Targeting the Gut Microbiota-Bile Acid-FXR Axis: The Therapeutic Mechanism of Yudantong Decoction in Cholestatic Liver Disease

  • Curr Med Sci. 2026 Jun;46(3):851-865. doi: 10.1007/s11596-026-00191-y.
Xiao-Ming Wu  1 ,  Lin-Yi Hou  1 ,  Chang Liu  1 ,  Yan Hu  2 ,  Qiang He  3
Affiliations
  • 1. Department of Traditional Chinese Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, 100045, China.
  • 2. Department of Traditional Chinese Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, 100045, China. [email protected].
  • 3. Department of Traditional Chinese Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, 100045, China. [email protected].
PMID: 42053886 DOI: 10.1007/s11596-026-00191-y
Abstract

Objective: To elucidate the therapeutic mechanism of Yudantong decoction (YDTD) in cholestatic liver disease (CLD), focusing on the gut microbiota-bile acid-intestinal farnesoid X receptor (FXR) axis.

Methods: A CLD mouse model induced by α-naphthylisothiocyanate was treated with YDTD. Hepatic injury, gut microbiota composition (16S rRNA Sequencing), bile acid profiles (high-performance liquid chromatography-tandem mass spectrometry, HPLC-MS/MS), intestinal FXR/NLRP3 signaling, and barrier function were assessed. Fecal microbiota transplantation, bile salt hydrolase (BSH) inhibition, and FXR antagonism were employed for mechanistic validation.

Results: CLD mice exhibited hepatocellular steatosis, lobular necrosis, and elevated serum markers. These pathological changes were associated with gut dysbiosis, impaired bile acid metabolism via bile salt hydrolase (BSH) suppression, FXR signaling inhibition, and NLRP3 inflammasome activation. YDTD restored BSH activity and bile acid homeostasis, upregulated FXR expression, suppressed NLRP3 inflammasome activation, and improved intestinal barrier integrity. Fecal microbiota transplantation experiments confirmed that YDTD-modified microbiota mediated these therapeutic benefits, whereas pharmacological inhibition of BSH or FXR attenuated YDTD's therapeutic effects.

Conclusion: YDTD alleviates CLD, at least in part, by targeting the gut microbiota-bile acid-FXR signaling pathway, highlighting the gut microbiota as a promising therapeutic target for CLD.

Keywords
Bile acids; Bile salt hydrolase; Cholestatic liver disease; Fecal microbiota trasplantation; Gut microbiota; Intestinal Barrier; Intestinal farnesoid X receptor; NLRP3 inflammation; Yudantong decoction.
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