{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:41:10Z","timestamp":1790372470809,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut\u2013biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide \u03b2-glucuronidase, phospholipase A2, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints\u2014sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines\u2014and outline a translational agenda: validated microbial\/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics.<\/jats:p>","DOI":"10.3390\/microorganisms13091980","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:57Z","timestamp":1756189557000},"page":"1980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Microbial Landscapes of the Gut\u2013Biliary Axis: Implications for Benign and Malignant Biliary Tract Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"David","family":"Meacci","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0895-1225","authenticated-orcid":false,"given":"Angelo","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"},{"name":"Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Cocquio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-5468","authenticated-orcid":false,"given":"Giuseppe","family":"Dell\u2019Anna","sequence":"additional","affiliation":[{"name":"Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Hospital, 20132 Milan, Italy"},{"name":"Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9931-7221","authenticated-orcid":false,"given":"Francesco Vito","family":"Mandarino","sequence":"additional","affiliation":[{"name":"Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Hospital, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-8773","authenticated-orcid":false,"given":"Giovanni","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-5952","authenticated-orcid":false,"given":"Paolo","family":"Cecinato","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Barbara","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"},{"name":"Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-8619","authenticated-orcid":false,"given":"Rocco Maurizio","family":"Zagari","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Universitaria di Bologna, 40126 Bologna, Italy"},{"name":"Gastro-Esophageal Organic Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","first-page":"2750","article-title":"Biliary tract microbiota: A new kid on the block of liver diseases?","volume":"24","author":"Nicoletti","year":"2020","journal-title":"Eur. 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