Resveratrol Ameliorated Hyperlipidemia: Association with Modulation of the Gut Microbiota and Bile Acid Metabolism

Background: Hyperlipidemia represents a pivotal risk factor for multiple cardiovascular and metabolic diseases, creating an urgent demand for safe, effective novel therapeutic interventions. Resveratrol (RES), a natural plant polyphenol, has exhibited great potential as a hypolipidemic agent for hyperlipidemia treatment. Methods: In this work, we established a high-fat diet (HFD)-induced hyperlipidemic mouse model to systematically investigate the lipid-regulating efficacy of RES. Results: Oral administration of RES significantly decreased serum levels of total cholesterol and low-density lipoprotein cholesterol, while markedly increasing high-density lipoprotein cholesterol concentrations. Histopathological analyses further demonstrated that RES alleviated HFD-induced hepatic and ileal injury. Moreover, RES significantly decreased the circulating levels of several bile acids (BAs), including taurodeoxycholic acid, taurolithocholic acid, lithocholic acid, and tauro-(α + β)-muricholic acid. RES also ameliorated HFD-induced gut microbial dysbiosis, as evidenced by a reduction in the Firmicutes/Bacteroidetes ratio, increased relative abundances of non_f_Muribaculaceae, Lactobacillus, Ileibacterium, and Bacteroides, and decreased abundances of Lachnospiraceae_NK4A136_group and unclassified f_Lachnospiraceae. Spearman correlation analysis revealed significant associations between gut microbial taxa and BA profiles, suggesting that coordinated regulation of the gut microbiota and BA metabolism contributes to the hypolipidemic effects of RES. Conclusions: Collectively, RES alleviates HFD-induced hyperlipidemia by remodeling gut microbiota composition and restoring bile acid metabolic homeostasis.