It marks the first time researchers have been able to establish a direct link between microbes living in the body and genetic alterations that can drive cancer and could lead to new treatments for colorectal cancer.
New research shows that a common gut bacteria carried by many people can cause cancer mutations. It marks the first time researchers have been able to establish a direct link between microbes living in the body and genetic alterations that can drive cancer and could lead to new treatments for colorectal cancer.
The research was conducted by scientists from the Hubrecht Institute and Princess Máxima Center in the Netherlands and published in Nature. The research team exposed cultured human mini-guts, organoids, to a particular strain of Escherichia coli bacteria. After five months of bacterial exposure, they sequenced the DNA of the human cells and studied the number and types of mutations caused by the bacteria. The research team verified that the bacteria within the gut induced a pattern of mutation within the cellular structure.
According to the institute, the mutation was found in the DNA of patients with colon cancer, which implies that the mutations were induced by this “bad” bacteria. The researchers believe that the findings from this study could lead the way to the prevention of colorectal cancer by developing a product that could eliminate this harmful bacteria. Hans Clevers of the Hubrecht Institute said the bacteria within the body that is potentially harmful is a strain of Escherichia coli (E. coli). This particular E. coli strain is “genotoxic,” meaning it produces a small chemical, called colibactin, which can damage the DNA of human cells, Clevers said. It is estimated that 20% of adults carry this genotoxic E. coli.
“There are probiotics currently on the market that contain genotoxic strains of E. coli. Some of these probiotics are also used in clinical trials as we speak. These E. coli strains should be critically re-evaluated in the lab. Though they may provide relief for some bodily discomfort in the short term, these probiotics could lead to cancer decades after the treatment,” Clevers said in a statement.
After the research team sequenced the organoids, they revealed the specific mutation pattern. Ruben van Boxtel of the Princess Máxima Center for pediatric oncology said the signatures have great value in determining the causes of cancer and can potentially direct treatment strategies from them. The signature from the E. coli caused “two co-occurring mutational patterns in the DNA of the organoids: the change of an A to any other of the four possible letters of the DNA code, and the loss of a single A in long stretches of A’s.”
Once they established the footprint of genotoxic E. coli, the research team began to look for traces of it in the DNA of cancer patients. They examined more than 5,000 tumors and discovered that more than 5% of colorectal cancer had high levels of the footprint. Less than .1% of other cancers had the particular signature, said Jens Puschhof, one of the researchers. The other cancers that had the signature included cancers of the oral cavity and bladder.
“It is known that E. coli can infect these organs, and we are keen to explore if its genotoxicity may act in other organs beyond the colon. The signature we defined experimentally helps us with this,” Puschhof said in a statement.
Now, the research team wonders if a potential screening for the presence of these genotoxic bacteria could benefit some patients. They speculate that antibiotic treatment could eradicate the bad bacteria and potentially prevent the development of some tumors.
