These molecules that damage DNA could be the link between colon cancer and inflammatory bowel disease
Scientists have found molecules made by gut bacteria that damage DNA. This may help explain why people with inflammatory bowel disease (IBD) are more likely to get colorectal cancer than those who don’t have IBD.
In a new study which was published Thursday (October 27) in the journal Science, scientists found a type of molecules that damage DNA that had not been known before, which they named it “indolimines.”
Morganella morganii is a type of bacteria that grows in the guts of people with IBD and colorectal cancer. This bacterium makes these molecules.
In lab dish experiments, indolimines broke down DNA, and they also promoted cancer growth in mice with colon cancer.
And scientists found that they could stop mice from getting tumors by stopping M. morganii from making indolimines.
Cynthia Sears, a professor of medicine and oncology at the Johns Hopkins University School of Medicine in Baltimore who was not involved in the study, said that other gut bugs have been linked to IBD and colorectal cancer in the past.
For example, some strains of Escherichia coli are linked to IBD and make a toxin called colibactin that damages DNA and makes tumors grow in mice.
The new study helps us learn more about how other bacteria could be causing these diseases.
Sears said, “We have a lot of evidence, and this is just one more piece, that links the microbiome to colon diseases and colon cancer.”
Long-term, this line of research could lead to screening tools that help doctors figure out which patients have a high chance of getting colon cancer just by taking a sample of their poop.
It could also lead to treatments that keep people from getting sick by lowering the number of cancer-causing bacteria in their guts.
At this point, Sears said, “we know these clinical associations, but we don’t know how to stop them or change them to lower the risk of cancer.”
“We need to find out what the mediators are on a molecular level so that we can bring something to the bedside for patients.”
To find the unknown molecules that damage DNA, researchers first looked for more than 100 different types of gut bacteria in the stools of 11 IBD patients. IBD is a term that includes ulcerative colitis, which causes inflammation and sores in the lining of the colon and rectum, and Crohn’s disease, which causes inflammation in all or part of the digestive tract, most often in the small intestine.
The team grew each strain of bacteria in a lab dish with DNA and found that 18 of the strains damaged the DNA.
From these strains, scientists were able to figure out what molecules the bacteria made and test to see which ones damaged DNA.
In an interesting twist, the damage to the DNA that the researchers saw didn’t match what colibactin does, and the flagged bacteria couldn’t make colibactin.
In their report, the researchers said, “These data suggested the existence of microbiota-derived genotoxins that had not been known before.”
To figure out what some of the unknown genotoxins were, the researchers focused on M. morganii, which had been found in the guts of people with IBD and colon cancer.
Through this work, they not only found the indolimines, but also found the aspartate aminotransferase (aat) gene, which codes for an enzyme that the bacteria need to make them.