Clinical and molecular hepatology · 2025
Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Tu Dianji, Lu Cheng, Guo Junfeng, Chen Qiao, Li Xin, Wang Yingjie, Cheng Lulu, Jiang Hongfei, Jian Jincheng, Ge Yusong, Hou Zhanjie, Feng Xiaojie, Feng Yunxuan, Zhou Jianchun, Lei Yuanyuan, Diao Hua, Ran Lei, Zhou Yuanyuan, Xu Zhengguo, Zhou Jiyin, Tang Bo, Yang Shiming
Аннотация
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.
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.