Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling
Qiaoling Wang,
Huibin Lin,
Chongrong Shen,
Minchun Zhang,
Xingyu Wang,
Miaomiao Yuan,
Mingyang Yuan,
Sheng Jia,
Zhiwen Cao,
Chao Wu,
Banru Chen,
Aibo Gao,
Yufang Bi,
Guang Ning,
Weiqing Wang,
Jiqiu Wang,
Ruixin Liu
Affiliations
Qiaoling Wang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Huibin Lin
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chongrong Shen
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Minchun Zhang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xingyu Wang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Miaomiao Yuan
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Mingyang Yuan
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Sheng Jia
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhiwen Cao
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chao Wu
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Banru Chen
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Aibo Gao
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yufang Bi
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Guang Ning
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Weiqing Wang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jiqiu Wang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Ruixin Liu
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
ABSTRACTThe 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.
