TY - JOUR
T1 - Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism
AU - Huang, Fengjie
AU - Zheng, Xiaojiao
AU - Ma, Xiaohui
AU - Jiang, Runqiu
AU - Zhou, Wangyi
AU - Zhou, Shuiping
AU - Zhang, Yunjing
AU - Lei, Sha
AU - Wang, Shouli
AU - Kuang, Junliang
AU - Han, Xiaolong
AU - Wei, Meilin
AU - You, Yijun
AU - Li, Mengci
AU - Li, Yitao
AU - Liang, Dandan
AU - Liu, Jiajian
AU - Chen, Tianlu
AU - Yan, Chao
AU - Wei, Runmin
AU - Rajani, Cynthia
AU - Shen, Chengxing
AU - Xie, Guoxiang
AU - Bian, Zhaoxiang
AU - Li, Houkai
AU - Zhao, Aihua
AU - Jia, Wei
N1 - Funding Information:
This work was funded by the National Key R&D Program of China (2017YFC0906800), National Natural Science Foundation of China (81974073, 81772530).
Publisher copyright:
Copyright © 2019, The Author(s)
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074273494&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-12896-x
DO - 10.1038/s41467-019-12896-x
M3 - Journal article
C2 - 31672964
AN - SCOPUS:85074273494
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4971
ER -