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 evaluate the clinical translational value of fecal metagenomic signatures as non-invasive biomarkers for early polyp detection and for predicting post-polypectomy recurrence, noting that microbial resilience after surgery correlates significantly with long-term outcomes. Furthermore, we discuss current evidence for microbiota-targeted interventions, including dietary prebiotics (e.g., resistant starch), probiotic supplementation, and natural bioactive small-molecule compounds (e.g., berberine), which demonstrate chemopreventive potential through modulation of the bile acid enterohepatic circulation and restoration of epithelial barrier integrity. In conclusion, targeting the gut microbiome offers a paradigm shift from the traditional “resect and surveil” approach toward an integrated “resect, restore, and maintain” strategy for colorectal polyp management. However, distinguishing causality from mere correlation across diverse populations and standardizing microbiota-based diagnostic thresholds remains critical challenges for future large-scale prospective validation.