NBC News
An intestinal toxin that has been linked to colorectal cancer for more than two decades could be contributing to the strong increase in disease in younger people, according to a historic research published Wednesday in Nature magazine.
Several species of harmful intestinal bacteria, including certain strains of E. coli, Klebsiella pneumoniae and Citrobacter Koseri, produce a toxin called colibactin. Since the mid -2000s, various studies have repeatedly demonstrated that this toxin can cause specific damage to the DNA of colon cells that are difficult to repair and that, over time, they can cause cancer development.
This DNA damage is especially notable in people who developed colorectal cancer at an earlier age, researchers from the University of California said Wednesday in San Diego. The new study sequenced the DNA of colorectal cancer tumors collected from 981 patients from 11 countries around the world and discovered that DNA mutations related to colibactin were 3.3 times more frequent in patients under 40 years, compared to those over 70.
“About 50 % of colorectal cancer types of early appearance in people under 40 presented the distinctive firm of colibactin exposure,” said the main author of the study, Ludmil Alexandrov, a professor of bioengineering and cellular and molecular medicine at the University of California in San Diego.
The finding could have fundamental implications for public health amid the increase in colorectal cancer rates in young people. Two years ago, American society against cancer reported that colorectal cancer diagnoses in patients under 55 had doubled between 1995 and 2019, and that Advanced disease rates now increased approximately 3% each year In people under 50 years.
Christopher Johnston, associate professor and director of Microbial Genomics of the MD Anderson Cancer Center, described the connection with the colibactin as potentially crucial to explain this alarming trend.
“It can be a fundamental piece of the puzzle,” said Johnston, who did not participate in the new research.
According to Alexandrov, the new findings indicate that the harmful effects of colibactin begin in childhood, and that the initial changes in the DNA that lead to the formation of tumors seem to occur during the first decade of life. Changes in lifestyle during the last 40 years may be predisposing more children to have a greater abundance of strains of colibactin -producing bacteria in their intestines.
“There are several plausible hypotheses, including the use of antibiotics in the early stages of life, which can facilitate the establishment of these strains; changes in the diet, such as the increase in consumption of processed foods or the reduction of fiber consumption; the increase in the rates of cesarean birth rates or the reduction of breastfeed Microbial during a critical period of development, “said Alexandrov. “Together, these changes may be tilting the balance towards the acquisition of these microbes in the early stages of life.”
At the same time, Many questions are left unanswered.
Dr. Shuji Ogino, a professor of pathology and epidemiology at Harvard University, said that it is still not clear if some people are simply more susceptible than others for the harmful effects of colibactin on DNA, or if this can be definitively attributed to specific lifestyle patterns.
Colibactin producing microbes Nor are the only bacteria that have been related to colorectal cancer. In recent years, both Ogino and Johnston have published studies that involve another intestinal bacterium, called fusobacterium nucleatum, in the development of the disease. Alexandrov suggested that, although colibactin producing species can cause the initial mutations that drive tumor formation, F. nucleatum can contribute to the development of the disease by allowing the tumor to proliferate and evade the immune system.
However, Johnston said that more research is needed in this area, since the original cause of colorectal cancer could be the result of a combination of microbes and toxins.
“Microbial interactions could amplify these effect,” he said. “For example, in patients with a hereditary colorectal cancer syndrome called family adenomatous polyposis, studies have shown that when Bacteroids Fragilis coexists with E. coli colibactin producer, DNA damage increases significantly.”
Alexandrov said that he and his colleagues plan to develop a non -invasive test in the next two or three years that use stool samples to determine if people have previously been exposed to colibactin -producing bacteria.
“The objective is to identify people with a high risk of developing colorectal cancer of early appearance, ideally before the disease develops,” he said. “We would like these people to undergo periodic controls.”
Given the large amount of tests that continue to appear on the role of colibactin in these diseases, scientists believe that it is also important to explore preventive approaches, such as specific probiotics or vaccines.
“Taking into account the abundance of reproducible tests, specific interventions are now justified that seek to eliminate these concrete microbes“Johnston said.
“Vaccination -based approaches are the next logical step, such as the development of a children’s vaccine, possibly with reinforcements, which generates immune memory against the E. coli colibactin producer,” he said. “The exception here is that it is a long process, which requires examining the incidence of colorectal cancer of early appearance over time in vaccinated people, which would have decades.”
