A common bacteria in our gut might be stirring up more trouble than we knew. A study out this week has found evidence that a mutagenic toxin produced by some strains of Escherichia coli can trigger early onset colorectal cancer.
Scientists at the University of California San Diego led the research, published Wednesday in Nature. They found a link between exposure to the toxin, called colibactin, and colorectal cancers more likely to happen in young adults. The findings could help explain why the rate of early onset colorectal cancer has mysteriously risen in recent years, though more research is needed to confirm a causative connection, the researchers say.
Colorectal cancer is the fourth most common cancer, with roughly 150,000 Americans diagnosed with it every year. It’s also the second most leading cause of death by cancer, killing around 50,000 Americans annually.
As with many types of cancer, the incidence and death rate of colorectal cancer has been steadily declining over time. However, this decline isn’t equally distributed, since the incidence of colorectal cancer has been increasing in young and middle-aged adults. According to the American Cancer Society, rates of colorectal cancer among people younger than 50 have increased by 2.4% per year between 2012 and 2021.
Scientists aren’t sure why these cancers have become more common in younger Americans, though some research has pointed the finger at processed foods, higher obesity rates, and other lifestyle factors. But this new study appears to add another suspect.
The study researchers weren’t specifically looking to unravel this mystery; they were more interested in understanding why some parts of the world have higher reported rates of colorectal cancer than others. To do so, they analyzed the genetic signature of colorectal cancers taken from nearly 1,000 people across the world. These samples included people with both late and early onset cancer.
Colibactin is already known to cause mutations in our cells that could raise the risk of cancer, and past studies have linked it to colorectal cancer. But the researchers were surprised to find that colibactin-related mutations were about three times more commonly found in the early onset cancers they studied compared to the late onset cancers. They also found molecular evidence that these colibactin-related mutations tend to show up early in a tumor’s development, suggesting they play a vital role in fueling these cancers.
Coupled with other research showing that colibactin-related mutations often appear in the first ten years of life, the authors argue that this toxin could be a major instigator of early onset colorectal cancer.
“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 senior study author Ludmil Alexandrov, a researchers specializing in cancer genomics at UC San Diego, in a statement from the university.
The researchers note that colibactin may still only be one big piece of a larger puzzle. They note that colibactin-related mutations were rarely found in more rural parts of the world. So it’s possible that other environmental factors like diet or antibiotic use are encouraging the growth of colibactin-producing E. coli bacteria in the gut in places like the U.S. Outside of colibactin, there might be other exposures that could explain higher cancer rates in different countries.
But the team’s findings do provide fertile ground for future research, and could possibly even lead to interventions that could slow or reverse the rise in early onset colorectal cancer. The researchers are already hoping to study whether probiotics might be able to eliminate these more harmful E. coli stains, and they’re trying to develop early detection tests that can screen for colibactin-related mutations.
All of this work, however, is contingent on further funding. And the researchers are quick to note that the U.S. government under President Donald Trump has aggressively limited funding from the National Institutes of Health in recent months—the same sort of funding that might go to important cancer research like theirs.
“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 U.S., but globally,” said 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.”
