The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally. Beyond established genetic and environmental risk factors, the gut microbiome is now recognized as a pivotal contributor to CRC pathogenesis, progression, and therapeutic response. This review synthesizes current evidence on how dysbiosis and specific pathogenic bacteria—notably Fusobacterium nucleatum (Fn), Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli carrying the polyketide synthase genomic island (pks+ E. coli)—may drive carcinogenesis through chronic inflammation, genotoxic metabolite production, immune evasion, and epigenetic reprogramming. Critically, we explore the microbiome’s dual role in modulating conventional therapies: Fn is linked to chemotherapy resistance and metastasis, while certain commensals may enhance radiotherapy and immunotherapy efficacy. We further evaluate emerging microbiota-targeted strategies, including fecal microbiota tra nsplantation (FMT), probiotics, prebiotics, postbiotics and precision antibiotics, which hold promise for restoring microbial balance and overcoming treatment resistance. By integrating mechanistic insights with clinical evidence, this review provides a foundation for leveraging the microbiome in CRC diagnosis, prognosis, and next-generation therapeutic approaches.