Phytosterol of lotus seed core powder alleviates hypercholesterolemia by regulating gut microbiota in high-cholesterol diet-induced C57BL/6J mice

The present study aimed to investigate the regulatory mechanisms of lotus seed core powder phytosterol extract (LSP-PE) on hypercholesterolemia and intestinal microbiota in high-cholesterol diet (HCD)-induced C57BL/6 J mice. Gavage with LSP-PE reduced levels of serum total cholesterol (TC), ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C), hepatic TC, hepatic triglyceride (TG), hepatic LDL-C, hepatic very low-density lipoprotein (VLDL), fecal TC and fecal total bile acid (TBA), while augmented hepatic HDL-C content. In contrast with HCD group, high-dose LSP triggered significant diminutions of serum ALT, serum AST, hepatic ALT and hepatic AST levels in HCD-fed mice, which were 16.49, 28.94, 43.42, and 44.47%, respectively, thus remarkably ameliorating the pathological changes of liver and small intestine. In-depth genetic research found that LSP was effective in down-regulating the expression of cholesterol metabolism related genes including Niemannpick C1-like protein 1 (NPC1L1), acyl-coA cholesterol acyl-transferase 2 (ACAT2), microsomal triglyceride transporter (MTP) and ATP binding cassette subfamily G member 5 (ABCG5). Moreover, LSP-PE could restore the disorder of intestinal flora via augmenting the Actinobacteria abundance as well as decreasing the Firmicutes/Bacteroidetes ratio and abundances of Proteobacteria and Verrucomicrobia to regulate cholesterol metabolism-related genes. In summary, LSP-PE possessed excellent cholesterol-lowering activity by positively regulating the gut microbiota and the expression levels of genes related to cholesterol absorption and metabolism. Therefore, this work suggested LSP phytosterol as a potential supplement to alleviate the symptoms of hypercholesterolemia.