The microbiome-product colibactin hits unique cellular targets mediating host–microbe interaction Original paper

What was reviewed?

This review examined colibactin as a microbiome-derived small molecule that acts beyond a simple “genotoxin,” because it targets both host cells and neighboring bacteria to shape host–microbe and microbe–microbe interactions. The author focused on what makes colibactin clinically and ecologically important: its difficult-to-capture chemistry, its dependence on close contact and specific niches, and its capacity to drive colorectal cancer–relevant DNA injury while simultaneously altering microbial community behavior through DNA damage–linked signaling in bacteria.

Who was reviewed?

Because this was a review, it synthesized findings across multiple studied systems rather than one cohort. It integrated evidence from human-associated Enterobacteriaceae that carry the colibactin gene cluster, mechanistic work in cultured mammalian cells and animal models that demonstrate DNA damage and tumor promotion, and bacterial co-culture and phage–bacteria systems that reveal how colibactin changes bacterial survival and virulence traits. The review also considered contexts such as colitis and inflammation-prone states, because those settings repeatedly modify colibactin effects on both epithelial integrity and microbial ecology.

What were the most important findings?

For a microbiome signatures database, the key major microbial association is functional: the presence of colibactin-producing, gene-cluster–positive Enterobacteriaceae signals a potential genotoxic and ecosystem-shaping capability, not merely a taxonomic shift. The review described colibactin as a DNA-alkylating, crosslinking agent that can generate interstrand crosslinks and downstream double-strand breaks, which activate DNA repair signaling and can push epithelial cells toward cell-cycle arrest, death, or carcinogenesis under permissive conditions. The author also highlighted a major expansion of colibactin’s relevance to microbial community dynamics: colibactin damages bacterial DNA, activates the SOS response, and triggers prophage induction in lysogenic bacteria, which can selectively kill competitors and alter virulence gene expression in pathogens. A parallel microbial signature emerges through resistance biology, because the clbS resistance function and clbS-like genes can spread within microbial communities and blunt colibactin-triggered DNA damage and phage lysis, indicating active ecological “arms races” around this toxin system. The review further reinforced that host barriers matter, noting evidence that an intact mucus layer can reduce colibactin genotoxicity, while inflammation-associated barrier disruption can plausibly increase exposure and amplify downstream harm.

What are the greatest implications of this study/ review?

This review reframes clinical interpretation of colibactin from a narrow colorectal cancer trigger to a broader, context-dependent microbiome effector that can reshape microbial communities and host risk simultaneously. It implies that clinicians and translational teams should interpret colibactin risk through combined signals that include toxin-gene carriage, inflammatory status, and barrier integrity, because these factors influence whether DNA damage becomes biologically meaningful. It also highlights a practical caution: colibactin activity can indirectly worsen outcomes by increasing prophage-driven toxin expression in other pathogens, so the presence of colibactin producers may amplify virulence within a community rather than acting alone. At the same time, the review keeps clinical nuance by describing evidence that colibactin-linked pathways can associate with anti-inflammatory effects in probiotic contexts, which argues for precision approaches that reduce harmful genotoxic pressure without assuming every colibactin-positive strain behaves identically in every host.