis and disease include altered short-chain fatty acid and bile acid metabolism, impairment of epithelial barrier integrity with translocation of microbial products, shifts in Th17/Treg balance and related immune activation, molecular mimicry, and disturbed handling of micronutrients involved in thyroid hormone synthesis and metabolism. The oral-gut microbial connection has also emerged as a potentially relevant dimension of disease-associated dysbiosis. In parallel, microbiota-directed approaches, including probiotics, prebiotics, synbiotics, dietary modulation, and fecal microbiota transplantation, are being explored as possible adjuncts in GD management. Overall, gut microbial disturbance offers a biologically plausible link between environmental exposure, immune disequilibrium, and thyroid dysfunction in GD; however, stronger mechanistic, longitudinal, and interventional evidence is still required before these findings can be translated into precision clinical practice.},
}

Humans
*Graves Disease/microbiology/immunology/therapy
*Gastrointestinal Microbiome/immunology
Dysbiosis
Thyroid Gland/immunology
Animals
Probiotics
Intestinal Barrier Function
Autoimmunity

@article {pmid42746112,
year = {2026},
author = {Yang, C and Wang, D and Peng, W},
title = {Antibiotic-induced gut microbiota dysbiosis in the PICU: mechanisms, clinical outcomes, and management strategies - a narrative review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1910105},
pmid = {42746112},
issn = {1664-3224},
mesh = {Humans ; *Dysbiosis/chemically induced/therapy ; *Gastrointestinal Microbiome/drug effects ; *Intensive Care Units, Pediatric ; *Anti-Bacterial Agents/adverse effects ; Child ; Critical Illness ; },
abstract = {BACKGROUND: Antibiotic exposure is highly prevalent in the paediatric intensive care unit (PICU) and constitutes a major modifiable driver of gut microbiota dysbiosis. However, a systematic synthesis focusing specifically on the PICU population has been lacking. This narrative review addresses how antibiotic exposure drives gut dysbiosis in the PICU, its clinical consequences with emphasis on immunological pathways, and its management.

METHODS: This review was informed by a structured search of PubMed, Web of Science, Cochrane Library, and Chinese databases up to June 2026, including studies on antibiotic exposure, microbiota alterations, clinical outcomes, and management in critically ill children.

RESULTS: Antibiotic use in PICU children ranges from 58% to 94%, with broad-spectrum and combination therapy being common. Anti-anaerobic antibiotics-particularly piperacillin-tazobactam, meropenem, and clindamycin-cause the most pronounced disruption, as quantified in adult ICU cohorts. In PICU children, clinical consequences include a higher incidence of Clostridioides difficile infection and an increased risk of ventilator-associated pneumonia following carbapenem exposure. Antibiotic stewardship, encompassing de-escalation and avoidance of unnecessary anaerobic coverage, is the first-line microbiota protection strategy. Probiotics reduce ventilator-associated pneumonia and shorten PICU stay, but should not be used routinely in high-risk children. High-fibre enteral nutrition has shown feasibility, whereas postbiotics and faecal microbiota transplantation lack PICU-specific trial data.

CONCLUSIONS: Antibiotics are among the most significant modifiable drivers of gut dysbiosis in the PICU, with dose-dependent, class-specific effects. Antibiotic stewardship should be prioritised before any microbiota-directed intervention. Live probiotics require caution in high-risk populations, while non-live interventions are promising but need larger trials. Future research should employ longitudinal, multicentre studies with standardised reporting to elucidate host-microbe interactions in critically ill children.},
}

Humans
*Dysbiosis/chemically induced/therapy
*Gastrointestinal Microbiome/drug effects
*Intensive Care Units, Pediatric
*Anti-Bacterial Agents/adverse effects
Child
Critical Illness

@article {pmid42746344,
year = {2026},
author = {Chooklin, S and Chuklin, S},
title = {Beyond the Pancreas: The Gut Microbiota in Acute Pancreatitis - From Mechanisms to Therapeutic Perspectives.},
journal = {Clinical and experimental gastroenterology},
volume = {19},
number = {},
pages = {636881},
pmid = {42746344},
issn = {1178-7023},
abstract = {Acute pancreatitis is a heterogeneous inflammatory disease in which severe forms are frequently complicated by intestinal barrier failure, dysbiosis, bacterial translocation, infected necrosis, systemic inflammation, and organ dysfunction. Growing clinical and experimental evidence suggests that the gut microbiota may contribute to disease progression and represents a potential, although incompletely validated, therapeutic target. Importantly, acute pancreatitis-associated dysbiosis involves not only taxonomic shifts but also functional metabolic reprogramming, including reduced short-chain fatty acid production, altered microbial bile acid transformation, and disturbances in amino acid and lipid metabolism that may contribute to barrier dysfunction and systemic inflammation. This review synthesizes current evidence on microbiota-oriented strategies in acute pancreatitis, with emphasis on clinical applicability, mechanistic rationale, and safety. This narrative review integrates clinical guidelines, randomized trials, meta-analyses, cohort studies, metagenomic and metabolomic investigations, and experimental studies published mainly between 2002 and 2026. Among clinically supported strategies, early oral or enteral nutrition has the strongest evidence base and may help preserve mucosal integrity while limiting the ecological consequences of fasting and critical illness. Antimicrobial stewardship is also fundamental, because unnecessary antibiotic exposure may aggravate dysbiosis, impair colonization resistance, and promote resistant organisms. Selective digestive decontamination has historical clinical evidence but is not established for routine contemporary practice. Prebiotics, dietary fibers, postbiotics, and metabolite-oriented approaches are mechanistically promising, but clinical evidence remains limited. GV-971 is currently supported predominantly by preclinical experimental data. Probiotics and synbiotics require caution, particularly in predicted severe disease, because clinical benefits are inconsistent and important safety concerns have been reported. Fecal microbiota transplantation and washed microbiota transplantation remain investigational and should not be used routinely outside controlled protocols. At present, microbiota-oriented management should prioritize evidence-based supportive measures, particularly early oral or enteral nutrition and rational antimicrobial use. Future studies should combine clinical outcomes with standardized microbiome, metabolome, barrier, and resistance endpoints to determine whether direct microbiota modulation can become a safe and reproducible component of personalized therapy.},
}

@article {pmid42748486,
year = {2026},
author = {El Mheddeb, S and El Kettani, A and Bousfiha, AA and Ezzikouri, S and Ouladlahsen, A},
title = {Gut Microbiota Alterations in People Living With HIV: Dysbiosis, Immune Dysfunction and Therapeutic Perspectives.},
journal = {Reviews in medical virology},
volume = {36},
number = {5},
pages = {e70202},
doi = {10.1002/rmv.70202},
pmid = {42748486},
issn = {1099-1654},
mesh = {Humans ; *Dysbiosis/therapy ; *HIV Infections/complications/immunology/drug therapy/microbiology/therapy ; *Gastrointestinal Microbiome ; Probiotics ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; },
abstract = {The interaction between the human immunodeficiency virus (HIV) and the gut microbiota is attracting growing interest due to its potential role in the progression of infection and the development of comorbidities. This review provides a comprehensive and critically appraised synthesis of current evidence on the bidirectional relationship between HIV infection and gut microbiota disruption, structured around four central themes: the mechanistic basis of HIV-associated gut dysbiosis and mucosal immune dysfunction and its link to chronic inflammation; the effects of different antiretroviral therapy (ART) classes on the intestinal ecosystem; the emerging role of the microbiota-gut-brain axis in the pathogenesis of HIV-associated neurocognitive disorders (HAND); and the therapeutic potential of microbiota-targeted interventions, including probiotics, prebiotics, synbiotics, faecal microbiota transplantation (FMT), and dietary strategies in people living with HIV (PLWH). By synthesising the current mechanistic, clinical, and translational evidence, this review aims to delineate the critical knowledge gaps and define the research priorities that will drive the next generation of microbiota-informed strategies for improving long-term outcomes in PLWH. This summary highlights the importance of considering the gut microbiota as a key player in the overall management of HIV infection.},
}

Humans
*Dysbiosis/therapy
*HIV Infections/complications/immunology/drug therapy/microbiology/therapy
*Gastrointestinal Microbiome
Probiotics
Prebiotics/administration & dosage
Fecal Microbiota Transplantation

@article {pmid42748780,
year = {2026},
author = {Zhou, Z and Wang, S and Shao, K and Qu, M and Qian, X and Shao, G and Hu, J and Qiao, G and Huang, P},
title = {Sodium L-lactate alleviates DSS-induced colitis through gut microbiota remodeling and Akkermansia enrichment.},
journal = {International immunopharmacology},
volume = {189},
number = {},
pages = {117353},
doi = {10.1016/j.intimp.2026.117353},
pmid = {42748780},
issn = {1878-1705},
abstract = {L-lactate, a byproduct of glycolysis and hypoxia, accumulates in the gut during disease progression and may affect host responses and microbial metabolism. Here, we investigated the protective effect of sodium L-lactate on dextran sulfate sodium (DSS)-induced colitis in mice and the involvement of the gut microbiota. Oral sodium L-lactate significantly alleviated colitis, as shown by reduced body weight loss, fecal occult blood score, colon shortening, and histological injury. It also improved mucus secretion and intestinal barrier integrity, decreased serum IL-6, and increased IL-10. In specific pathogen-free mice, fecal lactate did not accumulate after sodium L-lactate administration, whereas marked accumulation was observed in antibiotic-treated mice, suggesting active microbial utilization of exogenous lactate in vivo. Antibiotic treatment weakened the protective effect of sodium L-lactate, while fecal microbiota transplantation from treated donors transferred protection to recipient mice. Gut microbiota analysis showed that sodium L-lactate reshaped the microbial community and consistently enriched Akkermansia. Oral administration of Akkermansia alone also ameliorated DSS-induced colitis. Together, these findings indicate that sodium L-lactate alleviates intestinal inflammation at least partly through gut microbiota modulation and highlight its potential as a functional strategy for gut health.},
}

@article {pmid42735570,
year = {2026},
author = {Zhang, Z and Li, Q and Wang, X and Wang, W and Zhang, F},
title = {Gut microbiota on sleep disorders throughout the lifespan.},
journal = {Microbiological research},
volume = {314},
number = {},
pages = {128724},
doi = {10.1016/j.micres.2026.128724},
pmid = {42735570},
issn = {1618-0623},
abstract = {The gut microbiota undergoes dynamic changes and plays a crucial role in human health and disease throughout life. Studies have revealed gut microbiota disruption in various microbiota‑gut‑brain axis‑related diseases at different life stages, transcending boundaries of traditional medical disciplines. This article reviews the literature on gut microbiota and sleep disorders throughout the human life cycle, encompassing obstructive sleep apnea, circadian rhythm sleep disorders, and insomnia. Gut microbiota dysbiosis has been implicated in sleep disorders comorbid with neurodevelopmental diseases in children, psychiatric and gastrointestinal diseases in adults, and neurodegenerative and cardiovascular diseases in the elderly. The mechanisms by which gut microbiota regulates sleep through the immune, neuronal, and endocrine pathways are explored. The therapeutic potential of microbiota‑based interventions for sleep disorders is investigated, with particular emphasis on clinical evidence and controversies regarding probiotics and fecal microbiota transplantation (FMT) at each critical life stage. The quality of clinical studies on FMT and probiotics for sleep disorders is assessed according to the latest guidelines of the preferred reporting items for microbiotherapy (PRIM). Of the 106 included studies, according to PRIM criteria, 40.0% (6/15) of FMT studies and 57.1% (52/91) of probiotic studies were classified as low‑quality research (defined as PRIM score < 14). This review provides future directions to facilitate the development of microbiota‑based research and therapeutic strategies for sleep disorders. A comprehensive understanding of the microbiota‑gut‑brain axis in sleep disorders across life stages holds transformative potential for the development of personalized therapies.},
}

@article {pmid42735684,
year = {2026},
author = {Wang, Y and Fan, C and Varatharajalu, K and Shatila, M and Cruz, CC and Sun, B and Lermi, NO and Hayase, T and Thomas, A and Szymonowicz, KA and Espiridion, BS and Duose, DY and Hayase, E and Tan, L and Liu, Y and Chang, CC and Arias, CA and Junek, K and DuPont, HL and Jiang, ZD and Kim, ST and Nurieva, R and Campbell, MT and Tannir, NM and Gao, J and Watowich, SS and Wang, XS and Chen, K and Lorenzi, PL and Haymaker, C and Parra, ER and Jenq, RR},
title = {First-line fecal microbiota transplantation for the management of immune checkpoint inhibitor-mediated diarrhea and colitis.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {103044},
doi = {10.1016/j.xcrm.2026.103044},
pmid = {42735684},
issn = {2666-3791},
abstract = {Immune checkpoint inhibitor (ICI) therapy commonly leads to adverse events such as ICI-mediated diarrhea and colitis (IMDC). Fecal microbiota transplantation (FMT) remains an option for patients with refractory colitis. We report a multi-omics profiling of patients receiving first-line FMT for IMDC. In our preliminary analysis, 10 (76.9%) patients achieve clinical response, with a median time to clinical improvement of 1.5 (1-10.5) days. Among responder patients with baseline and follow-up samples, 6 (75%) show an increase in alpha-diversity post-FMT. Pre-FMT samples show an increase in the abundance scores of plasma cells, neutrophils, macrophages (M1 and M2), memory activated and resting memory CD4[+] T cells, CD8[+] T cells, T follicular helper (Tfh) cells, and regulatory T cells (Tregs), all of which decrease post-FMT. In a small cohort of patients, we identify potential mechanisms for FMT response and demonstrate that first-line FMT in patients with IMDC (NCT04038619) can be effective.},
}

@article {pmid42735796,
year = {2026},
author = {Zhou, H and Wu, T and Fan, Z and Shi, Y and Wang, F and He, J and Da, Y and Lin, J and Zhang, J and Liang, J},
title = {Dietary iron imbalance disrupts enterohepatic homeostasis via the gut microbiota-bile acid-FXR signaling axis.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110508},
doi = {10.1016/j.jnutbio.2026.110508},
pmid = {42735796},
issn = {1873-4847},
abstract = {Dietary iron deficiency and excess may both disturb enterohepatic homeostasis, yet their differential effects on organ-specific iron distribution and the microbiota-bile acid-FXR signaling axis remain unclear. Here, we integrated multi-cohort cross-sectional analyses with mouse experiments, cell co-culture assays, organoid models, metabolomics, and fecal microbiota transplantation experiments. In population analyses, higher dietary iron, rather than serum iron, was associated with diarrhea, fatty liver, and liver fibrosis. In mice, iron deficiency induced widespread reductions in tissue iron content, whereas iron excess caused marked iron accumulation in the small intestine, colon, liver, spleen, kidney, and skeleton. Both iron-deficient and iron-excess diets impaired colonic barrier homeostasis, as indicated by reduced goblet cell abundance, lower Muc2 expression, disrupted tight junctions, and increased intestinal permeability. However, iron excess caused more profound gut microbiota dysbiosis, perturbed bile acid-related bacterial taxa, depleted primary bile acids, suppressed intestinal and hepatic farnesoid X receptor (FXR) signaling, and exacerbated hepatic steatosis, fibrosis, inflammation, and dysfunction. Importantly, chenodeoxycholic acid, cholic acid, and fecal microbiota transplantation partially restored bile acid-FXR signaling, improved barrier integrity, and alleviated liver injury under iron-excess conditions. Collectively, dietary iron imbalance disrupts enterohepatic homeostasis via the gut microbiota-bile acid-FXR signaling axis, with iron excess emerging as the predominant driver of bile acid dysregulation, impaired FXR signaling, and gut-liver injury. These findings identify dietary iron as an important determinant of enterohepatic homeostasis and support bile acid- and microbiota-targeted strategies for iron-related metabolic disorders.},
}

@article {pmid42736672,
year = {2026},
author = {Nadeem, MS and Rahman, S and Murtaza, BN and Al-Zharani, M and Afzal, M and Nasr, FA and Iftikhar, S and Chaieb, K and Alzarea, SI and Kazmi, I},
title = {The Microbiome-Gut-Brain Axis: Decoding the Molecular Dialogue for Next-Generation Neurotherapeutics.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X491341260902051725},
pmid = {42736672},
issn = {1875-6190},
abstract = {The human brain has traditionally been considered an isolated organ until the establishment of the microbiome-gut-brain axis (MGBA) overturned that concept. Based on recent reports, the present review provides confirmatory evidence that there is a complex communication in the MGBA that links the central nervous system with the resident microbial community of the gastrointestinal tract. A complex, highly sophisticated molecular dialogue involving immune and neuroinflammatory molecules, signaling via the vagus nerve and neural pathways, and key metabolic and endocrine routes facilitates cross-talk between the brain and the gut microbiome. Crucial microbial metabolites, such as bile acids and short-chain fatty acids (SCFAs), neurotransmitter release, and modulation of systemic inflammation are highlighted as primary mediators of gut-brain interactions. In recent times, research has shifted from establishing associations to elucidating precise mechanisms between brain physiology and the composition of the gut microbial community. Recent studies have emphasized linking specific bacterial taxa to neurological outcomes in Alzheimer's disease (AD), Parkinson's disease (PD), and autism spectrum disorder (ASD). Emerging therapeutic modalities such as engineered live biotherapeutics, next-generation psychobiotics, precision nutrition, and fecal microbiota transplantation are promising avenues for next-generation neurotherapeutics. However, the path to clinical translation is fraught with challenges, including methodological heterogeneity and reproducibility, establishing causality, and confounding host factors. This review concludes with a forward-looking roadmap that emphasizes multi-omics integration, standardization, human-relevant disease models, and personalized therapeutic strategies to decode the MGBA and exploit its full potential, which could revolutionize the treatment of brain disorders.},
}

@article {pmid42737447,
year = {2026},
author = {Ostafe, MR and Volovat, SR and Clement, A and Litcanu, CI and Tabarcea, SI and Volovat, CC and Panaite, DI and Augustin, IG and Volovat, C},
title = {Microbiome-Immune Interactions as Determinants of Checkpoint Inhibitor Efficacy in Hepatocellular Carcinoma.},
journal = {International journal of molecular sciences},
volume = {27},
number = {17},
pages = {},
pmid = {42737447},
issn = {1422-0067},
mesh = {Humans ; *Liver Neoplasms/immunology/drug therapy/microbiology ; *Carcinoma, Hepatocellular/immunology/drug therapy/microbiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/immunology/drug effects ; Dysbiosis/immunology ; Animals ; Immunotherapy/methods ; },
abstract = {Hepatocellular carcinoma (HCC) remains a major global health challenge and one of the leading causes of cancer-related mortality, with advanced disease continuing to be associated with limited therapeutic options and substantial heterogeneity in response to systemic treatment. Recent evidence has established the gut microbiota, through the gut-liver axis, as a critical determinant of immunotherapy efficacy, while also influencing antitumor immunity and liver carcinogenesis. Microbial dysbiosis may promote chronic inflammation, intestinal barrier disruption, bacterial translocation, and immune dysfunction, thereby contributing to hepatocarcinogenesis. Moreover, gut microbial composition and microbial-derived metabolites, including bile acids, short-chain fatty acids (SCFAs), and inosine, have been associated with modulation of antitumor immune responses and differential outcomes to immune checkpoint inhibitors (ICIs). Emerging clinical evidence in HCC has identified distinct gut microbial signatures associated with response to nivolumab, pembrolizumab, and atezolizumab-based regimens, including enrichment of Akkermansia muciniphila and SCFA-producing taxa such as Ruminococcaceae, Roseburia, and Prevotella in responders. However, these findings remain inconsistent across studies, with no reproducible microbial signature identified because of small cohort sizes, heterogeneous patient populations, geographic variation, cirrhosis-related confounding factors, and methodological differences in microbiome analysis. This review summarizes the current understanding of microbiome-immune interactions in HCC, examines mechanistic pathways linking the microbiota to immunotherapy response, critically evaluates available clinical evidence, and discusses current limitations and future therapeutic strategies, including fecal microbiota transplantation, probiotics, dietary modulation, and engineered bacterial platforms. Collectively, microbiome-based approaches may contribute to the development of personalized immunotherapeutic strategies in HCC, although larger standardized prospective studies are required before microbiome-derived biomarkers can be implemented in routine clinical practice.},
}

Humans
*Liver Neoplasms/immunology/drug therapy/microbiology
*Carcinoma, Hepatocellular/immunology/drug therapy/microbiology
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Gastrointestinal Microbiome/immunology/drug effects
Dysbiosis/immunology
Animals
Immunotherapy/methods

@article {pmid42738532,
year = {2026},
author = {Jin, J and Xu, C and Bao, W},
title = {Fecal Microbiota Transplantation in Dogs and Cats: Evidence for Gastrointestinal and Emerging Extra-Intestinal Applications.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {17},
pages = {},
pmid = {42738532},
issn = {2076-2615},
abstract = {Fecal microbiota transplantation (FMT) is an emerging microbiome-directed intervention for dogs and cats, but its clinical role remains incompletely defined. This structured narrative review integrates peer-reviewed clinical, mechanistic, methodological, and safety evidence on companion-animal FMT published between 2005 and 2026, with emphasis on efficacy, tolerability, mechanisms, product preparation, donor screening, and research priorities. In dogs, the most consistent clinical signal concerns chronic enteropathy (CE), where observational studies frequently report reduced disease activity scores after FMT, whereas small randomized trials have shown mixed results; however, causal inference remains limited by small sample sizes, heterogeneous diagnostic criteria and treatment protocols, and concurrent therapies. The strongest controlled canine signal comes from parvoviral enteritis, where adjunctive enema-based FMT accelerated diarrhea resolution and shortened hospitalization. Feline data support short-term tolerability and measurable microbiome activity, but clinical efficacy remains preliminary; notably, the first controlled feline chronic enteropathy (CE) trial showed no significant improvement in dysbiosis index or clinical activity scores compared with controls. Proposed mechanisms include donor microbial engraftment, metabolic restoration, immune modulation, and gut-brain and gut-skin axis signaling, although veterinary-specific validation remains limited. Standardized donor screening, batch-level quality control, dose-finding studies, long-term safety surveillance, and adequately powered sham-controlled trials are the main prerequisites for responsible clinical translation.},
}

@article {pmid42738574,
year = {2026},
author = {Sabetti, MC and Pilla, R and Fidanzio, F and Vecchiato, CG and Galiazzo, G and Tirolo, A and Ablondi, M and Scorza, S and Colosini, M and Suchodolski, JS and Corsini, A},
title = {Temporal Dynamics of Clinical Response Following Fecal Microbiota Transplantation in Dogs with Chronic Enteropathy.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {17},
pages = {},
pmid = {42738574},
issn = {2076-2615},
abstract = {Fecal microbiota transplantation (FMT) is a promising adjunctive treatment for dogs with chronic enteropathy (CE), but response is usually assessed at scheduled follow-up visits, potentially overlooking day-to-day fluctuations. This prospective observational study evaluated temporal response after a single FMT administered by retention enema using daily owner-completed Canine Inflammatory Bowel Disease Activity Index (CIBDAI) monitoring. Fourteen dogs with CE refractory or incompletely responsive to dietary management were enrolled. CIBDAI scores were assigned by a veterinarian at baseline and on days 7 and 30, while owners completed a daily clinical diary for 30 days. Changes over time were assessed using the Friedman test, longitudinal trends using a generalized additive mixed model, and agreement between owner and veterinarian-assigned scores using quadratic-weighted Cohen's kappa and Bland-Altman analysis. Clinician-assigned CIBDAI scores showed a significant overall effect of time (p < 0.01), but no pairwise comparison remained significant after correction. Daily monitoring showed a significant nonlinear pattern in the primary diary-only model, although no interval of significant change was identified. In the secondary baseline-inclusive model, the derivative was significantly negative between Days 2 and 5. In within-dog descriptive comparisons, dogs experienced a median of 3.5 days (range: 0-14) with daily CIBDAI scores at or above their individual T0 value. Weighted kappa was 0.680 (95% CI: 0.266-1.000) at T7 and 0.821 (95% CI: 0.690-0.952) at T30. Bland-Altman analysis identified no proportional bias at T7, whereas significant proportional bias was observed at T30, indicating greater divergence between owner and veterinarian-assigned scores at higher CIBDAI values. Daily owner-reported monitoring captured day-to-day fluctuations that would likely have been missed by conventional outpatient assessments performed only at predefined follow-up time points and may therefore support more individualized post-FMT follow-up in dogs with CE.},
}

@article {pmid42739016,
year = {2026},
author = {Deleu, S and Hoekx, S and Sabino, J},
title = {The Gut Microbiome in Pouchitis: A Narrative Review of Pathogenesis and Therapeutic Modulation.},
journal = {Nutrients},
volume = {18},
number = {17},
pages = {},
pmid = {42739016},
issn = {2072-6643},
support = {1255426N//Research Foundation - Flanders/ ; 1805926N//Research Foundation - Flanders/ ; },
mesh = {Humans ; *Pouchitis/microbiology/therapy/etiology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis ; Colitis, Ulcerative/surgery ; Proctocolectomy, Restorative/adverse effects ; Prebiotics/administration & dosage ; },
abstract = {Pouchitis is the most common long-term complication following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), with a cumulative prevalence of up to 50% within the first two years after IPAA surgery. Accumulating evidence implicates gut microbial dysbiosis in the pathogenesis of pouch inflammation, supported by characteristic microbial alterations and the clinical responsiveness of pouchitis to microbiota-directed therapies such as antibiotics and probiotics. This narrative review synthesizes evidence mainly published in the last decade on microbiota alterations in pouchitis, the mechanisms of microbiota-host interactions that may contribute to inflammation, and the clinical evidence linking the gut microbiota to disease development and progression. Therapeutic strategies for modulating the pouch microbiota, including probiotics, prebiotics, dietary interventions, antibiotics, and fecal microbiota transplantation, are critically evaluated. Finally, future directions in multi-omics profiling, precision microbiome medicine, and next-generation live biotherapeutics are discussed. Overall, current evidence supports antibiotics as the first-line treatment for pouchitis, although it does not restore microbial eubiosis. Among microbiota-targeted interventions, the eight-strain De Simone formulation has the strongest evidence for prevention, whereas faecal microbiota transplantation remains investigational and is not currently supported outside clinical trials. Further research integrating multi-omics and microbiome profiling is needed to better define disease mechanisms and enable personalized microbiome-based approaches to prevention and treatment.},
}

Humans
*Pouchitis/microbiology/therapy/etiology
*Gastrointestinal Microbiome/drug effects
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Anti-Bacterial Agents/therapeutic use
Dysbiosis
Colitis, Ulcerative/surgery
Proctocolectomy, Restorative/adverse effects
Prebiotics/administration & dosage

@article {pmid42739043,
year = {2026},
author = {Trofin, F and Buzila, ER and Iancu, IR and Tuchilus, CG and Temneanu, OR and Iancu, LS and Vlad, MA and Anton-Păduraru, DT and Armasu, I and Badescu, AC and Gisca, L and Dorneanu, OS},
title = {The Bile Acid-Diet-Microbiome Axis in Clostridioides difficile Infection.},
journal = {Nutrients},
volume = {18},
number = {17},
pages = {},
pmid = {42739043},
issn = {2072-6643},
mesh = {*Bile Acids and Salts/metabolism ; Humans ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Diet ; Animals ; Anti-Bacterial Agents/adverse effects ; Dysbiosis ; },
abstract = {Clostridioides difficile infection (CDI) remains a major cause of antibiotic-associated diarrhea, with recurrence largely driven by disruption of the gut microbiota and impaired colonization resistance. Bile acids have emerged as key mediators in this process, as primary conjugated bile acids promote C. difficile spore germination, whereas microbiota-derived secondary bile acids can inhibit germination, vegetative growth, and toxin activity. Diet further modulates CDI susceptibility by shaping microbial composition, short-chain fatty acid production, bile acid transformation, epithelial barrier integrity, and intestinal inflammation. Western-style diets, and low fiber intake, may favor dysbiosis and a bile acid profile permissive to CDI, while fiber-rich and Mediterranean-type dietary patterns may support beneficial anaerobes, microbial metabolites, and mucosal resilience. This narrative review summarizes current evidence on the bile acid-diet-microbiome axis in CDI pathogenesis, recurrence, and therapy. It also discusses standard treatment limitations, microbiome-based therapeutics, dietary interventions, and emerging bile acid-targeted strategies. Understanding this axis may support future precision approaches aimed not only at suppressing C. difficile, but also at restoring microbiota function and durable colonization resistance.},
}

*Bile Acids and Salts/metabolism
Humans
*Clostridioides difficile
*Clostridium Infections/microbiology/therapy
*Gastrointestinal Microbiome/physiology
*Diet
Animals
Anti-Bacterial Agents/adverse effects
Dysbiosis

@article {pmid42740641,
year = {2026},
author = {Hussain, Z and Gali, M and Patel, D and Kumar, AS and Kumar, AS and Ranganatha, A and Swathi, NL},
title = {Microbiome and atherosclerosis: hype or future therapeutic target?.},
journal = {Journal of basic and clinical physiology and pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42740641},
issn = {2191-0286},
abstract = {From 2010 to 2025, evidence increasingly identifies the gut microbiome, microbial dysbiosis, trimethylamine-N-oxide (TMAO), and short-chain fatty acids (SCFAs) as modulators of atherosclerosis and cardiovascular disease. We conducted a narrative review of literature retrieved from PubMed, Scopus, and the Clinical Trials Registry-India (CTRI), covering studies published between January 2010 and March 2025. A total of 103 primary studies (animal, n=15; human cohort, n=28; mechanistic, n=22; randomized controlled trials, n=38) and 10 ongoing clinical trials were reviewed. Germ-free and antibiotic-treated murine models support a role for TMA-producing microbial communities in plaque formation, whereas SCFA-producing communities attenuate inflammation and atherogenesis. In humans, elevated TMAO levels are associated with a 2-5-fold higher risk of major adverse cardiovascular events (MACE), although causal inference remains limited. Probiotics, synbiotics, dietary interventions, and fecal microbiota transplantation may improve TMAO, LDL cholesterol, and inflammatory markers, but definitive reductions in cardiovascular events have not been demonstrated. Overall, microbiome-targeted strategies remain promising but require large, diverse clinical trials to establish causality and clinical benefit.},
}

@article {pmid42741704,
year = {2026},
author = {Jiang, Y and Zeng, Q and Ma, L and He, Y and Zhu, S and Xiong, Y and Jing, Y and Zhang, Q and Qi, S and Hu, J and Li, Q and Yang, S},
title = {Gut microbiome dysbiosis is associated with aldosterone overproduction in idiopathic hyperaldosteronism.},
journal = {iScience},
volume = {29},
number = {9},
pages = {117426},
pmid = {42741704},
issn = {2589-0042},
abstract = {Idiopathic hyperaldosteronism (IHA) is a significant cause of secondary hypertension. Emerging evidence links the gut microbiota to endocrine and cardiovascular diseases. We integrated human genetics, multi-omics, and fecal microbiota transplantation (FMT) to investigate the association between IHA and gut microbiome. Two-sample Mendelian randomization identified seven bacterial taxa associated with IHA. Metagenomic analysis of 30 patients with IHA and 30 healthy control subjects revealed lower microbial diversity and depletion of protective genera identified by Mendelian randomization. Plasma metabolomics showed alterations in tryptophan metabolism and other metabolic pathways that overlapped with microbial functional changes. Tryptophan-derived metabolites correlated with the abundance of protective genera. FMT from patients with IHA increased serum aldosterone and elevated 5-hydroxy-L-tryptophan in germ-free mice. These findings support an association between gut microbiome dysbiosis, metabolic alterations, and aldosterone dysregulation, highlighting the gut microbiome as a potential target for the diagnosis and treatment of IHA.},
}

@article {pmid42741853,
year = {2026},
author = {de Araujo, A and Sree Kumar, H and Yang, T and Otmanowski, EB and Alviter Plata, A and Dirr, EW and Bearss, NR and Baekey, DM and Dreier, MR and de la Serna, I and Miller, DS and Donertas-Ayaz, B and Singh, A and Kalinoski, AL and Garrett, TJ and Short, B and Anderson, ML and Martyniuk, CJ and de Lartigue, G and Zubcevic, J},
title = {Intestinal Serotonergic Vagal Signaling as a Mediator of Microbiota-Induced Hypertension.},
journal = {Circulation},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCULATIONAHA.124.072363},
pmid = {42741853},
issn = {1524-4539},
abstract = {BACKGROUND: Hypertension is a pervasive global health challenge, impacting more than 1 billion individuals worldwide. Despite strides in therapeutic strategies, a significant proportion of patients remain resistant to the currently available therapies. Although conventional treatments predominantly focus on cardiac, renal, and cerebral targets, emerging research underscores the pivotal role of the gut and its microbiota. Yet, the precise mechanisms governing interactions between the gut microbiota and the host blood pressure remain unclear.

METHODS: We combined fecal microbiota transplantation between normotensive and hypertensive rats, an intersectional genetic strategy in a serotonin receptor 3a (5HT3a) receptor Cre rat line to activate, ablate, and restore serotonin-sensing colonic vagal neurons, in vivo calcium imaging and radiotelemetric blood pressure recordings, and measurements of intestinal serotonin (5-hydroxytryptamine [5-HT]) and 5HT3a receptor signaling in rats and in colonic biopsies from normotensive and hypertensive human subjects (N=5 per group; 36 to 75 years of age).

RESULTS: A marked decrease in both intestinal 5-HT and vagal 5HT3a receptor signaling was observed in hypertensive rats and humans, and in rats subjected to fecal microbiota transplantation from hypertensive rats. Leveraging the intersectional genetic strategy in a Cre rat line, we demonstrate that intestinal 5HT3a receptor vagal signaling is a crucial link between the gut microbiota and blood pressure homeostasis and that recovery of 5-HT signaling in colon innervating vagal neurons can alleviate hypertension.

CONCLUSIONS: Here, we describe a neural host-microbiota interaction that is mediated by intestinal serotonin (5-HT) signaling via the vagal 5HT3a, which is crucial for maintenance of blood pressure homeostasis. This finding enhances our comprehension of hypertensive pathophysiology and unveils a promising new therapeutic target for combating resistant hypertension associated with gut dysbiosis.},
}