Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice

Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.