REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1638352
This article is part of the Research TopicThe Role of Metabolic Reprogramming in Tumor TherapyView all 19 articles
Interplay Between Bile Acids, Gut Microbiota, and the Tumor Immune Microenvironment: Mechanistic Insights and Therapeutic Strategies
Provisionally accepted
- 1Zhejiang Chinese Medical University, Hangzhou, China
- 2Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, 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
The interplay between the gut microbiota, bile acid (BA) metabolism, and the tumor immune microenvironment (TIME) is a critical and rapidly advancing field in cancer immunology. Microbiota-transformed bile acids act as pivotal signaling molecules. This review systematically dissects how these BAs engage host receptors (e.g., FXR, TGR5, VDR, S1PR2) to influence the differentiation and activity of key innate (macrophages, NK cells, MDSCs, DCs) and adaptive (CD8+ T cells, Tregs, Th1/Th17 cells) immune cell populations within the TIME. We underscore that dysregulation of this microbiota-BA-immune axis, prevalent in gastrointestinal and hepatobiliary cancers, frequently cultivates a pro-inflammatory, immunosuppressive TIME, thereby facilitating tumor immune evasion and progression. In light of this, we examine emerging therapeutic strategies aimed at reprogramming this axis, including pharmacological BA receptor modulation, microbiota-based interventions (e.g., engineered microbes, FMT, dietary strategies), and their synergistic potential with established cancer treatments like immune checkpoint inhibitors. Finally, this review addresses significant challenges in clinical translation, including inherent axis complexity, inter-individual variability, and methodological hurdles. Future directions highlighted include tackling heterogeneity, employing advanced multi-omics, and developing robust biomarkers for precision immuno-oncology. Unraveling this complex immunometabolic network is crucial for identifying novel diagnostic tools and advancing next-generation cancer immunotherapies.
Keywords: Bile acids, Gut Microbiota, Tumor immune microenvironment, cancer immunotherapy, Immunometabolism
Received: 30 May 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Tong and Lou. 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: Xiaojun Lou, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, 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.