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Mini-guts expose that common gut bacteria secretes carcinogen

Thursday, 30 April

Cancer mutations in the colon can be caused by common gut bacteria that produce the carcinogen colibactin. This was demonstrated by researchers from Hubrecht Institute (KNAW) and Princess Máxima Center in Utrecht in the Netherlands. The results of this research were published in Nature.

By exposing cultured human mini-guts (organoids) to a particular strain of Escherichia coli bacteria (pks+ E. coli), they revealed that these bacteria induce a unique pattern of mutations in the DNA of human gut cells. This mutation pattern was also found in the DNA of patients with colon cancer, implying that these mutations were induced by these genotoxic 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.


Schematic representation of the injection of bacteria into the lumen of an organoid, and a fluorescent microscopy image of such an organoid. Human intestinal organoid (green) filled with labelled bacteria (blue). Credit: Cayetano Pleguezuelos-Manzano, Jens Puschhof, Axel Rosendahl Huber, ©Hubrecht Institute.

Damage in the dish

Cancer cells are driven by specific DNA mutations, which allow these cells to grow into a tumor. Exposure to UV light or smoking can directly cause DNA damage, which induces mutations and thus increase the chance that normal cells transform into cancers. But until now, it was unknown that the bacteria in our gut can similarly induce cancer mutations in cells through their DNA damaging effects. 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.

An early warning

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.

Video: Cayetano Pleguezuelos-Manzano, Jens Puschhof and Axel Rosendahl Huber explain their research on genotoxic E. coli bacteria. Credit: DEMCON | nymus 3D and Melanie Fremery, ©Hubrecht Institute.

Read the full article on the website of Hubrecht Institute.

Source: NOCI, Hubrecht Institute

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