Colorectal cancer is one of the most common cancers in the world, and scientists have been trying to understand why some people are more likely to develop it than others.
Although diet, lifestyle and genetics all play important roles, researchers have also discovered that bacteria living in the gut may influence cancer risk. Most gut bacteria are helpful, but a few produce harmful substances that can damage the lining of the bowel over time.
A research team led by Johns Hopkins University has now solved a mystery that has challenged scientists for more than 15 years. Their findings were published in the journal Nature. The study explains how a toxin made by a common gut bacterium is able to enter cells in the colon and begin causing damage.
The toxin is called BFT and is produced by certain strains of the bacterium Bacteroides fragilis. This bacterium is found naturally in the intestines of up to one in five healthy people. Most strains are harmless, but some release BFT, which can trigger inflammation and increase the risk of tumour growth.
For many years, researchers knew that BFT damaged an important protective protein called E-cadherin. However, the toxin did not appear to attach directly to E-cadherin, leaving scientists puzzled about how it entered colon cells.
To answer this question, the team used a powerful gene-editing technique called CRISPR. They switched off thousands of genes one by one in colon cells to identify which proteins were essential for the toxin to work. One protein stood out clearly above all the others: claudin-4.
When claudin-4 was removed, the toxin could no longer attach to the cells. As a result, E-cadherin remained healthy and the cells avoided damage. This discovery showed that claudin-4 acts as the doorway that allows the toxin to reach its target.
The researchers confirmed the finding by working with scientists in Spain and the United States. Laboratory experiments showed that BFT and claudin-4 bind tightly together before the toxin begins damaging colon cells. Mouse studies then demonstrated that this interaction is also important inside living animals.
The team also designed an experimental treatment using a soluble version of claudin-4. This acted like a decoy by attracting the toxin away from the bowel lining. In mice, the decoy successfully protected the colon from injury caused by the toxin.
The researchers hope this discovery could eventually lead to medicines that block the toxin before it starts damaging cells. More work is still needed, including studies in people and research to understand the exact three-dimensional structure of the toxin and its receptor.
This study provides an important breakthrough because it identifies the first step that allows this bacterial toxin to harm the colon. A major strength is that the scientists combined genetic testing, laboratory experiments and animal studies to support their conclusions.
However, the findings are still at an early stage, and treatments based on this discovery must be tested carefully in humans before they can become part of routine medical care.
If you care about gut health, please read studies about how probiotics can protect gut health ,and Mycoprotein in diet may reduce risk of bowel cancer and improve gut health.
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