{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:56:41Z","timestamp":1781326601018,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The biliary and pancreatic tract is increasingly recognized as a microbial ecosystem rather than a sterile environment. Dysbiosis contributes to inflammation, bile acid alterations, and carcinogenesis, with distinct microbiota profiles linked to progression from benign to malignant conditions. Clinical factors, including gut\u2013liver axis disruption and biliary stenting, may further exacerbate microbial imbalance. Objective: The objective of this study is to synthesize current evidence and identify knowledge gaps on the role of biliary microbiota in pancreaticobiliary carcinogenesis and its implications for diagnosis, prognosis, and therapy. Methods: This scoping review was conducted following PRISMA-ScR guidelines. A systematic search of PubMed, Web of Science, and Scopus was performed for studies published between January 2015 and December 2025, guided by the PICo framework. Results: Included studies primarily characterized changes in microbiota composition to identify microbial biomarkers associated with pancreaticobiliary diseases. Predictive bioinformatics analyses suggest that dysbiosis may promote carcinogenesis through metabolic and inflammatory pathways. Machine learning approaches identified microbiota-based signatures with potential diagnostic value for precancerous lesions, although discrimination remains limited. Biliary dysbiosis was also associated with outcomes related to biliary stenting, chemoprophylaxis, postoperative complications, and responses to chemotherapy or surgery. Conclusions: Integration of microbiota profiling with predictive bioinformatics and machine learning may improve understanding of pancreaticobiliary carcinogenesis. Identifying microbial and functional biomarkers could enable personalized diagnostic and therapeutic strategies, ultimately improving patient outcomes.<\/jats:p>","DOI":"10.3390\/cancers18121875","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:25:16Z","timestamp":1780935916000},"page":"1875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biliary Tract and Pancreatic Cancer (BTPC) in Adult Patients: The Role of the Biliary Microbiota in Cancer and Therapeutic Strategies\u2014A Scoping Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4418-5855","authenticated-orcid":false,"given":"Paola","family":"Di Carlo","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D\u2019Alessandro, Section of Infectious Disease, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-6362","authenticated-orcid":false,"given":"Nicola","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Sciences and Dentistry Department, Audiology Section, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aducio","family":"Thiesen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-4207","authenticated-orcid":false,"given":"Vito","family":"Rodolico","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D\u2019Alessandro, Section of Infectious Disease, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-1796","authenticated-orcid":false,"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D\u2019Alessandro, Section of Infectious Disease, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Maria Assunta","family":"Fasciana","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D\u2019Alessandro, Section of Infectious Disease, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Giammanco","sequence":"additional","affiliation":[{"name":"Legionella Reference Laboratory, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D\u2019Alessandro, Section of Infectious Disease, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Cocorullo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-1950","authenticated-orcid":false,"given":"Giuseppe","family":"Salamone","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Carollo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-7879","authenticated-orcid":false,"given":"Consolato M.","family":"Sergi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00284-024-03694-w","article-title":"Microbiota and Gut\u2013Liver Axis: An Unbreakable Bond?","volume":"81","author":"Sivaprasadan","year":"2024","journal-title":"Curr. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11218","DOI":"10.1038\/s41598-018-29571-8","article-title":"Metagenomics of pigmented and cholesterol gallstones: The putative role of bacteria","volume":"8","author":"Kose","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ye, C., Dong, C., Lin, Y., Shi, H., and Zhou, W. (2023). Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy. Microorganisms, 11.","DOI":"10.20944\/preprints202309.0099.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100204","DOI":"10.1016\/j.esmogo.2025.100204","article-title":"The increasing burden of early-onset pancreatic and biliary tract cancers: A review of risk factors","volume":"9","author":"Brugel","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Takrori, E., Abdulmajid, M., Devagudi, D., Sohail, R., Sadiq, Z., Berneau, C., Shenouda, A., Adelli, R., Peshin, S., and Singal, S. (2026). Recent Advances in Pancreatic Cancer and Biliary Tract Cancers: Biology, Biomarkers, and Evolving Systemic Therapy. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27104413"},{"key":"ref_6","unstructured":"Surveillance Research Program, National Cancer Institute (2026, June 01). Data Source(s): U.S. Mortality Data (1969\u20132024). 22 April 2026. [Updated: 12 May 2026]. National Center for Health Statistics, CDC, Available online: https:\/\/seer.cancer.gov\/statistics-network\/explorer\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41575-025-01153-w","article-title":"Cholangiocarcinoma 2026: Status quo, unmet needs and priorities","volume":"23","author":"Banales","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Di Carlo, P., Serra, N., Alduina, R., Guarino, R., Crax\u00ec, A., Giammanco, A., Fasciana, T., Cascio, A., and Sergi, C.M. (2022). A systematic review on omics data (metagenomics, metatranscriptomics, and metabolomics) in the role of microbiome in gallbladder disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.888233"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Merali, N., Chouari, T., Terroire, J., Jessel, M.-D., Liu, D.S.K., Smith, J.-H., Wooldridge, T., Dhillon, T., Jim\u00e9nez, J.I., and Krell, J. (2023). Bile Microbiome Signatures Associated with Pancreatic Ductal Adenocarcinoma Compared to Benign Disease: A UK Pilot Study. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316888"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Miyabe, K., Chandrasekhara, V., Wongjarupong, N., Chen, J., Yang, L., Johnson, S., Chia, N., Walther-Antonio, M., Yao, J.Z., and Harrington, S.C. (2022). Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma. Cancers, 14.","DOI":"10.3390\/cancers14092120"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.3390\/cimb46080463","article-title":"The Microbiota in Cancer: A Secondary Player or a Protagonist?","volume":"46","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jiang, H., Tian, Y., Xu, L., Chen, X., Huang, Y., Wu, J., Wang, T., Liu, T., Wu, X., and Ye, C. (2024). Alterations of the bile microbiome is associated with progression-free survival in pancreatic ductal adenocarcinoma patients. BMC Microbiol., 24.","DOI":"10.1186\/s12866-024-03371-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S2468-1253(22)00235-7","article-title":"The tumour immune microenvironment and microbiome of pancreatic intraductal papillary mucinous neoplasms","volume":"7","author":"Pollini","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Romeo, M., Dallio, M., Di Nardo, F., Napolitano, C., Vaia, P., Martinelli, G., Federico, P., Olivieri, S., Iodice, P., and Federico, A. (2025). The Role of the Gut\u2013Biliary\u2013Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications. J. Pers. Med., 15.","DOI":"10.3390\/jpm15040124"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.surg.2024.03.025","article-title":"Postoperative prophylactic antibiotic therapy after pancreaticoduodenectomy in bile duct-stented patients reduces postoperative major complications","volume":"176","author":"Steffani","year":"2024","journal-title":"Surgery"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.dld.2023.05.012","article-title":"Alarming correlation between multidrug-resistant bacteriobilia and morbidity after pancreatic surgery","volume":"55","author":"Gibiino","year":"2023","journal-title":"Dig. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1016\/j.gassur.2024.08.030","article-title":"Bacterial shift and resistance pattern in pancreatic head resections after selective decontamination of the digestive tract\u2014A propensity score-matched analysis","volume":"28","author":"Mibelli","year":"2024","journal-title":"J. Gastrointest. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Di Carlo, P., Serra, N., Sergi, C.M., Toia, F., Battaglia, E., Fasciana, T.M.A., Rodolico, V., Giammanco, A., Salamone, G., and Cordova, A. (2025). Seasonal Change in Microbial Diversity: Bile Microbiota and Antibiotics Resistance in Patients with Bilio-Pancreatic Tumors: A Retrospective Monocentric Study (2010\u20132020). Antibiotics, 14.","DOI":"10.3390\/antibiotics14030283"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/jso.27281","article-title":"Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer","volume":"128","author":"Behrens","year":"2023","journal-title":"J. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1080\/14796694.2025.2539018","article-title":"ABC-12: Exploring the microbiome in patients with advanced biliary tract cancer in a first-line study of durvalumab (MEDI4736) in combination with cisplatin\/gemcitabine","volume":"21","author":"Vrana","year":"2025","journal-title":"Future Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_22","first-page":"359","article-title":"Evaluation of PICO as a knowledge representation for clinical questions","volume":"2006","author":"Huang","year":"2006","journal-title":"AMIA Annu. Symp. Proc."},{"key":"ref_23","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":"Guitron","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1002\/bjs.10450","article-title":"Effect of preoperative biliary drainage on bacterial flora in bile of patients with periampullary cancer","volume":"104","author":"Scheufele","year":"2017","journal-title":"Br. J. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Goel, N., Nadler, A., Reddy, S., Hoffman, J.P., and Pitt, H.A. (2018, January 4\u20137). Biliary microbiome in pancreatic cancer: Alterations with neoadjuvant therapy. Proceedings of the 13th World Biennial Congress of the International-Hepato-Pancreato-Biliary-Association (IHPBA), Geneva, Switzerland.","DOI":"10.1016\/j.hpb.2018.02.229"},{"key":"ref_26","first-page":"1","article-title":"A Preliminary Study of Biliary Microbiota in Patients with Bile Duct Stones or Distal Cholangiocarcinoma","volume":"2019","author":"Chen","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.2147\/IDR.S200378","article-title":"The microbiota of the bilio-pancreatic system: A cohort, STROBE-compliant study","volume":"12","author":"Serra","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.amjsurg.2020.09.042","article-title":"Neoadjuvant chemotherapy for pancreatic cancer and changes in the biliary microbiome","volume":"222","author":"Nadeem","year":"2021","journal-title":"Am. J. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8766","DOI":"10.1038\/s41598-022-12658-8","article-title":"Unveiling microbiome profiles in human inner body fluids and tumor tissues with pancreatic or biliary tract cancer","volume":"12","author":"Okuda","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ito, Z., Koido, S., Kato, K., Odamaki, T., Horiuchi, S., Akasu, T., Saruta, M., Hata, T., Kumagai, Y., and Fujioka, S. (2022). Dysbiosis of the Fecal and Biliary Microbiota in Biliary Tract Cancer. Cancers, 14.","DOI":"10.3390\/cancers14215379"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kirishima, M., Yokoyama, S., Matsuo, K., Hamada, T., Shimokawa, M., Akahane, T., Sugimoto, T., Tsurumaru, H., Ishibashi, M., and Mataki, Y. (2022). Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02557-3"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0283021","DOI":"10.1371\/journal.pone.0283021","article-title":"Microbiomic profiles of bile in patients with benign and malignant pancreaticobiliary disease","volume":"18","author":"Poudel","year":"2023","journal-title":"PLoS ONE"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"238","DOI":"10.18683\/germs.2023.1390","article-title":"Microbiome analysis of bile samples in patients with choledocholithiasis and hepatobiliary disorders","volume":"13","author":"Azimirad","year":"2023","journal-title":"Germs"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Di Carlo, P., Serra, N., Fasciana, T.M.A., Giammanco, A., D\u2019Arpa, F., Rea, T., Napolitano, M.S., Lucchesi, A., Cascio, A., and Sergi, C.M. (2024). Microbial profile in bile from pancreatic and extra-pancreatic biliary tract cancer. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0294049"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sidiropoulos, T., Dovrolis, N., Katifelis, H., Michalopoulos, N.V., Kokoropoulos, P., Arkadopoulos, N., and Gazouli, M. (2024). Dysbiosis Signature of Fecal Microbiota in Patients with Pancreatic Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasms. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051040"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Park, W., Lee, S.K., Gwack, J., Lee, S.Y., Cho, Y.G., Kang, S.-B., and Park, J. (2025). Dysbiosis of Bile Microbiota in Cholangiocarcinoma Patients: A Comparison with Benign Biliary Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041577"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00841","DOI":"10.14309\/ctg.0000000000000841","article-title":"Characterization of Bile Microbiota in Patients with Obstructive Jaundice Associated with Biliary Tract Diseases","volume":"16","author":"Wang","year":"2025","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.aay9189","article-title":"The human tumor microbiome is composed of tumor type\u2013specific intracellular bacteria","volume":"368","author":"Nejman","year":"2020","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Qi, X., Liu, Y., Hussein, S., Choi, G., Kimchi, E.T., Staveley-O\u2019carroll, K.F., and Li, G. (2022). The Species of Gut Bacteria Associated with Antitumor Immunity in Cancer Therapy. Cells, 11.","DOI":"10.3390\/cells11223684"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/msp2.15","article-title":"Gastric microbiota and its role in gastric carcinogenesis","volume":"1","author":"Jiang","year":"2023","journal-title":"Malig. Spectr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jiph.2020.11.005","article-title":"Human bile microbiota: A retrospective study focusing on age and gender","volume":"14","author":"Serra","year":"2021","journal-title":"J. Infect. Public Health"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xu, J., Song, J., Fu, Z., Zhou, H., Zhang, Y., and Shi, C. (2025). Unraveling gut microbiome interferences in cancer immunotherapy: A meta-analysis of diverse drug effects. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-15094-9"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.ccell.2024.07.005","article-title":"Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers","volume":"42","author":"Sun","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/1875\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:18:47Z","timestamp":1781324327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/1875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cancers18121875"],"URL":"https:\/\/doi.org\/10.3390\/cancers18121875","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}