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Research ArticleArticle

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Yuan Tian, Jingwei Cai, Wei Gui, Robert G. Nichols, Imhoi Koo, Jingtao Zhang, Mallappa Anitha and Andrew D. Patterson
Drug Metabolism and Disposition February 2019, 47 (2) 86-93; DOI: https://doi.org/10.1124/dmd.118.083691
Yuan Tian
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Jingwei Cai
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Wei Gui
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Robert G. Nichols
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Imhoi Koo
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Jingtao Zhang
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Mallappa Anitha
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Andrew D. Patterson
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People’s Republic of China (Y.T.)
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Abstract

Intestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR- and mass spectrometry–based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSH-expressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

Footnotes

    • Received July 31, 2018.
    • Accepted November 7, 2018.
  • This work was supported in part by the Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds], the National Institutes of Health National Library of Medicine [Grant T32LM12415-1], and the U.S. Department of Agriculture National Institute of Food and Agriculture [Award 2914-38420-21822].

  • https://doi.org/10.1124/dmd.118.083691.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 47 (2)
Drug Metabolism and Disposition
Vol. 47, Issue 2
1 Feb 2019
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Research ArticleArticle

Berberine Affects Gut Microbiota to Promote Intestinal FXR Activation

Yuan Tian, Jingwei Cai, Wei Gui, Robert G. Nichols, Imhoi Koo, Jingtao Zhang, Mallappa Anitha and Andrew D. Patterson
Drug Metabolism and Disposition February 1, 2019, 47 (2) 86-93; DOI: https://doi.org/10.1124/dmd.118.083691

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Research ArticleArticle

Berberine Affects Gut Microbiota to Promote Intestinal FXR Activation

Yuan Tian, Jingwei Cai, Wei Gui, Robert G. Nichols, Imhoi Koo, Jingtao Zhang, Mallappa Anitha and Andrew D. Patterson
Drug Metabolism and Disposition February 1, 2019, 47 (2) 86-93; DOI: https://doi.org/10.1124/dmd.118.083691
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