Gut Microbiota and Colorectal Cancer: Mechanistic Insights, Diagnostic Advances, and Microbiome-Based Therapeutic Strategies

Bingbing Bai^1,2,3,4*Jianing Ma^1,2,3,4Wenlong Xu^1,2,3,4Xiaomin Chen^1,2,3,4Xu Chen^1,2,3,5Chao Lv^1,2,3,4Wei Su^1,2,3,4Yaoxu Li^1,2,3,4Hongyin Sun^1,2,3,4Baoyin Zhang^1,2,3,4Dejuan Xiang^1,2,3,4Zhongsha Li^1,2,3,4Yuesong Wu^1,2,3,6Jian Sun^1,2,3,4*Mingzhu Yin^1,2,3,4*

• ¹Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou District, Chongqing 404100, China, Chongqing, China
• ²Chongqing University Three Gorges Hospital and Academy for Advanced Interdisciplinary Technology, CQU-Ferenc Krausz Nobel Laureate Scientific Workstation, Chongqing, China, Chongqing, China
• ³Chongqing Technical Innovation Center for Quality Evaluation and Identification of Authentic Medicinal Herbs, Wanzhou District, Chongqing, China, Chongqing, China
• ⁴School of Medicine Chongqing University, Chongqing University, Shapingba District, Chongqing 400030, China, Chongqing, China
• ⁵State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, Hainan 572025, China, Sanya, China
• ⁶Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China., Chengdu, China

Colorectal cancer (CRC) is closely linked to gut microbiota dysbiosis. We synthesize evidence that carcinogenic microbes promote CRC through chronic inflammation, bacterial genotoxins, and metabolic imbalance, highlighting key pathways involving Fusobacterium nucleatum, pks⁺ Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF). Building on these mechanisms, we propose a minimal diagnostic signature that integrates multi-omics with targeted qPCR, and a pathway–therapy– microbiome matching framework to guide individualized treatment. Probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy show promise as adjunctive strategies; however, standardization, safety monitoring, and regulatory readiness remain central hurdles. We advocate a three-step path to clinical implementation—stratified diagnosis, therapy matching, and longitudinal monitoring—supported by spatial multi-omics and AI-driven analytics. This approach aims to operationalize microbiome biology into deployable tools for risk stratification, treatment selection, and surveillance, advancing toward microbiome-informed precision oncology in CRC.