Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 16, 2025

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on CD4+ T cell functions inflammatory bowel disease (IBD) remain elusive. Here we investigated roles of modulating cells and its therapeutic potential treatment human IBD. Leveraging metabolomics microbial community analyses, observed that levels IPA-producing microbiota (e.g. Peptostreptococcus, Clostridium, Fournierella) were decreased, IPA-consuming Parabacteroides, Erysipelatoclostridium, Lachnoclostridium) increased feces IBD patients than those healthy donors. Dextran sulfate sodium (DSS)-induced acute colitis CD45RBhighCD4+ transfer-induced chronic models then established mice treated orally with to study inflammation vivo. We found oral administration attenuated both mice, as characterized by body weight, reduced pro-inflammatory cytokines TNF-α, IFN-γ, IL-17A) histological scores colon. further utilized RNA sequencing, docking simulations, surface plasmon resonance analyses identified exerts biological effects interacting heat shock protein 70 (HSP70), leading inducing Th1/Th17 apoptosis. Consistently, ectopic expression HSP70 conferred resistance IPA-induced Therefore, these findings identify a previously unrecognized pathway which modulates provide promising avenue for

Language: Английский

GPR171 restrains intestinal inflammation by suppressing FABP5-mediated Th17 cell differentiation and lipid metabolism

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 334010

Published: March 12, 2025

Background GPR171 suppresses T cell immune responses involved in antitumour immunity, while its role inflammatory bowel disease (IBD) pathogenesis remains unclear. Objective We aimed to investigate the of modulating CD4 + effector functions IBD and evaluate therapeutic potential. Design analysed expression colon biopsies peripheral blood samples from patients with assessed impact on differentiation through administration endogenous ligand (BigLEN). further determined dextran sulfate sodium (DSS)-induced colitis CD45RB high T-cell transfer model deciphered underlying mechanisms using RNA sequencing (RNA-seq) lipidomics. developed a novel BigLEN-based Fc fusion protein (BigLEN-Fc) evaluated potential preventing treating colitis. Results was markedly increased inflamed mucosa cells compared controls. BigLEN-triggered activation inhibited Th17 vitro. deficiency exacerbated DSS- cell-induced mice, characterised by intestinal mucosa. Mechanistically, promoted altered lipidome profile via cAMP-pCREB-FABP5 axis. Blockage FABP5 reduced vitro ameliorated DSS-induced Gpr171 −/− mice. Furthermore, BigLEN-mutFc potently mitigated Conclusions promotes causes lipid metabolism perturbation, contributing inflammation FABP5-dependent manner. Target therapy (eg, BigLEN-Fc) represents approach for treatment.

Language: Английский

A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107608 - 107608

Published: April 1, 2025

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, microbiological influences. The gut microbiota plays a crucial role in the development treatment of IBD, though exact mechanisms remain uncertain. Current research has yet to definitively establish beneficial effects microbiome on IBD. Bacteria viruses (both prokaryotic eukaryotic) are key components uniquely related Numerous studies suggest that dysbiosis microbiota, bacteria, viruses, bacteriophages, contributes IBD pathogenesis. Conversely, some indicates bacteria bacteriophages may positively impact outcomes. Additionally, plant metabolites play alleviating due their anti-inflammatory microbiome-modulating properties. This systematic review discusses patients evaluates potential connection between context pathophysiology.

Language: Английский