Physiological drivers of pks+ E. coli in colorectal cancer.

Colorectal cancer (CRC) is a significant global health challenge, with rising incidence, particularly among individuals under 50. Increasing evidence highlights the gut microbiota as key contributors to CRC development, with certain oncogenic bacteria influencing cancer initiation, progression, and therapy response. Among these is pks+ Escherichia coli, which produces colibactin, a genotoxic compound that induces DNA damage and leaves a distinct mutational signature in healthy individuals and CRC patients. While research has focused on its genotoxic effects, this review examines the kinetics of colibactin-induced mutations and the epithelial and environmental changes that promote E. coli expansion and colibactin exposure. We also explore the broader role of pks+ E. coli in cancer initiation and progression beyond genotoxicity, and discuss potential therapeutic approaches.