Mycobacterium avium Subspecies paratuberculosis and Colorectal Cancer: Putting MAP on the Map

The rising incidence of early-onset colorectal cancer (CRC) remains incompletely explained despite extensive investigation into genetic, environmental and metabolic factors. Emerging evidence suggests that infectious agents may contribute to colorectal carcinogenesis. A recent study by Tehrani et al. demonstrated the presence of Mycobacterium avium subspecies paratuberculosis (MAP) in a majority of colorectal cancer lesions and in approximately half of precancerous lesions, providing a critical epidemiologic anchor. MAP, a zoonotic intracellular pathogen long associated with Crohn's disease, exhibits biological features consistent with inflammation-driven carcinogenesis, including persistence, immune modulation and systemic dissemination. Mechanistically, MAP infection may promote tumorigenesis through chronic mucosal inflammation, epithelial barrier disruption and activation of human endogenous retroviruses (HERVs) linking persistent infection to genomic instability. Detection of MAP in early lesions argues against secondary colonization and supports a potential initiating or promoting role. Within a One Health framework, MAP represents a plausible, pleiotropic and potentially modifiable contributor to CRC. While causality remains unproven, the convergence of epidemiologic association, mechanistic plausibility and early lesion involvement warrants rigorous investigation.