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Common gut bacteria may cause bowel cancer

2 March 2020
Appeared in BioNews 1037

A common strain of gut bacteria may drive genetic changes that cause bowel cancer, according to research published in Nature.

The study showed a toxin called colibactin, which is released by a particular strain of E. coli that is part of the normal gut flora (the trillions of bacteria that naturally live in the bowel), can induce specific DNA changes in cells that line the gut. These unique DNA alterations are also found in bowel cancer tumours, demonstrating a direct link between the toxin and cancer.

Professor David Dearnaley, professor of uro-oncology at The Institute of Cancer Research, London, said: 'In recent years, the number of studies looking at the impact of the gut microbiome on diseases like cancer has increased. This exciting study is the first to find a clear relationship between a specific type of gut bacteria and the development of colorectal cancer in a small group of patients.'

The research, funded by a £20 million Cancer Research UK Grand Challenge award and carried out by scientists in the Netherlands, UK and USA, used miniature, lab-grown replicas of the human gut, called organoids, to test the effects of colibactin.

After five months of toxin exposure, the intestinal organoids had double the amount of DNA damage compared to those that were toxin free. The DNA damage was also found to be very specific, as if colibactin left a fingerprint.

In order to assess whether colibactin-induced DNA changes contribute to cancer, the scientists compared the pattern of DNA damage they observed in lab cultures to real life patient tumour samples.

First, they analysed DNA sequences of more than 3600 tumour samples taken from a range of cancer types. They found colibactin changes appeared more often in bowel cancer.

Next, they narrowed their search, using 2000 tumour samples, collected from bowel cancer patients as part of the 100,000 Genomes Project. Among these samples, colibactin-induced DNA changes were present in four to five percent of cases.

'Things like tobacco or UV light are known to cause specific patterns of DNA damage, and these fingerprints can tell us a lot about past exposures that may have caused cancer to start.' Professor Hans Clevers, Grand Challenge co-investigator at the Hubrecht Institute and study lead said. 'But this is the first time we've seen such a distinctive pattern of DNA damage in bowel cancer, which has been caused by a bacterium that lives in our gut.'

More than 42,000 new cases of bowel cancer are diagnosed every year in the UK. Scientists suggest colibactin may contribute to one in 20 (approximately 2100) of these cases.

Exactly how colibactin is triggering or contributing to bowel cancer needs to be studied further, but knowing these specific DNA alterations could help to better identify people at a higher risk of cancer.

John Barnes, patient advocate for Grand Challenge said: 'As a cancer survivor, I don't want others to go through what I've gone through. Catching bowel cancer at an earlier stage while it's still treatable has the potential to save thousands of people's lives. This brilliant research gives me hope that people may not have to suffer from bowel cancer in the future.'

SOURCES & REFERENCES
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