Scientists discover bacterial toxin driving colorectal cancer in younger people

A study has found that the bacterial toxin colibactin is triggering the rates of colorectal cancer among young people. Researchers from the University of California, San Diego, US, explain that the substance is produced by certain Escherichia coli strains that alter DNA.

The genetic mutations were seen to be 3.3 times more common in people under the age of 40 than in those over 70. 

Additionally, scientists note that the mutation patterns were prevalent in countries with high cases of early colorectal cancer, particularly in countries with high early-onset cases.

The finding suggests that bacteria producing colibactin could be silently growing in children’s colons and changing their DNA, setting the conditions for colorectal cancer before symptoms arise.

Rising cases worldwide 

The study, published in Nature, examined 981 patients’ colorectal cancer genomes across 11 countries who had early- and late-onset disease and varying risk levels.

“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,” says study senior author Ludmil Alexandrov, professor in the Shu Chien-Gene Lay Department of Bioengineering and the Department of Cellular and Molecular Medicine at the university.

The study reveals that young people across at least 27 countries are diagnosed with colorectal cancer. For those under 50, the rate has doubled every decade for the past 20 years. 

“When we started this project, we weren’t planning to focus on early-onset colorectal cancer,” comments the study’s 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.”

Although colibactin alters DNA at a young age, research has found that diet plays an integral role in colorectal cancer development.

Scientists have linked alcohol and red or processed meat to increased colorectal cancer risk, while dietary calcium can offer significant protective benefits. Other research has linked the Western diet, which is “dominated” by ultra-processed foods and unhealthy oils, to chronic inflammation that triggers colorectal tumor growth.

Colibactin-related DNA damage may begin in childhood, decades before cancer develops.The health and nutrition advocacy nonprofit Physicians Committee for Responsible Medicine called on the American Cancer Society to recommend a plant-based diet and the reduction of processed red meat as a preventative measure to address rising US colorectal cancer rates.

Early mutations

The cause of these rising colorectal cancer rates has remained unknown since patients often had no family history of the disease, and few risk factors like obesity and hypertension.

The team’s analysis found that colibactin’s damage began early, as evidenced by the timing of each mutational signature identified. This finding aligned with previous studies, which found that the mutations occur within the first ten years of life.

Colibactin-driven mutations make up approximately 15% of APC (gene) driver mutations, and they are some of the earliest DNA changes leading to cancer.

“If someone acquires one of these driver mutations by the time they’re ten years old, they could be decades ahead of schedule for developing colorectal cancer, getting it at age 40 instead of 60,” notes Alexandrov. He also says further research is needed to establish causality.

NIH funding cuts threaten future research

The researchers emphasize the importance of sustained funding to explore questions like: “How are children being exposed to colibactin-producing bacteria, and what can be done to prevent or mitigate that exposure? Are certain environments, diets, or lifestyle behaviors more conducive to colibactin production? How can people find out if they already have these mutations?”

Early-onset colorectal cancer rates have doubled every decade for 20 years.They say there is an ongoing investigation on colibactin and the risk of early-onset colorectal cancer’s correlation, other hypotheses, and exploring whether probiotics could safely eliminate harmful bacterial strains.

“To further investigate our hypotheses and develop safe, ethical interventions, we’re going to need tens of millions of dollars,” says Alexandrov. “This research has important implications for the future health of children globally. Without adequate support, it will be difficult to understand and address the issue fully.”

Cancer Research UK and Cancer Grand Challenges fund the research, but a large portion comes from the US National Institutes of Health (NIH). However, with NIH facing budget cuts, the team worries that their project and others are at risk.

“If NIH funding cuts impact our ability to do this work, that will be, in my opinion, a substantial hit to cancer research not just in the US, but globally,” says Alexandrov. 

“Our funding has allowed us to collaborate with cancer researchers around the world, collecting and analyzing large datasets from patient samples in multiple countries. That kind of scale is what makes discoveries like this possible.”

Meanwhile, the study found increased colorectal cancer prevalence in Argentina, Brazil, Colombia, Russia, and Thailand, suggesting local environmental exposures may also contribute to risk.

“It’s possible that different countries have different unknown causes,” says Díaz-Gay, who is launching a new study phase. “That could open up the potential for targeted, region-specific prevention strategies.”

Alexandrov adds: “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. Sustained investment in this type of research will be critical in the global effort to prevent and treat cancer before it’s too late.”