Gut Microbiota Dysbiosis in Colorectal Polyp Formation and Progression: Mechanisms, Biomarkers, and Therapeutic Potentials
Abstract
Colorectal polyps, particularly adenomatous polyps, are well-established precursor lesions for colorectal cancer (CRC). Although endoscopic polypectomy effectively removes visible lesions, the postoperative recurrence rate remains persistently high (ranging from 30% to 40%), highlighting an urgent need to address the underlying systemic microenvironment that fosters polyp emergence. In recent years, accumulating evidence has positioned gut microbiota dysbiosis as a pivotal, modifiable driver in the initiation and malignant transformation of colorectal polyps. This review systematically synthesizes current mechanistic insights into how microbial perturbations contribute to colorectal polypogenesis. We delineate three interconnected pathogenic cascades: (1) direct genotoxicity, primarily mediated by pathogens such as pks+ Escherichia coli and enterotoxigenic Bacteroides fragilis, which induce host DNA double-strand breaks and characteristic mutational signatures; (2) metabolic reprogramming of the intestinal milieu, characterized by an elevation of pro-carcinogenic secondary bile acids (e.g., deoxycholic acid) alongside a depletion of protective short-chain fatty acids, particularly butyrate, thereby activating the Wnt/β-catenin oncogenic pathway; (3) chronic immune microenvironment remodeling, driven by Th17/Treg imbalance and the recruitment of myeloid-derived suppressor cells, which facilitates immune evasion in premalignant niches. Beyond pathogenesis, we critically…
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