Cancer mutations can be caused by common gut bacteria, a particular strain of Escherichia coli, induce a unique mutational pattern in human DNA in colon cancer patients.
Genotoxic E.coli contain colibactin which will damage human DNA cells.
This bacteria may be present in a few probiotics.
This bacteria may be present in 1 in 5 adults
Cancer mutations can be caused by common gut bacteria carried by many people. This was demonstrated by researchers from the Hubrecht Institute (KNAW) and Princess Máxima Center in Utrecht, the Netherlands. By exposing cultured human mini-guts to a particular strain of Escherichia coli bacteria, they uncovered that these bacteria induce a unique pattern of mutations in the DNA of human cells. This mutation pattern was also found in the DNA of patients with colon cancer, implying that these mutations were induced by the 'bad' bacteria. It is the first time that researchers establish a direct link between the microbes inhabiting our bodies and the genetic alterations that drive cancer development. This finding may pave the way to prevention of colorectal cancer by pursuing the eradication of harmful bacteria. The results of this research were published in Nature on the 27th of February.
Our body contains at least as many bacterial as human cells. Most of these microbes contribute to a healthy life, while others may cause diseases. Among the bacteria with potentially harmful consequences is a strain of the best-known gut bacterium: Escherichia coli (E. coli). This particular E. coli strain is "genotoxic": it produces a small chemical, called "colibactin," which can damage the DNA of human cells. It has therefore long been suspected that the genotoxic E. coli, which live in the intestines of 1 out of 5 adults, could be harmful to their human hosts. "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" explains Hans Clevers (Hubrecht Institute). "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."
After five months of bacterial exposure, researchers sequenced the DNA of the human cells and studied the number and types of mutations caused by the bacteria. A number of mutational footprint or signatures were found in these specimens.
"More than 5% of colorectal cancer had high levels of the footprint, while we only saw it in less than 0.1% of all other cancers," recalls Jens Puschhof, Only a few other cancers, known to be exposed to the bacteria, such as cancers in the oral cavity and the bladder, also had the footprint. "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."
This study may have direct implications for human health. Individuals may be screened for the presence of these genotoxic bacteria; it is reported that 10-20 percent of people can harbor the 'bad' version of E. coli in their intestines. Antibiotic treatment could eradicate these bacteria early on. In the future it may be possible to catch colorectal cancer development very early or to even prevent tumors from developing
Source: Cayetano Pleguezuelos-Manzano, Jens Puschhof, Axel Rosendahl Huber, Arne van Hoeck, Henry M. Wood, Jason Nomburg, Carino Gurjao, Freek Manders, Guillaume Dalmasso, Paul B. Stege, Fernanda L. Paganelli, Maarten H. Geurts, Joep Beumer, Tomohiro Mizutani, Reinier van der Linden, Stefan van Elst, Janetta Top, Rob J. L. Willems, Marios Giannakis, Richard Bonnet, Phil Quirke, Matthew Meyerson, Edwin Cuppen, Ruben van Boxtel, Hans Clevers. Mutational signature in colorectal cancer caused by genotoxic pks E. coli. Nature, 2020; DOI: 10.1038/s41586-020-2080-8
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