REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1585923
This article is part of the Research TopicImpact of oral and gut microbiome on health and diseasesView all 17 articles
Oral Microbiota and Biliary Tract Cancers: Unveiling Hidden Mechanistic Links
Provisionally accepted
Yuhan Zhang1,2
Shu Zhang2*- 1Chongqing Medical University, Chongqing, China
- 2Nursing Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Biliary tract cancers (BTCs), a group of rare aggressive malignancies, posed significant clinical challenges due to late diagnosis and limited therapies. While gut microbiota had been extensively studied in gastrointestinal cancers, the role of oral microbiota-a primary microbial reservoir entering the digestive system-remained poorly understood. Emerging evidence indicated that oral bacteria might affect biliary carcinogenesis through direct colonization, immune modulation, and metabolic interactions via the oral-gut-liver axis. This narrative review analyzed current research connecting oral microbial imbalance with BTCs. It explored how bacterial translocation, inflammatory metabolites, and immune alterations could promote cancer development. Established BTC risk factors-including gallstones, primary sclerosing cholangitis, cirrhosis, and H. pylori infection-were evaluated for their associations with oral microbiota changes. Epidemiological studies revealed that periodontal disease and poor oral hygiene elevated BTC risk. Sequencing analyses identified oral-origin bacteria (Prevotella, Fusobacterium, Streptococcus) in bile and tumor tissues, suggesting microbial migration through swallowing or bloodstream. Mechanistic investigations showed microbial components (e.g., lipopolysaccharides, membrane vesicles) activated inflammatory pathways (TLR4/NF-κB, STAT3) and modified immune checkpoints, while metabolites potentially altered biliary cell metabolism. Different studies have found variable changes in oral microbiota in the presence of BTCs, thus a novel "biphasic dysbiosis" hypothesis was proposed to explain differing oral microbial diversity patterns across BTC subtypes. Despite progress, critical knowledge gaps persisted regarding causality, spatial microbial variations, and functional impacts of metabolites in BTCs. Future research was recommended to employ multiomics approaches, single-cell analysis, and AI tools to enhance early detection and prevention strategies.
Keywords: Oral microbiota, Oncogenic bacteria, Biliary tract cancer, Bacterial Translocation, mechanisms
Received: 01 Mar 2025; Accepted: 26 May 2025.
Copyright: © 2025 Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shu Zhang, Nursing Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.