Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota.

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.

Anti-inflammatory effect of luteolin is related to the changes in the gut microbiota and contributes to preventing the progression from simple steatosis to nonalcoholic steatohepatitis.

Increasing intestinal barrier function is one of the basic methods to suppress inflammation in the progression from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Luteolin exists widely in vegetables, fruits and natural herbs and has various biological activities, including benefits on nonalcoholic fatty liver disease (NAFLD). However, its regulatory effects on the gut microbiota and involvement in its biological activities remain to be investigated. We fed rats a high-fat diet containing 0.5% luteolin for 12 weeks and determined the effects of luteolin on lipid metabolism, inflammation, and the gut microbiota. Supplementation with luteolin for 12 weeks significantly reduced blood lipids and hepatic lipid levels and improved liver fat accumulation and inflammation. Moreover, supplementation with luteolin led to the significant enrichment of more than 10% of gut bacterial species, which contributed to increase the abundance of ZO-1, reduce intestinal permeability, reduce plasma lipopolysaccharide, and inhibit the TLR4/NF-κB pathway. In summary, the anti-inflammatory effect of luteolin might be related to changes in the gut microbiota and contribute to preventing the progression from SS to NASH. Our research provides new insights into the anti-inflammatory mechanism of luteolin and supports its use as a dietary supplement for NAFLD patients.