Chen ZK, Zhao JW, Wang YG, Wang C, Shi M. Gut microbiota and the colorectal cancer tumor microenvironment: From carcinogenic mechanisms to therapeutic opportunities. World J Gastrointest Oncol 2026; 18(1): 115309 [DOI: 10.4251/wjgo.v18.i1.115309]
Corresponding Author of This Article
Min Shi, PhD, Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. sm1790@shtrhospital.com
Research Domain of This Article
Gastroenterology & Hepatology
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jan 15, 2026 (publication date) through Jan 12, 2026
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Publication Name
World Journal of Gastrointestinal Oncology
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1948-5204
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Chen ZK, Zhao JW, Wang YG, Wang C, Shi M. Gut microbiota and the colorectal cancer tumor microenvironment: From carcinogenic mechanisms to therapeutic opportunities. World J Gastrointest Oncol 2026; 18(1): 115309 [DOI: 10.4251/wjgo.v18.i1.115309]
World J Gastrointest Oncol. Jan 15, 2026; 18(1): 115309 Published online Jan 15, 2026. doi: 10.4251/wjgo.v18.i1.115309
Gut microbiota and the colorectal cancer tumor microenvironment: From carcinogenic mechanisms to therapeutic opportunities
Zi-Ke Chen, Jia-Wei Zhao, Yu-Gang Wang, Chen Wang, Min Shi
Zi-Ke Chen, Jia-Wei Zhao, Yu-Gang Wang, Chen Wang, Min Shi, Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Co-first authors: Zi-Ke Chen and Jia-Wei Zhao.
Co-corresponding authors: Chen Wang and Min Shi.
Author contributions: Chen ZK and Zhao JW contribute equally to this study as co-first authors; Wang C and Shi M contribute equally to this study as co-corresponding authors; Chen ZK and Zhao JW were responsible for discussion and conception, writing first draft with references; Wang YG, Wang C and Shi M were responsible for oversight of the effort, discussion and conception, editing and approval of final draft.
Supported by National Natural Science Foundation of China, No. 82170638; Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality, No. 23ZR1458300; Key Discipline Project of Shanghai Municipal Health System, No. 2024ZDXK0004; and Pujiang Project of Shanghai Magnolia Talent Plan, No. 24PJD098.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Min Shi, PhD, Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. sm1790@shtrhospital.com
Received: October 15, 2025 Revised: November 5, 2025 Accepted: December 3, 2025 Published online: January 15, 2026 Processing time: 90 Days and 14.4 Hours
Abstract
Colorectal cancer (CRC) is ranked as the third most common tumor globally, representing approximately 10% of all cancer cases, and is the second primary cause of cancer-associated mortality. Existing therapeutic approaches demonstrate limited efficacy against CRC, partially due to the immunosuppressive tumor microenvironment (TME). In recent years, substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation, progression, and prognostic outcomes of CRC. In this minireview, we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity, activate cancer-associated fibroblasts, remodel tumor vasculature, and critically, sculpt an immunosuppressive landscape by modulating T cells, dendritic cells, and tumor-associated macrophages. We highlight the translational potential of targeting the gut microbiota, including fecal microbiota transplantation, probiotics, and engineered microbial systems, to reprogram the TME and overcome resistance to immunotherapy and chemotherapy. A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
Core Tip: This minireview synthesizes current insights into how gut microbiota and their metabolites bidirectionally shape the colorectal cancer tumor microenvironment, moving beyond epithelial barrier disruption to delineate direct immunomodulatory effects on stromal and immune cells. We highlight the translational potential of microbiota-targeting strategies, such as fecal microbiota transplantation and engineered microbes, in reprogramming the immunosuppressive niche to overcome therapy resistance.
