Scientists finally solve how common gut bacteria triggers colon cancer

Scientists have uncovered a long-sought explanation for how a common gut bacterium can promote the development of colorectal cancer.

The research, published in Nature, focuses on Bacteroides fragilis, a bacterium that can be found in up to 20 percent of healthy people.

While scientists have known for more than 15 years that certain strains of the microbe can contribute to colon tumor formation, exactly how its cancer-linked toxin gains access to colon cells has remained a mystery.

Now, researchers led by Johns Hopkins Medicine have identified the missing link.

They discovered that a toxin produced by the bacterium—known as BFT—must first attach to a protein on the surface of colon cells called claudin-4.

Once attached, the toxin can damage the gut lining and trigger the inflammatory processes that have previously been linked to tumor growth.

Rosario Ligresti, MD, chief of the Gastroenterology Division at Hackensack University Medical Center, said the findings provide one of the clearest explanations yet of how certain gut bacteria may contribute to colorectal cancer.

He said the research strengthens evidence that the relationship is not merely an association, but may represent a direct biological pathway by which bacterial toxins damage the colon lining, trigger inflammation and, over time, increase cancer risk.

“For a long time, we’ve known that certain factors like genetics and diet play a role, but this growing body of research, including the new study, emphasizes that the composition of our gut microbiome is a critical factor in colon health,” Ligresti told Newsweek.

The finding helps explain a puzzle that emerged from earlier research.

Previous studies had shown that BFT damages a protein called E-cadherin, which plays a critical role in maintaining the colon’s protective barrier.

The toxin’s activity was also linked to chronic inflammation and the development of colon tumors.

However, researchers could never determine how the toxin initially attached to cells because it did not appear to bind directly to E-cadherin.

To solve the mystery, the team used a genome-wide CRISPR screening approach, systematically switching off genes in colon cells to identify which ones were necessary for the toxin to work.

The search pinpointed claudin-4 as the crucial receptor. When researchers removed claudin-4, the toxin could no longer bind to cells, preventing the damage cascade from starting.

The discovery has already yielded a potential therapeutic approach. The researchers designed a molecular “decoy” that mimics the claudin-4 receptor.

In animal studies, the decoy intercepted the toxin before it could attach to colon cells, successfully preventing tissue damage.

Colorectal cancer is one of the most common cancers worldwide, and growing evidence suggests the gut microbiome—the trillions of bacteria living in the digestive tract—plays an important role in determining risk.

While many gut microbes are beneficial, some species can promote inflammation or produce compounds that damage DNA and increase the likelihood of cancer development.

Ligresti said people shouldn’t be concerned simply because Bacteroides fragilis is found in the gut, since only certain strains produce the toxin linked to colorectal cancer.

“The key distinction is that only certain strains, known as enterotoxigenic Bacteroides fragilis (ETBF), produce the harmful toxin linked to colorectal cancer,” he said. “The presence of the non-toxin-producing strain is not a cause for concern.”

Maintaining a healthy lifestyle, including eating a fiber-rich diet with plenty of fruits, vegetables and whole grains, limiting red and processed meats, exercising regularly and maintaining a healthy weight are practical steps people can take to support colon health and reduce their overall risk of colorectal cancer, Ligresti said.

The discovery is promising, but researchers told Newsweek it’s still too early to know whether blocking the toxin will help prevent colon cancer in people.

“First we have to develop safe, effective, deployable anti-BFT decoys or drugs and understand, through preclinical and then clinical studies, if these are successful in humans in blocking the action of BFT in the colon,” said senior author Cynthia Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy and professor of medicine at Johns Hopkins.

“The next steps—using as a prevention or adjunctive therapy for the treatment of colon cancer—would require complex, carefully designed studies with clear endpoints to assess efficacy in blocking or attenuating the risk of progressive colon polyps or colon cancer,” she said.

Reference

White, M.T., Wang, K., Zhang, H. et al. A pro-carcinogenic bacterial toxin binds claudin-4 to cleave E-cadherin. Nature 654, 504–512 (2026). https://doi.org/10.1038/s41586-026-10375-0

Contact Newsweek editors on this story: Kara Dolman and Emma Lee-Sang