Gut bacterium could cause bowel cancer, study finds
A common type of bacteria found in the gut could contribute to bowel cancer, according to a new study published in the journal Nature.
A toxin released by a strain of E. coli causes unique patterns or fingerprints of DNA damage to the cells lining the gut, the researchers said. The fingerprints were also seen in bowel cancer tumors, showing a direct link between the bacterial toxin and the genetic changes that drive cancer development.
The team suggests that detecting this specific DNA damage in the cells lining the gut could one day allow doctors to identify people at higher risk of the disease and become used alongside current bowel cancer screening tests. Other bacterial toxins from gut bacteria might have similar effects and the hunt for them is now on as researchers seek to determine whether this mechanism of DNA damage is widespread.
For the study, the researchers, led by Hans Clevers, MD, PhD, from the Hubrecht Institute in Utrecht, Netherlands, focused on one strain of E. coli producing a toxin called colibactin, which is more often present in the stool samples of people with bowel cancer compared to healthy people. Since colibactin can cause DNA damage in cells grown in the lab, they thought the toxin might be doing the same to cells lining the gut.
The research team used human intestinal organoids, miniature replicas of the gut grown in the lab, and exposed them to colibactin-producing E. coli. They analyzed the DNA sequence of the gut cells in the organoids after five months and found about double the DNA damage in them, compared to organoids exposed to regular E. coli that didn't produce the colibactin. The researchers also found that the DNA damage caused by colibactin followed two very specific patterns, which were unique to the toxin.
To determine whether the DNA damage caused by the bacterium played a role in bowel cancer, the researchers then analyzed the DNA sequences of more than 5,500 tumor samples from the United Kingdom and the Netherlands. The researchers checked for the two colibactin DNA damage fingerprints in over 3,600 Dutch samples of various cancer types. The fingerprints were present in multiple tumors, and much more often in bowel cancers than other cancer types.
The researchers then refined their investigation on bowel cancer tumors specifically, and analyzed over 2,000 bowel cancer samples from the U.K., collected as part of the 100,000 Genomes Project run by Genomics England. Among these samples, the colibactin fingerprints were present in 4 to 5 percent of patients. This suggests that colibactin-producing E. coli may contribute to 1 in 20 bowel cancer cases in the U.K. It will be up to further studies to shed light on just how much of a role the toxin could play in these cases, and what other components of the microbiome may be involved in the early stages of bowel cancer.
Further down the line, the researchers say that looking for DNA damage fingerprints like the ones associated with colibactin in the cells of the gut lining could be used to identify those who are at a greater risk of developing the disease.