Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism
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 associ...
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| Published in | Nature communications Vol. 10; no. 1; pp. 4971 - 17 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
31.10.2019
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
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| 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.
Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis. |
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| AbstractList | 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.
Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis. 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. Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis. 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.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. |
| ArticleNumber | 4971 |
| Author | Liang, Dandan Xie, Guoxiang Shen, Chengxing Zhao, Aihua Zhang, Yunjing Wang, Shouli Kuang, Junliang Wei, Meilin Huang, Fengjie Ma, Xiaohui Rajani, Cynthia Han, Xiaolong You, Yijun Chen, Tianlu Jia, Wei Liu, Jiajian Wei, Runmin Jiang, Runqiu Li, Mengci Zhou, Wangyi Zheng, Xiaojiao Yan, Chao Li, Yitao Zhou, Shuiping Bian, Zhaoxiang Li, Houkai Lei, Sha |
| Author_xml | – sequence: 1 givenname: Fengjie surname: Huang fullname: Huang, Fengjie organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Pharmacy, Shanghai Jiao Tong University – sequence: 2 givenname: Xiaojiao surname: Zheng fullname: Zheng, Xiaojiao organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 3 givenname: Xiaohui surname: Ma fullname: Ma, Xiaohui organization: Department of Pharmacology and Toxicology, Tasly Pharmaceutical Co. Ltd – sequence: 4 givenname: Runqiu orcidid: 0000-0003-2720-1366 surname: Jiang fullname: Jiang, Runqiu organization: University of Hawaii Cancer Center – sequence: 5 givenname: Wangyi surname: Zhou fullname: Zhou, Wangyi organization: Department of Pharmacology and Toxicology, Tasly Pharmaceutical Co. Ltd – sequence: 6 givenname: Shuiping surname: Zhou fullname: Zhou, Shuiping organization: Department of Pharmacology and Toxicology, Tasly Pharmaceutical Co. Ltd – sequence: 7 givenname: Yunjing surname: Zhang fullname: Zhang, Yunjing organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 8 givenname: Sha surname: Lei fullname: Lei, Sha organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 9 givenname: Shouli surname: Wang fullname: Wang, Shouli organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 10 givenname: Junliang surname: Kuang fullname: Kuang, Junliang organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 11 givenname: Xiaolong surname: Han fullname: Han, Xiaolong organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 12 givenname: Meilin surname: Wei fullname: Wei, Meilin organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 13 givenname: Yijun surname: You fullname: You, Yijun organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 14 givenname: Mengci surname: Li fullname: Li, Mengci organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 15 givenname: Yitao surname: Li fullname: Li, Yitao organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 16 givenname: Dandan surname: Liang fullname: Liang, Dandan organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 17 givenname: Jiajian surname: Liu fullname: Liu, Jiajian organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 18 givenname: Tianlu surname: Chen fullname: Chen, Tianlu organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 19 givenname: Chao surname: Yan fullname: Yan, Chao organization: School of Pharmacy, Shanghai Jiao Tong University – sequence: 20 givenname: Runmin orcidid: 0000-0001-7707-0160 surname: Wei fullname: Wei, Runmin organization: University of Hawaii Cancer Center – sequence: 21 givenname: Cynthia surname: Rajani fullname: Rajani, Cynthia organization: University of Hawaii Cancer Center – sequence: 22 givenname: Chengxing surname: Shen fullname: Shen, Chengxing organization: Department of Cardiology, Shanghai Jiao Tong University Affiliated Six People’s Hospital – sequence: 23 givenname: Guoxiang surname: Xie fullname: Xie, Guoxiang organization: University of Hawaii Cancer Center – sequence: 24 givenname: Zhaoxiang orcidid: 0000-0001-6206-1958 surname: Bian fullname: Bian, Zhaoxiang organization: Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University – sequence: 25 givenname: Houkai surname: Li fullname: Li, Houkai email: houkai1976@126.com organization: Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine – sequence: 26 givenname: Aihua surname: Zhao fullname: Zhao, Aihua email: zhah@sjtu.edu.cn organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital – sequence: 27 givenname: Wei orcidid: 0000-0002-3739-8994 surname: Jia fullname: Jia, Wei email: wjia@cc.hawaii.edu organization: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, University of Hawaii Cancer Center, Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31672964$$D View this record in MEDLINE/PubMed |
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| Snippet | Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant... Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces... |
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| SubjectTerms | 13 13/1 13/51 38/77 45 631/326/2565/2134 631/443/319/1642 631/443/319/2723 64/60 692/4020/2741/2135 82/80 Adult Amidohydrolases - metabolism Animals Bile Bile acids Bile Acids and Salts - metabolism Catechin - analogs & derivatives Catechin - pharmacology Chenodeoxycholic acid Chenodeoxycholic Acid - metabolism Cholesterol Cholesterol - metabolism Diet, High-Fat Digestive system Fecal Microbiota Transplantation Fermented Foods and Beverages Fibroblast Growth Factors - drug effects Fibroblast Growth Factors - metabolism Gastrointestinal Microbiome - drug effects Gastrointestinal Microbiome - genetics Gastrointestinal Microbiome - physiology Gastrointestinal tract Gene expression Gut microbiota Humanities and Social Sciences Humans Hydrolase Hypercholesterolemia Hypercholesterolemia - metabolism Hyperlipidemia Ileum - drug effects Ileum - metabolism Intestinal microflora Intestine Lipid metabolism Lipids Lipogenesis Lipogenesis - drug effects Lipolysis Liver Liver - drug effects Liver - metabolism Male Metabolomics Mice Microbiota multidisciplinary Pigments Plant Extracts - pharmacology Receptors, Cytoplasmic and Nuclear - drug effects Receptors, Cytoplasmic and Nuclear - metabolism RNA, Ribosomal, 16S Science Science (multidisciplinary) Signal Transduction Signaling Tea Young Adult |
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| Title | Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism |
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