Bacteriophages as an ecological driver of bacterial carcinogenesis in colorectal cancer

The occurrence and development of colorectal cancer (CRC) are rooted in the complex gut microbiota. Moving beyond the bacteria-centric paradigm, the gut virome, predominantly bacteriophages, may be involved in the transmission of environmental factors to carcinogenic phenotypes, but their ecological functions and mechanisms still lack systematic integration. Based on an ecological perspective, this review summarizes and integrates current evidence on viral ecological imbalance, lysis-lysogeny switching, horizontal gene transfer, metabolic reprogramming, and host immune regulation. We discuss how bacteriophages play an “ecological amplifier” role between environmental disturbances and bacterial oncogenic reprogramming. Existing evidence suggests that environmental stress disrupts the homeostasis of the virome, potentially driving some bacteriophages from a stable lysogenic to a dysbiotic lytic state. This shift may reshape bacterial transcription programs, altering metabolic functions, disrupting microbial interaction networks, and regulating host immune responses. This multi-level amplification is hypothesized to converge to establish a tumor-promoting niche characterized by genotoxic metabolites, chronic inflammation, and barrier dysfunction. Recent human studies have observed enrichment of lytic bacteriophages in the stage of colorectal adenomas, suggesting that they may serve as candidate biomarkers for early events. Consequently, the virome presents a novel landscape for early warning, risk stratification, and ecological intervention of CRC. Within this framework, bacteriophages are not passive companions, but may serve as key mediators between environmental factors and CRC. Future studies should integrate longitudinal human cohorts, functional validation, and safe delivery platforms to advance virome-targeted strategies from concept to clinic.