Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Nat Commun. 2019 Oct 31;10(1):4971. doi: 10.1038/s41467-019-12896-x.
Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.
普洱茶具有降低胆固醇的特性，但作用机制尚未阐明。茶褐素是普洱茶中最活跃、含量最丰富的色素之一。在这里，我们表明茶褐素改变了小鼠和人类的肠道微生物群，主要抑制与胆盐水解酶（BSH）活性相关的微生物。茶褐素增加了回肠共轭胆汁酸（BAs）的水平，而后者又抑制了肠道 FXR-FGF15 信号通路，导致肝脏产生和粪便排泄 BAs 增加，肝脏胆固醇减少，脂肪生成减少。抑制肠道 FXR-FGF15 信号伴随着替代 BA 合成途径中酶的基因表达增加、肝脏鹅脱氧胆酸的产生、肝脏 FXR 的激活和肝脂肪分解。我们的研究结果揭示了普洱茶降低胆固醇和血脂的作用机制，并表明肠道 BSH 微生物减少和/或 FXR-FGF15 信号减少可能是潜在的抗高胆固醇血症和抗高脂血症疗法。
