DRP007310
Inulin supplementation globally changed gut microbial community
Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear. We found that the consumption of a prebiotic, inulin, markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice. Inulin consumption resulted in global changes in the gut microbiome and increased the concentrations of short-chain fatty acids, particularly acetate, in the gut lumen and portal blood. The consumption of acetate-releasing resistant starch protected against NAFLD development. Furthermore, the absence of G-protein-coupled receptor 43 (GPR43), an acetate receptor, abolished the protective effect of inulin, indicated by more sever liver hypertrophy, hypercholesterolaemia and inflammation. These effects can be attributed to an exacerbation of insulin resistance in the liver, but not in muscle or adipose tissue. These findings demonstrate that the commensal microbiome-acetate-GPR43 axis improves insulin sensitivity in the liver and prevents the development of NAFLD/NASH.