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Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.

ABSTRACT: The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.

SUBMITTER: Wang Q

PROVIDER: S-EPMC10730136 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.

Wang Qiaoling Q Lin Huibin H Shen Chongrong C Zhang Minchun M Wang Xingyu X Yuan Miaomiao M Yuan Mingyang M Jia Sheng S Cao Zhiwen Z Wu Chao C Chen Banru B Gao Aibo A Bi Yufang Y Ning Guang G Wang Weiqing W Wang Jiqiu J Liu Ruixin R

Gut microbes 20231109 2

The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ...[more]

PMID: 37942583

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Dataset Information

Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.

Publications

Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.

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