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Vancomycin (VCM) has been shown to improve cholestasis in human patients, but its biological effects remain unclear. This study aimed to investigate the therapeutic effects of VCM on microbiome modulation and the restoration of liver function. VCM was administered in a modified\n                    <jats:italic>Abcb11<\/jats:italic>\n                    knockout (KO) mice model with pre\u2010existing cholestasis to examine its therapeutic effects and microbiome changes. After 2\u2009weeks of treatment, VCM significantly decreased serum bilirubin while maintaining stable transaminase in the KO mice. Three\u2010dimensional imaging of pan\u2010CK expression by immunofluorescence revealed improvement of the disrupted biliary epithelium and interconnected bile duct network, as evidenced by increased coverage and cumulative duct length in the liver. Gene expression and hepatic bile acid profiling demonstrated that VCM enhanced canalicular\/sinusoidal bile acid export while repressing bile acid synthesis, with a reduction in tauro\u2010\u03b2\u2010muricholic acid, the predominant bile acid in mice, in KO livers. Fecal microbial analysis using next\u2010generation sequencing identified\n                    <jats:italic>Parabacteroides goldsteinii<\/jats:italic>\n                    (PG) as the predominant species after VCM treatment. KO mice fed PG demonstrated improved cholestasis, with significantly reduced direct bilirubin, alkaline phosphatase, total bile acids in serum, as well as fewer reactive ductules in the liver.\n                    <jats:italic>In vitro<\/jats:italic>\n                    culture of ductal organoids suggested that PG directly promoted the growth of cholangiocytes. RNA sequencing results suggested that PG suppressed pro\u2010inflammatory\n                    <jats:italic>Lyz1<\/jats:italic>\n                    (mouse orthologous gene of human\n                    <jats:italic>LYZ<\/jats:italic>\n                    ) and\n                    <jats:italic>Aqp4<\/jats:italic>\n                    and increased pro\u2010proliferative\n                    <jats:italic>Muc6<\/jats:italic>\n                    and\n                    <jats:italic>Chrm3<\/jats:italic>\n                    . This study highlights the therapeutic potential of VCM in cholestasis by enriching PG in the gut and improving biliary structures in the liver, identifying PG as a potential probiotic with beneficial effects in cholestasis. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70101","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:34:01Z","timestamp":1785839641000},"page":"303-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vancomycin enriches\n                    <scp>\n                      <i>P<\/i>\n                    <\/scp>\n                    <i>arabacteroides goldsteinii<\/i>\n                    in the gut and promotes reconstruction of the hepatobiliary system in cholestasis"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-4192","authenticated-orcid":false,"given":"Shu\u2010Hao","family":"Hsu","sequence":"first","affiliation":[{"name":"Graduate Institute of Anatomy and Cell Biology National Taiwan University College of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey\u2010Huey","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Taiwan University College of Medicine and Children's Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang\u2010Yu","family":"Liou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Taiwan University College of Medicine and Children's Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Yuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of 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