{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:40:45Z","timestamp":1790372445988,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiomes"],"abstract":"<jats:p>The gut microbiota and bile acids (BAs) exist in a tightly regulated, bidirectional relationship that influences host metabolism, immune function, and disease. Primary BAs synthesized in the liver are chemically transformed by intestinal microbes into a diverse pool of secondary BAs, which exert antimicrobial effects and activate host signaling pathways including Farnesoid X Receptor (FXR), Takeda G protein\u2013coupled receptor 5 (TGR5), and sphingosine-1-phosphate receptor 2 (S1PR2). These pathways regulate BA homeostasis, epithelial barrier integrity, inflammation, and carcinogenesis. Disruption of this BA\u2013microbiome axis has been implicated in biliary tract cancers (BTCs), a group of aggressive malignancies with rising global incidence and limited therapeutic options. Secondary BAs and BA receptor signaling contribute to tumor initiation and progression through NF-\u03baB activation, oxidative stress, and altered cell survival, whereas reduced FXR signaling and obstructed enterohepatic circulation further promote inflammatory dysregulation. Emerging evidence demonstrates that microbial dysbiosis and altered BA metabolism are associated with distinct BTC microbial profiles, enriched in taxa such as Fusobacterium, Salmonella, Prevotella, and Actinomyces, alongside depletion of commensals including Lactobacillus. These taxa influence inflammatory signaling, BA transformation, and epithelial injury, contributing to carcinogenesis. Microbiome\u2013BA interactions also shape anti-tumor immunity and responses to immune checkpoint inhibitors (ICIs). Specific microbial signatures\u2014particularly enrichment of Lachnospiraceae, Erysipelotrichaceae, Bacteroidetes, and Alistipes\u2014correlate with enhanced immune activation and improved clinical outcomes in hepatobiliary cancers. Modulation of gut microbiota through antibiotics, probiotics, or fecal microbiota transplantation can influence BA composition, immune surveillance, and therapeutic efficacy. Collectively, these data highlight the central role of the BA\u2013microbiome axis in BTC pathogenesis and treatment response. Microbial and BA metabolite profiling represent promising avenues for biomarker development, while targeted manipulation of BA signaling and microbial ecology offers potential therapeutic strategies to improve BTC outcomes.<\/jats:p>","DOI":"10.3389\/frmbi.2026.1774429","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:16:33Z","timestamp":1779948993000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The interplay between bile acid metabolism and gut microbiome in biliary tract cancers"],"prefix":"10.3389","volume":"5","author":[{"given":"Ifeoma","family":"Ike","sequence":"first","affiliation":[{"name":"Department of Medicine, Eisenhower Health","place":["Rancho Mirage, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Teymouri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Eisenhower Health","place":["Rancho Mirage, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Crook","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Hazeltine","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daneng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep","family":"Brar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"178.e11","DOI":"10.1016\/j.cmi.2015.10.008","article-title":"Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma","volume":"22","author":"Avil\u00e9s-Jim\u00e9nez","year":"2016","journal-title":"Clin. 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