Skip to main content
Evidence-Based Supplement Research
Evidence-Based Supplement Research
Pillser
Search
Sign UpLog In

Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.

  • 2025-10-14
  • Clinical and molecular hepatology 32(1)
    • Dianji Tu
    • Cheng Lu
    • Junfeng Guo
    • Qiao Chen
    • Xin Li
    • Yingjie Wang
    • Lulu Cheng
    • Hongfei Jiang
    • Jincheng Jian
    • Yusong Ge
    • Zhanjie Hou
    • Xiaojie Feng
    • Yunxuan Feng
    • Jianchun Zhou
    • Yuanyuan Lei
    • Hua Diao
    • Lei Ran
    • Yuanyuan Zhou
    • Zhengguo Xu
    • Jiyin Zhou
    • Bo Tang
    • Shiming Yang

Study Design

Type
Randomized Controlled Trial (RCT)
Population
patients with cholestatic liver disease (CLD)
Methods
randomized, controlled clinical trial of berberine in patients with CLD

Background/aims

Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.

Methods

We administered berberine (BBR) or dihydroberberine (dhBBR) in bile duct ligation-, ANIT-, and mdr2-/- CLD mouse models to evaluate the anti-CLD effect. We conducted fecal microbiota transplantation to determine the role of gut microbiota in BBR's effect. We conducted a randomized, controlled clinical trial to evaluate the effects of BBR in patients with CLD.

Results

Oral BBR alleviates cholestatic liver injury in multiple mouse models. Gut microbes can transform BBR into dhBBR, which suppresses 5-hydroxytryptamine (5-HT) production in gut enterochromaffin cells by antagonizing tryptophan hydroxylase 1 (TPH1) activity and downregulating Tph1 transcription. This further ameliorates CLD by interrupting the 5-HT/5-HTR axis. A clinical study validated that BBR improved blood biochemical indicators in patients with CLD and decreased 5-HT levels.

Conclusions

BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.

Research Insights

Back to top