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Published on: July 27, 2022
Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine
Dianji Tu1, Cheng Lu1, Junfeng Guo1
1Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
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.
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