1776-P: Gut Microbiota Remodeling and Intestinal FXR Inhibition Mediate the Antimetabolic Syndrome Properties of Gynostemma Pentaphyllum

Abstract

Gynostemma pentaphyllum (G. pentaphyllum) is widely used as a traditonal chinese medicine with anti-metabolic syndrome properties in Asian countries, however, the critical mechanism with the metabolic benefits of G. pentaphyllum remained unclarified. Herein, we performed metabolomic analysis (LC-MS/MS) of samples from obese mice treated with G. pentaphyllum, and identified 2α-OH-PPD (GP2) may be the principal bioactive constituent responsible for the anti-metabolic syndrome effect of G. pentaphyllum. In mouse model of high fat diet-induced obesity, GP2 prevented diet-induced obesity, along with hepatic steatosis and insulin resistance after 5 weeks treatment. The metabolic benefits of GP2 treatment were abrogated in the antibiotic treated DIO mice, which indicated GP2 improves metabolic syndrome dependent on gut microbiota remodeling. Mechanically, GP2, play as an inhibitor of bile salt hydrolase (BSH) in the gut microbiota, increased the bile acid tauro-α/β-muricholic acid (Tα/βMCA) and tauroursodeoxycholic acid (TUDCA) in the gut through decrease in level of the genus Clostridium, but not the genus Lactobacillus (LefSe Analysis for gut microbiota composition). The expression of FGF-15 and shp gene were dramatically decreased in the ileum, and the expression of pro-glucagon in the L cell and glucose induced GLP-1 secretion were markedly increased in the GP2 treated mice, which were accompanied by farnesoid X receptor (FXR) signaling inhibition in the intestine. Finally, after transplanted the fecal microbiota of mice treated by GP2 into recipient mice pretreated with antibiotics, the mice reflected much more GLP-1 secretion after glucose stimulated and high Tα/βMCA level in the gut than the mice received control microbiota. These results indicated that GP2 as well as G. pentaphyllum improved metabolic syndrome in part through intestinal FXR inhibition induced by gut microbiota remodeling. Disclosure Z. Xie: None. L. Hu: None. J. Li: None. J. Li: None. Funding National Natural Science Foundation of China