Researchers at Harvard have identified how colibactin — a toxin produced by certain gut bacteria — directly damages human DNA in ways long associated with colorectal cancer, according to a new study published in Science.
The work, led by Emily Balskus and Victoria D’Souza, shows that colibactin creates rare and highly toxic DNA inter-strand cross-links, binding both strands of the DNA double helix together. These lesions disrupt normal DNA replication and repair, increasing the likelihood of mutations that can drive cancer development.
Using living bacteria to generate the unstable toxin in real time, the team demonstrated that colibactin preferentially targets adenine- and thymine-rich regions of DNA. Structural analysis revealed that these sequences create a groove ideally shaped and charged to bind the toxin — explaining why colibactin-related mutations appear at specific genomic sites in colorectal tumors.Notably, these mutation patterns are more common in cancers diagnosed in younger patients. Because colibactin-producing E. coli strains are most prevalent in the infant gut microbiome, the findings raise new questions about early-life microbial exposures and the rising incidence of early-onset colorectal cancer.