{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tu D"],"funding":["National Natural Science Foundation of China"],"pagination":["221-238"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12835802"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(1)"],"pubmed_abstract":["<h4>Background/aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use."],"journal":["Clinical and molecular hepatology"],"pubmed_title":["Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production."],"pmcid":["PMC12835802"],"funding_grant_id":["82030020","82370586"],"pubmed_authors":["Tu D","Chen Q","Hou Z","Diao H","Feng X","Jiang H","Feng Y","Lu C","Tang B","Zhou Y","Jian J","Li X","Guo J","Ge Y","Lei Y","Cheng L","Ran L","Wang Y","Yang S","Xu Z","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.","description":"<h4>Background/aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-14T06:03:00.34Z","creation":"2026-06-14T03:15:14.922Z"},"accession":"S-EPMC12835802","cross_references":{"pubmed":["41087029"],"doi":["10.3350/cmh.2025.0577"]}}