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.


C. Xie: None. Y. Liu: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at