MINI REVIEW article
Front. Physiol.
Sec. Gastrointestinal Sciences
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1676796
This article is part of the Research TopicNext-Generation Technologies in Assessing Gastrointestinal Health and DiseaseView all 3 articles
The Gut Microbiome and Gastrointestinal Cancers: Mechanisms, Biomarkers and therapeutic opportunities
Provisionally accepted
Sarbjeet Makkar1,2*
Kumar Bishnupuri3- 1University of Michigan, Ann Arbor, United States
- 2University of Michigan Medical Center Rogel Cancer Center, Ann Arbor, United States
- 3Washington University in St Louis School of Medicine, St. Louis, United States
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Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis—characterized by disrupted microbial diversity and function—in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including early diagnosis, prognosis assessment, and therapeutic response prediction. The intricate interactions between microbiota and standard cancer therapies—chemotherapy, immunotherapy, and radiation therapy—are discussed, highlighting microbiome influences on therapeutic efficacy and adverse effect profiles. We also critically assess the impact of modifiable factors such as diet, medications, lifestyle, and environmental exposures on microbiome composition and cancer risk. The review evaluates emerging therapeutic interventions, including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered live biotherapeutics. Despite notable advancements, significant hurdles remain, including clarifying causality, methodological standardization, and equitable global research representation. Addressing these challenges, we propose a strategic research agenda aimed at harnessing microbiome insights to advance precision oncology and improve GI cancer outcomes globally.
Keywords: gut microbiome, Gastrointestinal cancers, Microbial dysbiosis, Cancerimmunotherapy, Microbiome-derived biomarkers, Microbiota-targeted therapy
Received: 31 Jul 2025; Accepted: 08 Oct 2025.
Copyright: © 2025 Makkar and Bishnupuri. 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: Sarbjeet Makkar, smakkar49@gmail.com
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.