A toxin released by a strain of E. coli could contribute to the development of bowel cancer, a new study has revealed.
Researchers in The Netherlands, the UK and USA say the toxin causes fingerprints of DNA damage to the cells lining the gut.
With those fingerprints also being seen in bowel cancer tumours, the team says it is the first time a direct link between the bacterial toxin and the genetic changes that drive cancer development has been made.
Writing in Nature, published yesterday (27 February 2020), they say detecting the specific DNA damage in the cells lining the gut could one day enable doctors to identify those at higher risk of the disease and could also be used alongside current bowel cancer screening tests.
Professor Hans Clevers and his team at the Hubrecht Institute, in The Netherlands, focused on colibactin, a strain of e-coli that is more often present in the stool samples of people with bowel cancer compared to healthy people.
Because colibactin can cause DNA damage in cells grown in the lab, the team thought the toxin might do the same to cells lining the gut.
To test their theory, they exposed human intestinal organoids to colibactin-producing E. coli and when they analysed the DNA sequence of the gut cells in the organoids after five months, they found there was about double the DNA damage in them, compared to organoids exposed to ‘regular’ E. coli that did not produce the colibactin.
When the researchers also found that the DNA damage caused by colibactin followed two specific patterns that were unique to the toxin, they analysed the DNA sequences of more than 5500 tumour samples from the UK and Netherlands, with the help of Dr Henry Wood and Professor Philip Quirke from the University of Leeds.
They checked for the two colibactin DNA damage fingerprints in more than 3600 Dutch samples of various cancer types and established that the fingerprints were present in multiple tumours, and much more often in bowel cancers than other cancer types.
They went on to refine their research on bowel cancer tumours specifically, analysing more than 2000 bowel cancer samples from the UK, collected as part of the 100,000 Genomes Project.
The researchers found colibactin fingerprints in 4-5% of patients, which suggests that colibactin-producing E. coli may contribute to 1 in 20 bowel cancer cases in the UK.
Professor Clevers said: "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. 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."
The study is the first major outcome of a £20 million Grand Challenge Cancer Research UK project, which aims to understand how the microbiome impacts on cancer risk, development and treatment.
Pleguezuelos-Manzano C., Puschhof J. et al. 2020. A mutational signature in human colorectal cancer induced by genotoxic pks+ E. coli. Nature 27 February 2020; doi: 10.1038/s41586-020-2080-8
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