Windows of Opportunity for Genotoxic E. coli in Colorectal Cancer Initiation.

Authors

Jarryd Michael Boath, Luigi Lukas Nardella, Jens Puschhof

Published in

Journal of applied microbiology. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Polyketide synthase-positive Escherichia coli (pks+ E. coli) has attracted significant attention following the discovery that its genotoxic metabolite, colibactin, imprints distinct mutational signatures in intestinal epithelial cells that are detectable in ∼12% of colorectal cancer (CRC) cases. Although these signatures are present in established tumors, growing evidence suggests that colibactin acts early in tumorigenesis, positioning pks+ E. coli as a potential contributor to CRC initiation. Mechanistic studies show that colibactin genotoxicity is highly context dependent and requires direct epithelial contact-a condition that is typically restricted in the healthy adult intestine. Here, we propose that colibactin mutagenesis occurs during discrete temporal windows when host barriers and microbial ecology transiently permit pks+ E. coli-epithelial interactions. These windows may arise during inflammatory disease states or early-life gut development, two contexts that share disrupted epithelial defenses, expansion of facultative anaerobes, and dynamic oxygen gradients. Defining such permissive states will be essential for establishing causal links between pks+ E. coli exposure and CRC initiation and may reveal opportunities for prevention by targeting microbial colonization during critical periods of susceptibility.

PMID:
42530560
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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