Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism

Fengjie Huang, Xiaojiao Zheng, Xiaohui Ma, Runqiu Jiang, Wangyi Zhou, Shuiping Zhou, Yunjing Zhang, Sha Lei, Shouli Wang, Junliang Kuang, Xiaolong Han, Meilin Wei, Yijun You, Mengci Li, Yitao Li, Dandan Liang, Jiajian Liu, Tianlu Chen, Chao Yan, Runmin Wei, Cynthia Rajani, Chengxing Shen, Guoxiang Xie, Zhaoxiang Bian, Houkai Li (), Aihua Zhao () and Wei Jia ()
Additional contact information
Fengjie Huang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Xiaojiao Zheng: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Xiaohui Ma: Tasly Pharmaceutical Co. Ltd
Runqiu Jiang: University of Hawaii Cancer Center
Wangyi Zhou: Tasly Pharmaceutical Co. Ltd
Shuiping Zhou: Tasly Pharmaceutical Co. Ltd
Yunjing Zhang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Sha Lei: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Shouli Wang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Junliang Kuang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Xiaolong Han: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Meilin Wei: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Yijun You: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Mengci Li: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Yitao Li: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Dandan Liang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Jiajian Liu: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Tianlu Chen: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Chao Yan: Shanghai Jiao Tong University
Runmin Wei: University of Hawaii Cancer Center
Cynthia Rajani: University of Hawaii Cancer Center
Chengxing Shen: Shanghai Jiao Tong University Affiliated Six People’s Hospital
Guoxiang Xie: University of Hawaii Cancer Center
Zhaoxiang Bian: Hong Kong Baptist University
Houkai Li: Shanghai University of Traditional Chinese Medicine
Aihua Zhao: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Wei Jia: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12896-x

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