258-LB: Iridoid Glycoside Modulates Gut Microbiota and Ameliorates Nonalcoholic Fatty Liver Disease–Related Metabolic Disorders

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with glucose and lipid metabolism disturbance. The development of herbal medicine interventions for NAFLD is presently a popular topic in pharmaceutical research. However, although many active natural ingredients have been reported as promising agents for NAFLD, their potential benefits are contrasted by their poor oral absorption. GG-01, an effective iridoid glycoside discovered from a clinical prescription of traditional Chinese medicine (TCM), is exposed first in the intestinal tract, and gut microbes may quickly react to GG-01. Therefore, it is intriguing to explore the role of gut microbiota and microbial metabolites in the beneficial effects of GG-01 on NAFLD-related disorders. Our research intends to commence with the intestinal nutritional characteristics of GG-01. Firstly, the crucial role of intestinal microbiota in the pharmacological effects of GG-01 is confirmed using different animal models. Subsequently, we identify the key microbes by combining high-throughput sequencing and an in vitro culture system of intestinal microbiota. We then focus on one of the key microbes, Akkermansia muciniphila, and elucidate how GG-01 can treat NAFLD-related metabolic disorders by stimulating the bile acid biotransformation of Akkermansia muciniphila based on “TCM-microbiome-host” interaction. Finally, we present a novel therapeutic strategy of the synergistic effect of Akkermansia muciniphila and GG-01 via TGR5 to activate epithelial regeneration, promote GLP-1 production, and further treat NAFLD-related metabolic disorders. We also propose GG-01 as a new type of probiotic for the treatment of NAFLD. Disclosure C. Xie: None. Y. Liu: None.