@article {pmid43025422,
year = {2026},
author = {Jiang, S and Lin, X and Ni, L and Zhang, Y and Chen, H and Liu, C and Yuan, H and Kang, Z and Jiao, J and Han, T and Zhuo, M and Wu, X and Zhou, J and Sun, R and Hu, M and Deng, Z and Jiang, Y and Zhang, C and Xu, P and Li, P and Li, Q and Chen, YX and Xiao, XY and Fang, JY},
title = {Targeting F.nucleatum with metronidazole plus tislelizumab and fruquintinib in MSS colorectal cancer: A multicenter phase 2 study.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2026.10.012},
pmid = {43025422},
issn = {1878-3686},
abstract = {Fusobacterium nucleatum has been linked to chemoresistance and immune evasion in colorectal cancer (CRC), but therapeutic strategies targeting this bacterium remain limited. In this multicenter, single-arm, phase 2 trial (NCT06356597), 33 patients with Fusobacterium nucleatum-positive, microsatellite-stable metastatic CRC received the combination treatment of tislelizumab, fruquintinib, and the antimicrobial metronidazole. The primary endpoint was met, with a median progression-free survival of 6.0 months. The objective response rate and disease control rate were 19.4% and 83.9%, respectively. Grade 3 treatment-related adverse events occurred in 30.3% of patients, with no grade 4 or 5 events. Metagenomic analysis showed that metronidazole reduced Fusobacterium nucleatum abundance. Exploratory analyses associated clinical benefit with enrichment of Lactobacillus species and nonresponse with Enterococcus. Fecal microbiota transplantation from responders sensitized germ-free mice to the treatment, which enhanced cytotoxic CD8[+] T cell differentiation and reduced terminal exhaustion. These findings support further evaluation of this combination in Fusobacterium nucleatum-positive metastatic CRC.},
}

@article {pmid43025638,
year = {2026},
author = {Copes, J and Godeaux, E and Yan, S},
title = {Chronic ethanol feeding drives gut microbiome remodeling and influences cholestatic liver injury in mice.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.10.012},
pmid = {43025638},
issn = {1525-2191},
abstract = {Alcohol-associated liver disease (ALD) is a major cause of liver-related mortality worldwide and encompasses steatosis, cirrhosis, and alcohol-associated hepatitis (AH). AH is frequently accompanied by cholestasis, characterized by impaired bile flow and disrupted bile acid homeostasis. Although gut microbiome (GM) dysbiosis has been linked to ALD progression and cholestatic injury, its functional role in alcohol-associated cholestasis remains unclear. Mice were subjected to chronic ethanol-feeding (EF) or pair-feeding (PF) for 4 weeks. Fecal samples collected at 10 days and 4 weeks underwent shotgun metagenomic sequencing. To assess the functional impact of microbiome alterations, cecal contents from male mice after 4 weeks of EF or PF were used for fecal microbiota transplantation (FMT). Recipient mice received antibiotics during acclimatization, followed by 10 days of EF and FMT every other day. Forty-eight hours before sacrifice, mice were challenged with α-naphthylisothiocyanate (ANIT; 25 mg/kg) to induce cholestatic liver injury. Liver injury, cholestasis, and inflammation were evaluated biochemically and histologically. EF induced progressive GM remodeling, whereas PF did not. Unexpectedly, FMT from PF donors aggravated ANIT-promoted liver injury, cholestasis, and hepatic inflammation in EF recipients of both sexes. In contrast, FMT from EF donors did not significantly alter injury compared with non-FMT controls. These findings suggest that GM derived from PF and chronic EF mice differentially influence susceptibility to cholestatic liver injury in EF recipients.},
}

@article {pmid43026137,
year = {2026},
author = {Rich, S and Fawad, JA and Baldassano, RN and Zackular, JP and Pai, N},
title = {Microbial medicine in clinical pediatrics: evolving approaches to diagnosis and management.},
journal = {Current problems in pediatric and adolescent health care},
volume = {},
number = {},
pages = {102003},
doi = {10.1016/j.cppeds.2026.102003},
pmid = {43026137},
issn = {1538-3199},
abstract = {Our increasing understanding of the microbiome has revealed its critical role in immunity, metabolism, infectious disease susceptibility, and overall human health. Advances in the detection of microbial species using new sequencing technologies has led to the emergence of a new frontier in medicine. Integrating the microbiome with diagnostics and therapeutics has introduced the field of 'microbial medicine', representing a major translational advance in pediatric healthcare. The early-life microbiome is particularly important serving as a critical developmental window during which rapidly altering microbial communities can contribute to immune tolerance and confer disease risk. Factors that can shape the early-life microbial landscape include delivery mode, breastfeeding, diet, antibiotic exposure and geography. Disruptions in the microbiome have been linked to numerous pediatric diseases including necrotizing enterocolitis, inflammatory bowel disease, neonatal sepsis, allergic diseases, metabolic syndrome, neurodevelopmental disorders and psychiatric conditions. While early microbiome research has been largely correlational, growing mechanistic insights into host-microbe interactions have paved the way for the development of microbiome-targeted therapeutics. Promising approaches include prebiotics, probiotics, fecal microbiota transplantation, liver biotherapeutic products, genetically engineered microbes and microbiome-derived metabolites. Studies are however lacking in the pediatric population and therefore there is a growing need for a coordinated effort to increase access to microbiome-based therapeutics in children. Significant challenges include a lack of age-specific reference standards, understanding long-term safety, and standardizing available treatments. In this review we discuss the emergence of microbial medicine in pediatric care. We examine the current evidence evaluating the development of the microbiome, the factors that shape early-life microbial colonization and the use of microbial therapeutics in clinical practice. We highlight the challenges and opportunities associated with translating these discoveries into pediatric practice and suggest research priorities and infrastructure development required to establish microbial medicine as a mainstay in pediatric practice.},
}

@article {pmid43026582,
year = {2026},
author = {Zhai, F and Tao, L and Xia, Y and He, Q and Lin, H and Liu, D},
title = {Xiao Chai Hu Decoction ameliorates doxorubicin-induced cardiotoxicity through an Akkermansia muciniphila-associated gut-heart mechanism.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {43026582},
issn = {1749-8546},
support = {82560807//National Natural Science Foundation of China/ ; 20252BAC250152//Natural Science Foundation of Jiangxi Province/ ; 2022Z019//Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan/ ; },
abstract = {BACKGROUND: Doxorubicin (DOX) induces cardiotoxicity partly through ferroptosis. Xiao Chai Hu Decoction (XCHD) has anti-inflammatory and organ-protective activities, but its effects on DOX-induced cardiac injury and the gut-heart axis remain unclear.

PURPOSE: This study investigated whether XCHD attenuates DOX-induced cardiotoxicity through gut microbiota remodeling, with particular emphasis on the contribution of Akkermansia muciniphila and the downstream involvement of BMP10-associated ferroptosis.

METHODS: Male C57BL/6 mice received DOX (5 mg/kg/week for 4 weeks; cumulative dose, 20 mg/kg) and XCHD (5-20 g/kg/day). Cardiac function, myocardial injury, histopathology, iron accumulation, and ferroptosis-related indices were evaluated. Cardiac transcriptomics and fecal 16S rRNA sequencing were combined with antibiotic-mediated microbiota depletion, fecal microbiota transplantation (FMT), and A. muciniphila supplementation to assess microbiota involvement. H9c2 cells treated with XCHD-containing serum and subjected to BMP10 knockdown were used to examine the downstream role of BMP10.

RESULTS: XCHD improved cardiac function and reduced myocardial injury, fibrosis, iron accumulation, and ferroptosis-associated alterations. Transcriptomic analysis identified BMP10 as a candidate downstream factor suppressed by DOX and restored by XCHD. In H9c2 cells, XCHD-containing serum attenuated ferroptosis-associated changes, whereas BMP10 knockdown weakened these effects, supporting a functional contribution of BMP10 in vitro. XCHD also preserved intestinal barrier integrity, reshaped the gut microbiota, and enriched A. muciniphila. Microbiota depletion abolished the protective effects of XCHD, whereas FMT transferred the protective phenotype. A. muciniphila supplementation reproduced key cardiac and anti-ferroptotic effects, with live bacteria producing greater benefits than heat-inactivated bacteria; these changes were accompanied by restoration of myocardial BMP10 expression.

CONCLUSION: XCHD alleviates DOX-induced cardiotoxicity through an A. muciniphila-associated, microbiota-dependent gut-heart mechanism involving intestinal barrier preservation and attenuation of ferroptosis-associated injury. These findings support a "TCM formula-gut microbiota-host response-regulated cell death" framework for XCHD-mediated cardioprotection.},
}

@article {pmid43026748,
year = {2026},
author = {Yang, X and Ge, X and Gong, S and Zhu, T and Ni, C and Ma, R and Tao, Q},
title = {Fecal Microbiota Transplantation in Colorectal Cancer: From Immune Regulation to Immunotherapy.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026748},
issn = {2072-6694},
support = {2026-YRDFHI-141//Shanghai YRD Foundation for Innovation in Health Industry/ ; },
abstract = {The gut microbiome influences colorectal cancer (CRC) progression and responses to immune checkpoint inhibitors (ICIs), with immunotherapy resistance remaining a major challenge in microsatellite-stable/mismatch repair-proficient (MSS/pMMR) CRC. This review examines the mechanisms and translational potential of fecal microbiota transplantation (FMT) in CRC immunotherapy, focusing on the interplay among microbial functions, metabolic alterations, and immune microenvironment remodeling. Current evidence suggests that FMT may influence antitumor immunity beyond restoring microbial diversity by transferring functionally relevant microbial communities, metabolic profiles, and immunomodulatory signals. These changes may affect antigen presentation, inflammatory signaling, T-cell activity, and myeloid-cell states, thereby shaping the tumor immune microenvironment and potentially modulating responses to PD-1/PD-L1 blockade. However, the clinical efficacy of FMT in CRC, the determinants of successful microbial engraftment, and the mechanisms linking donor-derived microbial functions to therapeutic outcomes remain incompletely understood. Integrating defined microbial consortia, metabolite-based interventions, and multi-omics-guided patient stratification may help advance FMT toward mechanism-driven precision microbiome therapy and inform strategies to improve CRC immunotherapy outcomes.},
}

@article {pmid43027438,
year = {2026},
author = {Nie, C and Yuan, X and Liu, H and Ma, Q and Tian, B and Li, J and Zhang, M and Chen, Z and Li, J},
title = {Galacto-Oligosaccharides Preserve the Colonic Mucus Barrier Against Dietary Advanced Glycation End Products Through Modulation of Mucin Glycosylation and ERK Signaling.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43027438},
issn = {2304-8158},
support = {2022TD-15//Shaanxi Provincial Science and Technology Innovation Team/ ; 2024NC-YBXM-157//Study of Key Factors and Control Techniques Affecting the Formation of Maillard Reaction Prod-uctsin Sheep Milk Powder/ ; LJ212610167008//Study of Inhibitory Mechanism of Hydrolyzed Peptides from Mactra veneriformis on the Formation of Advanced Glycation End Products in Processed Food/ ; BDHYYJY2024007//Open Research Project of the Bohai University Marine Research Institute/ ; },
abstract = {Advanced glycation end products (AGEs) are prevalent in thermally processed foods. Long-term intake of AGEs has been linked to intestinal barrier damage, contributing to the development of chronic diseases. Galacto-oligosaccharides (GOS) restored mucus barrier damage induced by dietary AGEs, but the underlying mechanisms remained unclear. This study focused on investigating the effects of GOS on mucin synthesis-related glycosyltransferases, as well as differentiation and apoptosis of goblet cells (GCs) in dietary AGEs-fed C57BL/6 mice. Fecal microbiota transplantation (FMT) was used to probe a possible contribution of the intestinal microbiota. The findings demonstrated that GOS upregulated the mRNA expression of glycosyltransferases (St3gal1 and St3gal3) while inhibiting p-ERK signaling. In addition, no marked changes in mRNA expression of the Wnt, BMP, Notch, and CHOP pathways (which are involved in GC proliferation, differentiation, and apoptosis) were observed following GOS intervention. FMT data suggested the hypothesis that the gut microbiota may participate in mediating changes in St3gal1 and p-ERK/ERK in response to GOS. These findings provided valuable insights into potential interventions for intestinal mucus barrier damage induced by AGEs.},
}

@article {pmid43028169,
year = {2026},
author = {Figura, M and Zając, W and Otto-Ślusarczyk, D and Milanowski, Ł and Nowak, JM and Antoniak, A and Kopczyński, M and Sadowski, K and Hołubiuk, Ł and Walęcik-Kot, W and Szlufik, S and Biliński, J and Struga, M and Koziorowski, D},
title = {Effects of Fecal Microbiota Transplantation on Inflammatory Markers in Parkinson's Disease: Exploratory Results from the EFFACE-PD Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028169},
issn = {1422-0067},
support = {2021 National Grant, Poland//Biocodex Microbiota Foundation/ ; 1/Z/MG/N/24//Medical University of Warsaw/ ; },
mesh = {Humans ; *Parkinson Disease/therapy/blood/microbiology ; Female ; Male ; Biomarkers/blood ; Aged ; *Fecal Microbiota Transplantation/methods ; *Inflammation/therapy/blood ; Middle Aged ; Interleukin-18/blood ; Double-Blind Method ; Leukocyte L1 Antigen Complex/blood ; Gastrointestinal Microbiome ; },
abstract = {Inflammation and gut dysbiosis are increasingly recognized as important contributors to the pathophysiology of Parkinson's disease (PD). Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy aimed at restoring gut microbial balance and modulating inflammatory pathways. The aim of the study was to evaluate the effect of single fecal microbiota transplantation on systemic and gut-related inflammatory biomarkers in patients with PD. This exploratory analysis was conducted as part of the randomized, double-blind, placebo-controlled EFFACE-PD study. Fifty-nine participants with PD were randomized to receive either donor-derived FMT or placebo. Serum levels of IL-18 and calprotectin were measured using ELISA before intervention and 3 months after the procedure. Ferritin, leukocyte count, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) were assessed at baseline and after twelve months. No statistically significant between-group differences in changes in inflammatory biomarker concentrations were observed. Broader inflammatory markers, including ferritin and leukocyte parameters, also did not differ significantly between groups. We conclude that single FMT did not induce significant changes in systemic inflammatory biomarkers in this exploratory cohort of PD patients. Larger studies with standardized inflammatory assessments are needed to clarify the immunomodulatory effects of FMT in PD.},
}

Humans
*Parkinson Disease/therapy/blood/microbiology
Female
Male
Biomarkers/blood
Aged
*Fecal Microbiota Transplantation/methods
*Inflammation/therapy/blood
Middle Aged
Interleukin-18/blood
Double-Blind Method
Leukocyte L1 Antigen Complex/blood
Gastrointestinal Microbiome

@article {pmid43028246,
year = {2026},
author = {Pető, A and Sipos, D and Kappéter, Á and Feiszt, Z and Dembrovszky, F and Halda-Kiss, B and Péterfi, Z},
title = {Fecal Microbiota Transplantation in the Treatment Strategy of Inflammatory Bowel Disease: Molecular Mechanisms, Clinical Evidence, and the Transition Toward Defined Microbial Therapeutics.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028246},
issn = {1422-0067},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/therapy ; },
abstract = {Inflammatory Bowel Disease (IBD) comprises two clinically and pathologically distinct chronic intestinal inflammatory diseases, ulcerative colitis (UC) and Crohn's disease (CD). Both diseases result from a dysregulated mucosal immune response to the commensal gut microbiota in genetically predisposed individuals. Because gut dysbiosis is a constant feature of both diseases, Fecal Microbiota Transplantation (FMT) has recently been investigated as a potential therapeutic strategy to restore a balanced microbiota composition in patients with IBD. There are five placebo-controlled randomized controlled trials (RCTs) in UC and several meta-analyses, which showed that treatment with FMT using material from multiple donors can lead to clinical and endoscopic remission in patients with mild-to-moderate UC and may thus double to triple the rate of remission compared with placebo (number needed to treat [NNT] ≈ 3-5). In contrast, evidence for CD is limited and inconsistent, with one promising pilot study being contrasted with a large multicenter induction trial that was stopped for futility. This review provides an update of the current molecular understanding of FMT-induced recovery of mucosal barrier function and inflammation control in intestinal inflammation (α-diversity restoration and subsequent donor strain engraftment, production of short-chain fatty acids and secondary bile acids, tryptophan-AhR signaling, IL-10-mediated induction of Tregs vs. suppression of Th17 cells and restoration of epithelial barrier function). The review also summarizes the current clinical evidence for the use of FMT in IBD, its safety, and the current regulatory status. It also describes recent developments in FMT, including the use of defined bacterial consortia, 'live biotherapeutic products' (LBPs), and donor-recipient pairing. Collectively, FMT provides evidence of principle for manipulating intestinal microbial ecosystems to treat immune-mediated intestinal inflammation.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Inflammatory Bowel Diseases/therapy/microbiology
*Gastrointestinal Microbiome
Animals
Dysbiosis/therapy

@article {pmid43028288,
year = {2026},
author = {Li, S and Chen, M and Yang, H and Zhao, X and Tian, Y and Cheng, Y and Wu, Q and Feng, Y and Chen, L and Yi, A and Ruan, G and Wei, Y},
title = {Age-Related Alterations in Human Gut Microbiota and Intestinal Aging: Microbial Signatures, Disease Associations and Intervention Strategies.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028288},
issn = {1422-0067},
support = {82370539//National Natural Science Foundation of China/ ; ZXAIZD006//Medical Research Projects of the Army Medical Center of PLA/ ; 2024ZDXM010//Chongqing Joint Project of Science and Health/ ; 2023XLC008//University Science and Technology Innovation Project/ ; CSTB2022TIAD-KPX0161//Chongqing Special Key Project for Technological Innovation and Application Development/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; *Aging ; *Dysbiosis/microbiology ; Intestinal Barrier Function ; *Intestines/microbiology ; Animals ; Fecal Microbiota Transplantation ; Prebiotics ; Probiotics ; },
abstract = {Aging is accompanied by progressive alterations in gut homeostasis, characterized by gut microbiota dysbiosis, impaired intestinal barrier function, immune dysregulation, and chronic low-grade inflammation. Increasing evidence indicates that age-related gut microbial remodeling is closely associated with the development of multiple age-associated disorders, including frailty, sarcopenia, cardiovascular diseases, and neurodegenerative diseases. However, existing reviews have primarily focused on individual aspects of gut microbiota-mediated aging, whereas a systematic framework integrating gut microbial dysbiosis, intestinal aging, and the development of multiple age-related diseases through shared pathogenic mechanisms remains lacking. This review provides a comprehensive synthesis of age-related alterations in human gut microbiota, with particular emphasis on bacterial taxa consistently associated with healthy aging and age-related diseases. We further integrate current evidence to examine the associations between age-related microbial alterations and intestinal aging, with particular attention to microbial function, barrier integrity, and host immune responses. Finally, we review microbiota-targeted interventions, including fecal microbiota transplantation, probiotics, prebiotics, and dietary modulation, and discuss their potential and limitations in promoting healthy aging. By integrating mechanistic evidence with findings from human observational cohorts and clinical intervention studies, this review provides a translational framework for understanding microbiota-mediated intestinal aging and highlights future directions for precision microbiota-based strategies to promote healthy aging.},
}

Humans
*Gastrointestinal Microbiome
*Aging
*Dysbiosis/microbiology
Intestinal Barrier Function
*Intestines/microbiology
Animals
Fecal Microbiota Transplantation
Prebiotics
Probiotics

@article {pmid43030137,
year = {2026},
author = {Rodríguez-Arellano, SN and González-Gómez, JP and Aguirre-Sánchez, JR and Gomez-Gil, B and Barrón-Cabrera, E and Chaidez, C and Vergara-Jiménez, MJ},
title = {Targeted Modulation of the Gut Microbiota in Obesity: From Dietary Interventions to Bacteriophage-Based Precision Therapies.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030137},
issn = {2072-6643},
mesh = {Humans ; *Obesity/microbiology/therapy ; *Gastrointestinal Microbiome ; Dysbiosis/therapy/microbiology ; *Bacteriophages ; *Phage Therapy/methods ; Prebiotics/administration & dosage ; Probiotics ; Animals ; *Precision Medicine/methods ; Fecal Microbiota Transplantation ; Inflammation/microbiology ; },
abstract = {Obesity is a complex chronic disease associated with metabolic and inflammatory alterations in which the gut microbiota has emerged as an important contributing factor. Obesity-associated gut dysbiosis involves not only changes in microbial composition but also alterations in microbial functions and metabolites that may affect intestinal barrier integrity, immune regulation, adipose tissue metabolism, insulin sensitivity, and glucose homeostasis. Current microbiota-modulating strategies, including dietary interventions, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, can influence the gut microbial ecosystem; however, their effects are often highly variable among individuals and generally lack the specificity required to selectively target disease-associated bacterial populations. These limitations have increased interest in precision microbiota modulation, which aims to selectively modify microbial populations, functions, or products while minimizing unnecessary alterations to the remaining microbial community. In this context, bacteriophages represent a promising biological tool because of their ability to specifically target bacterial hosts, offering the possibility of selectively reducing bacterial populations associated with obesity-related metabolic and inflammatory disturbances. Experimental studies and early human trials have shown that bacteriophage-based interventions can modulate gut microbial communities and influence inflammatory responses, supporting their potential relevance to obesity-associated chronic low-grade inflammation. However, no published clinical trials specifically evaluating targeted bacteriophage therapy for obesity treatment were identified, and its efficacy for obesity management remains unestablished. Further research is needed to identify and validate bacterial targets, optimize phage selection and cocktail design, and evaluate phage stability, bacterial resistance, immunomodulatory effects, safety, and host-microbiota interactions before clinical translation can be considered.},
}

Humans
*Obesity/microbiology/therapy
*Gastrointestinal Microbiome
Dysbiosis/therapy/microbiology
*Bacteriophages
*Phage Therapy/methods
Prebiotics/administration & dosage
Probiotics
Animals
*Precision Medicine/methods
Fecal Microbiota Transplantation
Inflammation/microbiology

@article {pmid43030191,
year = {2026},
author = {Kim, J and Nemet, I},
title = {Microbial Aromatic Amino Acid Metabolism in Cardiometabolic Disease.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030191},
issn = {2072-6643},
support = {/NH/NIH HHS/United States ; //Cleveland Clinic/ ; },
mesh = {Humans ; *Amino Acids, Aromatic/metabolism ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/metabolism ; Animals ; *Metabolic Diseases/microbiology/metabolism ; Host Microbial Interactions ; },
abstract = {The gut microbiota generates a diverse array of metabolites that influence host physiology. Among these, products of microbial metabolism of the aromatic amino acids tryptophan, phenylalanine, tyrosine, and histidine have emerged as important components of host-microbiome interactions relevant to cardiometabolic disease. This Review summarizes the microbial pathways, enzymes, and metabolic networks involved in aromatic amino acid metabolism and examines how dietary substrate availability, microbial community composition, microbial enzymatic capacity, host metabolism, and environmental factors influence metabolite production and biological activity. Microbiota-derived metabolites and host-microbial co-metabolites are associated with inflammation, vascular function, thrombosis, metabolic homeostasis, and host signaling pathways. Their biological effects are context-dependent and influenced by microbial pathway activity, host metabolic processing, tissue compartment, disease stage, and substrate availability. We further distinguish evidence derived from human observational studies, experimental metabolite administration, and demonstrated molecular mechanisms. Finally, we discuss strategies to modulate aromatic amino acid metabolism, including dietary interventions, functional foods, probiotics, fecal microbiota transplantation, microbial enzyme inhibitors, and metabolite sequestration approaches. Current evidence supports a framework linking dietary substrates, microbial enzyme activity, host responses, and cardiometabolic phenotypes, while highlighting important opportunities and challenges for developing precision microbiome-based therapeutics.},
}

Humans
*Amino Acids, Aromatic/metabolism
*Gastrointestinal Microbiome/physiology
*Cardiovascular Diseases/microbiology/metabolism
Animals
*Metabolic Diseases/microbiology/metabolism
Host Microbial Interactions

@article {pmid43030219,
year = {2026},
author = {Potu, BK and Arulkandan, A and Gopalakrishna, PK and Thanu, AS and Omar, NA and Nasr El-Din, WA and Vishnumukkala, T},
title = {Anatomical and Molecular Foundations of the Gut-Brain Axis in Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Translation.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030219},
issn = {2072-6643},
mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/metabolism/physiopathology ; Animals ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Brain/metabolism ; *Brain-Gut Axis/physiology ; Probiotics ; *Gastrointestinal Tract ; },
abstract = {Alzheimer's disease (AD) is a complex disease that involves systemic, vascular, and metabolic components affecting the brain, in addition to amyloid-beta (Aβ) and tau pathology. The microbiota-gut-brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system, involving neural, immune, endocrine, and metabolic pathways, has arisen as a mechanistically plausible and clinically relevant contributor to AD pathogenesis among these systemic contributors. This review integrates information from human observational research, preclinical transgenic and germ-free models, and clinical trials to assess how gut dysbiosis, intestinal barrier dysfunction, and microbial metabolites converge on amyloidogenic and tau-associated pathways. In preclinical models, disruption of intestinal barrier integrity is proposed to allow translocation of lipopolysaccharide and bacterial amyloids into the systemic circulation, activating Toll-like receptor and NLRP3 inflammasome signaling that may prime microglia and astrocytes towards a chronic neuroinflammatory state. Further, dysbiosis-mediated changes in short-chain fatty acid, tryptophan-kynurenine, and bile acid metabolism may influence amyloid precursor protein processing, microglial clearance capability, and tau phosphorylation. Preclinical germ-free and fecal-transfer investigations provide fundamental evidence for these pathways in rodent models, while human case-control and Mendelian randomization data indicate converging yet diverse associations that have not yet established underlying directionality in human disease. Therapeutic modulation of the axis has shown promising early phase and observational signals using probiotics, synbiotics, dietary pattern interventions, fecal microbiota transplantation and pharmacological targeting of the GLP-1 pathway; however, the phase 3 EVOKE and EVOKE+ trials of oral semaglutide did not meet their primary cognitive endpoint, and heterogeneity of trials, short follow-up, and inconsistent reporting of biomarkers currently preclude definitive conclusions. We conclude that the microbiota-gut-brain axis is a biologically plausible and therapeutically tractable component of AD pathophysiology, but translation from mechanistic plausibility to clinical utility will depend upon longitudinal, biomarker-anchored and adequately powered interventional trials in genetically and microbiologically diverse populations. Because diet is among the most readily modifiable determinants of gut microbiome composition and function, this review prioritizes dietary patterns, prebiotic fibers, and probiotic or synbiotic supplementation as practical strategies for investigating the microbiota-gut-brain axis in AD. Their disease-modifying efficacy remains unproven; therefore, mechanistic and pharmacological approaches are discussed as complementary avenues for informing future research.},
}

Humans
*Alzheimer Disease/therapy/microbiology/metabolism/physiopathology
Animals
*Gastrointestinal Microbiome/physiology
Dysbiosis
*Brain/metabolism
*Brain-Gut Axis/physiology
Probiotics
*Gastrointestinal Tract

@article {pmid43030253,
year = {2026},
author = {Zeng, Y and Zhang, M and Ren, K and Yang, T and Li, J and Yi, SQ},
title = {Remodeling and Alteration of the Gut Microbial Community in Suncus murinus Receiving Fecal Microbiota Transplantations from Mice with High-Fat Diet-Induced Obesity.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030253},
issn = {2072-6643},
support = {No. 25K10147//Ministry of Education, Culture, Sports, Science and Technology/ ; },
mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Fecal Microbiota Transplantation ; *Obesity/microbiology/therapy/etiology ; *Gastrointestinal Microbiome/physiology ; Male ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Mice ; Cecum/microbiology ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Obesity-associated gut microbiota can transmit metabolic traits in permissive recipients; however, microbial engraftment following fecal microbiota transplantation (FMT) is also constrained by the recipient's intestinal environment. Suncus murinus (S. murinus) is an insectivorous and naturally obesity-resistant species with a distinctive gut ecology, making it a potential model for examining recipient filtering during cross-species FMT.

OBJECTIVES: To determine whether cecal microbiota from high-fat diet (HFD)-fed mice induces persistent donor diet-specific microbial and host phenotypes in S. murinus relative to microbiota from normal chow diet (NCD)-fed donors.

METHODS: S. murinus recipients (n = 12) were randomly allocated to high-fat diet-recipient (HFD-r) and normal chow diet-recipient (NCD-r) groups (n = 6 per group). All recipients received the same normal trout diet throughout the study. The recipients were administered supernatants of donor cecal microbiota via oral gavage for three consecutive days. A 16S rRNA gene sequencing analysis was performed on fecal samples collected before antibiotic treatment and at weeks 4 and 8 post-FMT. Longitudinal microbial outcomes were analyzed using common baseline-constrained longitudinal models, restricted PERMANOVA, and false discovery rate correction.

RESULTS: Bacillota was the predominant phylum in both the HFD-r and NCD-r groups. The most consistent taxonomic response was a shared decrease in Campylobacterota and its major constituent genus Helicobacter after treatment, particularly at 4 weeks, whereas no robust phylum- or genus-level differences were detected between the HFD-r and NCD-r groups. Observed ASV richness and Faith's phylogenetic diversity did not differ significantly among the groups. Principal coordinate analyses showed extensive overlap, and a restricted PERMANOVA detected no significant separation between the HFD-r and NCD-r groups. Histological examination revealed crown-like arrangements and heterogeneous adipocyte morphology, and variation in villus and crypt appearance in representative recipient sections.

CONCLUSIONS: No significant differences in fecal microbial composition, body weight, or glucose tolerance were detected between the HFD-r and NCD-r groups. Recipient-associated ecological constraints remain a possible explanation requiring direct assessment of donor engraftment. Further work is needed to evaluate S. murinus as a model for investigating recipient-side constraints on microbiota colonization.},
}

Animals
*Diet, High-Fat/adverse effects
*Fecal Microbiota Transplantation
*Obesity/microbiology/therapy/etiology
*Gastrointestinal Microbiome/physiology
Male
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Mice
Cecum/microbiology
Mice, Inbred C57BL

@article {pmid43031878,
year = {2026},
author = {Yan, Y and Bao, L and Chen, X and Xiao, H},
title = {The role of nasal and gut microbiota in allergic rhinitis: immunomodulation and therapeutic prospects.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1984960},
pmid = {43031878},
issn = {1664-3224},
mesh = {Humans ; *Immunomodulation ; *Rhinitis, Allergic/immunology/therapy/microbiology ; Animals ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; *Nasal Mucosa/immunology/microbiology ; *Microbiota/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Allergic rhinitis (AR) is a prevalent immunoglobulin E (IgE)-mediated inflammatory disorder of the nasal mucosa that imposes substantial global health and socioeconomic burdens. The pathogenesis of AR involves complex interactions among epithelial barrier dysfunction, immune dysregulation, and environmental factors. Emerging evidence underscores the critical role of the human microbiota, particularly communities residing in the nasal cavity and gut, in modulating immune homeostasis and susceptibility to AR. Early-life microbial exposure profoundly shapes initial microbiota colonization. Observational and longitudinal studies associate nasal and gut dysbiosis with impaired immune tolerance and an increased risk of AR, although the causal direction of these associations remains incompletely established. At a mechanistic level, microbial communities may influence AR through short-chain fatty acids and other metabolites, epithelial barrier integrity, and an integrated innate/adaptive network comprising type 2 innate lymphoid cells, dendritic cell subsets, Th 1, Th2, Th17, and regulatory T cells, together with epigenetic regulation. Among microbiota-targeted interventions, selected probiotic strains and bacterial lysates show modest, strain- and regimen-specific benefits in some randomized trials, whereas fecal microbiota transplantation remains experimental in AR, with current support extrapolated from other conditions and preclinical models. This review synthesizes current insights into microbiota-AR interactions and their underlying mechanisms, explicitly distinguishing human, preclinical, and mechanistic evidence, and critically appraises the therapeutic potential and limitations of microbiota-targeted strategies for AR prevention and treatment.},
}

Humans
*Immunomodulation
*Rhinitis, Allergic/immunology/therapy/microbiology
Animals
*Gastrointestinal Microbiome/immunology
Dysbiosis/immunology
*Nasal Mucosa/immunology/microbiology
*Microbiota/immunology
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid43032184,
year = {2026},
author = {Zhao, S and Yu, E and Wu, F and Zhang, Y and Zhao, X and Wu, X},
title = {Regulation of diabetic wound healing by the gut-liver axis via immunometabolic reprogramming of macrophages: from systemic pre-programming to targeted therapy.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1991888},
doi = {10.3389/fimmu.2026.1991888},
pmid = {43032184},
issn = {1664-3224},
mesh = {Humans ; *Macrophages/immunology/metabolism ; *Wound Healing/immunology ; Animals ; *Liver/metabolism/immunology ; Metabolic Reprogramming ; *Gastrointestinal Tract/immunology/metabolism ; Exosomes/metabolism ; },
abstract = {Diabetic wounds, particularly diabetic foot ulcers, remain a major clinical challenge due to their recalcitrance to healing and limited response to conventional therapies. Successful wound healing critically depends on timely macrophage phenotypic switching from a pro-inflammatory M1-like to a reparative M2-like state; however, the diabetic milieu-characterized by hyperglycemia and advanced glycation end products (AGEs)-impedes this transition, establishing macrophage dysfunction as a hallmark of chronic non-healing wounds. We propose a conceptual framework in which gut-liver axis dysfunction in diabetes does not merely act through direct delivery of metabolites to the wound bed, but may contribute to a state of systemic immunometabolic dysregulation that "pre-programs" bone-marrow-derived monocytes toward a pro-inflammatory M1-like bias before they reach the wound site. We discuss three potential components of this pre-programming: (i) the cellular targets-hematopoietic stem and progenitor cells and circulating monocyte precursors; (ii) the candidate signaling mediators-gut-derived lipopolysaccharide (LPS), inflammatory cytokines, and exosomes acting via the toll-like receptor 4 (TLR4)/NF-κB pathway; and (iii) the proposed molecular imprint-persistent modifications of histone marks such as H3K4me3 and H3K27ac at promoters of pro-inflammatory genes, accompanied by a metabolic shift toward aerobic glycolysis. Importantly, direct evidence that gut-liver-derived exosomes epigenetically remodel hematopoietic progenitors in diabetic wound healing is currently lacking, and this remains a hypothesis generated by integrating separate lines of evidence. Reduced gut-derived short-chain fatty acids (SCFAs) and disrupted hepatic bile acid metabolism may further exacerbate immune dysregulation within the wound microenvironment. On this basis, targeting the gut-liver axis to restore macrophage homeostasis has emerged as a promising therapeutic strategy. We summarize current evidence on probiotics, fecal microbiota transplantation, bile acid modulation, exosome-based delivery, and metabolic interventions, and discuss how these approaches may restore gut-liver axis homeostasis and reprogram macrophage phenotypes to promote wound healing. We clearly indicate the evidence level of each proposed intervention-human clinical trial, animal model, in vitro, or not yet tested. Looking ahead, the integration of multi-omics technologies with smart nanodelivery systems and personalized medicine strategies is expected to accelerate the translation of this regulatory network from basic research to clinical application, providing new conceptual and therapeutic avenues for the management of diabetic wounds.},
}

Humans
*Macrophages/immunology/metabolism
*Wound Healing/immunology
Animals
*Liver/metabolism/immunology
Metabolic Reprogramming
*Gastrointestinal Tract/immunology/metabolism
Exosomes/metabolism

@article {pmid43032381,
year = {2026},
author = {Delgado, K and Espitia, A and PopeJoy, K and Mace, L and Lew, M and Song, BS and Kumar, R and Song, J},
title = {The Indole-AhR-Treg axis as a microbiome-encoded immune checkpoint in type 1 diabetes.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1949305},
pmid = {43032381},
issn = {1664-3224},
mesh = {Humans ; *Receptors, Aryl Hydrocarbon/metabolism/immunology ; *Diabetes Mellitus, Type 1/immunology/metabolism/microbiology ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Indoles/metabolism/immunology ; Animals ; *Gastrointestinal Microbiome/immunology ; *Basic Helix-Loop-Helix Proteins/metabolism/immunology ; Signal Transduction ; Dysbiosis/immunology ; },
abstract = {Type 1 diabetes (T1D) is an autoimmune disease driven by the progressive destruction of pancreatic β-cells following failure of peripheral immune tolerance. Increasing evidence identifies the gut microbiome as a critical upstream regulator of this process through its control of microbiota-derived immunoregulatory metabolites. Among these, tryptophan-derived indole metabolites have emerged as central modulators of the aryl hydrocarbon receptor (AhR)-regulatory T cell (Treg) axis, a key checkpoint governing mucosal and systemic immune homeostasis. In individuals at risk for T1D, gut dysbiosis has been associated with altered commensal composition and tryptophan metabolism that may reduce the availability of selected AhR-active indole metabolites, including indole-3-acetic acid (IAA), indole-3-carboxaldehyde (ICA), and indole-3-propionic acid (IPA). These metabolites regulate Treg differentiation, macrophage polarization, epithelial barrier integrity, and effector T cell activation through context-dependent AhR- and PPAR-mediated signaling pathways. Disruption of this axis promotes inflammatory Th1/Th17 responses, intestinal barrier dysfunction, and progression of islet autoimmunity. A central concept emerging from recent studies is that the immunological outcome of AhR activation depends not only on ligand identity, but also on delivery compartment, concentration, cellular target, and inflammatory context - a framework we term the "Indole Paradox." This paradigm helps reconcile why some AhR-targeting interventions exacerbate autoimmunity whereas others restore immune tolerance. In this review, we synthesize current mechanistic and translational evidence linking microbiome-derived indole signaling to T1D pathogenesis and evaluate emerging therapeutic strategies targeting this axis, including dietary modulation, postbiotic metabolites, pharmacological AhR agonists, fecal microbiota transplantation, and engineered bacterial therapeutics. We propose that context-directed modulation of the indole-AhR-Treg axis represents a promising next-generation strategy for restoring immune tolerance and preventing autoimmune progression in T1D.},
}

Humans
*Receptors, Aryl Hydrocarbon/metabolism/immunology
*Diabetes Mellitus, Type 1/immunology/metabolism/microbiology
*T-Lymphocytes, Regulatory/immunology/metabolism
*Indoles/metabolism/immunology
Animals
*Gastrointestinal Microbiome/immunology
*Basic Helix-Loop-Helix Proteins/metabolism/immunology
Signal Transduction
Dysbiosis/immunology

@article {pmid43018394,
year = {2026},
author = {Jiang, X and Wang, Y and Luo, Y and Jin, C and Zeng, Z and Hu, Y and Chen, H and Gong, S and Wu, J and Yang, M and , },
title = {Amino acid-based formula and Clostridioides difficile-associated disease in infants: concerns regarding causal interpretation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2761714},
doi = {10.1080/19490976.2026.2761714},
pmid = {43018394},
issn = {1949-0984},
mesh = {Humans ; *Amino Acids/adverse effects/analysis ; Infant ; *Infant Formula/chemistry/adverse effects ; *Clostridioides difficile/physiology ; *Clostridium Infections/microbiology/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; },
abstract = {Wang et al. recently reported an association between amino acid-based formula (AAF) feeding and Clostridioides difficile-associated disease (CDAD) in children younger than two years, integrating clinical observations, microbiome profiling, and fecal microbiota transplantation experiments. The authors appropriately framed their findings as associative; our aim is not to allege over-interpretation, but to delineate the evidentiary gap between their reported association and a causal claim. Several methodological and interpretative issues limit such inference, including confounding by the clinical indication for AAF, the difficulty of distinguishing C. difficile colonization from clinically attributable disease in young children, developmental differences in age and complementary feeding, and the selected nature of the fecal microbiota transplantation (FMT) donor population. For example, the multivariable model included only 27 outcome events against approximately six predictors (events-per-variable ≈ 4.5, far below the accepted 10-20 threshold), rendering the adjusted odds ratios unstable. The cross-sectional microbiome data further cannot establish whether microbial alterations preceded disease or resulted from underlying clinical, dietary, or inflammatory states. We therefore suggest interpreting the findings as an association between AAF feeding and CDAD status, rather than evidence that AAF itself increases CDAD risk. Our skepticism concerns the causal link to CDAD specifically; we do not dispute that reduced Bifidobacterium with formula feeding is a well-established finding. This distinction has important clinical implications, as AAF remains an essential nutritional intervention for children with appropriate indications, and in young children microbiological detection and microbiome alterations must be interpreted alongside age, clinical symptoms, underlying disease, dietary history, and other relevant exposures. An overly causal interpretation could create unnecessary concern among families and complicate clinical decision-making. To make these considerations operational, we specify the elements of a decisive prospective study, including a minimum event count of ~60 adjudicated CDAD cases, a blinded tiered diagnostic algorithm, and detailed AAF exposure ascertainment.},
}

Humans
*Amino Acids/adverse effects/analysis
Infant
*Infant Formula/chemistry/adverse effects
*Clostridioides difficile/physiology
*Clostridium Infections/microbiology/etiology
Fecal Microbiota Transplantation
Gastrointestinal Microbiome

@article {pmid43019935,
year = {2026},
author = {Jia, X and Zhang, Z and Hu, Y and Feng, M and Li, G and Li, Y and Li, F},
title = {Advances in research on the gut microbiota-bile acid-immune homeostasis axis in the regulation of bone metabolism in osteoporosis.},
journal = {International immunopharmacology},
volume = {191},
number = {Pt 1},
pages = {117679},
doi = {10.1016/j.intimp.2026.117679},
pmid = {43019935},
issn = {1878-1705},
abstract = {Osteoporosis is characterized by reduced bone mass, disrupted bone microarchitecture, and an increased risk of fragility fractures. In recent years, the gut microbiota and its metabolites are increasingly recognized as components of an upstream regulatory network linking nutrition, immunity, and bone remodeling. After being metabolized by the gut microbiota, bile acids can influence intestinal barrier function and immune homeostasis through the farnesoid X receptor (FXR), TGR5/GPBAR1, the vitamin D receptor (VDR), and the pregnane X receptor (PXR). This review summarizes the bidirectional regulation between the microbiota and the bile acid pool, FXR/TGR5-mediated osteogenic and osteoclastic signaling, and the effects of bile acid metabolites on Th17/Treg balance and monocyte-macrophage function. It also compares the relevant evidence across different types of osteoporosis. Animal studies support the involvement of this axis in bone mass regulation, whereas human studies are predominantly cross-sectional or small-sample intervention studies and remain insufficient to establish causal relationships between specific bile acids or microbial strains and fracture outcomes. Probiotics, prebiotics, diet, exercise, fecal microbiota transplantation, and bile acid receptor modulators hold potential for clinical application, but strain specificity, host variability, dose- and tissue-dependent effects, and long-term safety still warrant attention. Future research should include standardized longitudinal cohorts, multi-omics causal studies, tissue-specific mechanistic validation, and randomized controlled trials with bone mineral density or fracture as endpoints, thereby promoting the translation of this axis into stratified prevention and treatment strategies.},
}

@article {pmid43020530,
year = {2026},
author = {Tang, D and Wu, YN and Ding, L and Ding, X and Chen, J and Sun, Y and Guo, J and Lu, L and Wang, R},
title = {Wenyang Jiedu Huayu Formula alleviates acute-on-chronic liver failure by modulating gut microbiota composition and restoring intestinal-hepatic homeostasis.},
journal = {Journal of pharmacological sciences},
volume = {162},
number = {4},
pages = {253-267},
doi = {10.1016/j.jphs.2026.08.006},
pmid = {43020530},
issn = {1347-8648},
mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Acute-On-Chronic Liver Failure/drug therapy/metabolism/microbiology ; Male ; *Liver/metabolism/pathology ; *Homeostasis/drug effects ; Disease Models, Animal ; Rats ; Rats, Sprague-Dawley ; *Intestines ; *Phytotherapy ; Apoptosis/drug effects ; Interleukin-6/metabolism ; },
abstract = {Acute-on-chronic liver failure (ACLF) is a life-threatening condition associated with systemic inflammation, hepatic necroptosis, and disrupted gut-liver axis signaling. Wenyang Jiedu Huayu Formula (WYJDHY), a traditional Chinese medicine formulation, was investigated for its potential therapeutic effects on ACLF and its relationship with gut microbiota modulation. In the ACLF rat model, WYJDHY significantly alleviated liver histopathological damage, reduced neutrophil infiltration and necroptosis, suppressed hepatocyte apoptosis, and improved liver function markers, including alanine aminotransferase (ALT), aspartate transferase (AST), albumin, and total protein. WYJDHY also inhibited inflammation by reducing interleukin-6 (IL-6), vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and c-reactive protein (CRP) expression. 16S rRNA gene sequencing revealed that WYJDHY showed a trend toward improving gut microbiota diversity and evenness, partially reversing the altered composition observed in ACLF, including key taxa such as Lachnospiraceae_NK4A136_group, Turicibacter, and Allobaculum. The therapeutic benefits of WYJDHY were significantly diminished in pseudo-germ-free (PG) rats and were transferable through fecal microbiota transplantation (FMT) from WYJDHY-treated rats. These findings demonstrate that WYJDHY alleviates ACLF in a gut microbiota-dependent manner, highlighting the gut-liver axis as a therapeutic target and supporting microbiota-based interventions in ACLF treatment.},
}

Animals
*Drugs, Chinese Herbal/pharmacology/therapeutic use
*Gastrointestinal Microbiome/drug effects
*Acute-On-Chronic Liver Failure/drug therapy/metabolism/microbiology
Male
*Liver/metabolism/pathology
*Homeostasis/drug effects
Disease Models, Animal
Rats
Rats, Sprague-Dawley
*Intestines
*Phytotherapy
Apoptosis/drug effects
Interleukin-6/metabolism

@article {pmid43021348,
year = {2026},
author = {Liu, S and Li, A and Jia, A and Chen, Q and Nan, Z and Qiu, Z and Qiu, Y},
title = {Network pharmacology, gut microbiota, and metabolomics integration reveal that Shenshuai 'an enema prescription (SSAEP) improves CRF mechanisms by reshaping the gut microbiota and correcting host-microbe cometabolism.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {43021348},
issn = {1749-8546},
support = {No 1000080305//Nan Zheng Traditional Chinese Medicine Master Inheritance Studio/ ; No. 010501318//the Jilin Province Postdoctoral Talent Selective Funding Project/ ; No DZJ202402034CXJD//Jilin Province Science and Technology Development Program Project/ ; },
abstract = {BACKGROUND: Chronic renal failure (CRF) is a global health issue, and the "gut-kidney axis" plays a key role in its pathogenesis. Shenshuai 'an enema prescription (SSAEP) is a Chinese medicine compound based on the TCM theory of "regulation of bowel movement and removal of turbid qi", which has shown good adjunctive therapeutic effects in delaying the progression of CRF in clinical practice. However, its specific mechanisms remain unclear.

PURPOSE: Herein, from the perspective of indirect pharmacology, the therapeutic effects of SSAEP on CRF rats were explored. We hypothesize that its mechanism of action may be largely indirect and occurs primarily through the gut-kidney axis. This study aimed to systematically elucidate the potential mechanism through which SSAEP improves CRF through the regulation of gut microecology using multidisciplinary approaches such as network pharmacology, 16S rRNA gene sequencing, and metabonomics.

METHODS: A CRF rat model was established by induction with 2.5% adenine. Low and high doses of SSAEP were administered via enema, and antibiotic intervention and fecal microbiota transplantation (FMT) experiments were performed to verify the key mediating role of the gut microbiota. The chemical composition of the SSAEP and the metabolic profiles of the serum and colonic contents of the rats were analyzed using UHPLC‒MS/MS; the composition of the gut microbiota was analyzed through 16S rRNA sequencing; and the core targets and pathways were predicted using network pharmacology and molecular docking. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-β1 or glycochenodeoxycholic acid (GCDCA) to verify the anti-inflammatory and antifibrotic effects of quercetin (the main active component of SSAEP) and the role of the IL-17 signaling pathway in this process.

RESULTS: SSAEP treatment significantly improved renal function indicators (BUN, SCR, Cys-C, and UA) in CRF rats and alleviated pathological damage, the inflammatory response, and fibrosis in kidney tissue. Antibiotic intervention attenuated the protective effect of SSAEP, while FMT experiments confirmed that the efficacy of SSAEP could be transferred to recipient rats through the transplantation of treated fecal microbiota. SSAEP reshaped the gut microbiota, significantly increasing the abundance of Akkermansia while reducing that of Clostridium. Metabolomic analysis revealed CRF-related metabolic disturbances and identified 29 key differentially expressed metabolites regulated by SSAEP, among which glycochenodeoxycholic acid (GCDCA) was a key pathogenic metabolite. Network pharmacology predictions combined with in vitro experiments confirmed that the quercetin in SSAEP could effectively antagonize the TGF-β1- and GCDCA-induced epithelial‒mesenchymal transition and inflammatory response in HK-2 cells by inhibiting the IL-17/NF-κB signaling pathway.

CONCLUSIONS: This study revealed that SSAEP improves CRF through an indirect pharmacological mechanism dependent on the gut microbiota: SSAEP reshapes the balance of the gut microbiota, thereby correcting host-microbe cometabolic disorders (particularly by reducing the level of the pathogenic metabolite GCDCA) and ultimately alleviating renal inflammation and fibrosis through the inhibition of signaling pathways such as the IL-17/NF-κB pathway. This study provides new experimental evidence for the "gut-kidney axis" theory and lays the foundation for the development of CRF treatment strategies based on the regulation of the gut microbiome.},
}

@article {pmid43021363,
year = {2026},
author = {Zhang, X and Qin, C and Zhao, Y and Li, Z and Xie, Y and Yan, Y and Li, T and Huang, L and Shi, H and Lin, C and Wang, W},
title = {Gut microbiota-driven hippuric acid hydrolysis promotes pancreatic tumorigenesis by suppressing NK cell activity.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {43021363},
issn = {1479-5876},
support = {No. 82573412//National Natural Science Foundation of China/ ; No. 82503800//National Natural Science Foundation of China/ ; 2025-PUMCH-C-018//National High Level Hospital Clinical Research Funding/ ; 2025-PUMCH-A-073//National High Level Hospital Clinical Research Funding/ ; 2025-PUMCH-A-075//National High Level Hospital Clinical Research Funding/ ; 2024-2-4017//Capital's Funds for Health Improvement and Research/ ; ZK12101//National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Building Project for Major Diseases/ ; No.UGG04598//Peking Union Medical College Hospital Talent Cultivation Program (Category B)/ ; No. 2024-I2M-ZD-001//CAMS Innovation Fund for Medical Sciences/ ; No. 2024bkjg015，No.2025bkjg005//Peking Union Medical College Hospital Undergraduate Educational Reform Project/ ; No. 2024dcxm100, No.2026dcxm275//Student Research Training Project, Chinese Academy of Medical Sciences & Peking Union Medical College/ ; Number GZC20240146//Postdoctoral Fellowship Program of CPSF under Grant/ ; 3332025001//Fundamental Research Funds for the Central Universities, Peking Union Medical College/ ; },
mesh = {*Killer Cells, Natural/immunology ; Animals ; Humans ; *Pancreatic Neoplasms/pathology/microbiology/immunology ; *Hippurates/metabolism ; *Carcinogenesis/pathology ; *Gastrointestinal Microbiome ; Hydrolysis ; Cell Line, Tumor ; Carcinoma, Pancreatic Ductal/pathology/microbiology ; Mice, Inbred C57BL ; Male ; Signal Transduction ; },
abstract = {BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by a lack of effective early detection, profoundly immunosuppressive microenvironment, and poor responsiveness to current therapies. Emerging evidence suggests that gut microbiota and their metabolites play important roles in pancreatic tumorigenesis. Glycoproteins shed from pancreatic precancerous lesions may influence the composition of the gut microbiota and their metabolites.

METHODS: We established a pancreatic precancerous lesion mouse model and performed integrated fecal metagenomic sequencing and non-targeted metabolomic profiling to characterize microbiota composition and metabolite alterations. Further we use plasma samples from patients, in vitro cytotoxicity assays and in vivo orthotopic pancreatic tumor models, fecal microbiota transplantation and pancreatic homogenate gavage to assess the effect of microbiota and metabolite alterations. And we conduct RNA sequencing, qPCR, ELISA, flow cytometry, molecular docking, and surface plasmon resonance to further explore its mechanisms.

RESULTS: We identified hippuric acid as a key microbiota-derived metabolite that was significantly reduced during pancreatic tumorigenesis, which was associated with suppressed anti-tumor immunity and enhanced PDAC progression. This reduction was associated with enrichment of microbiota harboring hippurate hydrolase and correlated with poor prognosis in PDAC patients. Mechanistically, hippuric acid activated IL-21R-STAT3-TBX21 signaling axis, promoting the expression of cytotoxic effector molecules, including granzyme B and perforin, thus enhancing NK cell cytotoxicity. Molecular docking and surface plasmon resonance analyses further suggested a direct interaction between hippuric acid and IL-21R.

CONCLUSIONS: Collectively, our study uncovers a previously unrecognized positive feedback regulatory loop involving the PDAC-gut microbiota-hippuric acid-NK cell-PDAC axis and highlights the critical role of gut microbiota and their metabolites in pancreatic tumorigenesis.},
}

*Killer Cells, Natural/immunology
Animals
Humans
*Pancreatic Neoplasms/pathology/microbiology/immunology
*Hippurates/metabolism
*Carcinogenesis/pathology
*Gastrointestinal Microbiome
Hydrolysis
Cell Line, Tumor
Carcinoma, Pancreatic Ductal/pathology/microbiology
Mice, Inbred C57BL
Male
Signal Transduction

@article {pmid43021973,
year = {2026},
author = {Wan, X and Zhou, Y and Long, T and Yuan, R and Bao, L and Li, H and Shi, P and Gong, R and Yan, S and Wu, Q and Jiang, H},
title = {Tolerogenic dendritic cells attenuate collagen-induced arthritis through a mucosal immunity-gut microbiota-butyrate axis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1971542},
pmid = {43021973},
issn = {1664-3224},
mesh = {Animals ; *Arthritis, Experimental/immunology/therapy/metabolism/microbiology ; *Dendritic Cells/immunology/transplantation/metabolism ; *Immunity, Mucosal ; *Gastrointestinal Microbiome/immunology ; Rats ; *Butyrates/metabolism ; Fecal Microbiota Transplantation ; *Immune Tolerance ; Male ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; },
abstract = {BACKGROUND: Tolerogenic dendritic cells (TolDCs) are being developed to restore antigen-specific immune tolerance in autoimmune diseases. However, whether their therapeutic effects in autoimmune arthritis involve modulation of the gut-joint axis remains unclear.

METHODS: TolDCs generated using an NF-κB decoy oligodeoxynucleotide were loaded with bovine type II collagen and administered to rats with collagen-induced arthritis (CIA). Arthritis severity was assessed clinically and histologically. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to assess microbiota involvement. Colonic tight-junction protein expression, mesenteric lymph node Treg/Th17 balance, fecal microbial communities, PICRUSt2-predicted short-chain fatty acid (SCFA)-related metabolic functions based on 16S rRNA sequencing data, serum SCFAs, and the effects of sodium butyrate supplementation were also evaluated.

RESULTS: TolDCs reduced paw swelling and arthritis scores and ameliorated ankle-joint pathology. In the concurrent antibiotic-depletion experiment, TolDC-associated improvements in arthritis outcomes did not reach statistical significance, whereas FMT from TolDC-treated donors partially transferred protection to antibiotic-pretreated CIA recipients. TolDC treatment increased colonic ZO-1 and occludin expression, shifted the mesenteric lymph node Treg/Th17 balance toward a regulatory profile, altered gut microbial community structure and composition, and was accompanied by higher predicted abundances of selected butyrate-associated MetaCyc pathways and KEGG Orthology (KO) functional groups, along with increased serum butyrate concentrations. Sodium butyrate supplementation partially reproduced the protective phenotype.

CONCLUSION: These findings support a microbiota-dependent component of TolDC-mediated protection and suggest that a coordinated mucosal immunity-gut microbiota-butyrate axis may contribute to arthritis control.},
}

Animals
*Arthritis, Experimental/immunology/therapy/metabolism/microbiology
*Dendritic Cells/immunology/transplantation/metabolism
*Immunity, Mucosal
*Gastrointestinal Microbiome/immunology
Rats
*Butyrates/metabolism
Fecal Microbiota Transplantation
*Immune Tolerance
Male
T-Lymphocytes, Regulatory/immunology
Th17 Cells/immunology

@article {pmid43022205,
year = {2026},
author = {Hu, X and Ma, G and Han, J and Zhu, L and He, Y and Zhu, D},
title = {From maternal microbial transmission to neonatal gut microbiota restoration: the potential and challenges of maternal fecal microbiota transplantation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1972665},
pmid = {43022205},
issn = {1664-302X},
abstract = {Early-life gut microbiota establishment is a critical developmental process shaped by maternal microbial transmission and ecological succession. Microorganisms from the maternal gut, vagina, breast milk, skin, and oral cavity contribute to neonatal microbial acquisition, while strain-resolved studies increasingly support the maternal gut as an important reservoir of strains capable of persistent colonization in the infant intestine. This transmission can be disrupted by cesarean delivery, prematurity, perinatal antibiotic exposure, and neonatal intensive care, resulting in delayed acquisition of maternal commensals, altered microbial succession, and increased colonization by opportunistic microorganisms. Current restoration strategies, including probiotics, synbiotics, and vaginal microbiota seeding, can modify early microbial communities but do not fully reproduce the diversity, maternal specificity, and persistence of naturally transmitted maternal gut strains. Maternal fecal microbiota transplantation (FMT) has therefore emerged as a potential strategy to restore disrupted maternal gut-to-infant microbial transmission. Initial proof-of-concept and strain-resolved studies suggest that carefully screened maternal FMT can increase mother-to-infant strain sharing, promote recovery from cesarean-associated microbiota perturbations, and reduce colonization by potential pathogens. However, evidence for durable engraftment, functional benefits, clinical efficacy, and long-term safety remains limited. Future studies should prioritize rigorous donor screening, standardized intervention protocols, appropriate recipient selection, and longitudinal integration of strain-resolved metagenomics, metabolomics, immune profiling, and clinical outcomes. Maternal FMT remains investigational but provides a promising framework for precision early-life microbiota restoration.},
}

@article {pmid43023447,
year = {2026},
author = {Pandey, SK and Mishra, A and Dash, SG},
title = {Gut Microbiota and Cancer Therapy Resistance: Mechanistic Insights with Emphasis on Colorectal Cancer.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673525110261104074049},
pmid = {43023447},
issn = {1875-533X},
abstract = {Therapeutic resistance remains a major limitation to the durable control of cancer despite advances in chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Resistance is shaped not only by tumor-intrinsic genetic and epigenetic alterations but also by extrinsic factors, including the gut microbiota. The intestinal microbial ecosystem can influence treatment response through direct drug biotransformation, modulation of host immunity and inflammation, production of bioactive metabolites, alteration of epithelial barrier function, and interactions with the tumor microenvironment. This narrative review synthesizes these mechanisms across chemotherapy, radiotherapy, and immune checkpoint blockade, with particular emphasis on Colorectal Cancer (CRC), while incorporating evidence from breast, lung, melanoma, and other relevant tumor types. Microbial metabolites, including short-chain fatty acids, bile-acid derivatives, tryptophan metabolites, and microbially generated organic acids, can influence signaling, immune-cell function, redox balance, and treatment sensitivity. We further evaluate microbiome-directed approaches, including dietary modulation, probiotics, fecal microbiota transplantation, antibiotic stewardship, and inhibition of microbial drug-metabolizing enzymes. Particular attention is given to the translational challenges of patient-to-patient microbiome variability, safety, biomarker reproducibility, treatment timing, and cancer-type specificity. Collectively, current evidence supports the gut microbiota as a biologically plausible and potentially modifiable determinant of cancer therapy response, but clinical implementation will require mechanism-based biomarkers and rigorously controlled prospective studies.},
}

@article {pmid43023597,
year = {2026},
author = {Chin, A and Gardner, C and Menon, S and Makanyanga, J and Gliddon, T and Li, A and Waters, O},
title = {Faecal microbiota transplantation for severe, refractory Clostridioides difficile infection: a multicentre real-world experience.},
journal = {Internal medicine journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/imj.70702},
pmid = {43023597},
issn = {1445-5994},
abstract = {BACKGROUND: Severe Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality. Although most patients respond to CDI-directed antimicrobial therapy, a subset develops refractory disease. Faecal microbiota transplantation (FMT) is established for recurrent CDI, but data supporting its use in severe, refractory CDI remain limited.

AIMS: To evaluate the safety and effectiveness of FMT in hospitalised patients with severe, refractory CDI across tertiary centres.

METHODS: This was a retrospective multicentre study of adults with severe, refractory CDI who underwent FMT at three tertiary hospitals in Western Australia between January 2021 and April 2025. Severe CDI was defined according to Australasian Society of Infectious Diseases criteria and refractory disease as failure to demonstrate clinical improvement following appropriate CDI-directed antimicrobial therapy. Primary cure was defined as resolution without recurrence within 90 days following a single FMT. Secondary outcomes included secondary cure, colectomy, FMT-related complications and hospital length of stay.

RESULTS: Fourteen patients underwent FMT for severe, refractory CDI. Median age was 68.5 years (range 32-84), 57.1% were female, and 71.4% were immunosuppressed. Median Charlson Comorbidity Index was 5.5 (range 0-11). FMT was delivered via colonoscopy, flexible sigmoidoscopy or nasogastric tube. Median sessions was 1.5 (range 1-4); five (35.7%) patients received consolidative antibiotics following repeat FMT. Primary cure after a single FMT was achieved in seven (50%) patients. The remaining seven required repeat FMT, with a secondary cure rate of 100% at 3 months. One patient died from an unrelated cause. No patients required colectomy, experienced recurrence or FMT-related complications. Median hospital stay was 24.5 days (range 7-65).

CONCLUSION: FMT was associated with high rates of clinical cure as salvage therapy for hospitalised patients with severe, refractory CDI. While only half achieved primary cure after a single FMT, sequential FMT achieved a secondary cure rate of 100%. Further studies are needed to define optimal treatment protocols.},
}

@article {pmid43024353,
year = {2026},
author = {Wu, Y and Zhang, T and Shu, X and Ma, S and Chen, L and Zhang, R and Yang, C},
title = {Lactiplantibacillus plantarum postbiotics attenuate Salmonella LPS-triggered neuroinflammation by modulating the microbiota-gut-brain axis in a pig model.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo03671f},
pmid = {43024353},
issn = {2042-650X},
abstract = {This study explored the effects of Lactiplantibacillus plantarum (LP) postbiotics on Salmonella LPS-induced neuroinflammation, and elucidated the underlying mechanisms. Sixty pigs were randomly divided into control, lipopolysaccharide (LPS), cell-free supernatant of LP (CFS) and CFS + LPS groups. The pigs were fed with 0.8% CFS or MRS medium for 28 days, and then exposed to 30 μg kg[-1] LPS. The results showed that CFS alleviated damage of the liver, colon and brain, and improved brain tight junctions. LPS significantly upregulated the levels of IL-1β, IL-6 and TNF-α (P < 0.05) and downregulated IL-4 and IL-10 (P < 0.05), while CFS pretreatment markedly reversed this trend. LPS activated the brain inflammasome by increasing NLRP3, IL-1β, IL-18 and GSDMD (P < 0.05), and CFS pretreatment significantly decreased NLRP3 and IL-1β (P < 0.05). CFS modulated the levels of neurotransmitters, particularly the tryptophan metabolism. Moreover, CFS markedly increased the contents of microbial metabolites (P < 0.05) and optimized the gut microbiota through improving Lactobacillus amylovorus and Lactobacillus reuteri (P < 0.05). To further clarify the role of the microbiota on alleviating neuroinflammation, the fecal microbial transplantation (FMT) model in mice was established. The mice were administered with fecal suspension from CFS-treated pigs for 14 days and challenged with 3 × 10[8] CFU Salmonella Typhimurium (ST) for three days. The results showed that the weight loss caused by ST was significantly alleviated by CFS and FMT-CFS pretreatment (P < 0.05). FMT-CFS markedly inhibited ST translocation in the spleen and brain (P < 0.05), and attenuated tissue damage. FMT-CFS dramatically suppressed neuroinflammation and NLRP3 activation. In summary, LP postbiotics attenuated Salmonella LPS-induced neuroinflammation via modulating the microbiota-gut-brain axis. Our findings provide the potential of postbiotics as a nutritional supplement to alleviate neuroinflammation.},
}

@article {pmid43025194,
year = {2026},
author = {Ohbayashi, Y and Imataki, O and Takeuchi, A and Sakaji, M and Ishida, T and Uchida, S and Uemura, M and Nakayama-Imaohji, H and Tada, A and Kuwahara, T and Miyake, M},
title = {Longitudinal dynamics of the oral microbiota during allogeneic hematopoietic stem cell transplantation: an exploratory study with complementary gut microbiota analysis.},
journal = {Journal of oral biosciences},
volume = {68},
number = {6},
pages = {100836},
doi = {10.1016/j.job.2026.100836},
pmid = {43025194},
issn = {1880-3865},
abstract = {OBJECTIVES: The oral microbiota undergoes substantial ecological disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT), potentially contributing to systemic infections. Although allo-HSCT-associated gut microbiota dysbiosis has been extensively investigated, longitudinal changes in oral microbiota and their relationship with bloodstream infections (BSIs) remain incompletely understood. We therefore aimed to characterize longitudinal changes in oral and gut microbiota and examine their association with BSIs.

METHODS: We prospectively analyzed the oral and gut microbiota of 16 adult allo-HSCT recipients using 16S rRNA gene sequencing. Salivary and fecal samples were collected before transplantation, on the day of transplantation, during neutropenia, at engraftment, and after engraftment.

RESULTS: Six patients developed 11 BSI episodes, with the first episode in each patient occurring at a median of 8 days after transplantation. Staphylococcus haemolyticus was the most common pathogen (7/11 episodes), followed by Enterococcus faecium (2/11 episodes). The oral microbiota underwent marked longitudinal alterations throughout the transplantation period, accompanied by similar changes in the gut microbiota. Differences in microbiota trajectories were observed between patients with and without BSIs despite comparable cumulative antibiotic exposure. Oral-associated genera, including Streptococcus, Fusobacterium, Veillonella, Actinomyces, and Lautropia, were detected in fecal samples, suggesting possible oral-to-gut translocation.

CONCLUSIONS: The oral and gut microbiota underwent substantial longitudinal alterations during allo-HSCT. Differences in microbiota dynamics between patients with and without BSIs were not explained solely by antibiotic exposure. These exploratory findings provide insights into the timing of oral and gut microbiota alterations during allo-HSCT and highlight potential relationships between oral and gut microbial changes and BSIs.},
}

@article {pmid43012689,
year = {2026},
author = {Liu, Y and Wang, S and Chen, G and Chen, ZY and Li, X and Lin, R and He, Z},
title = {Mangiferin Protects Gut Barrier Integrity by Remodeling the Gut Microbiota-Sphingolipid-S1PR4 Signaling Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {44},
pages = {34818-34836},
doi = {10.1021/acs.jafc.6c09634},
pmid = {43012689},
issn = {1520-5118},
support = {32302071//National Natural Science Foundation of China (NSFC)/ ; 32560559//National Natural Science Foundation of China (NSFC)/ ; 50//Innovation Project of Guangxi Medical University/ ; N.A.//First-class Discipline Innovation-driven Talent Program of Guangxi Medical University/ ; },
mesh = {*Xanthones/administration & dosage ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Sphingolipids/metabolism ; Humans ; Signal Transduction/drug effects ; Intestinal Barrier Function/drug effects ; Male ; Mice, Inbred C57BL ; *Sphingosine-1-Phosphate Receptors/metabolism/genetics ; *Protective Agents/administration & dosage ; Intestinal Mucosa/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Bacteria/isolation & purification/classification/genetics/metabolism/drug effects ; },
abstract = {Mangiferin, a poorly absorbed C-glycosyl xanthone derived from mango, exerts intestinal protective effects through unclear mechanisms. This study investigated whether mangiferin mitigates high-fat diet (HFD)-induced gut barrier dysfunction via the gut microbiota-sphingolipid signaling axis. In HFD-fed mice, mangiferin ameliorated gut barrier injury by strengthening the mucus layer and upregulating tight junction proteins. Integrated multiomics revealed that mangiferin remodeled the gut microbiota and enriched fecal bioactive sphingolipids. Fecal microbiota transplantation from mangiferin-treated donors substantially recapitulated both the sphingolipidomic signature and the barrier-protective phenotype, suggesting a contributory role of gut microbiota. Furthermore, pharmacological inhibition of sphingosine-1-phosphate receptor 4 (S1PR4) with CYM50358 attenuated mangiferin-induced barrier protection, supporting the functional contribution of S1PR4 activation. These findings propose a novel gut microbiota-sphingolipid-S1PR4 signaling axis through which mangiferin protects the intestinal barrier, at least in part, providing a mechanistic framework for dietary xanthone-host communication and identifying S1PR4 as a promising target for developing gut barrier-protective nutraceuticals.},
}

*Xanthones/administration & dosage
Animals
*Gastrointestinal Microbiome/drug effects
Mice
*Sphingolipids/metabolism
Humans
Signal Transduction/drug effects
Intestinal Barrier Function/drug effects
Male
Mice, Inbred C57BL
*Sphingosine-1-Phosphate Receptors/metabolism/genetics
*Protective Agents/administration & dosage
Intestinal Mucosa/metabolism/drug effects
Diet, High-Fat/adverse effects
Bacteria/isolation & purification/classification/genetics/metabolism/drug effects

@article {pmid43013155,
year = {2026},
author = {Al-Zaidi, OSSH and Ali, AH},
title = {Gut microbiome in leukemia: emerging insights, mechanistic and clinical implications.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {43013155},
issn = {1573-4978},
mesh = {Humans ; *Leukemia/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Animals ; },
abstract = {Leukemia is a hematological malignancy that arises from complex interactions among environmental factors, immune dysregulation, and genetic mutations. The Human Microbiome Project has contributed to understanding the potential role of the gut microbiome in the health of patients with leukemia, and its impact on leukemia development, progression, and response to therapies. This review summarizes how the gut microbiome and its constituent microorganisms may influence development and the new therapeutic approaches against leukemia. Recent findings indicate that microorganisms might influence leukemia through multiple mechanisms, including chronic inflammation, homeostasis disruption, and genomic instability. Dysbiosis of the gut microbiome might increase the risk of infection, impair response to immunotherapy and chemotherapy and increase the risk of clinical complications. Probiotics, postbiotics, and fecal microbiota transplantation (FMT) have emerged as promising microbiome-modulating approaches. Despite the abundance of emerging data suggesting potential therapeutic benefits, most studies remain small and preliminary. Integrating gut microbiome science into medical practice may open up new and potentially more effective therapeutic avenues for managing leukemia.},
}

Humans
*Leukemia/microbiology/therapy
Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/physiology
Dysbiosis/microbiology
Probiotics/therapeutic use
Animals

@article {pmid43013741,
year = {2026},
author = {Barcena-Varela, M and Shang, J and Lozano, A and Mogno, I and Liebling, I and Mead, K and Li, Z and Grinspan, LT and Lindblad, KE and Ruiz de Galarreta, M and Donne, R and Gnjatic, S and Merad, M and Jun, T and Ang, C and Marron, TU and Faith, JJ and Lujambio, A},
title = {Bacteroidetes promote hepatocellular carcinoma progression and resistance to immunotherapy.},
journal = {Hepatology communications},
volume = {10},
number = {12},
pages = {},
pmid = {43013741},
issn = {2471-254X},
mesh = {Animals ; *Carcinoma, Hepatocellular/microbiology/immunology/therapy/pathology/drug therapy ; *Liver Neoplasms/microbiology/immunology/therapy/pathology/drug therapy ; Mice ; *Bacteroidetes ; Humans ; *Immunotherapy/methods ; Disease Progression ; *Gastrointestinal Microbiome/immunology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Dysbiosis ; *Drug Resistance, Neoplasm ; Disease Models, Animal ; Tumor Microenvironment/immunology ; Male ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND AND AIMS: Growing evidence highlights the gut microbiome's critical role in tumorigenesis and immunotherapy response. However, the impact of gut microbes on hepatocellular carcinoma (HCC) progression and response to immune checkpoint blockade (ICB) remains unclear due to the lack of combined preclinical and clinical studies.

APPROACH AND RESULTS: We performed 16S rRNA sequencing of cross-cohort stool samples from 10 HCC responders (R) and 40 non-responders (NR) to ICB at baseline and on-treatment time points. We identified Bacteroidetes enrichment in NR. To study the microbiome's role in cancer immune response, we generated an immunogenic mouse model of HCC via hydrodynamic tail-vein injection (HDTVI) of DNA plasmids mimicking common HCC alterations and immunogenicity by expressing OVA model antigens (MYC-lucOS;CTNNB1 tumors). We found that antibiotic (ABX)-induced dysbiosis promoted a pro-tumorigenic effect in the MYC-lucOS;CTNNB1 HCC and reshaped the tumor immune microenvironment by reducing dendritic cells (DCs) through the expansion of the Bacteroidetes species, Parabacteroides distasonis. P. distasonis colonization in mice harboring MYC-lucOS;CTNNB1 liver tumors confirmed its pro-tumorigenic effect in vivo. Furthermore, fecal matter transplant of patient microbiotas into murine recipients demonstrated that microbiota from an NR donor enriched in Bacteroidetes promoted faster tumorigenesis compared with microbiota from an R donor with reduced Bacteroidetes. We isolated 6 Bacteroidetes species from the NR donor into a bacterial cocktail. After colonization with the Bacteroidetes cocktail, mice harboring MYC-lucOS;CTNNB1 HCC exhibited increased tumorigenesis, reduced survival, and impaired response to ICB.

CONCLUSIONS: This study identified Bacteroidetes enrichment as a potential biomarker of ICB resistance in HCC and, by using immunogenic mouse models, established that Bacteroidetes abundance influences tumor development and response to ICB.},
}

Animals
*Carcinoma, Hepatocellular/microbiology/immunology/therapy/pathology/drug therapy
*Liver Neoplasms/microbiology/immunology/therapy/pathology/drug therapy
Mice
*Bacteroidetes
Humans
*Immunotherapy/methods
Disease Progression
*Gastrointestinal Microbiome/immunology
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Dysbiosis
*Drug Resistance, Neoplasm
Disease Models, Animal
Tumor Microenvironment/immunology
Male
Mice, Inbred C57BL

@article {pmid43015280,
year = {2026},
author = {Ma, J and Liao, X and Wang, W and Quan, Y and Acharya, P and Bai, Y},
title = {Mesenchymal stem cells protect against diabetic nephropathy through gut microbiota-butyrate-mediated inhibition of neutrophil extracellular traps.},
journal = {Nutrition & diabetes},
volume = {16},
number = {1},
pages = {},
pmid = {43015280},
issn = {2044-4052},
mesh = {Animals ; *Diabetic Nephropathies/therapy/prevention & control/metabolism ; Rats ; *Extracellular Traps/metabolism ; Male ; *Gastrointestinal Microbiome/physiology ; *Mesenchymal Stem Cells/physiology ; *Mesenchymal Stem Cell Transplantation ; Fecal Microbiota Transplantation ; *Butyrates/metabolism ; Diabetes Mellitus, Experimental/complications ; Rats, Sprague-Dawley ; Fatty Acids, Volatile/metabolism ; Diet, High-Fat ; Neutrophils ; },
abstract = {BACKGROUND: Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential in diabetic nephropathy (DN), yet the underlying mechanisms remain incompletely understood, limiting strategies to enhance their efficacy. This study aimed to elucidate whether MSCs exert renoprotective effects by modulating the gut microbiota and its metabolite short-chain fatty acids (SCFAs).

METHODS: DN was induced in rats via a high-fat diet (HFD) combined with streptozotocin (STZ) injection. MSCs were administered via tail vein infusion. Therapeutic efficacy was evaluated by renal function parameters, urine biochemistry, and renal histopathology. Neutrophil extracellular trap (NET) formation was assessed using immunofluorescence staining and ELISA. Alterations in gut microbial composition and SCFA profiles were analyzed through 16S rRNA gene sequencing and targeted metabolomics, respectively. The causal role of the gut microbiota was validated using fecal microbiota transplantation (FMT).

RESULTS: Administration of MSCs, as well as FMT from MSC-treated donors, significantly ameliorated renal injury and suppressed NET formation in DN rats. Notably, pharmacological induction of NETs abolished the protective effects conferred by MSC-FMT. 16S rRNA sequencing revealed that MSC intervention enriched beneficial bacterial populations, particularly within the family Muribaculaceae. Targeted metabolomic analysis identified a significant elevation of butyrate among fecal SCFAs in MSC-treated rats. Furthermore, exogenous butyrate supplementation recapitulated the inhibitory effects on NET formation and attenuated DN progression.

CONCLUSION: MSC therapy alleviates diabetic nephropathy via a gut-kidney axis mechanism, driven by the enrichment of butyrate-producing microbiota and the subsequent inhibition of neutrophil extracellular trap formation.},
}

Animals
*Diabetic Nephropathies/therapy/prevention & control/metabolism
Rats
*Extracellular Traps/metabolism
Male
*Gastrointestinal Microbiome/physiology
*Mesenchymal Stem Cells/physiology
*Mesenchymal Stem Cell Transplantation
Fecal Microbiota Transplantation
*Butyrates/metabolism
Diabetes Mellitus, Experimental/complications
Rats, Sprague-Dawley
Fatty Acids, Volatile/metabolism
Diet, High-Fat
Neutrophils

@article {pmid43016980,
year = {2026},
author = {Khan, A and Tareen, A and Farid, AAM and Amin, A and Khan, HN and Hadi, DK and Khan, SR and Raza, A},
title = {The microbiome-metabolome axis in colorectal cancer therapy resistance: mechanisms, mediators, and therapeutic opportunities.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1985675},
pmid = {43016980},
issn = {2234-943X},
abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic resistance representing a significant barrier to improved patient outcomes. Although tumor-intrinsic genetic alterations are important determinants of treatment resistance, emerging evidence suggests that the gut microbiome and its metabolites may also influence responses to chemotherapy, targeted therapy, and immunotherapy. The microbiome and metabolome function as an interconnected axis that can influence host immunity, microbial drug metabolism, epithelial homeostasis, and tumor-associated signaling pathways, thereby contributing to variation in therapeutic response. Despite advances in microbiome research, the mechanisms by which the microbiome-metabolome axis promotes therapy resistance are not fully elucidated, and clinical translation is limited by the absence of standardized biomarkers and validated therapeutic strategies. This review synthesizes current evidence on the molecular mechanisms through which the microbiome-metabolome axis contributes to CRC therapy resistance, with emphasis on microbial dysbiosis, bacterial metabolites, and host-microbial interactions in modulating treatment efficacy. Emerging microbiome-directed therapeutic approaches, including fecal microbiota transplantation, defined microbial consortia, dietary interventions, microbial metabolites, and engineered microbial therapies, are examined, along with the methodological and translational challenges that must be addressed before their integration into routine clinical practice.},
}

@article {pmid43017404,
year = {2026},
author = {Chen, Y and Li, Y and Li, X and Xu, X and Chen, S},
title = {Therapeutic opportunities of fecal microbiota transplantation in the treatment of non-alcoholic fatty liver disease.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1962509},
pmid = {43017404},
issn = {2235-2988},
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; },
abstract = {Based on the emerging evidence in the crosstalk between gut microbiota composition and the non-alcoholic fatty liver disease (NAFLD), the application of fecal microbiota transplantation (FMT) on patients with NAFLD has become an attractive research field. Evidence from multiple studies have proved that lean patients with NAFLD were more sensitive to FMT in both microbiomic and metabolic aspects compared to obese patients, and more benefits were observed in patients receiving allogenic FMT from lean donors compared to those receiving autologous FMT, possibly due to the benefits derived from the successful engraftment of donor's microbiota post FMT. However, it has been observed from the clinical practice that an identified successful engraftment is not a promise of clinical efficacy in NAFLD patients. This review aims to summarize the current evidence supporting application of FMT in treatment of NAFLD. We realized that the clinical efficacy and long-term benefits of FMT on NAFLD patients warrant further investigation with more properly-designed randomized controlled trials.},
}

*Fecal Microbiota Transplantation/methods
Humans
*Non-alcoholic Fatty Liver Disease/therapy/microbiology
Gastrointestinal Microbiome
Treatment Outcome

@article {pmid43017556,
year = {2026},
author = {Huang, X and Zhang, X and Zhu, Q},
title = {Microbiome-targeted strategies for Alzheimer's disease: multi-omics signatures, mechanistic links, and intervention evidence.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1828118},
pmid = {43017556},
issn = {1664-302X},
abstract = {Alzheimer's disease (AD) is increasingly studied in relation to gut microbial mechanisms because microbial metabolism, mucosal barrier function, and peripheral immune activation may influence neuroinflammation and host metabolic stress. This review evaluates microbiome-linked evidence in AD with emphasis on studies that combine metagenomics, metabolomics, inflammatory markers, neuroimaging, cerebrospinal fluid or blood biomarkers, and cognitive phenotyping. Current data support several recurring but not yet causal axes, including bile acid transformation, short-chain fatty acid (SCFA) production, trimethylamine N-oxide (TMAO), bacterial product-related inflammatory signaling, and barrier dysfunction. We also review microbiome-targeted interventions, including diet and prebiotics, strain-specified probiotics and synbiotics, oligosaccharide-based agents, gut-restricted antimicrobials, and fecal microbiota transplantation (FMT). The strength of evidence differs substantially across these strategies: sodium oligomannate has been tested in a phase 3 trial, whereas many probiotic, antimicrobial, and FMT approaches remain early clinical, preclinical, or mechanism-generating. Future trials should define a priori microbial, metabolite, immune, and brain biomarker endpoints; control diet, medication, and comorbidity confounding; and validate candidate signatures across independent cohorts before using microbiome profiles for screening or treatment selection.},
}

@article {pmid43007607,
year = {2026},
author = {Wang, H and Wu, R and Gemingnuer, A and Xu, S and Meng, X},
title = {The Gut-Brain Axis in Binge Eating Disorder: From Pathophysiological Mechanisms to Emerging Therapeutic Targets.},
journal = {Obesity surgery},
volume = {},
number = {},
pages = {},
pmid = {43007607},
issn = {1708-0428},
abstract = {Binge-eating disorder (BED) is one of the most prevalent eating disorders worldwide; however, current pharmacological and psychological interventions provide limited long-term efficacy. Increasing evidence indicates that dysregulation of the gut-brain axis (GBA) via altered gut microbiota, impaired hormonal signaling, vagal dysfunction, and HPA axis hyperactivity disrupts energy homeostasis and feeding regulation in BED. These interconnected abnormalities may contribute to impaired satiety perception, enhance reward-driven eating behaviors, perpetuate stress-induced binge episodes, and may be associated with metabolic dysregulation, thereby contributing to obesity susceptibility in individuals with BED. In this review, we summarize recent clinical and preclinical advances on GBA involvement in BED pathogenesis and discuss emerging therapeutic strategies targeting this regulatory network. We pay particular attention to microbial metabolites, endocrine signaling, immune regulation, and neural pathways involved in appetite control and reward processing. Furthermore, we evaluate novel GBA-targeted interventions, including probiotics, prebiotics, fecal microbiota transplantation (FMT), glucagon-like peptide-1 receptor (GLP-1R) agonists, and vagus nerve stimulation (VNS), with emphasis on their underlying mechanisms, current evidence, and translational challenges. Finally, we propose an integrated framework for future research, highlighting the importance of large-scale longitudinal studies and biomarker-guided patient stratification to improve therapeutic precision. Targeting the gut-brain axis represents a promising investigational approach for BED management; however, clinical validation and biomarker-guided strategies remain necessary before its translation into routine practice.},
}

@article {pmid43008558,
year = {2026},
author = {Lin, X and Alioui, Y and Wang, W and Wu, L and Ao, J and Yan, C and Liao, J and Wang, Z and Wu, Y and Feng, Y and Ma, Z and You, H and Luo, L},
title = {Caffeic acid regulates the gut microbiota-tryptophan metabolic axis to improve intestinal barrier function and relieve ulcerative colitis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {163},
number = {},
pages = {158905},
doi = {10.1016/j.phymed.2026.158905},
pmid = {43008558},
issn = {1618-095X},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which current therapies remain inadequate. Caffeic acid (CA), a natural hydroxycinnamic acid polyphenol, possesses anti-inflammatory and antioxidant properties. However, whether CA engages the gut microbiota-tryptophan-aryl hydrocarbon receptor (AHR)-Nrf2 axis in UC has not been established.

PURPOSE: To evaluate the anti-UC activity of CA in vivo and in vitro and to elucidate its underlying mechanisms through a multi-platform integrative strategy.

STUDY DESIGN: A dextran sulfate sodium (DSS)-induced murine colitis model and lipopolysaccharide (LPS)-stimulated mouse colonic epithelial cells (MCECs) were used in parallel. Mechanism was addressed by combining microbiota, metabolomic, transcriptomic and proteomic profiling with faecal microbiota transplantation, computational and biophysical target validation, and siRNA-mediated AHR knockdown.

METHODS: CA was administered at 10 and 20 mg/kg/day, with 5-aminosalicylic acid as positive control. Complementary platforms included 16S rRNA gut microbiota sequencing, untargeted serum metabolomics, colonic transcriptomic profiling, data-independent acquisition mass spectrometry proteomics, human UC single-cell RNA sequencing (GEO: GSE214695), faecal microbiota transplantation into antibiotic-pretreated recipients, molecular docking, 100 ns molecular dynamics simulation, cellular thermal shift assay, dual-luciferase reporter assay, and co-immunoprecipitation.

RESULTS: CA dose-dependently alleviated dextran sulfate sodium-induced colitis, suppressed NF-κB activation, and reduced interleukin-6, interleukin-1β, and tumour necrosis factor alpha. Gut microbiota profiling revealed enrichment of Bifidobacterium and Dubosiella with depletion of Escherichia-Shigella. Transplantation of the CA-remodelled microbiota into antibiotic-pretreated recipients reproduced the protective phenotype and restored colonic AHR and cytochrome P450 1A1 expression, demonstrating that the remodelled community is sufficient to confer protection. Metabolomics showed enrichment of serotonin-branch tryptophan metabolites, with 5-hydroxytryptamine among the most significantly enriched differential metabolites. Molecular docking and 100 ns molecular dynamics simulation indicated stable binding of CA within the AHR ligand-binding domain, cellular thermal shift assay confirmed intracellular target engagement, and a dual-luciferase reporter assay demonstrated concentration-dependent activation of dioxin response element-driven transcription, establishing CA as an AHR agonist. CA increased Nrf2, NQO1 and HO-1 and restored Claudin-1, Occludin and zonula occludens-1; AHR knockdown reduced these effects and the suppression of NF-κB, indicating that both actions depend on AHR.

CONCLUSIONS: CA ameliorates UC through convergent AHR activation, arising from both microbiota-mediated tryptophan reprogramming and direct receptor binding, with AHR-dependent Nrf2/NQO1/HO-1 induction and NF-κB suppression to restore intestinal barrier integrity. These findings support CA as a multi-target phytochemical candidate for UC treatment.},
}

@article {pmid43009128,
year = {2026},
author = {Kain, V and Upadhyay, G and Suraksha, K and Li, S and Sundaraswamy, PM and Jayaprakash, J and Gowda, D and Chainani, N and Krishna, N and Ghobrial, M and Fouad, A and Hui, SP and Mishra, SP and Hall, N and Tan, Z and Soto, NH and Liu, R and Jain, S and Gowda, SGB and Yadav, H and Halade, GV},
title = {Multi-omics analyses of HFpEF progression and regression reveals multi-organ-specific metabolic dysregulation and impaired inflammation resolution.},
journal = {Metabolism: clinical and experimental},
volume = {},
number = {},
pages = {156838},
doi = {10.1016/j.metabol.2026.156838},
pmid = {43009128},
issn = {1532-8600},
abstract = {BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex cardiometabolic syndrome with limited effective therapies. Given its heterogeneity, whether withdrawal of cardiometabolic stress reverses HFpEF-associated inflammatory, metabolic, and molecular remodeling remains unclear.

OBJECTIVES: To characterize multi-organ metabolic, molecular, and bioactive-lipid remodeling in an obesity-hypertension HFpEF model and determine the extent of recovery during an 8-week combined high-fat diet withdrawal and L-NAME cessation protocol using parallel multi-omics profiling.

METHODS: HFpEF was induced in C57BL/6 mice using a high-fat diet plus nitric oxide synthase inhibition(H + L). A regression cohort(R-H + L) underwent simultaneous return to standard chow and L-NAME cessation for 8 weeks. Multi-omics profiling included targeted and untargeted lipidomics, cardiac transcriptomics, metabolomics, fecal microbiome, and plasma short-chain fatty acid analyses, with detailed assessment of the left ventricle.

RESULTS: H + L mice developed an obesity-hypertension HFpEF phenotype characterized by predominant diastolic dysfunction, concentric remodeling, hypertension, and increased fat mass. The combined regression of H + L protocol attenuated these phenotypic abnormalities but did not restore all measures to control levels. H + L was associated with multi-organ remodeling marked by altered arachidonic acid-derived oxylipid pathways, depletion of triacylglycerols and phospholipids, and enrichment of diacylglycerols and lysophospholipids, consistent with altered resolution-related lipid signaling. Cardiac transcriptomics revealed changes in immune, circadian, vascular, and mitochondrial gene programs, whereas metabolomics revealed altered energy, arginine, and redox metabolism. H + L was also associated with reduced microbial diversity and altered short-chain fatty acids, particularly acetate and propionate. Within the 8-week recovery window, partial reprogramming occurred, but differences remained in lipid signaling, metabolic stress responses, and microbiome-associated measures.

CONCLUSIONS: The HFD/L-NAME model is accompanied by extensive multi-organ metabolic and molecular remodeling. Combined withdrawal of HFD/L-NAME attenuates the HFpEF phenotype however did not fully normalize molecular profiles within the 8-week recovery period. Persistent lipid-remodeling and metabolic dysregulation may represent potential therapeutic targets thus warrants pathway specific investigation.},
}

@article {pmid43010179,
year = {2026},
author = {Tracey, H and Antolín, A and Teichenne, J and Jones, OAH and Van, TTH and Puig, J and Ramos, R and Garre-Olmo, J and Fernández-Real, JM and Mayneris-Perxachs, J and Del Bas, JM},
title = {Human cognitive performance-associated gut microbiota influences learning and memory in mice through arginine and pterin metabolism.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2750588},
doi = {10.1080/19490976.2026.2750588},
pmid = {43010179},
issn = {1949-0984},
mesh = {Animals ; Humans ; Male ; Mice, Inbred C57BL ; Mice ; *Cognition ; *Gastrointestinal Microbiome/physiology ; *Arginine/metabolism ; *Memory ; Fecal Microbiota Transplantation ; Feces/microbiology ; Aged ; Hippocampus/metabolism ; Bacteria/classification/isolation & purification/genetics/metabolism ; *Learning ; },
abstract = {The human gut microbiome undergoes changes across the lifespan and has been implicated in age-related decline. The symbol digit modalities test (SDMT) is a measure of information processing speed and is sensitive to mild cognitive impairment. Here, we assessed SDMT scores and fecal shotgun metagenomics in older individuals from the Imageomics cohort (n = 867) and performed fecal microbiota transplantation (FMT) from human donors to male C57BL/6 mouse recipients. In mice, we evaluated cognitive performance using the Morris water maze (MWM) and measured neurone density, fecal shotgun metagenomics, hippocampal metabolomics, and cortical gene expression to identify microbial-derived functional properties related to cognitive performance. In humans, both microbial species composition and functional profiles were associated with cognitive performance. FMT from high-SDMT donors improved cognitive performance and increased neuronal density in recipient mice compared with FMT from low-SDMT donors. In both humans and mice, higher cognitive performance was associated with arginine and proline metabolism and pterin-related pathways. In mice receiving microbiota from high-SDMT donors, cortical gene expression showed enrichment of dopamine receptor pathways and reduced dopamine reuptake and catecholamine biosynthesis. Our findings highlight the potential role of the gut microbiome in cognitive performance among older individuals, particularly information processing speed, and identify potential mechanisms involving alterations in arginine and pterin metabolism. Integrating human and mouse data supports a model in which microbiota-associated metabolic remodeling influences cognitive performance.},
}

Animals
Humans
Male
Mice, Inbred C57BL
Mice
*Cognition
*Gastrointestinal Microbiome/physiology
*Arginine/metabolism
*Memory
Fecal Microbiota Transplantation
Feces/microbiology
Aged
Hippocampus/metabolism
Bacteria/classification/isolation & purification/genetics/metabolism
*Learning

@article {pmid43010961,
year = {2026},
author = {Fu, A and Guo, R and Wang, K and Zhuge, H and Ying, G and Ma, W and Ding, Q and Li, S and Bao, J and Yu, W},
title = {Chaihuang weikuining protects against ethanol-induced gastric ulcer through modulation of gut microbiota and inhibition of JAK1/STAT3 signaling.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1924725},
pmid = {43010961},
issn = {1664-302X},
abstract = {BACKGROUND: Chaihuang weikuining (CHWKN) is a traditional Chinese medicinal formula with reported anti-ulcer activity. However, the underlying mechanisms remain unclear. This study aimed to investigate the protective effects of CHWKN against ethanol-induced gastric ulcer (GU) and to explore the role of gut microbiota in mediating these effects.

METHODS: An ethanol-induced GU model was established in rats. Histological staining (H&E and PAS) and biochemical analyses were used to evaluate gastric injury. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) were performed to determine the involvement of gut microbiota. 16S rDNA sequencing was conducted to analyse microbial composition.

RESULTS: CHWKN markedly alleviated ethanol-induced gastric mucosal injury, as evidenced by improved histopathological features and restored of gastric function. CHWKN significantly reduced myeloperoxidase (MPO) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and LPS) while increasing IL-10 levels, accompanied by suppression of JAK1/STAT3 signaling. Notably, depletion of gut microbiota abolished the protective and anti-inflammatory effects of CHWKN. Conversely, FMT from CHWKN-treated donors (the donor rats treated with ethanol and CHWKN) restored gastric mucosal integrity and reduced inflammation in recipient rats. Furthermore, CHWKN remodeled the composition of gut microbiota by increasing potentially beneficial bacteria and reversing ethanol-induced dysbiosis.

CONCLUSION: These findings demonstrate that CHWKN exerts protective effects against ethanol-induced GU by modulating of gut microbiota and subsequently inhibiting of JAK1/STAT3-mediated inflammation. This highlights a microbiota-dependent mechanism underlying its therapeutic action.},
}

@article {pmid43011569,
year = {2026},
author = {Akif, A and Sultana, N and Mikrani, I},
title = {The Microbiota-Metabolism Axis: Mechanistic Insights and Translational Targets Across Diabetes and Gastrointestinal Disorders.},
journal = {International journal of endocrinology},
volume = {2026},
number = {},
pages = {7761643},
pmid = {43011569},
issn = {1687-8337},
abstract = {The gut microbiota (GM) modulates host energy balance, glucose-lipid metabolism, and enteroendocrine signaling through metabolite-receptor axes that include short-chain fatty acids (SCFAs) acting on FFAR2/FFAR3 (GPR43/GPR41), microbially transformed bile acids signaling via FXR/TGR5, and amino-acid/choline-derived compounds such as imidazole propionate (ImP) and trimethylamine N-oxide (TMAO). These pathways regulate incretin biology (GLP-1/PYY), insulin sensitivity, hepatic glucose output, adipose lipolysis, and appetite, thereby shaping risk and progression of Type 2 diabetes mellitus (T2DM), obesity, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and related conditions. Here, we synthesize mechanistic and translational evidence, highlight bidirectional drug-microbiome interactions (GLP-1 receptor agonists), and review interventions spanning diet, pre/probiotics, fecal microbiota transplantation (FMT), and pharmacologic targeting of bile-acid and SCFA pathways. Together, these findings support precision strategies that profile GM-metabolite signatures (e.g., SCFAs, secondary bile acids, and ImP TMAO) to guide prevention and therapy in metabolic and gastrointestinal disease.},
}

@article {pmid43011761,
year = {2026},
author = {Sun, C and Han, F and Xu, W and Wang, X and Wang, X},
title = {Deciphering the gut-lung axis in non-small cell lung cancer: from immune microenvironment crosstalk to clinical translation.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1975256},
pmid = {43011761},
issn = {2234-943X},
abstract = {Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have established a new standard of care for non-small cell lung cancer (NSCLC); however, clinical efficacy is frequently limited by primary resistance, acquired (secondary) resistance, and immune-related adverse events. The heterogeneity of the tumor immune microenvironment (TIME) is a critical determinant of therapeutic response, a state effectively regulated by the gut microbiota via the gut-lung axis. This review systematically examines the mechanistic crosstalk between intestinal commensals and the pulmonary TIME. We first delineate how specific bacterial metabolites, such as short-chain fatty acids and indole-3-acetic acid, alongside bacterial-fungal trans-kingdom interactions, modulate innate and adaptive immune responses within the lung through epigenetic remodeling and metabolic signaling, and we map the discrete points at which these gut-derived signals converge on the intrinsic metabolic programmes of pulmonary tumor cells. Furthermore, we analyze the dual role of the microbiome as a predictive biomarker, discussing the evolution from simple taxonomic abundance profiling to complex ecological topology scores and the identification of therapeutic toxicity driven by molecular mimicry, and we examine whether pre-intervention alpha or beta diversity metrics are required for patient selection. Finally, we evaluate emerging therapeutic strategies, including next-generation probiotics, bacterial-derived extracellular vesicles, and combinational interventions that aim to overcome ICI resistance by restructuring the host-microbe ecosystem, with particular attention to acquired resistance to PD-1 blockade. We also critically appraise the barriers that currently impede clinical translation, including the inter-cohort non-reproducibility of taxonomic biomarkers, methodological heterogeneity between 16S amplicon and shotgun metagenomic profiling, and the safety and regulatory constraints on fecal microbiota transplantation in immunocompromised patients. This synthesis underscores the necessity of integrating microbiome profiling into standard oncological practice to facilitate precision immunotherapy.},
}

@article {pmid43011890,
year = {2026},
author = {Islam, MM and Yang, G and Kang, KS},
title = {Gut microbiome and aging-related disorders: mechanistic insights and emerging microbiome-targeted therapies for healthy aging.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1839461},
pmid = {43011890},
issn = {2296-861X},
abstract = {BACKGROUND: The human gut harbors a diverse and dense microbial community that maintains metabolic, immune, and intestinal homeostasis through a symbiotic relationship with the host. Aging is a complex biological process that involves alterations in the gut microbiome, including decreased microbial diversity and a decline in beneficial microbiota that produce useful metabolites, which impair intestinal barrier function and enhance chronic low-grade inflammation (inflammaging).

SCOPE: This review explores current evidence on the interaction between aging and the gut microbiome, emphasizing its impact on age-associated diseases, such as frailty and sarcopenia, cardiovascular issues, type 2 diabetes, obesity, osteoporosis, and neurodegenerative conditions. It further delves into the distinct microbial profiles of centenarians and evaluates microbiome-targeted interventions, such as dietary approaches, probiotics, prebiotics, synbiotics, fecal microbiota transplants, caloric restriction, intermittent fasting, and pharmaceutical agents, by synthesizing evidence from both human and animal research to emphasize their potential in fostering healthy aging and increased longevity.

KEY FINDINGS: Evidence from human and preclinical studies suggests that alterations in the gut microbiome associated with aging facilitate immune dysregulation, metabolic dysfunction, and the progression of various chronic diseases. Whereas, centenarians possess distinctive microbial signatures rich in beneficial metabolites that could promote healthy aging and prolonged life. Additionally, microbiome-targeted interventions have demonstrated promise in enhancing gut microbial diversity and host wellbeing, though their clinical effectiveness needs additional validation.

CONCLUSION: The gut microbiome is a potential focus for supporting healthy aging and warding off age-related illnesses. Nonetheless, its significant inter-individual variability emphasizes the necessity for personalized microbiome-based approaches, which require validation through extensive longitudinal studies and properly structured randomized controlled trials to demonstrate causality and verify long-term effectiveness.},
}

@article {pmid43001108,
year = {2026},
author = {Ruan, X and Liu, R and Cao, W and Wang, L and Guo, M and He, Z and Zhang, Y and Luo, Y and Gao, Y and Huang, C and Zhao, Y and Yuan, Y and Song, X and Wang, X},
title = {Dual Gut Microbiota-Dependent Mechanisms Underlying the Anti-Atherosclerotic Effect of Tilianin.},
journal = {MedComm},
volume = {7},
number = {11},
pages = {e71141},
pmid = {43001108},
issn = {2688-2663},
abstract = {Tilianin (Til), a flavonoid from Dracocephalum moldavica L. and Agastache species, exerts potent anti-atherosclerotic effects via gut microbiota-mediated mechanisms. In atherosclerotic mice, Til dose-dependently reduced plaque burden and enhanced plaque stability by reducing necrotic cores and increasing collagen. Til also improved lipid profiles, attenuated inflammation, and lowered trimethylamine N-oxide (TMAO) levels, accompanied by microbiota remodeling-specifically, enhancing α-diversity and enriching Akkermansia muciniphila. Fecal microbiota transplantation from Til-treated donors successfully transferred these protective phenotypes. Conversely, antibiotic-induced microbiota depletion selectively abrogated the plaque-stabilizing arm of Til's action, leaving its effect on overall plaque burden intact, despite maximized TMAO reduction and increased systemic exposure. This "antibiotic paradox" stemmed from short-chain fatty acid (SCFA) depletion and intestinal barrier breakdown (decreased ZO-1/occludin), triggering metabolic endotoxemia (elevated LPS). Mechanistically, Til directly inhibits microbial trimethylamine monooxygenase (TMM) with nanomolar potency (IC50 = 18.78 nM), blocking local TMA-to-TMAO conversion. Overall, Til's lipid-lowering, anti-inflammatory, and antioxidant activities in vivo are gated by a pivotal microbiota-metabolite-barrier axis, acting through dual enzymatic inhibition and homeostasis maintenance, offering novel insights for flavonoid-based multi-target atherosclerosis therapies.},
}

@article {pmid43002339,
year = {2026},
author = {Sasidharan Pillai, S and Ashraf, AP},
title = {From Dysbiosis to Vascular Disease: the Gut Microbiota in Type 2 Diabetes and Atherosclerosis.},
journal = {Current atherosclerosis reports},
volume = {28},
number = {1},
pages = {},
pmid = {43002339},
issn = {1534-6242},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/complications/metabolism ; *Dysbiosis/microbiology/complications ; *Atherosclerosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; },
abstract = {PURPOSE OF REVIEW: Type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) are closely linked chronic disorders and leading causes of morbidity and mortality worldwide. Increasing evidence identifies the gut microbiota (GM), including its microbial genes and metabolites, as potential modifiers of these processes. This narrative review summarizes mechanistic, translational, and clinical evidence linking GM dysbiosis with T2D and atherosclerosis and evaluates microbiota-directed therapeutic strategies.

RECENT FINDINGS: Converging mechanistic, translational, and clinical evidence supports GM dysbiosis as a plausible shared contributor to T2D and atherosclerosis through interconnected pathways involving impaired intestinal barrier integrity and metabolic endotoxemia, TLR4/NF-κB- and inflammasome-mediated inflammation, and microbial metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), and tryptophan-derived indoles. These pathways can influence glucose and lipid metabolism, insulin signaling, immune activation, endothelial function, and vascular inflammation, providing a biological framework linking dysglycemia with increased cardiovascular risk and supporting the GM as a potential therapeutic target. However, the field remains limited by predominantly observational and confounded human data, incomplete causal evidence, and heterogeneous responses to microbiota-directed interventions. Dietary modification, prebiotics, probiotics, synbiotics, next-generation probiotics and postbiotics, fecal microbiota transplantation, and microbiota-modulating antidiabetic therapies have shown signals of benefit on metabolic or vascular surrogate endpoints, but evidence for durable clinical benefit remains limited and inconsistent across strains, populations, and study designs. Future progress in GM manipulation to improve cardiometabolic outcomes will require function-focused, causally grounded research and adequately powered, outcome-driven clinical trials incorporating GM-guided patient stratification. Until such evidence is available, the GM should be viewed as a biologically compelling and promising, but not yet clinically actionable, link between metabolic and atherosclerotic disease.},
}

Humans
*Diabetes Mellitus, Type 2/microbiology/complications/metabolism
*Dysbiosis/microbiology/complications
*Atherosclerosis/microbiology
*Gastrointestinal Microbiome/physiology
Animals

@article {pmid43002898,
year = {2026},
author = {Yu, X and He, J and Liu, M},
title = {Critical advances and translational bottlenecks of gut microbiota-gut-brain axis targeted therapy for neurodegenerative and neurodevelopmental disorders.},
journal = {Journal of neuroimmunology},
volume = {423},
number = {},
pages = {579117},
doi = {10.1016/j.jneuroim.2026.579117},
pmid = {43002898},
issn = {1872-8421},
abstract = {Neurological diseases have become a major global public health burden. Existing central nervous system-targeted therapies can only alleviate clinical symptoms but fail to halt the progression of neurodegenerative diseases, presenting mechanistic limitations and therapeutic bottlenecks. The gut microbiota participates in the regulation of central nervous system (CNS) homeostasis and neuropathological processes via the microbiota-gut-brain axis (MGBA). Notably, dysbiosis may induce damage to the blood-brain barrier, neurotransmitter dysregulation, and immune imbalance, thereby mediating the onset and progression of various neurological diseases, including Parkinson's disease, Alzheimer's disease (AD), autism spectrum disorder (ASD), and multiple sclerosis (MS). This article provides a systematic review of the core mechanisms by which the gut microbiome regulates neurological diseases, including inflammation regulation, oxidative stress responses, and neuroendocrine remodeling mediated by microbial metabolites. It also comprehensively summarizes the research progress, application advantages, and existing limitations of novel gut-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), dietary interventions, and live biological therapies. At the same time, the article critically examines key bottlenecks prevalent in the field: the causal relationship between the microbiota and disease remains unclear; there is a significant translational gap between animal and human studies; there is a lack of unified standards for multi-omics analysis systems; and interference from confounding factors such as age, diet, and medications is significant. Existing research indicates that gut microbiota interventions complement traditional symptomatic treatments and hold promising prospects for early disease intervention and adjunctive therapy for refractory patients. Future efforts should integrate multi-omics and artificial intelligence technologies to decipher the causal networks governing gut-central nervous system regulation, establish standardized research frameworks, advance the clinical translation of precision gut microbiota therapies, and provide new approaches for the comprehensive prevention, control, and personalized treatment of neurological disorders.},
}

@article {pmid43004864,
year = {2026},
author = {Nachman, EJ and Neilson, T and White, MG},
title = {Therapeutic Targeting of the Cancer Microbiome and Metabolome: Ongoing Trials and Future Directions for the Surgical Oncologist.},
journal = {Journal of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jso.70451},
pmid = {43004864},
issn = {1096-9098},
support = {K12TR004908/NH/NIH HHS/United States ; },
abstract = {The role of the human microbiome in cancer development, progression, and response to therapy has moved from correlative curiosity to demonstrated impact on tumor biology. This represents a critical factor for surgical oncologists as they not only resect these tumors, but also direct perioperative antimicrobial exposure and increasingly co-manage neoadjuvant and surveillance pathways in which microbial state may predict and modify response. This review summarizes the basis for therapeutic modulation of the cancer microbiome and metabolome in a contemporary clinical-trial landscape across four broad strategies: additive (fecal microbiota transplantation, defined consortia, and live biotherapeutic products), subtractive (targeted antimicrobials), dietary and metabolome-directed interventions, and engineered or next-generation platforms. Particular attention is given to subtractive approaches in colon and rectal cancer and to the underexplored perioperative interface between the microbiome and surgical outcomes such as anastomotic leak. We outline the principal methodological and translational obstacles, including low-biomass contamination, causal inference, unintended antibiotic effects, and product standardization. Looking ahead, we propose roles for surgeons across the care continuum, from biospecimen stewardship and trial referral to integration of microbiome and circulating tumor DNA signals in surveillance.},
}

@article {pmid43005063,
year = {2026},
author = {Xie, W and Li, Z and Lin, J and Bai, H and Li, J and Cui, W and Jiang, Y and Song, B and Wang, X and Tang, L},
title = {Gut microbiota developmental trajectories in min and DLY pigs during lactation and nursery stages and the alleviation of ETEC-induced diarrhea by fecal microbiota transplantation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1939230},
pmid = {43005063},
issn = {1664-302X},
abstract = {INTRODUCTION: The gut microbiota plays a vital role in porcine growth, intestinal barrier function, and disease resistance, yet the influence of host genetics on microbiota development and breed-specific phenotypes remains unclear. This study investigated gut microbiota dynamics in genetically distinct pig breeds and evaluated the functional impact of breed-specific microbiota on intestinal health.

METHODS: A total of 76 healthy 3-day-old piglets from Min pigs and Duroc × Landrace × Yorkshire (DLY) pigs were monitored from day 3 to day 49. Microbiota composition was analyzed at eight developmental stages using high-resolution 2bRAD-M sequencing. Intestinal tissues were collected at day 49 for spatial microbiota profiling and barrier function assessment. Additionally, twelve 21-day-old DLY piglets were assigned to control, Enterotoxigenic Escherichia coli (ETEC) K88 challenge, and fecal microbiota transplantation (FMT) groups to evaluate the protective effects of Min pig microbiota.

RESULTS: Significant breed-specific differences were observed in microbial composition, developmental trajectories, and ecological succession patterns. Min pigs exhibited higher microbial diversity and greater community stability during early weaning compared to DLY pigs, accompanied by improved intestinal barrier integrity and reduced diarrhea incidence. FMT from Min pigs significantly enhanced microbial diversity, strengthened intestinal barrier function, and alleviated diarrhea following ETEC challenge.

DISCUSSION: These findings demonstrate that host genetics shapes gut microbiota development, influencing intestinal health and disease resistance. Microbiota derived from Min pigs confers protective effects against enteric infection, highlighting its potential as a microbial resource to improve gut health in commercial pig production.},
}

@article {pmid43005077,
year = {2026},
author = {Yang, X and Li, Y and Hu, Q and Pan, X and Hong, J and Li, L},
title = {Comparative efficacy of gut microbiota-targeted therapies for motor and non-motor symptoms in Parkinson's disease: a systematic review and network meta-analysis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1907410},
pmid = {43005077},
issn = {1664-302X},
abstract = {BACKGROUND: Gut dysbiosis may contribute to Parkinson's disease (PD) through the microbiota-gut-brain axis. Probiotics, synbiotics, and fecal microbiota transplantation (FMT) have been studied as potential treatments, but their comparative effects remain uncertain.

METHODS: We searched trial registries and electronic databases from inception to April 1, 2026 for randomized controlled trials of gut microbiota-targeted therapies in PD. We performed a frequentist network meta-analysis. Risk of bias was assessed with Cochrane RoB 2, and confidence in the evidence was assessed with CINeMA. Treatment rankings were summarized using SUCRA values.

RESULTS: Nineteen RCTs involving 1,156 participants and five treatment options (FMT, probiotics, synbiotics, routine care, and placebo) were included. Probiotics increased spontaneous bowel movement (SBM) frequency compared with placebo (MD = 1.93, 95% CI: 0.23 to 3.64; SUCRA = 88.3%). In the oral-administration subgroup, probiotics (MD = 2.01, 95% CI: 0.64 to 3.39) and synbiotics (MD = 1.23, 95% CI: 0.01 to 2.45) increased SBM frequency. No active treatment significantly improved MDS-UPDRS III scores compared with placebo, although synbiotics and FMT had higher SUCRA rankings. Evidence certainty was Moderate for oral probiotics on SBM frequency and Low to Very Low for motor function and quality of life.

CONCLUSION: Oral probiotics improved SBM frequency in patients with PD. Evidence for motor function and quality of life was uncertain, and the higher rankings of FMT and synbiotics should be considered exploratory. Larger head-to-head randomized trials are needed.

https://www.crd.york.ac.uk/PROSPERO/recorddashboard.},
}

@article {pmid43005289,
year = {2026},
author = {Zhou, L and Zang, Z and Zhang, H and Fei, X and Zhu, G and Mu, Y and Jiang, P and Wang, X and Zhao, M and Ai, Z and Cao, X and Liu, Z and Yin, H and Li, L and Tian, J and Yang, H and Fan, X and Tan, S and Li, S},
title = {Butyrate Deficiency due to Microbial Dysbiosis Promotes Anxiety.},
journal = {Research (Washington, D.C.)},
volume = {9},
number = {},
pages = {1470},
pmid = {43005289},
issn = {2639-5274},
abstract = {Individuals with diabetes frequently suffer from anxiety; however, the mechanism for this association remains incompletely understood. Diabetes-associated genes have been implicated in the control of central nervous system (CNS) disorders. In the current study, we observed a marked down-regulation of secretagogin (SCGN) across multiple organs in diabetic mouse models, and Scgn knockout (Scgn [-/-]) mice developed diabetes, confirming SCGN as a diabetes-associated gene. Behavioral analyses revealed that Scgn [-/-] mice exhibited anxiety-like phenotypes compared to wild-type (WT) mice. Notably, germ-free (GF) Scgn [-/-] mice did not manifest these behavioral abnormalities, suggesting that SCGN influences anxiety through gut microbiota-dependent mechanisms. Subsequent shotgun metagenomic sequencing confirmed gut microbiota dysbiosis in Scgn [-/-] mice. Fecal microbiota transplantation (FMT) from Scgn [-/-] donors into GF mice recapitulated the anxiety-like phenotypes. Given the established roles of microbial metabolites in gut-brain axis signaling, we identified a substantial depletion of butyrate, a key neuroactive metabolite, in fecal and plasma samples from Scgn [-/-] mice. Immunohistochemical analysis revealed neural overactivation, as reflected by c-Fos expression in the medial prefrontal cortex (mPFC) of Scgn [-/-] mice, which was corroborated by metabolomic profiling indicating dysregulated tryptophan metabolism in this region. Mechanistically, up-regulation of indoleamine 2,3-dioxygenase 1 (IDO1) and kynureninase (KYNU) led to excessive production of quinolinic acid, an NMDA receptor agonist that increased pyramidal neuron excitability in the mPFC, thereby promoting anxiety-like behaviors in Scgn [-/-] mice. Supplementation with Odoribacter splanchnicus, a butyrate-producing bacterium, could reverse this abnormal signaling pathway and alleviate anxiety-like behaviors. Critically, butyrate administration mitigated this anxiogenic cascade in vivo and in vitro, as validated by electrophysiological recordings. Taken together, our findings demonstrate that SCGN deficiency induces gut dysbiosis, reduces butyrate availability, and promotes excitotoxicity in the mPFC, at least in part, through disrupted tryptophan metabolism, ultimately leading to anxiety. This SCGN-modulated gut-brain axis highlights potential new therapeutic targets for the treatment of diabetes-associated anxiety.},
}

@article {pmid43006832,
year = {2026},
author = {},
title = {Correction to: Single Enema Fecal Microbiota Transplantation in Cats With Chronic Enteropathy.},
journal = {Journal of veterinary internal medicine},
volume = {40},
number = {6},
pages = {},
doi = {10.1093/jvimsj/aalag303},
pmid = {43006832},
issn = {1939-1676},
}

@article {pmid41904606,
year = {2026},
author = {Birkeland, S and Rohde Mæhlum, I and Senneset, M and Wik Taxerås, I and Snipen, L and Markov Arnesen, H and Boysen, P and Carlsen, H},
title = {A naturalized gut microbiome interacts with dietary fibers to protect against colonic inflammation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2649435},
pmid = {41904606},
issn = {1949-0984},
mesh = {Animals, Wild/microbiology ; Mice, Inbred C57BL ; Male ; Female ; Animals ; Mice ; *Gastrointestinal Microbiome/genetics ; *Dietary Fiber/metabolism ; *Intestinal Barrier Function ; *Colon/microbiology/physiology ; *Colitis/microbiology/prevention & control ; Fecal Microbiota Transplantation ; Dextran Sulfate ; Disease Models, Animal ; Metagenome ; Bacterial Proteins/genetics/metabolism ; },
abstract = {"Feralized" mice, housed in farmyard-type environments, show a matured immunophenotype, altered intestinal barrier, and a shifted gut microbiome compared to conventionally housed laboratory mice. Since dietary fibers support gut health in part by microbial fermentation into immunomodulatory short-chain fatty acids, we hypothesized that feralization influences the intestinal barrier by enhancing the fiber-degrading properties of the microbiome. We explored whether susceptibility to low-grade dextran sulfate sodium-induced colitis differed between feralized and clean laboratory mice fed diets high or low in fermentable fibers. Feralized mice were protected against colitis, displaying low disease scores and biomarkers of inflammation in feces, plasma, and liver; and altered colonic mucosal gene expression, compared to clean mice. This protection was strongest with a fiber-rich diet, which, in contrast, worsened colitis in clean mice. Transfer of fecal microbiota from feralized mice to clean recipients conferred colitis protection. Fecal metagenome-assembled genomes revealed that the fiber-rich diet enriched the microbiome with predicted genes encoding fiber-degrading enzymes, while the low-fiber diet promoted mucin-degrading enzyme genes. However, the dominant microbial species contributing to these functions differed between feralized and laboratory mice. Differential abundance of bacterial taxa in feralized and laboratory mice further identified potential microbial modulators of colitis that merit targeted investigation in future studies. Overall, these findings suggest that fibers affect intestinal inflammation in a microbiota-dependent manner, underscoring the complex interplay between diet and microbiota in disease development.},
}

Animals, Wild/microbiology
Mice, Inbred C57BL
Male
Female
Animals
Mice
*Gastrointestinal Microbiome/genetics
*Dietary Fiber/metabolism
*Intestinal Barrier Function
*Colon/microbiology/physiology
*Colitis/microbiology/prevention & control
Fecal Microbiota Transplantation
Dextran Sulfate
Disease Models, Animal
Metagenome
Bacterial Proteins/genetics/metabolism

@article {pmid42999505,
year = {2026},
author = {Liu, X and Wang, Z and Gong, Y and Wu, Z and Chen, S and Yang, H and Gao, X and Chen, Y},
title = {Gluten Aggravates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Gut Microbiota to Promote M1 Macrophage Polarization.},
journal = {Phenomics (Cham, Switzerland)},
volume = {6},
number = {5},
pages = {592-610},
pmid = {42999505},
issn = {2730-5848},
abstract = {UNLABELLED: Gluten, a protein complex found in wheat, rye, and barley, is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD), though its mechanistic role remains poorly understood. We identified a significant correlation between fecal gluten concentrations and disease activity in 30 IBD patients (six with ulcerative colitis, 24 with Crohn's disease). In a murine model, gluten intake exacerbated dextran sulfate sodium-induced colitis, worsening intestinal epithelial damage and increasing both local and systemic inflammation. Histological and flow cytometry analyses revealed that gluten promoted macrophage infiltration and M1 polarization in the intestines. Antibiotic-mediated microbiota depletion attenuated these effects, indicating a microbiota-mediated mechanism. Furthermore, fecal microbiota transplantation from gluten-exposed mice recapitulated macrophage dysregulation and barrier damage in recipients. Microbial profiling through 16S rRNA sequencing showed that gluten reduced beneficial bacteria like Lactobacillus and increased harmful bacteria such as Desulfovibrio. Pearson and Mantel tests demonstrated a negative correlation between gluten exposure and Lactobacillus abundance, while a corresponding increase in M1 macrophage pro-inflammatory markers was observed. Metagenomic analysis of IBD patient cohorts validated these findings, showing reduced Lactobacillus abundance in the high fecal-gluten subgroup. These results suggest that dietary gluten induces gut dysbiosis characterized by Lactobacillus depletion, which drives macrophage infiltration and M1 polarization, ultimately exacerbating inflammation and compromising intestinal barrier integrity in IBD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s43657-025-00287-w.},
}

@article {pmid43000087,
year = {2026},
author = {Mei, Z and Dai, DLY and Sifuentes, E and Petersen, C and Turvey, SE},
title = {Microbiome-Targeted Interventions for Pediatric Asthma and Allergic Diseases: Current and Emerging Approaches.},
journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.anai.2026.10.038},
pmid = {43000087},
issn = {1534-4436},
abstract = {Allergic diseases are among the most common chronic diseases of childhood and remain a major public health challenge. Increasing evidence indicates that the early-life gut microbiome plays a central role in immune maturation, making it an attractive target for allergy prevention. During the first 1000 days of life, interactions between the developing microbiome and the immune system help establish immune tolerance, while disruptions to this process increase the risk of asthma and allergic diseases. Current microbiome-targeted strategies largely focus on optimizing early-life microbial exposures through interventions such as mode of delivery, antibiotic stewardship, breastfeeding, and exposure to diverse environmental microorganisms. These approaches are already incorporated into public health recommendations and promote healthy microbiome development without directly manipulating microbial communities. Newer approaches seek to intervene more precisely through microbial transfer therapies, live biotherapeutic products, prebiotics, postbiotics, and microbial metabolite-based therapies. Although several have shown encouraging preclinical and early clinical results, evidence supporting routine clinical use remains limited. The next generation of microbiome therapeutics is likely to be defined less by changing which microbes are present than by restoring the microbial functions that establish immune tolerance. This conceptual advance is driving the development of increasingly targeted microbiome-based interventions and provides a framework for the next generation of allergy prevention strategies. Translating these mechanistic insights into safe, effective therapies that complement established public health measures represents the next major challenge in preventing asthma and allergic diseases.},
}

@article {pmid43000102,
year = {2026},
author = {Hayakawa, K and Fujishiro, M and Takamori, K and Morimoto, S},
title = {Auxiliary role of gut microbiota alterations in the pathogenesis of resiquimod-induced autoimmune disease.},
journal = {Immunology letters},
volume = {},
number = {},
pages = {107252},
doi = {10.1016/j.imlet.2026.107252},
pmid = {43000102},
issn = {1879-0542},
abstract = {Dysbiosis and leaky gut are common in systemic lupus erythematosus (SLE). However, currently, it is unclear whether they initiate the pathogenesis or simply worsen it. In this study, using a resiquimod (R848; Toll-like receptor 7/8 agonist)-induced murine model of SLE-like disease, we investigated the effects of immune activation and the gut environment to elucidate the precise role of the gut microbiota in SLE pathogenesis. To induce SLE-like disease, R848 was transdermally administered to BALB/c mice. To assess the role of the gut environment, 1) leaky gut was induced to test whether it initiates autoimmunity, 2) fecal microbiota transplantation (FMT) from R848-treated mice was performed to test disease transmissibility, and 3) dysbiosis was induced with an antibiotic cocktail to test its impact on autoimmune responses. We demonstrated that R848 treatment induced systemic autoimmunity with elevated autoantibodies and dysbiosis, characterized by increased Bacteroidetes and decreased Firmicutes. Induced leaky gut did not appear to trigger autoimmunity, and FMT from R848-treated mice failed to consistently or reproducibly transfer autoimmune disease phenotypes. Interestingly, mice with pre-existing antibiotic-induced dysbiosis showed significantly increased splenic effector T cells and serum autoantibody titers at an early stage of R848 stimulation. These results suggest that dysbiosis and leaky gut in this model may be secondary to R848-driven systemic inflammation rather than primary causes. However, dysbiosis appears to play a crucial role in amplifying early autoimmune responses, suggesting that the gut microbiota may serve as an important modulatory factor in SLE pathogenesis. Thus, these findings may support therapies that combine immune modulation with gut-targeted interventions.},
}

@article {pmid42998537,
year = {2026},
author = {Chu, Y and Qian, Y and Shi, J and Hu, M and Ling, R and Wu, Y and Dai, H and Yan, Z and Xian, Q and Chen, H and Jiang, H and Zhu, W},
title = {Fecal microbiota capsule transplantation plus immunotherapy as first-line maintenance therapy for patients with malignant solid tumors: A single-arm, dose-escalation, exploratory phase I study.},
journal = {Translational oncology},
volume = {75},
number = {},
pages = {103106},
doi = {10.1016/j.tranon.2026.103106},
pmid = {42998537},
issn = {1936-5233},
abstract = {BACKGROUND: Chemotherapy combined with programmed cell death protein-1 (PD-1) antibody immunotherapy has become the standard first-line treatment for most patients with malignant solid tumors. However, data from multiple phase III trials indicate that even with first-line induction followed by immunotherapy maintenance, median progression-free survival (PFS) remains less than one year.

METHODS: In this phase I dose-escalation trial (3 + 3 design), 12 patients who completed six cycles of first-line chemoimmunotherapy received oral fecal microbiota transplantation (FMT) capsules plus anti-PD-1 maintenance immunotherapy at escalating dose levels (i to i + 3). The primary endpoint was safety; secondary endpoints included the recommended phase II dose (RP2D), PFS, and disease control rate (DCR). Fecal and blood samples were collected for exploratory microbiome and metabolomic analyses.

RESULTS: No grade ≥3 FMT-related toxicities occurred. With a median follow-up of 36.9 months, median PFS was 19.8 months (95% CI 11.2-28.4); maintenance-phase PFS was 11.7 months (95% CI 4.1-19.3). 4 patients remained progression-free on continued immunotherapy. Four patients (33.3%) experienced grade 1-2 gastrointestinal events. Microbiomic analyses showed post-FMT expansion of Blautia and Faecalibacterium, with dose level i + 1 demonstrating the greatest α-diversity shift and engraftment rate. Metabolomic analysis showed that serum arachidonic acid levels increased after FMT.

CONCLUSION: Oral FMT combined with immunotherapy as first-line maintenance therapy for solid tumors was safe and well tolerated, showed promising preliminary efficacy, and induced favorable compositional changes in the gut microbiota. This study was registered with the Chinese Clinical Trial Registry (Registration No.: ChiCTR2100054928).},
}

@article {pmid42998704,
year = {2026},
author = {Wang, M and Guo, Q and Zhang, Q and Cheng, Z and Feng, C and Zhong, Z and Bai, J and Dong, Y},
title = {Milu antler powder demonstrates efficacy in mitigating kidney damage induced by the aging process through the modulation of intestinal microbiota.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122554},
doi = {10.1016/j.jep.2026.122554},
pmid = {42998704},
issn = {1872-7573},
abstract = {Aging significantly affects the structure and function of the kidney, leading to profound changes. Ancient texts document that deer antler powder can ameliorate renal damage and aging, but its exact mechanism of action remains unclear.

AIM OF STUDY: To evaluate the renal protective capabilities of Milu antler powder in senescent mice and elucidate its mechanism of action in alleviating renal injury.

MATERIALS AND METHODS: We prepared and conducted the ultramicro-grade Milu antler powder (UGM) and evaluated its effectiveness in improving kidney function in D-galactose-induced senescent mice through biochemical indices and histological studies. We then employed UPLC-MS/MS and 16S rRNA gene analysis to analyze the changes in intestinal microbiota and metabolites. Finally, the effects of UGM and its metabolites on the aging phenotype and renal function in mice were verified through fecal microbiota transplantation (FMT) and cell experiments.

RESULTS: UGM significantly ameliorated brain aging and immune decline in senescent mice. Notably, it significantly reduced renal structural damage and aging phenotype, and improved renal dysfunction. The 16S rRNA gene analysis and its metabolite analyses showed that UGM was able to upregulate Akkermansia, Lachnospiraceae_NK4A136_group and downregulate Desulfobacterota, as well as alter metabolite expression (especially sodium acetate). Furthermore, through FMT and HK-2 cell experiments, we confirmed that Milu antler powder was able to attenuate renal aging by modulating the intestinal microbiota and their metabolites (sodium acetate).

CONCLUSIONS: This study provides a scientific basis for the anti-aging application of Milu antler powder by demonstrating its ability to attenuate renal aging through modulation of the gut-kidney axis.},
}

@article {pmid42998856,
year = {2026},
author = {Qiao, Y and Cheng, R and Zhang, X and Li, X and Tian, R and Guo, J and Wang, X and Wang, Q and Wang, J and Bi, H and Wei, L and Gao, T},
title = {Temporal and Spatial Dynamics and Mechanisms of Brain-Gut Axis Injury Induced by Confinement-Like Physical Restraint Stress in Mice.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {109746},
doi = {10.1016/j.phrs.2026.109746},
pmid = {42998856},
issn = {1096-1186},
abstract = {BACKGROUND: Long-term SIS exposure across aerospace, deep-sea, underground, and quarantine settings increases depression and gut-brain axis dysfunction risk, but long-term nonlinear injury dynamics remain poorly understood.

METHODS: We analyzed GBD 2023 depression burden data in adults aged 15-49, then established a 0-35 day (d) chronic restraint stress mouse model that isolates the core physical confinement and activity-restriction component of SIS. Integrating behavior, histology, biochemistry, 16S sequencing, metabolomics, and formal nonlinear changepoint analysis, we validated picolinic acid (PLA) effects via in vivo intervention, in silico docking, and fecal microbiota transplantation (FMT).

RESULTS: Population data showed that the global depression burden during the COVID-19 period followed a rapid rise-partial recovery-persistent disability pattern, providing a temporal reference for the experimental model. In mice, confinement-like restraint stress induced triphasic nonlinear gut-brain injury with changepoints at ~7 and ~21 days: early HPA/inflammatory activation, mid-phase gut barrier disruption and anxiety-like behavior, and late hippocampal damage with despair-like behavior. Microbiota remodeling and tryptophan metabolic shift formed the core signaling cascade, with PLA identified as the key gut-brain metabolite. Exogenous PLA dose-dependently improved depressive phenotypes, repaired barriers, and suppressed HPA hyperactivity and inflammation. FMT provided suggestive evidence that gut microbiota contribute to PLA's protective effects.

CONCLUSION: Chronic confinement-like restraint stress induces triphasic nonlinear gut-brain axis injury rather than linear damage. PLA is a promising candidate target for mental health protection in isolated, confined, extreme environment populations and stress-related depression intervention.},
}

@article {pmid42990228,
year = {2026},
author = {Ferrer, DM and Holton, M and Yang, M and Villamil, I and Urtecho, G},
title = {Culturomics-Guided Precision FMT Enables Stable Antibiotic-Independent Engraftment via Metabolic Niche Targeting.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.25.761671},
pmid = {42990228},
issn = {2692-8205},
abstract = {The gut microbiome's functional architecture can be conceptualized as a network of metabolic niches, yet clinical approaches to fecal microbiota transplantation (FMT) do not leverage niche - level information to guide engraftment. Here, we present a culturomics-based framework that profiles the metabolic niche landscape of individual microbiomes to enable targeted, antibiotic-independent FMT. Using a panel of 60 diverse media conditions, we show that gut communities from genetically identical mice harboring distinct microbiomes exhibit reproducible, vendor - specific niche-occupancy profiles, with each condition selecting for compositionally distinct niche-associated communities (NACs). We demonstrate that antibiotic pretreatment prior to FMT compromises community resilience, yielding communities that lose donor taxa more rapidly and recover less taxonomic diversity after secondary perturbation compared to untreated recipients. By comparing donor and recipient niche profiles, we identify vacant metabolic niches in recipient microbiomes and show that NACs targeting these vacancies achieve stable engraftment persisting for over 72 days without antibiotic pretreatment, whereas NACs targeting occupied niches fail to colonize. Furthermore, complex NACs not only fill vacant niches but reshape the surrounding native community, while simpler NACs engraft with minimal collateral impact. This culturomics-guided framework provides a scalable, mechanistic approach for rational donor-recipient matching that could advance personalized microbiome-based therapies.},
}

@article {pmid42992114,
year = {2026},
author = {Castro E Silva, M and Silva, E and Nunes, C and Baldaia, L and Orelhas, L and Costa, J and Dias, P and Tavares, B and Fonseca, M},
title = {The gut microbiome and vascular disease - A systematic review of mechanistic insights and implications for vascular surgery.},
journal = {JVS-vascular science},
volume = {7},
number = {},
pages = {100454},
pmid = {42992114},
issn = {2666-3503},
abstract = {OBJECTIVE: Observational studies repeatedly linked gut microbial features and metabolites to vascular disease, but it is unclear which associations are reproducible, which remain significant after confounder adjustment, and how they relate to experimental evidence. This review aims to determine which taxa and metabolites are consistently associated across independent human studies; whether the population, phenotype, method, and sample type explain divergent findings; and where the human data converge with, diverge from, or remain untested with the animal and interventional literature.

METHODS: PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library were searched for human studies of the gut microbiome composition or gut-derived metabolites reporting atherosclerotic, aneurysmal, peripheral arterial, calcific, or arterial stiffness outcomes from database inception to December 31, 2025. Study screening and duplicate article extraction were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines. The study design was classified explicitly, the covariates in each primary analysis were extracted, and the risk of bias was assessed using the Newcastle-Ottawa Scale or the Joanna Briggs Institute checklist. The findings were then compared with the animal and human interventional literature identified through targeted searching.

RESULTS: All the 29 included reports were observational (19 cross-sectional, 3 case-control, and 7 cohort) studies, and none was interventional. The reproducible findings were the enrichment of Proteobacteria-affiliated genera (5 reports) and of oral-origin organisms (3 reports), and the depletion of butyrate producers in carotid disease. The carnitine pathway intermediates gamma-butyrobetaine and trimethyllysine were independently associated with cardiovascular death and major adverse limb events (hazard ratio, 1.93; 95% confidence interval, 1.35-2.76) in two independent cohorts. Trimethylamine N-oxide (TMAO) was outcome-specific; TMAO levels were associated with 5-year mortality in peripheral arterial disease (adjusted hazard ratio, 2.06; 95% confidence interval, 1.36-3.11) and with ankle-brachial-index-defined disease in diabetes (odds ratio, 1.051), but TMAO levels were lower in large-artery stroke than in controls and were unrelated to carotid or limb outcomes once renal function was modelled. In addition, 16 of 29 reports fitted a multivariable model, and only three included renal function; the compositional findings were almost exclusively unadjusted. The risk of bias was good in 11 reports, moderate in 16, and low in 2. Animal models causally implicate TMAO in atherogenesis and aneurysm formation and show butyrate and Roseburia intestinalis to be protective, but the results of germ-free experiments and the only human fecal transplantation trial are discordant.

CONCLUSIONS: A small number of gut microbial signals are reproducible, but most have not been adjusted for potential confounders, particularly renal function, which may partly explain the observed associations. The carnitine pathway metabolites with the strongest prognostic signal in surgical populations have never been tested in an animal vascular model. Microbiome profiling has no current role in vascular surgical practice.},
}

@article {pmid42994968,
year = {2026},
author = {Yuan, X and Wu, L and Wang, Y and Zhao, Y and Zhou, L and Zhao, J},
title = {From systemic to oral: Unifying immunological mechanisms via the gut microbiome axis.},
journal = {Virulence},
volume = {17},
number = {1},
pages = {2750615},
doi = {10.1080/21505594.2026.2750615},
pmid = {42994968},
issn = {2150-5608},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Intestinal Barrier Function ; Dysbiosis/immunology/microbiology ; *Mouth Diseases/immunology/microbiology ; Fecal Microbiota Transplantation ; Probiotics ; Immunity, Mucosal ; Mouth/immunology/microbiology ; },
abstract = {While the gut microbiome regulates host homeostasis and systemic disease via the gut-immune axis, its potential role in regulating oral diseases remains underexplored. This review examines how established gut microbiome-immune mechanisms may contribute to oral inflammation and their therapeutic potential. Gut microbiome dysbiosis may influence oral diseases through microbial metabolites, intestinal barrier dysfunction, inflammatory signaling, and immune regulation. Evidence from systemic diseases supports these mechanisms and provides a rationale for microbiome-targeted approaches, including probiotics, dietary interventions, and fecal microbiota transplantation. However, direct clinical evidence in oral diseases remains limited and heterogeneous. Future research should clarify bidirectional gut-oral interactions, standardize microbiome assessment and clinical outcomes. Well-designed clinical studies are needed to address these limitations and translate the gut-oral axis into meaningful interventions.},
}

Humans
*Gastrointestinal Microbiome/immunology
Animals
Intestinal Barrier Function
Dysbiosis/immunology/microbiology
*Mouth Diseases/immunology/microbiology
Fecal Microbiota Transplantation
Probiotics
Immunity, Mucosal
Mouth/immunology/microbiology

@article {pmid42996856,
year = {2026},
author = {Hou, X and Li, Y and Mu, W and Wang, H and Ji, S},
title = {Dietary fiber, gut microbiota, and host immunity: the immunomodulatory roles of short-chain fatty acids.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1941474},
pmid = {42996856},
issn = {2296-861X},
abstract = {Short-chain fatty acids (SCFAs) are a class of key metabolites produced by the gut microbiota through the fermentation of indigestible components such as dietary fiber. They primarily include acetate, propionate, and butyrate. In recent years, a large body of research has revealed that SCFAs are not only an important energy source for colonic epithelial cells but also key signaling molecules linking the gut microbiota to the host immune system. SCFAs play a central role in immune regulation. This review summarizes the production and characteristics of SCFAs. It explores the multifaceted roles of SCFAs in regulating immune homeostasis and inflammatory responses. Through key mechanisms such as activation of G protein-coupled receptors (GPCRs), inhibition of histone deacetylases (HDACs), and metabolic reprogramming, SCFAs broadly regulate the differentiation, function, and inflammatory responses of immune cells, maintain intestinal barrier integrity, and induce an anti-inflammatory state. At the same time, the manuscript analyzes the molecular mechanisms by which SCFAs contribute to inflammatory bowel disease, metabolic disorders, tumor immunity, and neuro-immune diseases through multi-organ pathways such as the "gut-liver axis" and the "gut-brain axis". In addition, this article summarizes treatment strategies targeting SCFAs, including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation. It also discusses the current challenges in this field and outlines future directions, with the aim of providing new insights for the prevention and treatment of immune-related diseases.},
}

@article {pmid42996894,
year = {2026},
author = {Wang, S and Hu, Y and Chu, H},
title = {Alcohol-Associated Liver Disease: Epidemiology, Pathogenesis, and Emerging Therapeutic Targets.},
journal = {MedComm},
volume = {7},
number = {11},
pages = {e71120},
pmid = {42996894},
issn = {2688-2663},
abstract = {Alcohol-associated liver disease (ALD) represents a leading cause of preventable liver-related morbidity and mortality worldwide. Despite its growing global burden, no pharmacological therapies targeting disease progression have achieved clinical approval, with management still centered on alcohol abstinence and supportive care. Classic pathogenic mechanisms, including ethanol metabolism, oxidative stress, innate immune activation, and regulated cell death, are well recognized, yet emerging evidence highlights the gut-liver axis and intestinal dysbiosis as critical, interactive drivers of disease pathophysiology. However, how gut microbial imbalance mechanistically intersects with these canonical pathways to accelerate ALD progression remains insufficiently integrated. This article summarizes the epidemiology, clinical manifestations, and pathogenesis of ALD. Importantly, we focus specifically on changes in the gut microbiota (including bacteria, fungi, and viruses) and microbial metabolites. We further discuss the interactive relationships between dysbiosis and these core mechanisms. Finally, we summarize progress in preclinical and clinical research on targeted strategies such as probiotics, fecal microbiota transplantation, and phage therapy. By synthesizing the research findings, we propose a stage-based, mechanism-oriented framework aimed at advancing the development of safer and more precise therapeutic interventions for ALD.},
}

@article {pmid42996903,
year = {2026},
author = {Nagy, S and Busznyák, C and Dézsi, C and Gulyás-Oldal, V and Paschali, E and Sallai, D and Gálóczi, I and Szili, K},
title = {The dietary axis of endometriosis prevention: a gut microbiota-estrobolome framework situated within a multidimensional model of risk modification, early recognition, and disease management.},
journal = {Frontiers in reproductive health},
volume = {8},
number = {},
pages = {1943184},
pmid = {42996903},
issn = {2673-3153},
abstract = {Endometriosis affects approximately 5%-10% of reproductive-aged women and imposes a substantial yet underexplored preventive research gap relative to treatment-focused literature. Diet is the central axis of this review: we organize the dietary evidence around an explicit mechanistic sequence-food-group-level epidemiological risk, hypothesised to be mediated by gut-microbiota dysbiosis and the estrogen-metabolizing "estrobolome", and thence to candidate dietary and probiotic interventions-and then situate this dietary axis within a broader multidimensional prevention framework spanning additional primary prevention (other modifiable lifestyle factors, environmental endocrine-disruptor exposure), secondary prevention (non-invasive early screening, adolescent menstrual-health education, and, as a conceptual proposal, targeted early hormonal intervention following the neo-evolutionary model of Vercellini and colleagues), and tertiary-level management of established disease. While, to our knowledge, six recent reviews and meta-analyses (2024-2026) have quantitatively synthesized randomized-trial evidence on dietary and nutraceutical interventions for endometriosis-associated pain, none situates this evidence within an explicit gut microbiota-estrobolome mechanistic framework or a broader multidimensional prevention model-the distinguishing contribution of this review. We advance this framework as a hypothesis-generating prevention research agenda rather than a set of clinically established preventive measures. Cost-effectiveness is treated as a cross-cutting dimension: endometriosis-specific economic evaluations of prevention and screening remain scarce-with a digital symptom-checker Markov model as a notable exception-so analogous frameworks from chronic-disease lifestyle-intervention economics are proposed as methodological templates. We synthesize current evidence, controversies, and priority directions, with particular emphasis on the dietary axis and its mechanistic underpinnings.},
}

@article {pmid42997460,
year = {2026},
author = {Li, LC and Cui, WH and Zhang, ZH and Song, J and Xu, YY and Cai, DG and Guan, Y and Mao, KL},
title = {Microbiota-targeted interventions in chronic kidney disease: probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and traditional Chinese medicine.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1900027},
doi = {10.3389/fcimb.2026.1900027},
pmid = {42997460},
issn = {2235-2988},
mesh = {Humans ; *Prebiotics/administration & dosage ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use/administration & dosage ; *Medicine, Chinese Traditional/methods ; *Renal Insufficiency, Chronic/therapy/microbiology ; *Synbiotics/administration & dosage ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; },
abstract = {Chronic kidney disease (CKD) is tightly associated with gut dysbiosis that fuels uremic toxin buildup, systemic inflammation, and renal fibrosis, yet conventional CKD therapies offer limited disease-modifying choices. This narrative review integrates preclinical and clinical evidence (searched PubMed, Web of Science, Cochrane up to May 31, 2026) for gut-microbiota interventions, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and traditional Chinese medicine (TCM), and compares their efficacy via network meta-analyses stratified by CKD stages. All microecological agents remodel gut flora, boost short-chain fatty acid producers and strengthen intestinal barriers to cut protein-bound uremic toxins, but eGFR benefits vary by strain, formulation, and disease stage, with most robust effects in non-dialysis CKD (stages 3-4). Dialysis patients gain minimal renal improvements, only mild anti-inflammatory and gastrointestinal relief. Network meta-analyses indicate distinct therapeutic strengths of each regimen, yet indirect cross-study comparisons yield low-to-moderate evidence certainty without direct head-to-head trials. FMT and herbal TCM show promising renoprotective gut-kidney regulatory effects in animal research and small preliminary human cohorts, though large controlled human trials remain absent. Subtype-specific CKD responses (diabetic nephropathy, IgA nephropathy) cannot be universally extrapolated. Despite encouraging mechanistic and early clinical signals, standardized testing, comparative trials and strict safety monitoring for fragile CKD patients are required before routine guideline use of gut-targeted therapies.},
}

Humans
*Prebiotics/administration & dosage
*Fecal Microbiota Transplantation
*Probiotics/therapeutic use/administration & dosage
*Medicine, Chinese Traditional/methods
*Renal Insufficiency, Chronic/therapy/microbiology
*Synbiotics/administration & dosage
Animals
*Gastrointestinal Microbiome
Dysbiosis/therapy

@article {pmid42997978,
year = {2026},
author = {Zhang, X and Cao, H and Zhang, Y and Shi, Y},
title = {β-glucan mitigates necrotizing enterocolitis-induced long-term cognitive impairment by remodeling gut microbiota and restoring tryptophan metabolite IAA-mediated gut-brain signaling.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2756699},
doi = {10.1080/19490976.2026.2756699},
pmid = {42997978},
issn = {1949-0984},
mesh = {Animals ; *beta-Glucans/administration & dosage/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Tryptophan/metabolism ; Mice ; *Enterocolitis, Necrotizing/complications/microbiology/metabolism/drug therapy ; *Indoleacetic Acids/metabolism ; Signal Transduction/drug effects ; *Cognitive Dysfunction/etiology/drug therapy/metabolism/microbiology ; *Brain/metabolism/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; Neuroprotective Agents/administration & dosage ; Dysbiosis ; Humans ; },
abstract = {Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder prevalent in preterm infants, and most NEC survivors suffer from persistent cognitive deficits and neurodevelopmental disorders, with no targeted therapeutic approaches available to date. β-glucan has been documented to regulate gut microbiota, suppress inflammation, and exert neuroprotective effects, yet its efficacy and molecular mechanisms against NEC-associated cognitive dysfunction remain unclear. In this study, we established a mouse NEC model with β-glucan intervention to explore its gut-brain axis protective effects. Behavioral assessments verified that β-glucan significantly rescued NEC-induced cognitive impairments, with comparable therapeutic effects between low and high doses. Multi-omics analyses demonstrated that β-glucan effectively reversed NEC-triggered gut microbiota dysbiosis and restored disrupted tryptophan metabolism, notably elevating the level of indole-3-acetic acid (IAA). Fecal microbiota transplantation and exogenous IAA supplementation recapitulated the neuroprotective phenotypes of β-glucan, which inhibited excessive hippocampal microglial activation and neuroinflammation, and repaired impaired synaptic ultrastructure and plasticity. Further mechanistic validation confirmed that IAA mediated neuroprotection via activating the AHR/MAP2K3/p38 signaling cascade. Collectively, β-glucan alleviates NEC-related cognitive injury through modulating the gut microbiota-tryptophan metabolism-IAA axis and subsequent AHR/MAP2K3/p38 signaling activation. This study elucidates a novel gut‒brain axis regulatory mechanism of β-glucan, providing reliable preclinical evidence for the clinical prevention and treatment of long-term neurodevelopmental complications in NEC survivors.},
}

Animals
*beta-Glucans/administration & dosage/pharmacology
*Gastrointestinal Microbiome/drug effects
*Tryptophan/metabolism
Mice
*Enterocolitis, Necrotizing/complications/microbiology/metabolism/drug therapy
*Indoleacetic Acids/metabolism
Signal Transduction/drug effects
*Cognitive Dysfunction/etiology/drug therapy/metabolism/microbiology
*Brain/metabolism/drug effects
Disease Models, Animal
Mice, Inbred C57BL
Fecal Microbiota Transplantation
Male
Neuroprotective Agents/administration & dosage
Dysbiosis
Humans

@article {pmid42998368,
year = {2026},
author = {Dall, SM and Møllekær, AH and Kousgaard, SJ and Jakobsen, SS and Larsen, L and Sørensen, B and Thorlacius-Ussing, O and Albertsen, M},
title = {Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis.},
journal = {Journal of Crohn's & colitis},
volume = {20},
number = {11},
pages = {},
doi = {10.1093/ecco-jcc/jjag150},
pmid = {42998368},
issn = {1876-4479},
support = {81-A.21//Svend Andersen Fonden/ ; 10.46540/4308-00176B//Independent Research Fund Denmark/ ; 101078234//European Union/ ; },
mesh = {Humans ; *Colitis, Ulcerative/microbiology/surgery ; *Pouchitis/microbiology ; Female ; *Colonic Pouches/microbiology ; Male ; Feces/microbiology ; Adult ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; *Gastrointestinal Microbiome/genetics ; *Drug Resistance, Bacterial/genetics ; Escherichia coli/genetics ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) from healthy donors with a normally functioning colon has limited clinical effect in the treatment of chronic pouchitis. However, a normally functioning ileal pouch-anal anastomosis (IPAA) physiology differs from individuals with a healthy intact colon. We aimed to investigate the microbial characteristics of patients with a normally functioning IPAA (HealthyPouch) compared with chronic pouchitis (SickPouch), ulcerative colitis (UC), and a healthy intact colon microbiome (NormalGut). Furthermore, we investigated how repeated antibiotic use influences antimicrobial resistance on a bacterial genome level.

METHODS: Fecal samples from 190 participants were collected; HealthyPouch (n = 38), SickPouch (n = 37), UC (n = 23), and NormalGut (n = 92) and sequenced with Illumina and taxonomically profiled. Samples from HealthyPouch, SickPouch, and NormalGut were also long-read sequenced using Oxford Nanopore Technologies for reconstruction of 12 282 metagenome-assembled genomes (MAGs). DNA methylation motifs were used for plasmid-host association.

RESULTS: The HealthyPouch microbiome is distinct from both the UC, NormalGut, and SickPouch microbiome. Escherichia coli MAGs in the SickPouch (n = 21) microbiome had significantly higher co-occurring ciprofloxacin resistance mutations in the gyrA and parC genes, compared to both HealthyPouch (n = 26; BH adjusted P < .05) and NormalGut (n = 40; BH adjusted P < .05). Based on DNA methylation pattern, three plasmids were associated with E. coli carrying extended-spectrum beta lactamase genes.

CONCLUSIONS: HealthyPouch microbiota differs from NormalGut microbiota, and could therefore be more appropriate for FMT treatment of chronic pouchitis. The association between E. coli and resistance gene-carrying plasmids underscores the importance of integrating plasmid analysis into metagenome-based approaches for personalized antibiotic treatment and resistance monitoring.},
}

Humans
*Colitis, Ulcerative/microbiology/surgery
*Pouchitis/microbiology
Female
*Colonic Pouches/microbiology
Male
Feces/microbiology
Adult
Middle Aged
Anti-Bacterial Agents/therapeutic use
*Gastrointestinal Microbiome/genetics
*Drug Resistance, Bacterial/genetics
Escherichia coli/genetics
Fecal Microbiota Transplantation

@article {pmid42998393,
year = {2026},
author = {Liu, K and Liu, Y and Wan, H and He, Y},
title = {Qiliqiangxin Capsule ameliorates post-myocardial infarction heart failure: associations with gut microbiota remodeling, altered fecal short-chain fatty acid profiles, and myocardial HDAC3-associated histone acetylation and JNK/TGF-β-related signaling.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {163},
number = {},
pages = {158909},
doi = {10.1016/j.phymed.2026.158909},
pmid = {42998393},
issn = {1618-095X},
abstract = {BACKGROUND: Qiliqiangxin Capsule (QLQX) is a guideline-recommended adjunctive therapy for heart failure with reduced ejection fraction, but mechanisms underlying post-myocardial infarction heart failure (post-MI HF) remain incompletely defined, particularly gut-heart microbial metabolism.

PURPOSE: This study aimed to characterize the gut microbial and fecal short-chain fatty acid (SCFA) alterations associated with the cardioprotective effects of QLQX and to determine whether gut-associated factors contribute functionally to its therapeutic effects in post-MI HF.

METHODS: A rat model of post-MI HF was established by permanent ligation of the left anterior descending coronary artery. Cardiac function, ventricular remodeling, histopathological injury, and inflammatory indices were evaluated after QLQX treatment. An integrated analytical strategy comprising fecal 16S rRNA gene sequencing, targeted fecal SCFA quantification, untargeted fecal and myocardial metabolomics, myocardial transcriptomics, and targeted protein analyses was used to characterize gut and cardiac responses. A publicly available human ST-segment elevation myocardial infarction transcriptomic dataset was included for exploratory pathway-level comparison. Spearman correlation analysis with Benjamini-Hochberg false discovery rate correction was performed to examine associations among microbial taxa, SCFAs, inflammatory markers, and cardiac functional indices. Molecular docking and molecular dynamics simulations were used to assess the structural plausibility of selected candidate interactions, and surface plasmon resonance (SPR) was performed to experimentally evaluate the predicted interaction between isobutyrate and JNK1. Antibiotic treatment and fecal microbiota transplantation (FMT) were further performed to evaluate the functional contribution and transferability of gut-associated fecal factors.

RESULTS: QLQX improved cardiac dysfunction, adverse ventricular remodeling, myocardial injury, and inflammatory responses in post-MI HF rats. Treatment reshaped the fecal microbial community and altered the fecal SCFA profile, including restoration of butyrate and isobutyrate. Selected SCFAs and bacterial taxa were associated with inflammatory markers and cardiac functional indices. Integrated omics and protein analyses further showed that these gut-associated alterations were accompanied by coordinated changes in myocardial cAMP, nuclear HDAC3 abundance, histone H3 acetylation, AMPK/mTOR signaling, and JNK/TGF-β related molecular indices. SPR analysis further demonstrated concentration-dependent binding of isobutyrate to JNK1, with an equilibrium dissociation constant (KD) of 5.89 × 10⁻⁵ M. Antibiotic treatment attenuated the therapeutic response to QLQX, whereas FMT from QLQX-treated donors partially transferred the protective phenotype, supporting a functional contribution of fecally transferable gut-associated factors.

CONCLUSION: QLQX ameliorated post-MI HF in association with remodeling of the gut microbial ecosystem, alterations in fecal SCFA profiles, and coordinated myocardial metabolic, epigenetic, and stress-signaling responses. The antibiotic and FMT experiments suggest that gut-associated factors partly contribute to the cardioprotective effects of QLQX. Butyrate and isobutyrate emerged as prioritized candidate metabolites, with SPR providing direct binding evidence for the isobutyrate-JNK1 interaction, although their broader causal roles and myocardial exposure require further validation.},
}

@article {pmid42971625,
year = {2026},
author = {Tranæs, K and Olsén, NN and Helms, M and Rasmussen, TS and Kyvsgaard, JN and Karlsen, MA and Hegaard, HK and Chloé Mirsepasi-Lauridsen, H and Munk Petersen, A and Aunsholt, L and Greisen, G and Nielsen, DS and Sørensen, SJ and Trivedi, U and Chawes, B and Bønnelykke, K and Vahman, N and Rasmussen, MA and Thorsen, J and Stokholm, J},
title = {RestoreGut - restoration of the gut microbiome after birth by caesarean section: study protocol for a double-blinded, randomised, placebo-controlled trial.},
journal = {BMJ open},
volume = {16},
number = {11},
pages = {e126018},
pmid = {42971625},
issn = {2044-6055},
abstract = {INTRODUCTION: Birth by caesarean section (CS) is associated with early gut microbiome perturbations and an increased risk of childhood asthma, likely reflecting long-term immune imprinting. This trial aims to restore the gut microbiota in CS-born infants through faecal microbiota transplantation (FMT) and faecal virome transplantation (FVT).

METHODS AND ANALYSIS: RestoreGut is a double-blinded, randomised, placebo-controlled trial enrolling 60 elective CS-born and 20 vaginally born infants. CS-born infants are randomised to receive maternal FMT, FVT or placebo in the first hours after birth. FMTs and FVTs are derived from pathogen-screened maternal stool samples collected during late pregnancy, using a novel bacterial enumeration technique to standardise dosing. Infant stool samples are collected on days 1, 3 and 7, and at 1, 3, 6 and 12 months after birth and analysed for microbiome composition over time using metagenomic sequencing. The primary outcome is differences in microbiome composition between the treatment and placebo groups at the 1-week timepoint. Secondary outcomes include longitudinal differences in gut microbiome and virome composition across all subsequent timepoints during the first year of life, differences in infection incidence during the first year of life, differences in faecal metabolomic profiles and comparisons of infant microbiomes in the FMT, FVT and placebo groups to those of a vaginally born reference cohort.

ETHICS AND DISSEMINATION: This trial has received approval from the Committees on Health Research Ethics in the Capital Region of Denmark (Approval ID H-24002284). The results will be disseminated through peer-reviewed publications and the trial website, targeting both scientific audiences and the general public.

TRIAL REGISTRATION NUMBER: NCT06264219.},
}

@article {pmid42985836,
year = {2026},
author = {Olekhnovich, EI and Kalachnyuk, TN and Zhgun, ES and Ivanov, AB and Fedorov, DE and Klimina, KM and Veselovsky, VA and Boldyreva, DI and Larin, AK and Matorin, RI and Lyamina, SV and Andreev, DN and Maev, IV and Balazs, I and Govorun, VM and Pavlenko, AV and Bespyatykh, JA and Ilina, EN},
title = {Dynamic alterations in stool microbiota composition following faecal transplantation in patients with inflammatory bowel disease.},
journal = {Clinical and translational medicine},
volume = {16},
number = {11},
pages = {},
pmid = {42985836},
issn = {2001-1326},
support = {26-15-00478//Russian Science Foundation/ ; },
}

@article {pmid42986298,
year = {2026},
author = {Lu, J and Wang, X and Zhou, S and Zhang, J and Fu, Q and Xiao, L and Lu, N},
title = {Lactylated MOESIN links gut metabolism to TGF-β-driven immune remodeling and bone protection in diabetic osteoporosis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2757330},
doi = {10.1080/19490976.2026.2757330},
pmid = {42986298},
issn = {1949-0984},
mesh = {Animals ; *Transforming Growth Factor beta/metabolism ; Humans ; Mice ; *Osteoporosis/immunology/therapy/metabolism ; Fecal Microbiota Transplantation ; *Bone Remodeling ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Female ; Signal Transduction ; Male ; *Microfilament Proteins/metabolism ; Disease Models, Animal ; },
abstract = {Diabetic osteoporosis is characterized by impaired bone homeostasis and immune dysregulation. We investigated how fecal microbiota transplantation (FMT) modulates microbial metabolism, immune signaling, and bone remodeling using a pilot clinical cohort and diabetic mouse models. The clinical component was treated as a safety/feasibility study with exploratory longitudinal BMD and serum biomarker endpoints. In experimental DOP models, FMT improved bone microarchitecture and reduced inflammatory and bone-resorption markers. Descriptive analysis of external PBMC scRNA-seq data (GSE274561) provided immune-cell context, while an independently replicated external splenic CD4[+] T-cell dataset (GSE267853; CONT n = 3, DM n = 3) provided disease-context support for Treg/Th17 and TGF-β/SMAD dysregulation. Replicated flow cytometry, RT-qPCR, Western blot, and functional perturbation experiments supported FMT-associated restoration of the Treg/Th17 balance and activation of lactate-MOESIN-TGF-β signaling in the experimental models.},
}

Animals
*Transforming Growth Factor beta/metabolism
Humans
Mice
*Osteoporosis/immunology/therapy/metabolism
Fecal Microbiota Transplantation
*Bone Remodeling
Th17 Cells/immunology
T-Lymphocytes, Regulatory/immunology
Female
Signal Transduction
Male
*Microfilament Proteins/metabolism
Disease Models, Animal

@article {pmid42988675,
year = {2026},
author = {Kuribayashi, R and Nakano, A and Kawasaki, M and Hariu, A and Sakurai, A},
title = {Regulatory science for microbiome-based medicines: lessons from Pharmaceuticals and Medical Devices Agency initiatives.},
journal = {Trends in biotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tibtech.2026.10.007},
pmid = {42988675},
issn = {1879-3096},
abstract = {Recent Pharmaceuticals and Medical Devices Agency initiatives for live biotherapeutic products, fecal microbiota transplantation, and phage therapy medicinal products illustrate a dialog-driven regulatory approach for microbiome-based medicines. We compare this strategy with evolving Food and Drug Administration and European Medicines Agency frameworks and identify priorities for future regulatory development and international alignment.},
}

@article {pmid42989389,
year = {2026},
author = {Liu, Z and Gao, Q and Ma, G and Li, Z and Lou, C and Wang, M and Guo, J},
title = {A ternary network model of gut microbiota, cellular senescence and the pathogenesis of osteoarthritis and its intervention strategies.},
journal = {Journal of orthopaedic surgery and research},
volume = {21},
number = {1},
pages = {},
pmid = {42989389},
issn = {1749-799X},
support = {GZY-KJS-SD-2024-025//Co-construction Project of the National Administration of Traditional Chinese Medicine and Shandong Health Commission/ ; },
mesh = {Humans ; *Osteoarthritis/therapy/etiology/microbiology/pathology ; *Gastrointestinal Microbiome/physiology ; Animals ; *Cellular Senescence/physiology ; Dysbiosis/complications ; },
abstract = {Osteoarthritis (OA) is a heterogeneous whole-joint disorder in which mechanical loading, ageing, obesity, metabolic inflammation and tissue-cell stress interact. Increasing evidence links gut microbiota dysbiosis and cellular senescence to OA, but the strength of this evidence differs across model systems and clinical settings. This review therefore reframes the proposed gut microbiota-cellular senescence-OA axis as an evidence-graded ternary network rather than a single linear pathogenic pathway. Current data support several links: dysbiosis and increased intestinal permeability can promote lipopolysaccharide (LPS)-driven TLR4/NF-κB/NLRP3 activation; inflammatory and metabolic signals can induce senescence-associated secretory phenotype (SASP) programmes in chondrocytes, synoviocytes and subchondral bone cells; and senescent joint cells can amplify matrix degradation through MMP-13, ADAMTS-4 and ADAMTS-5. By contrast, the reverse pathway in which SASP factors directly remodel the intestinal barrier and microbiota in OA remains plausible but incompletely demonstrated. Microbiota-directed approaches, including diet, prebiotics, selected probiotics and fecal microbiota transplantation, and senescence-modulating approaches, including senomorphics and senolytics, should therefore be viewed mainly as preclinical or early translational strategies. We highlight obesity, high-fat diet and ionic or biomechanical stress as contextual modifiers of this network, and propose that longitudinal cohorts, mechanistic animal models and multi-omics validation are needed before precision intervention can be claimed.},
}

Humans
*Osteoarthritis/therapy/etiology/microbiology/pathology
*Gastrointestinal Microbiome/physiology
Animals
*Cellular Senescence/physiology
Dysbiosis/complications

@article {pmid42989696,
year = {2026},
author = {Pai, N and Nicholson, M and Rich, S and Conrad, MA},
title = {Fecal microbiota transplantation and microbiota-based therapeutics in pediatric clinical practice: Current status and emerging indications.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70633},
pmid = {42989696},
issn = {1536-4801},
support = {//None/ ; },
abstract = {Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides difficile infection (rCDI) in children and adults. This review outlines the evidence behind FMT for rCDI, considerations in special pediatric populations, and limitations in current practice due to FMT access for patients under the age of 18.},
}

@article {pmid42980393,
year = {2026},
author = {Liu, X and Zhang, Z and Fang, Y and Yuan, B and Lian, H and Yin, W and Zhang, J and Yuan, Q and Wang, S},
title = {Polygonatum cyrtonema Polysaccharide Ameliorates Functional Constipation in Mice via the Gut Microbiota-Pentadecanoic Acid-GPR40 Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {43},
pages = {33918-33933},
doi = {10.1021/acs.jafc.6c06937},
pmid = {42980393},
issn = {1520-5118},
support = {0001/2025/TFP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 0002/2025/NRP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 0008/2025/EQP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 2023B1212120006//Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research/ ; TP-001-2025//National Leading Talent Project Funding of China/ ; },
mesh = {Animals ; Mice ; *Polysaccharides/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; *Constipation/drug therapy/microbiology/metabolism/physiopathology/genetics ; Male ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Humans ; *Polygonatum/chemistry ; Bacteria/isolation & purification/classification/genetics/metabolism ; Mice, Inbred C57BL ; *Plant Extracts/administration & dosage ; },
abstract = {Constipation is a widespread gastrointestinal dysfunction that severely diminishes life satisfaction, yet current pharmacological interventions frequently carry risks of dependency. This study investigates the therapeutic potential and underlying mechanism ofPolygonatum cyrtonema polysaccharide (PCP), an inulin neoseries-type fructan, in mitigating loperamide-induced constipation in mice. Our results demonstrated that PCP treatment significantly normalized defecation indicators, including increased fecal water content and accelerated small-intestinal transit. Fecal microbiota transplantation (FMT) confirmed that the anti-constipation efficacy of PCP was driven by the gut microbiota. Integrated 16S rRNA sequencing and metabolomic profiling revealed that PCP remodeled the gut microbiota, particularly enriching Lachnospiraceae, which subsequently drove the accumulation of pentadecanoic acid (PDA). Mechanistically, PDA served as a key microbial metabolite that enhanced colonic motility, likely by activating the GPR40 receptor. These findings identify the "PCP-microbiota-PDA-GPR40" axis as an novel pathway for alleviating functional constipation, supporting PCP as a promising prebiotic candidate or functional food ingredient.},
}

Animals
Mice
*Polysaccharides/administration & dosage
*Gastrointestinal Microbiome/drug effects
*Constipation/drug therapy/microbiology/metabolism/physiopathology/genetics
Male
*Receptors, G-Protein-Coupled/metabolism/genetics
Humans
*Polygonatum/chemistry
Bacteria/isolation & purification/classification/genetics/metabolism
Mice, Inbred C57BL
*Plant Extracts/administration & dosage

@article {pmid42980459,
year = {2026},
author = {Zhou, Z and Fang, Y and Luo, M and Du, H and Guo, X and Chen, Y and Han, Y and Xiao, H},
title = {Gut Microbiota-Mediated Liberation of Ellagic Acid from Strawberry Soluble Fiber and Its Metabolism: In Vitro and In Vivo Evidence.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {43},
pages = {34126-34136},
doi = {10.1021/acs.jafc.6c07831},
pmid = {42980459},
issn = {1520-5118},
support = {2019-67017-29249//National Institute of Food and Agriculture/ ; 2020-67017-30835//National Institute of Food and Agriculture/ ; 2020-67017-30844//National Institute of Food and Agriculture/ ; 2023-67017-40248//National Institute of Food and Agriculture/ ; 2026-67021-45661//National Institute of Food and Agriculture/ ; 3060-21650-002-057-S//Agricultural Research Service/ ; },
mesh = {*Ellagic Acid/metabolism/chemistry ; *Dietary Fiber/metabolism/analysis ; *Fragaria/metabolism/chemistry ; Animals ; Humans ; Mice ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Bacteria/metabolism/isolation & purification/genetics/classification ; Fruit/metabolism/chemistry ; Fermentation ; Male ; Coumarins/metabolism ; Hydrolyzable Tannins ; },
abstract = {This study investigated strawberry soluble fiber (SSF) as a reservoir of celobiotics and evaluated their microbial liberation and metabolism both in vitro and in vivo. In vitro colonic fermentation of SSF combined with untargeted metabolomics identified urolithin C/iso-urolithin C, a gut microbial metabolite derived exclusively from ellagic acid (EA), suggesting the microbial liberation of matrix-embedded EA from SSF. This hypothesis was validated by pectinase treatment, which increased total EA equivalents by approximately 10-fold. Time-course fermentation demonstrated rapid EA liberation from SSF and its subsequent urolithin conversion, which was further confirmed in human-microbiota-transplanted mice after SSF consumption in vivo. Notably, substantial interindividual variation was observed in the capacities of human fecal microbiota to release EAs and produce urolithins. Beyond SSF, EA is widely distributed among plant-derived dietary fibers (DFs) and is particularly abundant in berry fibers. This work expanded the celobiotic concept and highlighted the importance of the microbiota-mediated release of hidden phytochemicals from dietary fibers.},
}

*Ellagic Acid/metabolism/chemistry
*Dietary Fiber/metabolism/analysis
*Fragaria/metabolism/chemistry
Animals
Humans
Mice
*Gastrointestinal Microbiome
Feces/microbiology
*Bacteria/metabolism/isolation & purification/genetics/classification
Fruit/metabolism/chemistry
Fermentation
Male
Coumarins/metabolism
Hydrolyzable Tannins

@article {pmid42982582,
year = {2026},
author = {Wang, K and Liu, Y and Wang, L and Xu, Y and Gu, Z and Sun, R and Wei, C and Zhao, Q and Li, B and Yan, X and Qiu, Y},
title = {Chronic Arsenic Exposure Induces Hepatocyte Proliferation in Rats via the Gut-Liver Axis: Interventions With Fecal Microbiota Transplantation and/or Arsenic Withdrawal.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70494},
pmid = {42982582},
issn = {1099-1263},
support = {20250022//Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ ; //Shanxi Province Higher Education "Billion Project" Science/ ; TMSYSKF2025002//Technology Guidance Project and Open Project of Key Laboratory of Neurological Disease Prevention and Research of Shanxi Province/ ; },
abstract = {Arsenic (As) contamination in groundwater has been reported in many countries and is a major risk factor for liver injury. While the impact of arsenic exposure on gut microbiota and its role in liver diseases through the gut-liver axis has been documented, the underlying mechanism remains unclear. In this study, we established a chronic arsenic exposure rat model by administering sodium arsenite (NaAsO2) at concentrations of 30 and 100 mg/L through drinking water until 62 weeks of age. Subsequently, high As-exposed rats were subjected to fecal microbiota transplantation (FMT), arsenic cessation, or combined FMT and arsenic cessation interventions for 2 months. Liver pathological changes, hepatocyte proliferation, intestinal microbiota composition, fecal butyrate levels, and the expression of butyrate-related molecular markers were evaluated using hematoxylin-eosin staining, immunohistochemistry, 16S rRNA gene sequencing, gas chromatography, and quantitative real-time PCR. Chronic arsenic exposure increased hepatocyte proliferation, as evidenced by elevated PCNA and Ki-67 expression in liver tissues. Microbiota analysis revealed that arsenic exposure significantly altered gut microbial community structure and reduced the abundance of butyrate-producing bacteria, particularly Lachnospiraceae and Blautia. Consistently, fecal butyrate levels showed a decreasing trend after arsenic exposure. Furthermore, arsenic exposure significantly suppressed hepatic miR-22 expression, accompanied by increased expression of Sirt1 and Ctnnb1 and decreased expression of Gsk3b, suggesting activation of a proliferation-related signaling pathway. Intervention with FMT and/or arsenic cessation partially restored gut microbiota composition, alleviated miR-22 suppression, and improved arsenic-induced molecular alterations. Collectively, these findings demonstrate that chronic arsenic exposure promotes hepatocyte proliferation through disruption of gut microbiota and reduction of microbiota-derived butyrate, which may regulate the miR-22/Sirt1 signaling pathway. Restoration of intestinal microbiota by FMT or cessation of arsenic exposure may provide potential strategies for mitigating arsenic-induced hepatic abnormalities.},
}

@article {pmid42982767,
year = {2026},
author = {Passannante, M and Laudisi, A and Ghiso, A and Francia, G and Di Grazia, C and Dominietto, A and Bregante, S and Varaldo, R and Gambella, M and Angelucci, E and Raiola, AM},
title = {Managing acute graft-versus-host disease after allogeneic stem cell transplantation.},
journal = {Expert review of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17474086.2026.2760637},
pmid = {42982767},
issn = {1747-4094},
abstract = {INTRODUCTION: Acute graft-versus-host disease (aGVHD) remains a leading cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation. Despite progress in prophylactic strategies, its management remains challenging: corticosteroids are still the mainstay of first-line care, yet a substantial proportion of patients fail to achieve durable responses, underscoring the need for more effective and less toxic alternatives.

AREAS COVERED: This review outlines the current approach to aGVHD, from first-line management to steroid-refractory disease and beyond. It covers corticosteroid optimization, the established role of ruxolitinib in the steroid-refractory setting, and the use of extracorporeal photopheresis in selected patients. Cellular, microbiome-based, cytokine-directed, and regenerative strategies acting on complementary pathogenic mechanisms are also discussed. The literature was identified through a PubMed search using the terms 'acute graft-versus-host disease' and 'treatment,' including publications up to 30 June 2026, supplemented by manual screening of reference lists.

EXPERT OPINION: Ruxolitinib has reshaped the management of steroid-refractory aGVHD, although important unmet needs persist. Future progress will depend not only on new agents but on smarter use of existing options: minimizing steroid exposure, refining sequencing, and integrating combinations earlier. Biomarker-guided risk stratification may ultimately support a more individualized approach, improving disease control while limiting toxicity.},
}

@article {pmid42982830,
year = {2026},
author = {Song, Y and Xu, J and Zhao, J and Yang, R and Ma, Y and Hou, YM and Cao, Y and Li, J and Yu, S and Liang, X and Zhang, Y and Wang, K and An, L and Liu, Y and Meng, ZX and Fan, JG and Xie, C},
title = {Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42982830},
issn = {2041-1723},
support = {82530024//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92557304//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82570954//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92457301//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Sarcopenia/microbiology/metabolism/etiology/pathology ; Mice ; Female ; *Aging/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; Animals, Newborn ; Male ; *Gastrointestinal Microbiome/physiology ; *Overnutrition/complications ; Fecal Microbiota Transplantation ; *Metabolic Diseases/metabolism/microbiology/etiology ; Mice, Inbred C57BL ; Muscle, Skeletal/metabolism/pathology ; Dysbiosis ; Disease Models, Animal ; Akkermansia ; },
abstract = {Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. Here, we show that neonatal overfeeding acts as a developmental insult that accelerates age-related sarcopenia in both sexes. Using different mouse models, early overnutrition shortens lifespan and exacerbates late-life muscle atrophy, accompanied by metabolic dysfunction. Mechanistically, neonatal overfeeding disrupts goblet cell development, leading to persistent mucus barrier defects and consequently reduced Akkermansia muciniphila (A. muciniphila) colonization during aging. Fecal microbiota transplantation transfers the sarcopenic phenotype, implicating gut dysbiosis in disease propagation. Loss of A. muciniphila reduces acetate production, impairs muscle mitochondrial function at least in part via suppressed GPR43 signaling, and aggravates sarcopenia. Conversely, A. muciniphila reconstitution or acetate supplementation restores mitochondrial homeostasis and improves muscle performance in aged mice. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking early-life overnutrition to muscle aging, highlighting the preventive potential of optimizing early nutrition to support healthy aging.},
}

Animals
*Sarcopenia/microbiology/metabolism/etiology/pathology
Mice
Female
*Aging/metabolism
*Intestinal Mucosa/metabolism/microbiology
Animals, Newborn
Male
*Gastrointestinal Microbiome/physiology
*Overnutrition/complications
Fecal Microbiota Transplantation
*Metabolic Diseases/metabolism/microbiology/etiology
Mice, Inbred C57BL
Muscle, Skeletal/metabolism/pathology
Dysbiosis
Disease Models, Animal
Akkermansia

@article {pmid42982861,
year = {2026},
author = {Pomej, K and Frick, A and Scheiner, B and Baumgartner, M and Schmetterer, KG and Reyna-Blanco, CS and Balcar, L and Pajancic, L and Kreuter, A and Séneca, J and Hausmann, B and Köcher, T and Prinzensteiner, M and Lampichler, K and Rohr-Udilova, N and Chakrabarty, A and Klotz, A and Lampl, AC and Zinober, K and Regnat, K and Trauner, M and Berry, D and Tamandl, D and Vogl, T and Gasche, C and Pinter, M},
title = {FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42982861},
issn = {2041-1723},
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/adverse effects ; *Liver Neoplasms/therapy/immunology/mortality ; Pilot Projects ; *Bevacizumab/therapeutic use/administration & dosage/adverse effects ; *Carcinoma, Hepatocellular/therapy/immunology/mortality ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; Immunotherapy/methods ; Combined Modality Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Combined Antibody Therapeutics ; },
abstract = {Fecal microbiota transplantation (FMT) may help to overcome resistance to immunotherapy. In this single-center, single-arm phase II hypothesis-generating pilot study (FAB-HCC), we included 12 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab plus bevacizumab. Patients received a single FMT via colonoscopy from a donor with HCC who responded to anti-PD-1 treatment or a healthy donor, combined with atezolizumab plus bevacizumab. The primary endpoint was safety as measured by incidence and severity of treatment-related adverse events (TRAEs). Secondary endpoints included radiological response and survival. Grade 3-4 TRAEs included arterial hypertension (n = 5) and proteinuria (n = 3), both related to bevacizumab, and diarrhea (n = 1), related to FMT. No serious TRAEs were observed. Objective response rate was 33% (n = 4/12) and median progression-free survival was 6.9 (95%CI, 3.0-10.8) months. Following FMT, recipient microbiome composition appeared more similar to that of the donor, and healthy donor FMT seemed to be associated with higher engraftment. FMT appeared to be associated with enrichment of response-associated and loss of deleterious gut bacteria. Circulating PD-1[+]CD8[+] T cells decreased and CD32b[+]CD14[high]CD16[low] monocytes increased following FMT plus immunotherapy. Phage-display immunoprecipitation sequencing revealed that antibody repertoire stability, rather than global diversity or composition, changed over time. Taken together, FMT combined with atezolizumab plus bevacizumab was safe and associated with a high response rate in patients with atezolizumab plus bevacizumab-refractory HCC. Given the limited sample size, these findings need cautious interpretation and confirmation in larger, adequately powered trials. ClinicalTrials.gov identifier: NCT05750030.},
}

Humans
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/adverse effects
*Liver Neoplasms/therapy/immunology/mortality
Pilot Projects
*Bevacizumab/therapeutic use/administration & dosage/adverse effects
*Carcinoma, Hepatocellular/therapy/immunology/mortality
Female
Male
Middle Aged
*Fecal Microbiota Transplantation/methods/adverse effects
Aged
Immunotherapy/methods
Combined Modality Therapy
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Programmed Cell Death 1 Receptor/antagonists & inhibitors
Combined Antibody Therapeutics

@article {pmid42983789,
year = {2026},
author = {Chen, J and Guo, Z and Liu, M and Wei, Y and Wu, L and Li, J and Wang, W},
title = {Continuous fermentation-derived fecal microbiota transplantation improves intestinal barrier function and reshapes gut microbiota in weaned piglets.},
journal = {Animal microbiome},
volume = {8},
number = {1},
pages = {},
pmid = {42983789},
issn = {2524-4671},
abstract = {Weaning diarrhea in piglets poses a serious threat to the healthy development of the swine industry and is closely associated with gut microbiota dysbiosis. Fecal microbiota transplantation (FMT), as an effective strategy for modulating intestinal microecology, remains underexplored in swine production, particularly regarding the systematic evaluation of fecal microbiota suspension prepared via continuous fermentation on piglet health. In this study, fecal microbiota suspensions derived from adult pigs and piglets were prepared using a continuous fermentation system. A 28-day feeding trial was conducted with 18 piglets randomly assigned to three groups: control (CON), adult pig-derived FMT(FMT-A), and piglet-derived FMT(FMT-P). Growth performance, diarrhea incidence, gut microbiota, fecal short-chain fatty acids (SCFAs), and serum immune/inflammatory cytokines were measured. The results showed that compared with CON, both FMT treatments significantly increased average daily gain (ADG) and reduced diarrhea rate (P < 0.05), with FMT-A exhibiting superior effects to FMT-P. FMT improved intestinal barrier function, as evidenced by reduced serum levels of endotoxin (ET) and D-lactic acid (D-LA), raised immunoglobulin G (IgG) and anti-inflammatory cytokine interleukin-10 (IL-10), and lowered pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (P < 0.05). FMT-A significantly reduced diamine oxidase (DAO) and increased immunoglobulin M (IgM) and immunoglobulin A (IgA) (P < 0.05). 16S rDNA sequencing revealed that FMT reshaped the intestinal microbiota: FMT-A enhanced microbial uniformity, FMT-P improved richness; both tended to increase beneficial Lactobacillus, with FMT-A significantly increasing Firmicutes(P < 0.05). Furthermore, FMT increased fecal propionic acid and decreased valeric acid (P < 0.05). This study demonstrates the efficacy of fecal microbiota suspension prepared via continuous fermentation technology in improving intestinal health and growth performance of piglets, providing a novel strategy for developing standardized, stable, and active microbe-based interventions, and laying a foundation for further mechanistic understanding of FMT in livestock production.},
}

@article {pmid42983933,
year = {2026},
author = {Patel, A and Jain, P},
title = {Why Gut-Brain Axis Therapies Fail in Clinical Translation: The Case for Endophenotyping and Longitudinal Trial Design.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X546118261028104240},
pmid = {42983933},
issn = {1875-6190},
abstract = {Although there is strong preclinical evidence for the involvement of the gut-brain axis in neuroimmune, metabolic and behavioural regulation, translation of gut-centric therapies to consistent clinical outcomes is challenging. Although probiotics, postbiotics, faecal microbiota transplants and mucosal anti-inflammatory treatments show therapeutic promise in animal studies, clinical trials often provide inconsistent or unclear results. One major reason for this translational gap is the biological heterogeneity hidden behind broad diagnostic categories. Individuals with the same clinical features can vary considerably in gut barrier function, mucosal immune responses, microbial community composition, microbial metabolite production, and systemic inflammatory pathways. Therapies targeting specific gut-brain pathways might, therefore, be tested in groups that include individuals without the relevant biological abnormality, potentially decreasing measurable therapeutic effects. There is a shift away from diagnosis-based recruitment toward mechanism-based endophenotyping. The integration of standardised composite inflammatory and metabolic endophenotypes with longitudinal host and microbial biomarkers could help to define physiologically meaningful therapeutic cohorts and differentiate between target engagement and clinical outcomes. Future studies should include initial stratification, ongoing biological sampling, and prospective validation of biomarkers that predict treatment response. Such an approach may turn seemingly ineffective therapies into mechanistic findings to identify patients most likely to benefit from changes in microbial, metabolic, or mucosal factors. Therefore, accurate endophenotyping may represent an important tool to bridge the translational gap from promising gut-brain studies to practical therapeutic interventions.},
}

@article {pmid42984552,
year = {2026},
author = {Rocchetti, A and Gotta, F and Bottino, P and Vay, D and Pizzo, V and Gugliotta, V and Grossi, AA and Besutti, V and Bianchetti, M and Bona, E and Castagliuolo, I and Corbella, M and Gasbarrini, A and Marangoni, A and Masucci, L and Mauro, MV and Putignani, L and Quaranta, G and Sanguinetti, M and Drago, L},
title = {Development and expert appraisal of a lifestyle questionnaire for microbiome host metadata.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1932122},
pmid = {42984552},
issn = {2235-2988},
mesh = {Humans ; Surveys and Questionnaires ; *Life Style ; *Metadata ; Italy ; *Gastrointestinal Microbiome ; *Microbiota ; Diet ; Sleep ; Exercise ; },
abstract = {INTRODUCTION: Lifestyle information can help contextualize variation in the human gut microbiome, but its collection and operational definitions differ across studies. We developed a candidate questionnaire combining diet, physical activity and sleep for microbiome host metadata and undertook an initial appraisal by Italian experts. Candidate content was informed by a focused narrative literature appraisal and established lifestyle-assessment frameworks.

METHODS: Seventeen experts were invited and nine responded (53%). In a single anonymous rating round, experts assessed the relevance of 37 candidate items on a five-point scale. The prespecified agreement criterion was at least 70% of respondents assigning a rating of 4 or 5, corresponding to at least seven of nine experts.

RESULTS: Twenty-five items (67.6%) met this criterion: 18 of 23 dietary items (78.3%), six of eight physicalactivity items (75.0%), and one of six sleep items (16.7%). Twelve items remained exploratory.

DISCUSSION: These findings provide an initial prioritization of candidate lifestyle metadata within an Italian specialist network. They do not establish a stable iterative Delphi consensus, instrument reliability, construct validity, or associations between questionnaire responses and microbiome outcomes. Participant testing, operational refinement and empirical evaluation are required before research deployment or potential use in fecal microbiota transplantation donor characterization.},
}

Humans
Surveys and Questionnaires
*Life Style
*Metadata
Italy
*Gastrointestinal Microbiome
*Microbiota
Diet
Sleep
Exercise

@article {pmid42984758,
year = {2026},
author = {Rawat, A and Prasad, N and Rawat, P and Ahmed, S and Kumar, B and Singh, A and Nayak, T and Kushwaha, RS},
title = {Beyond solute clearance: the kidney-gut-immune-nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1931760},
pmid = {42984758},
issn = {2296-861X},
abstract = {Kidney disease affects approximately ~850 million people globally, with millions dependent on dialysis as life-sustaining renal replacement therapy. While dialysis corrects solute accumulation and fluid overload, it incompletely replicates normal renal physiology and introduces its own biological stressors, perpetuating a cycle of systemic dysfunction that extends well beyond the kidney. Central to this dysfunction is the kidney-gut-immune-nutrition (KGIN) axis: a bidirectional network linking renal clearance, intestinal microbial homeostasis, immune regulation, and nutritional metabolism. In end-stage renal disease, each component of this axis is simultaneously disrupted and becomes a driver of further deterioration. Uremic toxin accumulation remodels the gut microbiome toward a dysbiotic state, characterized by depletion of short-chain fatty acid-producing organisms and expansion of pathobionts. The resulting compromise of intestinal barrier integrity permits systemic translocation of lipopolysaccharide and other microbial products, sustaining chronic low-grade inflammation and a paradoxical state of immune dysfunction marked by heightened inflammatory signaling alongside impaired pathogen defense. These perturbations converge on nutritional status, driving protein-energy wasting through catabolic cytokine signaling, anorexia, and suppression of anabolic pathways, with sarcopenia reported in several dialysis cohorts to progress at two to three fold faster than age related muscle loss. Hemodialysis and peritoneal dialysis produce distinct patterns of axis disruption: hemodialysis is characterized by intermittent toxin peaks, bioincompatible membrane-driven complement activation, and more severe dysbiosis, whereas peritoneal dialysis introduces continuous peritoneal glucose exposure and a unique local immune microenvironment, with generally slower decline in residual kidney function. These modality-specific differences translate into divergent cardiovascular, infectious, and nutritional risk profiles that are incompletely explained by traditional clinical variables. Emerging multi-omics approaches, including metagenomics, metabolomics, and high-throughput immune profiling, are beginning to characterize axis disruption with unprecedented resolution, enabling in-depth characterization of host-microbiome-immune identification of patient subgroups with distinct mechanistic signatures that cannot be captured by single domain analysis alone. To bridge this analytical capability with clinical practice, we propose the Microbiome-Immune-Nutrition (MIN) Index, a conceptual, hypothesis generating composite biomarker framework designed to synthesize data across all three axis domains and stratify patients by the severity of disruption to guide targeted, personalized interventions, which remain to be demonstrated through prospective validation studies. Therapeutic strategies targeting the axis, including dietary fiber and plant-based approaches, synbiotics, fecal microbiota transplantation, advanced dialysis modalities, and omega-3 and polyphenol supplementation, show mechanistic promise but require larger, better-designed trials with hard clinical endpoints before routine clinical adoption. Standardization of microbiome research methodology, investment in longitudinal multi-omics cohorts, and development of international collaborative consortia are research priorities that will be essential to translate mechanistic insights into improvements in survival and quality of life for patients on maintenance dialysis.},
}

@article {pmid42984924,
year = {2026},
author = {Marano, G and Conci, L and Farsakh, L and Traversi, G and Mazza, O and Ricozzi, V and Rotondaro, S and Migliore, A and Capristo, E and Franceschini, G and Gaetani, E and Mazza, M},
title = {Microbiota Dysbiosis and the Gut-Brain Axis in Psychiatric Disorders: Molecular Mechanisms, Clinical Evidence, and Therapeutic Perspectives.},
journal = {Alpha psychiatry},
volume = {27},
number = {5},
pages = {54121},
pmid = {42984924},
issn = {2757-8038},
abstract = {The gut-brain axis provides a biologically plausible framework for understanding the bidirectional interactions among the intestinal microbiota, immune-inflammatory signaling, neuroendocrine regulation, neurotransmitter metabolism, and psychiatric symptoms. Although numerous recent reviews have examined individual psychiatric disorders, microbial composition, or microbiota-targeted therapies, the field still lacks a sufficiently integrated appraisal that clearly distinguishes associative findings from human studies, mechanistic evidence from preclinical research, and preliminary clinical interventions. This structured narrative review synthesizes clinical, translational, and preclinical studies across major depressive disorder, bipolar disorder, anxiety disorders, schizophrenia, and trauma-related conditions. The main literature search covered publications from January 2015 to January 2026; earlier foundational mechanistic studies of key relevance to gut-brain communication were also considered. Recurrent pathways include altered short-chain fatty acid production, tryptophan-kynurenine metabolism, immune-inflammatory activation, hypothalamic-pituitary-adrenal axis dysregulation, neurotransmitter-related signaling, impaired intestinal and blood-brain barrier integrity, and vagus nerve-mediated communication. Human studies predominantly demonstrate associations between microbial signatures and psychiatric phenotypes, symptom severity, inflammatory status, or treatment response, whereas preclinical models provide stronger mechanistic evidence that microbiota manipulation can influence behavioral, neurochemical, immune, and neuroendocrine outcomes. Probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation show therapeutic potential; however, the current evidence is limited by small sample sizes, methodological heterogeneity, insufficient standardization, and a lack of long-term validation. The distinctive contribution of this review is its structured comparison of three levels of evidence-human observational findings, experimental mechanistic studies, and emerging clinical interventions-thereby clarifying what has been consistently replicated, what remains mechanistically plausible, and what is not yet ready for routine application in psychiatric practice.},
}

@article {pmid42976978,
year = {2026},
author = {Ge, S and Li, L and Li, Y and Lv, S and Yang, Y and Liu, X and Wang, Y and Zhang, Y and Niu, L and Zhuang, P and Guo, H},
title = {Reversal of gut dysbiosis-related arachidonic acid deficiency alleviates Parkinsonian motor deficits and neuroinflammation.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179501},
doi = {10.1016/j.ejphar.2026.179501},
pmid = {42976978},
issn = {1879-0712},
abstract = {Gut microbiota dysbiosis has been increasingly implicated in Parkinson's disease (PD), but the relationship of microbiota-associated metabolic alterations to PD remains poorly understood. This study investigated the association between gut microbiota dysbiosis and arachidonic acid (AA) dysregulation in PD and evaluated whether modulation of AA homeostasis could ameliorate Parkinsonian phenotypes. Gut microbial alterations were characterized by 16S rRNA gene sequencing, and serum metabolic changes were assessed using untargeted metabolomics combined with microbiota-metabolite correlation analysis. Marked gut microbiota dysbiosis was observed in PD mice and was accompanied by reduced serum AA levels. Fecal microbiota transplantation (FMT) increased serum AA levels and improved motor performance, providing functional support for a link between gut microbiota alterations and disrupted AA homeostasis. In addition, exogenous AA supplementation attenuated motor dysfunction and neuroinflammation. Collectively, these findings support a functional association among gut microbiota dysbiosis, altered AA homeostasis, and Parkinsonian phenotypes, suggesting that modulation of gut microbiota composition or AA availability may represent potential strategies for alleviating PD-associated motor dysfunction and neuroinflammation.},
}

@article {pmid42977101,
year = {2026},
author = {El-Sherbiny, GM},
title = {Reprogramming the tumor microbiome: Opportunities for cancer prevention, diagnosis, and precision therapy.},
journal = {Biochimica et biophysica acta. Reviews on cancer},
volume = {},
number = {},
pages = {189748},
doi = {10.1016/j.bbcan.2026.189748},
pmid = {42977101},
issn = {1879-2561},
abstract = {Microbiota-cancer interactions operate across distinct anatomical compartments, including the gut microbiota, the distal gut-tumor axis, and intratumoral microbiota residing within tumor tissues. These microbial communities and their metabolites can influence carcinogenesis, tumor progression, immune surveillance, and therapeutic responses through inflammation, genotoxicity, metabolic remodeling, epithelial and tumor-barrier dysfunction, and immune regulation. However, the magnitude and direction of these effects are highly context dependent, varying with cancer type, tumor site, microbial composition, host factors, treatment exposure, and methodological approaches. Importantly, associations between microbial signatures and clinical outcomes do not necessarily establish causality, and findings from gut microbiome studies should not be extrapolated directly to local intratumoral communities. This review critically synthesizes current evidence linking gut and intratumoral microbiota to tumor biology and treatment response, distinguishing compartment-specific mechanisms and evaluating the strength and limitations of available evidence. We examine how microbial metabolites, microbe-host interactions, and microbiota-driven immune and metabolic pathways shape the tumor microenvironment and may modify responses to immunotherapy, chemotherapy, radiotherapy, and targeted therapies. We further assess multi-omics and spatial approaches for resolving microbial heterogeneity and identifying clinically relevant biomarkers, alongside emerging microbiome-directed interventions, including probiotics, fecal microbiota transplantation, engineered microorganisms, and nanotechnology-based strategies. Particular emphasis is placed on discrepancies between preclinical and clinical findings, causal inference, reproducibility, interindividual variability, contamination and sampling challenges, and the barriers to clinical translation. Collectively, the evidence supports a context-specific role for microbiota in cancer biology while underscoring the need for standardized methodologies, longitudinal and mechanistic studies, and well-controlled clinical trials before microbiome-based strategies can be reliably incorporated into precision oncology.},
}

@article {pmid42979424,
year = {2026},
author = {Oulkadi, D and Van Oers, F and Vanden Driessche, L and Vandamme, S and Matheeussen, V and Mairesse, C and Martiny, D and Anguille, S and Demuyser, T},
title = {Persistent Campylobacter jejuni enterocolitis after CAR T-cell therapy in a patient with hypogammaglobulinemic follicular lymphoma.},
journal = {ASM case reports},
volume = {2},
number = {6},
pages = {},
pmid = {42979424},
issn = {2996-2684},
abstract = {BACKGROUND: Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide and typically results in self-limiting enterocolitis in immunocompetent individuals. In contrast, immunocompromised patients are at risk for severe, recurrent, or persistent infection. Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 induces prolonged B-cell aplasia and hypogammaglobulinemia, predisposing patients to atypical infections. We report the first case of persistent and disseminated C. jejuni infection following CD19-directed CAR T-cell therapy, confirmed by whole-genome sequencing.

CASE SUMMARY: A 68-year-old man with relapsed follicular lymphoma underwent autologous CD19-directed CAR T-cell therapy and achieved complete remission. Pre-existing hypogammaglobulinemia worsened after treatment. Eighteen months later, he developed recurrent bacteremia and chronic enterocolitis caused by C. jejuni. Over the following year, he experienced severe watery diarrhea, 20 kg weight loss, and disseminated infection with a prosthetic hip abscess. More than 10 stool cultures remained positive despite multiple antibiotic regimens and two fecal microbiota transplantations. Whole-genome sequencing demonstrated a single clonal strain with minimal variation, confirming persistent infection rather than reinfection. Microbiological clearance was achieved after 8 weeks of oral gentamicin, followed by 2 weeks of intravenous meropenem and azithromycin, with sustained negative cultures and PCR.

CONCLUSION: Persistent and disseminated C. jejuni infection can occur in patients with hypogammaglobulinemia after CD19-directed CAR T-cell therapy. Whole-genome sequencing may help distinguish persistence from reinfection. Standard immunoglobulin replacement may be insufficient due to limited IgA and IgM, and prolonged combination antimicrobial therapy may be required for durable remission.},
}

@article {pmid42979661,
year = {2026},
author = {Li, G and Dong, S and Liu, C and Yan, H and Yang, J and Rensen, PCN and Shi, B and Wang, Y},
title = {Dietary butyrate alleviates high-fat diet-induced colonic mucosal impairment accompanied by increased gut-derived indole-3-acetic acid and enhanced PPARγ signaling.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1971187},
pmid = {42979661},
issn = {1664-2392},
mesh = {Animals ; Male ; Mice ; *Diet, High-Fat/adverse effects ; *Intestinal Mucosa/metabolism/drug effects/pathology ; Humans ; *Colon/metabolism/drug effects/pathology ; *PPAR gamma/metabolism ; Gastrointestinal Microbiome/drug effects ; *Indoleacetic Acids/metabolism ; Signal Transduction/drug effects ; *Butyric Acid/pharmacology ; Caco-2 Cells ; Intestinal Barrier Function ; *Butyrates/pharmacology ; },
abstract = {INTRODUCTION: High-fat diet (HFD) induces intestinal barrier impairment, associated with gut microbiota dysbiosis, endotoxin translocation and metabolic dysfunction. Dietary butyrate has been reported to improve intestinal homeostasis, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of dietary butyrate on HFD-induced colonic mucosal dysfunction and to explore underlying mechanisms with respect to the role of gut microbiota and its metabolites.

METHODS: Male APOE*3-Leiden.CETP mice, a well-established translational model for diet-induced metabolic dysfunction, were fed an HFD with or without 5% sodium butyrate. Metabolic phenotypes, plasma lipopolysaccharide (LPS), colonic histology, inflammatory responses, and tight junction-associated changes were assessed. Fecal microbiota transplantation (FMT) was performed in antibiotic-treated recipient mice to assess the contribution and transferability of butyrate-shaped gut microbiota. Cecal metagenomic sequencing and LC/MS-based colonic indole-3-acetic acid (IAA) measurement were performed. Caco-2 cells were used to assess the direct effects of sodium butyrate and IAA on enterocytes and to determine, through pioglitazone treatment and PPARγ knockdown, whether PPARγ mediates IAA-induced enterocyte responses.

RESULTS: Dietary butyrate induced favorable changes in multiple colonic barrier-associated parameters, including improved colonic architecture, lower circulating LPS levels, decreased Tnf-a and Il-1b expression, and increased CLDN2, Reg-family, and PPARγ expression in the colon. In addition, butyrate reduced body weight gain, fat mass accumulation and improved glucose metabolism. FMT from butyrate-treated donors partially reproduced these beneficial effects in HFD-fed recipients. Metagenomic analysis showed enrichment of Bacteroidota and Bacteroides, particularly B. uniformis and B. thetaiotaomicron, accompanied by increased colonic IAA levels. In Caco-2 cells, IAA increased the expression of PPARγ, Reg4, and CLDN2. While PPARγ agonist pioglitazone mimicked the upregulation of REG4 and CLDN2 expression by IAA, siRNA-induced PPARγ knockdown attenuated IAA-induced REG4 and CLDN2 upregulation.

CONCLUSION: Dietary butyrate improves colonic mucosal homeostasis under HFD feeding, accompanied by gut microbial remodeling and increased colonic IAA levels. Together with the PPARγ-dependent epithelial response to IAA observed in Caco-2 cells, these findings suggest a potential mechanistic framework linking butyrate-associated microbial changes, IAA metabolism, and epithelial PPARγ signaling.},
}

Animals
Male
Mice
*Diet, High-Fat/adverse effects
*Intestinal Mucosa/metabolism/drug effects/pathology
Humans
*Colon/metabolism/drug effects/pathology
*PPAR gamma/metabolism
Gastrointestinal Microbiome/drug effects
*Indoleacetic Acids/metabolism
Signal Transduction/drug effects
*Butyric Acid/pharmacology
Caco-2 Cells
Intestinal Barrier Function
*Butyrates/pharmacology

@article {pmid42979739,
year = {2026},
author = {Kumar, BK and Caputi, V and Gill, KK and Nanduri, B and Leroith, T and Fox, R and Rosa, F and Lyte, JM and Yeruva, L},
title = {Microbiota From Human Infants Consuming Secretors Mothers' Milk Affects Murine Intestinal Motility and Enteric Nervous System Development in a Sex-Dependent Manner.},
journal = {Neurogastroenterology and motility},
volume = {38},
number = {11},
pages = {},
pmid = {42979739},
issn = {1365-2982},
support = {6026-10700-001-000D//U.S. Department of Agriculture/ ; 6026-51000-012-000D//U.S. Department of Agriculture/ ; },
mesh = {Animals ; Female ; Male ; Humans ; *Enteric Nervous System/growth & development ; Mice ; *Milk, Human/microbiology ; Mice, Inbred C57BL ; *Gastrointestinal Motility/physiology ; Infant ; Sex Characteristics ; *Gastrointestinal Microbiome/physiology ; },
abstract = {BACKGROUND: Early life is a critical period in which the gut microbiome and the enteric nervous system (ENS) develop together, shaping long-term gastrointestinal (GI) function. Human milk feeding and particularly maternal secretor phenotype strongly influence early microbiome composition. However, how human milk promoted microbiomes impact ENS development is still largely unknown.

METHODS: Male and female juvenile (three weeks old) C57BL/6 germ-free mice were colonized with fecal microbiota from infants whose mothers were secretors (SMM, 2-fucosyl lactose in milk) or non-secretors (NSM) or from infants consuming cow's milk formula (MFM). Non-transplanted male and female germ-free mice served as controls. GI transit was assessed at post-natal day 35-37. ENS neuronal and glial organization was evaluated in full-thickness colon preparations using immunohistochemistry and confocal microscopy.

KEY RESULTS: Female germ-free mice receiving SMM exhibited higher distal GI transit efficiency and a higher proportion of nitrergic neurons in the myenteric plexus compared to sex-matched controls and to males. Choline acetyltransferase (ChAT; marker for excitatory cholinergic neurons) immunoreactivity was higher in the myenteric ganglia of germ-free female compared to male mice. ChAT immunoreactivity increased in SMM and MFM males, while it was significantly reduced in NSM and MFM females compared to controls. Infant microbiomes did not affect myenteric glial cells, which were more abundant in males than females across all groups.

CONCLUSIONS AND INFERENCES: Our findings demonstrate that early-life maternal secretor-associated infant microbiomes exert sex-specific effects on ENS neuronal phenotypes and GI motility, underlying a previously unrecognized link between infant-derived microbiomes and ENS development that warrants investigation in larger cohorts.},
}

Animals
Female
Male
Humans
*Enteric Nervous System/growth & development
Mice
*Milk, Human/microbiology
Mice, Inbred C57BL
*Gastrointestinal Motility/physiology
Infant
Sex Characteristics
*Gastrointestinal Microbiome/physiology

@article {pmid42980207,
year = {2026},
author = {Mutanen, A and Pini Prato, A and Erculiani, M and Lambe, C and Lindert, J and Märzheuser, S and Fusaro, F and Stensrud, KJ and Bjornland, K and Qvist, N and Ellebæk, MB and Tabbers, MM and Derikx, JPM and Sfeir, R and Reinshagen, K and Ludwiczek, J and Poš, L and Bartošová, T and Miserez, M and Granström, AL and Wester, T and Hilberath, J and Bonnard, A and Di Fabrizio, D and Guz-Mark, A and Poinsot, P and Van Renterghem, K and Destro, F and Stenström, P and Friedmacher, F and Rolle, U and Coletta, R and Morabito, A and Fascetti Leon, F and Duci, M and Sloots, CEJ and Versteegh, H and Atouguia, D and Campos, M and Spector Cohen, I and Cavar, S and Sabolic, I and Tarrado, X and Langer, S and Norsa, L and Pakarinen, MP},
title = {Long-term outcomes after total colonic aganglionosis: retrospective European multicentre cohort study.},
journal = {BJS open},
volume = {10},
number = {6},
pages = {},
pmid = {42980207},
issn = {2474-9842},
support = {//The Foundation for Pediatric Research, Finland/ ; },
mesh = {Humans ; *Hirschsprung Disease/surgery/genetics/mortality ; Retrospective Studies ; Europe/epidemiology ; Female ; Male ; Cross-Sectional Studies ; Child, Preschool ; Child ; Adolescent ; Treatment Outcome ; Postoperative Complications/epidemiology ; Colorectal Surgical Procedures ; },
abstract = {BACKGROUND: Total colon aganglionosis (TCA), a severe form of Hirschsprung disease, is a rare and complex condition with variable management and limited outcome data. This retrospective cross-sectional multicentre study assessed current long-term outcomes of TCA in Europe.

METHODS: Patients with TCA under follow up at participating ERNICA and ESPGHAN centres were included. Data were collected on genetics, nutritional, functional, and surgical outcomes, intestinal inflammatory lesions, and mortality during the preceding 10 years.

RESULTS: Thirty-one centres from 15 countries contributed 401 patients (median age 7.9 years; interquartile range 4.0-13.6 years). Genetic testing was performed in 52% of patients, with pathogenic variants identified in 62%, mainly RET. Aganglionosis was limited to the colon in 26%, extended to the small bowel in 71%, and was total intestinal in 3%, without association with genetic status. At the latest follow-up, 25% of patients were receiving parenteral nutrition (PN); PN dependency was associated with small intestine extension of aganglionosis > 50 cm (72% of patients with >50 cm small bowel aganglionosis versus 15% of patients aganglionosis <50 cm small bowel or limited to the colon; P < 0.001). Overall, 77% of patients underwent pull-through, most commonly ileoanal anastomosis (62%) or Duhamel (31%). Complications included anastomotic leak (4%), strictures (12%), redo surgery (24%), recurrent enterocolitis (36%), obstructive symptoms (24%), and faecal incontinence (25%). Recurrent enterocolitis was associated with obstructive symptoms (P = 0.007). Endoscopy showed intestinal inflammatory lesions in 22% of patients, particularly those with recurrent enterocolitis (odds ratio (OR) 6.43; 95% confidence interval (c.i.) 3.27 to 12.63) and obstructive symptoms (OR 2.64; 95% c.i. 1.26 to 5.53). The 10-year mortality rate was 3.4%.

CONCLUSION: TCA shows a high prevalence of genetic abnormalities and substantial postoperative and long-term morbidity, independent of surgical technique.},
}

Humans
*Hirschsprung Disease/surgery/genetics/mortality
Retrospective Studies
Europe/epidemiology
Female
Male
Cross-Sectional Studies
Child, Preschool
Child
Adolescent
Treatment Outcome
Postoperative Complications/epidemiology
Colorectal Surgical Procedures

@article {pmid42971666,
year = {2026},
author = {Frandsen, EV and Hvas, CL and Baunwall, SMD and Friis, RB and Guldbrandt, LM and Schmidt, H},
title = {Faecal microbiota transplantation to enhance immune checkpoint inhibitor response in solid cancers: a systematic review.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {83},
number = {},
pages = {102152},
doi = {10.1016/j.bpg.2026.102152},
pmid = {42971666},
issn = {1532-1916},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms/therapy/drug therapy/immunology ; Treatment Outcome ; Combined Modality Therapy ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are pivotal in cancer treatment, but some patients develop resistance. In this systematic review, we aimed to summarise efficacy and safety of faecal microbiota transplantation (FMT) to enhance ICI therapy responses in patients with solid cancers.

METHODS: We systematically searched PubMed, Embase and Web of Science on May 12, 2025 for studies evaluating FMT in combination with ICI for solid cancers.

RESULTS: We included five clinical trials, of which none included comparator therapy, describing 78 patients. Notably, some patients previously refractory to anti-PD-1 therapy achieved partial or complete responses following FMT combined with ICIs. Assessing safety, 76% had grade 1-2 adverse events, and grade ≥3 events were only observed after ICI initiation.

CONCLUSION: Small uncontrolled studies indicate a potential effect for FMT to enhance efficacy of ICI therapy without increasing toxicity.},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
*Immune Checkpoint Inhibitors/therapeutic use
*Neoplasms/therapy/drug therapy/immunology
Treatment Outcome
Combined Modality Therapy

@article {pmid42971669,
year = {2026},
author = {Margarita, E and Saito, K and Bisegna, P and Ferrari, M and Valeriani, E and Guerrieri, M and Funaro, B and Feliciani, D and Gasbarrini, A and Porcari, S and Ianiro, G},
title = {Gut microbiome in immuno-oncology: potential for clinical exploitation.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {83},
number = {},
pages = {102143},
doi = {10.1016/j.bpg.2026.102143},
pmid = {42971669},
issn = {1532-1916},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; Probiotics/therapeutic use ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; *Immunotherapy/methods/adverse effects ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; },
abstract = {Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of multiple malignancies, yet durable clinical benefit remains limited to a subset of patients, while immune-related adverse events still represent a major therapeutic challenge. Over the past decade, compelling evidence has established the gut microbiota as a key host determinant of both the efficacy and toxicity of cancer immunotherapy. Given its profound diversity and plasticity, as well as its impact on systemic immunity, gut commensals are now considered as both a promising predictive biomarker of response and a potentially actionable therapeutic target. As a result, different microbiota-informed approaches are being explored for precision immune-oncology. Specifically, emerging biomarker strategies are moving beyond single bacterial taxa toward ecological and functional microbial signatures with improved reproducibility across patient cohorts. At the same time, therapeutic modulation of the gut microbiome, through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation, is being actively investigated to enhance responsiveness to ICIs and mitigate immune-related adverse events. In this review, we discuss the biological mechanisms linking gut microbiota and immunotherapy, evaluate its role as biomarker and therapeutic target, and address the current challenges that need to be overcome to integrate microbiota into precision immune-oncology.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Neoplasms/immunology/therapy/microbiology/drug therapy
Probiotics/therapeutic use
*Immune Checkpoint Inhibitors/therapeutic use/adverse effects
*Immunotherapy/methods/adverse effects
Fecal Microbiota Transplantation
Prebiotics/administration & dosage

@article {pmid42973594,
year = {2026},
author = {Wang, L and Xie, J and Sun, Y and Zhang, Y and Gao, X and Li, Y and Liu, L},
title = {Akkermansia muciniphila improves synaptic remodeling and alleviates sepsis-associated cognitive dysfunction via regulating the gut-brain axis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1925161},
pmid = {42973594},
issn = {1664-3224},
mesh = {Animals ; Mice ; *Sepsis/complications/microbiology ; *Neuronal Plasticity ; Male ; *Cognitive Dysfunction/etiology ; Disease Models, Animal ; Gastrointestinal Microbiome ; *Brain-Gut Axis ; Mice, Inbred C57BL ; Hippocampus/metabolism ; Intestinal Barrier Function ; Akkermansia ; Fecal Microbiota Transplantation ; Synapses ; },
abstract = {BACKGROUND: Sepsis-associated cognitive impairment (SACI) is a frequent long-term complication of sepsis characterized by hippocampal neuroinflammation, synaptic loss and gut microbial dysbiosis. Akkermansia muciniphila (AKK) possesses anti-inflammatory and intestinal barrier-protective functions, yet its role and mechanism in SACI remain poorly understood.

METHODS: In this study, a CLP-induced septic mouse model was used to explore the protective effect of AKK. Behavioral tests were performed to evaluate anxiety and cognitive function. Hippocampal neuronal injury, microglial activation and synaptic plasticity were assessed by HE staining, immunofluorescence, Western blotting and TEM. Intestinal barrier function, gut microbiota composition and metabolic profiles were analyzed via 16S rRNA sequencing and untargeted metabolomics, with FMT applied for mechanistic verification.

RESULTS: AKK intervention remarkably alleviated anxiety-like behaviors and rescued cognitive deficits in septic mice. AKK inhibited microglial overactivation, activated the BDNF/P-TrkB pathway, and restored the expression of synaptic SYP and PSD95. Meanwhile, AKK preserved intestinal tight junction integrity, reshaped gut microbiota structure, and reversed sepsis-related metabolic disturbances. FMT further provided evidence that AKK-modulated gut microbiota improved survival and cognitive performance.

CONCLUSION: In conclusion, AKK ameliorates SACI by suppressing hippocampal neuroinflammation, restoring synaptic plasticity and remodeling the microbiota-gut-brain axis, indicating its potential as a promising candidate for SACI intervention.},
}

Animals
Mice
*Sepsis/complications/microbiology
*Neuronal Plasticity
Male
*Cognitive Dysfunction/etiology
Disease Models, Animal
Gastrointestinal Microbiome
*Brain-Gut Axis
Mice, Inbred C57BL
Hippocampus/metabolism
Intestinal Barrier Function
Akkermansia
Fecal Microbiota Transplantation
Synapses

@article {pmid42974254,
year = {2026},
author = {El-Sayed Ahmed, MAE and El-Lakany, RR and Ramadan, M and Goda, RM},
title = {Clostridioides difficile infections and beyond: molecular epidemiology, One Health transmission chains, under-surveilled regions, and the next generation of diagnostics, therapeutics, and vaccines.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1992944},
pmid = {42974254},
issn = {2235-2988},
mesh = {Humans ; *Clostridioides difficile/genetics/classification/isolation & purification ; Molecular Epidemiology ; *Clostridium Infections/epidemiology/diagnosis/transmission/prevention & control/drug therapy/therapy/microbiology ; *One Health ; Animals ; Whole Genome Sequencing ; Bacterial Vaccines/immunology ; Cross Infection/epidemiology/transmission/microbiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Ribotyping ; },
abstract = {Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhea and an urgent antimicrobial resistance threat, but the organism clinicians now face differs from the one that drove the ribotype 027 epidemics. This review is organized around a single question: which parts of the C. difficile transmission and treatment cycle are invisible to the methods used to observe them? Four developments define the answer. First, whole-genome sequencing consistently identifies genomic links between hospital cases that ward-based contact tracing cannot reconcile, and isolates from asymptomatically colonized patients are linked to subsequent cases as often as those from symptomatic patients, in some instances many months after an index encounter; we read a four-year single-center study from Guangzhou, China, in which one author participated, alongside comparable cohorts from England, Denmark and Canada. Second, One Health genomics places human and non-human compartments within a single transmission network, though the direction of transfer and the attributable fraction of human disease remain unquantified. Sequence type 11 and its ribotype 078 sublineage circulate between livestock and humans at clonal resolution, cryptic clades meet species-level divergence thresholds, and community-associated disease accounts for roughly a third of cases. Third, resistance to first-line therapy now has defined molecular mechanisms, including plasmid-borne and heme-dependent metronidazole resistance, constitutive vanG expression underlying reduced vancomycin susceptibility, and RNA polymerase substitutions conferring reduced fidaxomicin susceptibility that emerge during treatment; several of these are undetectable under standard laboratory conditions. Fourth, pathogenesis is being reframed as polymicrobial, with enterococci cross-feeding leucine and ornithine while depleting arginine as a virulence cue. We integrate these strands with age-stratified vulnerability in older and pediatric patients, with the diagnostic problem of separating infection from colonization, and with the diverging regulatory frameworks that now separate donor-derived fecal microbiota transplantation from licensed live biotherapeutic products.},
}

Humans
*Clostridioides difficile/genetics/classification/isolation & purification
Molecular Epidemiology
*Clostridium Infections/epidemiology/diagnosis/transmission/prevention & control/drug therapy/therapy/microbiology
*One Health
Animals
Whole Genome Sequencing
Bacterial Vaccines/immunology
Cross Infection/epidemiology/transmission/microbiology
Anti-Bacterial Agents/therapeutic use/pharmacology
Ribotyping

@article {pmid42976410,
year = {2026},
author = {Shimoyama-Ibuki, S and Iyama, S and Shirato, S and Sato, K and Yoshida, M and Goto, A and Horiguchi, H and Kobune, M},
title = {Longitudinal changes in diamine oxidase activity and gut microbiota in hematopoietic stem cell transplantation recipients.},
journal = {Leukemia research},
volume = {171},
number = {},
pages = {108358},
doi = {10.1016/j.leukres.2026.108358},
pmid = {42976410},
issn = {1873-5835},
abstract = {BACKGROUND: Gut microbiota disruption and intestinal epithelial injury are associated with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated longitudinal changes in the gut microbiota, circulating diamine oxidase (DAO), and short-chain fatty acids (SCFAs) in relation to GVHD.

METHODS: Eighteen allo-HSCT recipients were retrospectively analyzed. Plasma DAO activity and serum DAO concentration were measured before conditioning and on days 14, 28, and 60 after HSCT, and plasma SCFAs before and after HSCT. Pre- and post-HSCT fecal samples underwent 16S rRNA gene sequencing.

RESULTS: Nine patients developed grade 2-4 acute GVHD. DAO activity decreased significantly after HSCT, particularly in patients who developed GVHD. Changes in DAO activity showed a moderate, nonsignificant positive correlation with changes in the relative abundance of the [Eubacterium] hallii group. Before HSCT, Eubacterium was significantly more abundant in patients who did not subsequently develop GVHD. Pre- to post-HSCT Bray-Curtis dissimilarity was greater in the GVHD group than in the non-GVHD group, although not significantly. In the GVHD group, several butyrate-associated taxa, including Ruminococcaceae, the Clostridium methylpentosum group, and Oscillospirales, were depleted after HSCT. SCFA concentrations did not differ significantly by GVHD status and were not significantly associated with the relative abundance of the [Eubacterium] hallii group after correction for multiple testing.

CONCLUSIONS: Patients who developed acute GVHD showed altered gut microbial composition, including depletion of butyrate-associated taxa, together with decreased DAO activity. These exploratory findings suggest a potential relationship between gut microbial alterations and intestinal epithelial integrity after allo-HSCT.},
}

@article {pmid42976420,
year = {2026},
author = {Rendeiro, J and Santos, VH and Silva-Vaz, P},
title = {Psychobiotic modulation of the microbiome-gut-brain axis: A systematic review of the literature.},
journal = {Psychoneuroendocrinology},
volume = {195},
number = {},
pages = {108064},
doi = {10.1016/j.psyneuen.2026.108064},
pmid = {42976420},
issn = {1873-3360},
abstract = {BACKGROUND: Major depressive disorder (MDD) is incompletely explained by the monoaminergic model. The microbiome-gut-brain (MGB) axis may link gut microbial ecology to immune, metabolic, neuroendocrine and neural signalling relevant to mood and antidepressant response.

OBJECTIVES: To synthesise recent evidence on (I) microbiota-targeted (psychobiotic) interventions; (II) the gut microbiome as a diagnostic and treatment-response biomarker; and (III) biopsychosocial and immunometabolic correlates of depression.

METHODS: PubMed, Scopus and PubPsych were searched (January 2022 to February 2025) following PRISMA 2020. Risk of bias was assessed with RoB 2, ROBINS-I and the Newcastle-Ottawa Scale. Findings were synthesised narratively, stratified by population, intervention type and study design.

RESULTS: Sixty-six studies were included: 36 in diagnosed depressive disorders, 10 in non-clinical samples, 15 in other medical conditions and 5 genetic or biobank analyses; most were of low or very low methodological quality. Depression was associated with lower abundance of short-chain fatty acid-producing taxa and with altered tryptophan, bile acid, inflammatory and barrier-related markers, largely in cross-sectional designs. In MDD, some strain-specific add-on probiotics were associated with greater symptom reduction than placebo, whereas others showed no benefit; prebiotic, dietary and faecal microbiota transplantation data were sparse or derived from non-MDD populations. Diagnostic and treatment-response models came from small samples and were rarely externally validated.

CONCLUSIONS: The gut microbiome is a plausible contributor to depressive pathophysiology and treatment variability, but current evidence is heterogeneous, predominantly associative and of low certainty. Psychobiotic interventions and microbiome-based biomarkers remain investigational; adequately powered, strain- and dose-specific trials and independently validated models are required before clinical application.},
}

@article {pmid42967431,
year = {2026},
author = {Zhang, Q and Xu, J and Jiang, W and Jia, Q and Jiang, X and Zhang, L and Alhaskawi, A and Sun, R and Sun, Y and Wang, X and Zhao, F},
title = {Multi-omics reveals that polystyrene microplastic exposure induces bone loss in mice by disrupting intestinal glycine metabolism.},
journal = {Ecotoxicology and environmental safety},
volume = {326},
number = {},
pages = {121005},
doi = {10.1016/j.ecoenv.2026.121005},
pmid = {42967431},
issn = {1090-2414},
abstract = {Polystyrene microplastic exposure induced a pronounced bone-loss phenotype in C57BL/6 mice, characterized by reduced bone density and trabecular bone volume together with impaired osteogenic differentiation. To determine whether this skeletal toxicity was mediated by the gut microenvironment, we performed fecal microbiota transplantation and found that microbiota from microplastic-exposed donors was sufficient to recapitulate bone loss in recipient mice, supporting a causal role for microbiota alterations. Consistent with this mechanism, recipients exhibited compromised intestinal barrier integrity and heightened intestinal inflammation, alongside a dysbiotic microbial profile marked by depletion of beneficial taxa and enrichment of pro-inflammatory bacteria. Integrative multi-omics analyses further connected these gut changes to osteogenic dysfunction, revealing suppression of osteogenesis-related programs and inhibition of key signaling pathways, including PI3K-AKT and WNT/β-catenin signaling. Finally, metabolomic findings guided the selection of glycine for supplementation, which, when initiated concurrently with FMT, attenuated the development of bone loss in recipients receiving fecal microbiota from PS-MP-exposed donors.},
}

@article {pmid42967725,
year = {2026},
author = {Bai, L and Liu, L and Song, C and Zhao, Z and Chu, G and Ren, X and Ai, C and Song, S},
title = {Gut microbiota-dependent immunomodulatory effects of galactofucan: Evidence from fecal microbiota transplantation and pseudo-germ-free mice.},
journal = {Food research international (Ottawa, Ont.)},
volume = {245},
number = {Pt 4},
pages = {120909},
doi = {10.1016/j.foodres.2026.120909},
pmid = {42967725},
issn = {1873-7145},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; Mice ; Intestinal Barrier Function ; *Polysaccharides/pharmacology ; Mice, Inbred C57BL ; Male ; Dysbiosis ; Germ-Free Life ; *Immunologic Factors/pharmacology ; CD4-Positive T-Lymphocytes ; },
abstract = {In recent years, the relationship between the immunomodulatory mechanisms of fucoidans and the gut microbiota has attracted widespread attention. However, there is currently a lack of direct evidence confirming that gut microbiota is essential for fucoidan to exert its immunomodulatory functions. Therefore, the present study employed fecal microbiota transplantation (FMT) and pseudo-germ-free (PGF) mouse models to investigate the mechanism underlying the immunomodulatory activity of Undaria pinnatifida sporophyll galactofucan (UPSG). The results showed that recipients transplanted with UPSG-derived microbiota increased the proportions of CD4[+] and CD8[+] T lymphocytes to 1.8-fold of those in the CTX-FMT group, respectively, and alleviated intestinal barrier damage. In addition, UPSG-derived microbiota transplantation restored gut microbial dysbiosis, markedly enriched Muribaculaceae, and ameliorated metabolic disturbances accompanied by elevated guanidoacetic acid level. In contrast, depletion of the gut microbiota abolished the protective effects of UPSG on systemic immune function and intestinal barrier integrity. Collectively, these results demonstrated the immunomodulatory effects of UPSG depend on the presence of the gut microbiota and provides experimental evidence supporting the involvement of the gut microbiota in the immunomodulatory mechanism of UPSG.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Fecal Microbiota Transplantation
Mice
Intestinal Barrier Function
*Polysaccharides/pharmacology
Mice, Inbred C57BL
Male
Dysbiosis
Germ-Free Life
*Immunologic Factors/pharmacology
CD4-Positive T-Lymphocytes

@article {pmid42969769,
year = {2026},
author = {Huang, X and Wang, Y and Meng, Z and Zheng, P},
title = {The three-layer defense system of gut microbiota in regulating bone development and homeostasis: homeostatic maintenance, stress sensing, and programmed repair.},
journal = {EFORT open reviews},
volume = {11},
number = {11},
pages = {1211-1227},
doi = {10.1530/EOR-2026-0067},
pmid = {42969769},
issn = {2058-5241},
abstract = {The gut microbiota functions as a critical regulator of bone development and homeostasis through a proposed 'three-layer defense system': basal homeostatic maintenance, danger sensing, and active repair. Microbial metabolites such as short-chain fatty acids, tryptophan derivatives, and vitamin K modulate bone metabolism via GPCR signaling, epigenetic regulation, and immune modulation, establishing a foundation for skeletal health. Endocrine axes - including estrogen, GH/IGF-1, and PTH - interact with the gut microbiota to influence bone remodeling, with dysbiosis contributing to inflammatory amplification and osteoclast activation via RANKL/NF-κB pathways. The third-layer defense involves targeted repair through probiotics and bacterial extracellular vesicles, which restore immune homeostasis, enhance osteogenesis, and suppress bone resorption. Therapeutic strategies targeting this multi-layer system - including probiotic interventions, fecal microbiota transplantation, and bioactive compound supplementation - offer promising avenues for personalized prevention and treatment of metabolic bone diseases.},
}

@article {pmid42970314,
year = {2026},
author = {Xu, J and Cao, Z and Liu, Y and Gao, A and Kong, Y},
title = {Fecal Microbiota Transplantation in Alzheimer's Disease: A Scoping Review of Human, Registry, and Preclinical Evidence.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0883},
pmid = {42970314},
issn = {2152-5250},
abstract = {Fecal microbiota transplantation (FMT) is being explored as a microbiota-directed intervention for Alzheimer's disease (AD), with evidence drawn mainly from preclinical studies. This scoping review mapped published human reports, registered trials and animal microbiota-transfer studies to inform FMT research in AD. Five human reports, eight unique registered trials and 34 animal studies were included. Four human reports concerned FMT administered for Clostridioides difficile infection (CDI). The remaining report was an uncontrolled five-patient pilot comprising two patients with AD, two with mild cognitive impairment (MCI) and one with frontotemporal dementia (FTD). It described maintained cognition in AD and FTD and improvement or maintenance in MCI. The published human studies were nonrandomized. Among the eight registered trials, two required AD biomarker confirmation and two specified donor-referenced engraftment outcomes. Among 30 animal studies assessing cognition, 24 reported positive findings and six mixed findings. Restriction to genetic/transgenic AD models reduced the positive proportion from 24/30 (80.0%) to 17/23 (73.9%). Cognition-specific randomization and blinding were reported in 16/30 (53.3%) and 4/30 (13.3%) studies, respectively. The evidence supports early-phase investigation, with attention to donor and product characterization, appropriate comparators, and separate measurement of engraftment, microbial function, systemic responses and AD outcomes. Safety data remain insufficient for patients with AD, particularly outside the CDI setting. FMT should remain investigational for AD.},
}