Dietary germ oil-derived phytosterols ameliorate hyperlipidemia by suppressing bile salt hydrolase-producing gut microbiota to enrich taurohyodeoxycholic acid_Bile acid profile in rat liver tissue

Dyslipidemia is a major cardiovascular risk factor. While dietary phytosterols are known to lower cholesterol, the mechanisms involving the gut-liver axis are not fully understood. By integrating human clinical trials and mechanistic animal models, we demonstrate that phytosterols improve lipid profiles by modulating the gut microbiota-bile acid-farnesoid X receptor (FXR) axis. Phytosterol supplementation suppresses the abundance of bile salt hydrolase-active bacteria, such as Lactobacillus, leading to reduced intestinal enzymatic activity and the accumulation of conjugated bile acids. These bile acids act as intestinal FXR antagonists, downregulating the ileal fibroblast growth factor 15 (FGF15) signaling pathway. This suppression relieves feedback inhibition on hepatic bile acid synthesis, thereby accelerating cholesterol catabolism. Fecal microbiota transplantation validates that these metabolic benefits are gut microbiota dependent. Together, these findings link dietary phytosterols to host lipid metabolism through gut microbial bile acid regulation, providing a mechanistic framework for individualized, food-based strategies to manage dyslipidemia.

血脂异常是主要的心血管危险因素。尽管已知膳食植物甾醇可降低胆固醇，但涉及肠-肝轴（gut-liver axis）的具体机制尚未完全阐明。本研究通过整合人体临床试验与机制性动物模型数据，证实植物甾醇可通过调控肠道菌群-胆汁酸-法尼醇X受体（FXR）轴改善脂质谱。补充膳食植物甾醇可抑制胆汁盐水解酶活性菌（如乳酸杆菌属Lactobacillus）的丰度，进而降低肠道酶活性并促进结合型胆汁酸蓄积。此类结合型胆汁酸可作为肠道FXR拮抗剂，下调回肠成纤维细胞生长因子15（FGF15）信号通路。这种抑制作用可解除肝脏胆汁酸合成的反馈抑制，从而加速胆固醇分解代谢。粪便菌群移植实验证实，上述代谢获益依赖于肠道菌群。综上，本研究揭示了膳食植物甾醇可通过调控肠道菌群介导的胆汁酸代谢途径影响宿主脂质代谢，为基于食物的个体化血脂异常管理策略提供了机制框架。