Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.
Gut Microbes
; 15(2): 2274124, 2023 12.
Article
en En
| MEDLINE
| ID: mdl-37942583
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptido 1 Similar al Glucagón
/
Microbioma Gastrointestinal
Límite:
Animals
Idioma:
En
Revista:
Gut Microbes
Año:
2023
Tipo del documento:
Article
País de afiliación:
China