The function of the gut microbiota–bile acid–TGR5 axis in diarrhea-predominant irritable bowel syndrome

• DOI: 10.1128/msystems.01299-23
• Publication Date: 2024-02-08T18:14:15Z
• Authors: Kai Zhan; Haomeng Wu; Yongyin Xu; Kehan Rao; Huan Zheng; Shumin Qin; Yuanming Yang; Rui Jia; Weihuan Chen; Shaogang Huang
• Keywords: Gut–brain axis; Farnesoid X receptor

ABSTRACT Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but underlying mechanism remains unclear. Herein, we explore influence of GM–BA–Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients fifteen healthy controls were recruited perform BA-related metabolic metagenomic analyses. Further, microbiota-humanized rat model was established by microbial transplantation (FMT) investigate GM–BA–TGR5 effects colonic barrier visceral hypersensitivity (VH) in Finally, used chenodeoxycholic (CDCA), an important BA screened out metabolome, evaluate whether it affected diarrhea VH via TGR5 pathway. Clinical research showed that GM associated with salt hydrolase (BSH) activity such as Bacteroides ovatus markedly reduced IBS-D, accompanied elevated total primary levels. Moreover, found CDCA not only increased most also could induce through upregulating colon ileum normal rats. inhibitor reverse phenotype, depression-like behaviors, pathological change, level BSH a model. Our findings proved human-associated FMT successfully model, imbalanced may promote mucosal dysfunction enhance IMPORTANCE Visceral intestinal damage cause brain–gut interaction (IBS-D). Recently, imbalance microbiota–bile is closely related them. Therefore, understanding structure function acids mechanisms which they shape critical. An examination feces from revealed alterations metabolism underlie symptom onset. We expanded beyond existing knowledge well-studied potential bacteria involved pathogenesis our data integration reveals acid–TGR5 hypersensitivity.