Role of pks + Escherichia coli in colorectal cancer: Mechanisms, clinical evidence, and therapeutic perspective.

Abstract

Colorectal cancer (CRC) is a multifactorial disease influenced by genetic, environmental, and microbial factors. Among gut microbiota, pks+Escherichia coli has emerged as a key contributor to colorectal carcinogenesis through the production of colibactin, a genotoxic secondary metabolite. Colibactin induces DNA damage by forming interstrand crosslinks and promoting replication-associated double-strand breaks, thereby triggering host DNA damage response pathways and genomic instability. Recent advances in genomic profiling have identified distinct mutational signatures, such as SBS88 and ID18, in colorectal tumors, providing molecular evidence of prior colibactin exposure. Notably, emerging data suggest that these signatures are enriched in early-onset CRC, highlighting a potential role for bacterial genotoxins in tumor initiation at younger ages. In parallel, interactions between pks+E. coli and the tumor microenvironment, including inflammation and microbiota dysbiosis, further modulate disease progression. In addition to mechanistic insights, growing attention has focused on translational applications, including the use of microbial markers, exosomes, and miRNA profiles as potential diagnostic and prognostic tools. However, significant challenges remain, including the high prevalence of pks+E. coli among healthy individuals, population variability, and the difficulty of establishing causality from associative data. This review summarizes current evidence on the role of colibactin-producing bacteria in CRC pathogenesis, integrates recent genomic findings, and discusses emerging diagnostic and therapeutic perspectives, while highlighting key limitations and future research directions.