Discovery suggests screening for bug that creates toxin could prevent thousands of cases
The Guardian said:Scientists have raised fresh hopes for preventing bowel cancer after discovering that a common gut bacterium drives genetic mutations that can cause the disease.
Researchers found that a toxin secreted by a particular strain of the microbe E coli creates distinct mutations in DNA, which contribute to an estimated one in 20 bowel cancers in Britain.
The breakthrough suggests that thousands of cases of the disease might be prevented, or at least delayed, by screening for the strain and eradicating the bug in those who test positive. The treatment could involve a course of antibiotics followed by a faecal transplant to re-establish a healthy microbiome.
“W e will be looking at its presence in individuals with and without cancer and whether it helps in bowel cancer screening,” said Philip Quirke, a professor of pathology at Leeds University and a senior researcher on the study. About 20% of the healthy population are thought to carry the bug.
Bowel cancer is the fourth most common cancer in Britain, with 42,000 new cases diagnosed each year. More than half could be prevented by a better diet, foregoing alcohol, quitting smoking and maintaining a healthy weight. While gut microbes have also been implicated in the disease, scientists have struggled to nail down how.
Hans Clevers and others at Hubrecht University in the Netherlands investigated the effects of a toxin called colibactin, which is produced by certain strains of E coli and another gut microbe called Klebsiella pneumoniae. Previous studies have shown that colibactin can damage the DNA in living cells.
The scientists grew tiny pieces of human intestine known as “miniguts” and injected them with colibactin-producing E coli on weekdays for five months. At the end of each week, the miniguts were treated with antibiotics to wipe out the infections. “If we don’t treat them, they fill up with bacteria and explode,” Clevers told the Guardian.
After five months, the researchers extracted DNA from the miniguts and compared the genetic material with that taken from a control group. These had been treated the same way, but with a strain of E Coli that had its colibactin-making machinery disabled.
“What we noticed was a unique mutational signature,” Clevers said. Colibactin gets in among the Gs, Ts, Cs and As on the DNA double helix and binds an A on one strand to an A on the other, the scientists found. The linkage means the DNA cannot be unzipped, effectively rendering it useless. The affected cell tries to mend the glitch but often botches the repair.
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