{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:06:12Z","timestamp":1793387172180,"version":"4.5.0"},"reference-count":145,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad UTE"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract with rising global incidence and limited treatment options. Its pathogenesis involves a complex interplay of genetic mutations, epigenetic dysregulation, inflammatory signaling, and environmental influences. Emerging evidence highlights the pivotal role of the gut\u2013liver axis and microbiota dysbiosis in shaping biliary homeostasis and disease progression. Alterations in microbial composition disrupt apoptosis and autophagy, two key processes regulating cell survival and death, thereby contributing to tumorigenesis, metastasis, and therapy resistance. Specific taxa, including Enterococcus, Escherichia coli, Pseudomonas, Bifidobacterium, and Bacillus, demonstrate strain-dependent effects, acting either as tumor promoters through genotoxic metabolites and immune evasion or as potential tumor suppressors by inducing apoptosis and immune activation. These findings underscore the context-dependent roles of microbiota in CCA biology. Importantly, microbiota modulation offers novel therapeutic opportunities. Dietary interventions such as probiotics, prebiotics, and nutritional strategies, alongside innovative microbiome-targeted therapies, hold promise for restoring microbial balance, enhancing antitumor immunity, and improving patient outcomes. This review integrates current molecular and microbiological evidence to propose the gut microbiota as both a biomarker and a therapeutic target in CCA, opening avenues for precision medicine approaches in hepatobiliary oncology.<\/jats:p>","DOI":"10.3390\/ijms26209949","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular Mechanisms and Therapeutic Perspectives of Gut Microbiota, Autophagy, and Apoptosis in Cholangiocarcinoma Pathophysiology"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-2614","authenticated-orcid":false,"given":"Viviana A.","family":"Ruiz-Pozo","sequence":"first","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-6046","authenticated-orcid":false,"given":"Santiago","family":"Cadena-Ullauri","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-3653","authenticated-orcid":false,"given":"Patricia","family":"Guevara-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-3281","authenticated-orcid":false,"given":"Rafael","family":"Tamayo-Trujillo","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elius","family":"Paz-Cruz","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-6618","authenticated-orcid":false,"given":"Alejandro","family":"Cabrera-Andrade","sequence":"additional","affiliation":[{"name":"Grupo de Bio-Quimioinform\u00e1tica, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"},{"name":"Carrera de Enfermer\u00eda, Facultad de Ciencias de la Salud, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-3965","authenticated-orcid":false,"given":"Ana Karina","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica, Quito 170129, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41571-023-00770-1","article-title":"Cholangiocarcinoma\u2014Novel biological insights and therapeutic strategies","volume":"20","author":"Ilyas","year":"2023","journal-title":"Nat. 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