Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients

In people with unexplained colorectal polyps, nearly one in three tumor samples shows a specific type of DNA damage pattern that is commonly caused by a bacterial toxin called colibactin, suggesting this bacterium may be involved in causing DNA mutations in some cases.

In patients with unexplained polyps in the colon, those who have a specific DNA damage pattern linked to colibactin are more likely to carry bacteria in their gut that produce colibactin, compared to those without this DNA pattern.

Certain strains of Escherichia coli that produce colibactin cause distinct double-strand breaks in the DNA of cells lining the colon, leading to characteristic mutation patterns known as SBS88 and ID18.

Researchers found that DNA damage patterns linked to a specific bacterial toxin were present in 39% of colorectal tumors from individuals with APC gene variants, compared to 11% in individuals without these tumors. This suggests a statistical relationship between the bacterial toxin and the type of DNA damage observed in these cancers.

In patients with unexplained polyps and specific DNA damage patterns, detecting a bacterial gene in stool along with a unique tumor mutation pattern identifies colibactin exposure in 87% of cases, compared to 25% when only one method is used.

The presence of certain bacterial genes in stool samples does not reliably indicate how much DNA damage is present in colon tumors, meaning the amount of these bacteria alone cannot be used to predict tumor damage levels in individuals.