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The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.<\/jats:p>","DOI":"10.3390\/microorganisms11102598","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T11:53:56Z","timestamp":1697802836000},"page":"2598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9180-6648","authenticated-orcid":false,"given":"Cheng","family":"Ye","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlu","family":"Dong","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqing","family":"Shi","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-7777","authenticated-orcid":false,"given":"Wence","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","article-title":"Biliary tract cancer","volume":"397","author":"Valle","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1634\/theoncologist.2015-0446","article-title":"Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise","volume":"21","author":"Saha","year":"2016","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/liv.14086","article-title":"Clinical presentation, diagnosis and staging of cholangiocarcinoma","volume":"39","author":"Forner","year":"2019","journal-title":"Liver Int"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/liv.14095","article-title":"Cholangiocarcinoma: Epidemiology and risk factors","volume":"39","author":"Khan","year":"2019","journal-title":"Liver Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.apar.2018.10.001","article-title":"Update on Pathogenesis of Opisthorchiasis and Cholangiocarcinoma","volume":"102","author":"Sripa","year":"2018","journal-title":"Adv. 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