A bacterium that lives in the intestines singled out as a possible cause of colorectal cancer | Science and technology
A microbe common in the human gut is suspected to play a major role in the development of colorectal cancer, the second deadliest and third most common type in the world, with two million diagnosed cases and one million deaths annually.
A team of scientists from Yale University recently discovered in a group of volunteers that some strains of bacteria Morganella morganii they produce molecules called indolimines that are toxic to human DNA. In the laboratory, researchers have proven that these substances cause tumors in mice. The finding was published in journal Science October 28.
A human being has more bacterial cells (38 trillion) than human cells (30 trillion). However, defecation can reverse the proportion in favor human cells. By this act, in which a third of the microbes are expelled from the colon, a person ceases to be numerically bacterial and becomes fully human. Most of these microorganisms are harmless, or even beneficial, but some can cause disease, explains Noah Palm, lead author of the study, and it is possible that indolimines work on colorectal cancer. However, much more work will be needed to prove that they are indeed the cause.
The lifetime risk of colon cancer is 1 in 23 in men and 1 in 25 in women, according to data from European tumor registries. Common risk factors are age, smoking, alcohol consumption, obesity and a diet low in fruit and high in processed meat. Have inflammatory bowel diseases, such as ulcerative colitis or Crohn’s disease, it also increases the risk.
Palm’s team has developed a new technique that allows the simultaneous study of hundreds of types of microbes and their products. Researchers discovered (previously unknown) indolimines in the strains Morganella morganii in people with inflammatory diseases. However, although there is a higher amount of this bacteria in patients with inflammatory bowel disease or colorectal cancer, it is also present in apparently healthy people. Even the intestinal epithelial cells of healthy individuals show some mutations that can be caused by toxins from these communities of microorganisms, such as indolimines, Palm explains.
Morganella morganii, whose size is one-thousandth of a millimeter, is commonly found in water, soil and the intestines of mammals. It is usually a benign microbe, but it is also associated with urinary tract infections.
Spanish biotechnologist Cayetano Pleguezuelos and his colleagues from the Hubrecht Institute in the Netherlands were the first to show a direct link between the bacteria living in the human digestive system and the genetic changes they cause development of cancer. The researchers saw that the specific strain Escherichia coli it produces a toxic molecule called colibactin that damages the DNA of human cells. This was confirmed in miniature versions of intestinal tissue generated in the laboratory. Their discovery was published in journal Nature On February 27, 2020, as the human race turned its attention to another microorganism: the coronavirus that was spreading around the world from China.
Pleguezuelos welcomes the new work but suggests caution. “Our intestinal microbiota is very complex, with many different types of bacteria, and among them there are mutualistic relationships, symbiosis, negative competition… and many other parameters. Bacteria can produce these toxic compounds in humans, but for some reason they may not be able to reach the intestinal epithelial cells and damage the DNA. These factors are not seen in experiments with mice,” he warns.
The Spanish researcher believes that the new Yale University technique “opens the door to the evaluation of large numbers of bacteria and their ability to damage DNA.” A person weighing 70 kilograms has about 46 kilograms of human cells, according to a study by a team at the Weizmann Institute of Science in Rehovot, Israel. The most difficult are muscle and fat cells. 38 trillion bacteria weigh only about 200 grams, but make up an extremely complex universe. “Their ability to carry out different enzymatic reactions is enormous. And we don’t know most things,” says Pleguezuelos.
The Spanish biotechnologist explains that any agent that damages human DNA causes a specific pattern of mutations called a mutational signature. Pleguezuelos and his colleagues identified the mutational signature of the harmful strains Escherichia coli and found this characteristic trace in more than 5% of colorectal cancer patients analyzed, compared to 0.1% detected in other tumor types. Of course, this figure must be taken with a grain of salt – pending further research on other populations – but it gives an idea of the magnitude of the problem: 5% of the two million annual cases means 100,000 colorectal cancer patients with the mutational signature of these harmful strains Escherichia coli.
Dr. Palm points out that most cases of colorectal cancer occur in people who have no family history. therefore, environmental factors, including the microbiome, play a key role in most cases of colon cancer. However, he explains, it is still impossible to calculate the relative importance of the microbiome compared to other environmental factors.
Although there are currently no specific treatments to prevent microbiome-induced DNA damage, treatments can be developed to neutralize, or even eliminate, these toxin-producing microbes.
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