Colibactin

What it is. Some Escherichia coli carry a stretch of DNA called the pks island, which encodes the enzymes that build colibactin, a compound that alkylates adenine bases and causes double-strand breaks. Human intestinal organoids exposed to pks-positive bacteria by repeated injection into the lumen over five months acquired a distinct mutational signature that organoids exposed to isogenic pks-mutant bacteria did not, and the same signature was found in human cancer genomes, predominantly colorectal ones. That is the first demonstration that a gut bacterium directly causes the mutations in a human cancer rather than merely being associated with it (Pleguezuelos-Manzano 2020).

Why it is now central to the early-onset question. A study of 981 colorectal cancer genomes from 11 countries found the colibactin signatures SBS88 and ID18 carried higher mutation loads in countries with higher colorectal cancer incidence, and found them 3.3 times commoner in people diagnosed before 40 than in those diagnosed after 70. The signatures were imprinted early in the development of the tumour, and about a quarter of the APC driver insertions and deletions in colibactin-positive cases were attributable to ID18, which places the exposure upstream of the adenoma-carcinoma sequence and probably in early life (Nature 2025).

What it does not yet mean. No test, no intervention and no proven route from a strain in the gut to prevention. It is a mechanism with a dose and a timing, which is what a preventable cause looks like before anyone knows how to prevent it, and it is the reason the microbiome is being read as an exposure rather than as a passenger.