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Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy

Author

Listed:
  • Bo Tang

    (Xinqiao Hospital, Army Medical University)

  • Li Tang

    (Xinqiao Hospital, Army Medical University)

  • Shengpeng Li

    (Xinqiao Hospital, Army Medical University)

  • Shuang Liu

    (Xinqiao Hospital, Army Medical University)

  • Jialin He

    (Xinqiao Hospital, Army Medical University)

  • Pan Li

    (First People’s Hospital of Foshan)

  • Sumin Wang

    (Xinqiao Hospital, Army Medical University)

  • Min Yang

    (Xinqiao Hospital, Army Medical University)

  • Longhui Zhang

    (Xinqiao Hospital, Army Medical University)

  • Yuanyuan Lei

    (Xinqiao Hospital, Army Medical University)

  • Dianji Tu

    (Army Medical University)

  • Xuefeng Tang

    (Army Medical University)

  • Hua Hu

    (Xinqiao Hospital, Army Medical University)

  • Qin Ouyang

    (Army Medical University)

  • Xia Chen

    (First People’s Hospital of Foshan)

  • Shiming Yang

    (Xinqiao Hospital, Army Medical University
    Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory
    Chongqing Municipality Clinical Research Center for Gastroenterology)

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.

Suggested Citation

  • Bo Tang & Li Tang & Shengpeng Li & Shuang Liu & Jialin He & Pan Li & Sumin Wang & Min Yang & Longhui Zhang & Yuanyuan Lei & Dianji Tu & Xuefeng Tang & Hua Hu & Qin Ouyang & Xia Chen & Shiming Yang, 2023. "Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36981-4
    DOI: 10.1038/s41467-023-36981-4
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    References listed on IDEAS

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