Bacteria Silently Priming Children for Colorectal Cancer

A common bacterial toxin may be the hidden culprit behind the alarming rise in early-onset colorectal cancer among young adults, according to groundbreaking research published yesterday in Nature.

Scientists have identified a toxin called colibactin, produced by certain strains of E. coli bacteria in the colon, as potentially triggering genetic changes that can lead to cancer decades before symptoms appear.

“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.

Once primarily affecting older adults, colorectal cancer has become increasingly common in people under 50, with rates roughly doubling every decade for the past 20 years. If trends continue, it’s projected to become the leading cause of cancer death among young adults by 2030.

The international team, led by researchers at the University of California San Diego, analyzed 981 colorectal cancer genomes from patients across 11 countries with varying risk levels. They discovered that DNA mutation patterns linked to colibactin were 3.3 times more common in patients diagnosed before age 40 than in those diagnosed after 70.

What makes this finding particularly concerning is how early the damage begins.

“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.”

Young adults with colorectal cancer typically have no family history of the disease and few known risk factors, leaving doctors puzzled about the surge in cases. This study provides the first substantial evidence of a potential environmental cause.

The research team found that colibactin-related mutations account for approximately 15% of what are known as APC driver mutations—some of the earliest genetic alterations that directly promote cancer development.

“When we started this project, we weren’t planning to focus on early-onset colorectal cancer,” said study co-first author Marcos Díaz-Gay, a former postdoctoral researcher in Alexandrov’s lab. “Our original goal was to examine global patterns of colorectal cancer to understand why some countries have much higher rates than others. But as we dug into the data, one of the most interesting and striking findings was how frequently colibactin-related mutations appeared in the early-onset cases.”

The findings also revealed geographic patterns, with certain countries—notably Argentina, Brazil, Colombia, Russia and Thailand—showing increases in specific mutational signatures, suggesting local environmental factors may play a role.

“It’s possible that different countries have different unknown causes,” said Díaz-Gay, who is launching a new phase of the study at the Spanish National Cancer Research Center in Madrid.

The team is now investigating how children are exposed to colibactin-producing bacteria and whether certain diets or lifestyle factors increase risk. They’re also developing early detection tests analyzing stool samples for colibactin-related mutations and exploring whether probiotics could eliminate harmful bacterial strains.

Alexandrov noted broader implications for cancer research: “This reshapes how we think about cancer. It might not be just about what happens in adulthood—cancer could potentially be influenced by events in early life, perhaps even the first few years.”

The study was part of Cancer Grand Challenges team Mutographs, a global effort funded by Cancer Research UK that decodes patterns of DNA mutations caused by environmental exposures and lifestyle behaviors.