Childhood bacterial toxin exposure fuels young-onset colorectal cancer epidemic
A bacterial toxin produced by certain strains of Escherichia coli may explain the alarming increase in colorectal cancer among young adults, according to groundbreaking research published in Nature. The study reveals that colibactin exposure in early childhood creates distinct genetic signatures that significantly increase cancer risk before age 50.
Early-life exposure driving premature cancer development
The international research team, led by the University of California San Diego, analysed 981 colorectal cancer genomes from patients across 11 countries with varying disease risk profiles. Their analysis revealed that colibactin-related mutation patterns were 3.3 times more common in adults diagnosed before age 40 compared to those diagnosed after 70.
“These mutation patterns are a kind of historical record in the genome, and they point to early-life exposure to colibactin as a driving force behind early-onset disease,” said study senior author Ludmil Alexandrov, professor at UC San Diego and Deputy Director of Sanford Stem Cell Fitness and Space Medicine Center.
The findings provide a compelling explanation for a concerning public health trend: colorectal cancer incidence in adults under 50 has roughly doubled every decade for the past 20 years. This shift has puzzled medical experts, as young patients often lack traditional risk factors and family history of the disease.
Molecular timing reveals early damage
The team’s molecular analysis demonstrates that colibactin-associated mutations occur early in tumour development, consistent with previous research showing such mutations arise within the first decade of life. Significantly, these mutations account for approximately 15% of APC driver mutations – early genetic alterations that directly promote cancer development.
“If someone acquires one of these driver mutations by the time they’re 10 years old,” Alexandrov explained, “they could be decades ahead of schedule for developing colorectal cancer, getting it at age 40 instead of 60.”
This suggests a troubling scenario: colibactin-producing bacteria may be silently colonising children’s colons and initiating DNA changes years before symptoms appear, potentially setting the stage for early-onset colorectal cancer.
Building on genomic mutation research
This work represents the latest development in an extensive research programme by Alexandrov and colleagues, who specialise in decoding patterns of DNA mutations caused by environmental exposures and lifestyle behaviours. Each factor leaves a distinct genetic fingerprint that can help identify cancer origins.
The study is part of the Mutographs of Cancer – Cancer Research UK Grand Challenge Project, a collaboration between UC San Diego, the International Agency for Research on Cancer (France), and the Wellcome Sanger Institute (UK). The project has previously elucidated mutational processes underlying esophageal, kidney, and head and neck cancers worldwide.
“Every environmental factor or behaviour we study leaves a genomic mark,” said Alexandrov. “Colibactin, we’ve found, is one of those factors.”
Geographic variations suggest additional factors
Beyond the colibactin connection, the research revealed that colorectal cancers from specific countries – particularly Argentina, Brazil, Colombia, Russia and Thailand – showed increases in certain mutational signatures. This suggests local environmental exposures may contribute to cancer risk.
“It’s possible that different countries have different unknown causes,” said study first author Marcos Díaz-Gay, who is launching a new phase of research at the Spanish National Cancer Research Center. “That opens up the potential for targeted, region-specific prevention strategies.”
Future research directions
The findings raise important questions about how children are exposed to colibactin-producing bacteria and what can be done to prevent or mitigate that exposure. The team is investigating several hypotheses while further examining the correlation between colibactin and early-onset colorectal cancer risk.
Ongoing research includes exploring whether probiotics could safely eliminate harmful bacterial strains and developing early detection tests that analyse stool samples for colibactin-related mutations.
Alexandrov noted broader implications from the research: “This reshapes how we think about cancer. It’s not just about what happens in adulthood. It’s about what happens in the first decade of life – maybe even the first few years.”
If current trends continue, colorectal cancer is projected to become the leading cause of cancer-related death among young adults by 2030, underscoring the urgency of understanding and addressing this emerging epidemic.
Reference:
Díaz-Gay, M., et al. (2025). Geographic and age variations in mutational processes in colorectal cancer. Nature. https://doi.org/10.1038/s41586-025-09025-8
