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

被引：20
作者：
Wang, Qiaoling [1 ,2 ]
Lin, Huibin [1 ,2 ]
Shen, Chongrong [1 ,2 ]
Zhang, Minchun [1 ,2 ]
Wang, Xingyu [1 ,2 ]
Yuan, Miaomiao [1 ,2 ]
Yuan, Mingyang [1 ,2 ]
Jia, Sheng [1 ,2 ]
Cao, Zhiwen [1 ,2 ]
Wu, Chao [1 ,2 ]
Chen, Banru [1 ,2 ]
Gao, Aibo [1 ,2 ]
Bi, Yufang [1 ,2 ]
Ning, Guang [1 ,2 ]
Wang, Weiqing [1 ,2 ]
Wang, Jiqiu [1 ,2 ]
Liu, Ruixin [1 ,2 ,3 ]
机构：
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis,Sch Med, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Natl Clin Res Ctr Metab Dis, Sch Med,Key Lab Endocrine & Metab Dis Natl Hlth Co, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Natl Clin Res Ctr Metab Dis, Sch Med, 2nd Ruijin Rd, Shanghai 200025, Peoples R China
来源：
GUT MICROBES | 2023年 / 15卷 / 02期
关键词：
Microbiome; GLP-1; bile acid; TGR5; ileum; diabetes; GLUCAGON-LIKE PEPTIDE-1; HEALTHY-SUBJECTS; SECRETION; ACIDS; OBESITY; METABOLISM; ABSORPTION; RELEASE; PROTEIN; WEIGHT;
D O I：
10.1080/19490976.2023.2274124
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
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 omega-muricholic acid (omega MCA) 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 omega MCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or omega MCA 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 (omega MCA 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.
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页数：16
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