Abstract
The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.