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Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity

Author

Listed:
  • Fei Li

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Changtao Jiang

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Kristopher W. Krausz

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yunfei Li

    (Bioinformatics Consulting Center, The Pennsylvania State University)

  • Istvan Albert

    (Bioinformatics Consulting Center, The Pennsylvania State University)

  • Haiping Hao

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Kristin M. Fabre

    (Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • James B. Mitchell

    (Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Andrew D. Patterson

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health
    The Pennsylvania State University)

  • Frank J. Gonzalez

    (Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

Abstract

The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase (BSH) activity leading to the accumulation of intestinal tauro-β-muricholic acid (T-β-MCA). T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist, which is involved in the regulation of bile acid, lipid and glucose metabolism. Its increased levels during tempol treatment inhibit FXR signalling in the intestine. High-fat diet-fed intestine-specific Fxr-null (FxrΔIE) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice. Further, tempol treatment does not decrease weight gain in FxrΔIE mice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol. These studies demonstrate a biochemical link between the microbiome, nuclear receptor signalling and metabolic disorders, and suggest that inhibition of FXR in the intestine could be a target for anti-obesity drugs.

Suggested Citation

  • Fei Li & Changtao Jiang & Kristopher W. Krausz & Yunfei Li & Istvan Albert & Haiping Hao & Kristin M. Fabre & James B. Mitchell & Andrew D. Patterson & Frank J. Gonzalez, 2013. "Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3384
    DOI: 10.1038/ncomms3384
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    Cited by:

    1. Michael DiMarzio & Brigida Rusconi & Neela H Yennawar & Mark Eppinger & Andrew D Patterson & Edward G Dudley, 2017. "Identification of a mouse Lactobacillus johnsonii strain with deconjugase activity against the FXR antagonist T-β-MCA," PLOS ONE, Public Library of Science, vol. 12(9), pages 1-15, September.
    2. Qi Zhao & Man-Yun Dai & Ruo-Yue Huang & Jing-Yi Duan & Ting Zhang & Wei-Min Bao & Jing-Yi Zhang & Shao-Qiang Gui & Shu-Min Xia & Cong-Ting Dai & Ying-Mei Tang & Frank J. Gonzalez & Fei Li, 2023. "Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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