Impact of Gut Microbiota on Colorectal Carcinogenesis and Opportunities for Therapeutic Modulation

Background: Colorectal cancer is a significant global health concern, characterized by increasing incidence and mortality rates, including among younger demographics. Emerging evidence highlights the role of gut microbiota in CRC development, progression, and response to the therapy. Methodology: A narrative review was conducted, incorporating recent preclinical studies, clinical trials, cohort studies, and meta-analyses to examine the relationship between gut microbiota composition, metabolites, and colorectal cancer, as well as microbiota-targeted therapeutic strategies. Results: Colorectal cancer is linked to intestinal dysbiosis, where pro-carcinogenic bacteria (Fusobacterium nucleatum, Bacteroides fragilis) are enriched and beneficial butyrate-producing bacteria (Faecalibacterium, Roseburia, Bifidobacterium) depleted. This leads to impaired short-chain fatty acid production, chronic inflammation, epithelial barrier disruption, and immune and oncogenic pathway modulation. Metagenomic and metabolomic analyses have identified microbial and metabolite signatures that could be useful for early detection, prognosis and predicting therapy response. A plethora of microbiota-targeted interventions have demonstrated promising preclinical and early clinical results, including dietary modulation, probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and emerging strategies such as bacteriophage therapy. These interventions have been shown to improve antitumor immunity, reduce treatment-related toxicity, and potentially enhance therapeutic efficacy. Nevertheless, the presence of inter-study heterogeneity and the paucity of large-scale clinical validation currently serve as significant constraints on their routine implementation. Conclusions: The gut microbiota represents a promising avenue for precision oncology in colorectal cancer. While preclinical and translational studies suggest potential for microbiota-based diagnostics, prognostics, and therapeutic modulation, well-designed, large-scale clinical trials are required to establish efficacy, safety, and standardized implementation.