The microbiome, the living world of bacteria, viruses, archaea, fungi and other microorganisms that populate the human intestine, holds some of the keys to the development of colon cancer. The scientific community suspected that it had an impact on the incidence of cases, but the latest research also suggests that it could be crucial in the prognosis of the disease. A group of researchers from the La Paz University Hospital Research Institute (Idipaz) has found a connection between several groups of bacteria and the prognosis of colorectal tumors. “From the results we have obtained, we know that there are two bacteria that worsen the prognosis of patients with localized colorectal cancer and, on the other hand, there is a bacterium that seems to protect against it. So there are some bacteria with different roles, some protective and others increasing the risk,” summarizes Daniel Martínez, oncologist at the Central University Hospital of Asturias and co-author of the study that he presented at the Congress of the Spanish Society of Medical Oncology. Recently held in Barcelona.
For some time now, the scientific community has been intensively studying the intestinal microbiome and is investigating which microbes, how and to what extent they play a role in the development of an intestinal tumor, be it promoting, slowing down or wasting away. For example, a group of scientists at Yale University found that some strains of the bacterium Morganella morganii produce molecules toxic to human DNA (indolimines) and that these substances cause tumors in mice. In a review of the available evidence, researcher Martina Rebersek from the Ljubljana Institute of Oncology in Slovenia explained that the microbial ecosystem of colorectal cancer “has a composition of bacterial strains that is different from that of a healthy intestinal microbiome,” and this includes the presence of strains , which are individually associated with this tumor, such as Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis and Escherichia coli, or also Fusobacterium nucleatum, Parvimonas, Peptostreptococcus, Porphyromonas and Prevotella.
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“There is a lot of study,” admits Martínez (León, 30 years old). But they are still navigating a sea of unknowns. In any case, they are sure that this creature in the digestive tract plays “a fundamental role” in the development of colon cancer: “There are bacteria that cause an inflammatory reaction in human tissue, and as you know, inflammation is related to the deregulation of cells together and promote the development of cancer,” explains the oncologist. Colon cancer is the third most common type of cancer worldwide – around 1.9 million new cases were diagnosed worldwide in 2020 – and the second most common cause of death.
The Idipaz research, presented at the SEOM congress but not yet published in a scientific journal, focused on studying the role of the microbiome in predicting the prognosis of a colorectal tumor. Looking for bacteria in the microbiome that increase the risk of recurrence in certain patients with localized colorectal cancer, researchers analyzed the proteins in tumor samples from 158 stage II and III patients – IV is the most severe – and found that the larger or lower presence of certain bacteria was associated with disease-free survival. “Studying the microbiome in general is very complex because there are trillions of organisms in the digestive tract and everything interacts with each other. Therefore, it is very difficult to know the role of each of them individually. The aim of the study was to integrate these [bacterias] that may have greater weight. One of the results achieved is the development of a prognostic signature [como un puntaje] “Incorporating data from the three that we showed in the study to have the most power helps us identify more or less risk in patients.”
Among these thousands upon thousands of microbes, the suspicious bacteria found in the Idipaz investigation are also old friends of scientists. “Previous studies have shown what role some of them may play in the incidence of colorectal cancer. “This means that we see that a pattern of certain types of bacteria that are more or less at risk is repeated in several studies,” says the oncologist. Those that had a protective profile were those of the genus Bacterioides, and those that increased risk were Fusobacterium and Faecalibacterium.
Daniel Martínez Pérez, oncologist at the Central University Hospital of Asturias. Kike Rincon
Scientists also do not rule out the possibility that there are other important microorganisms for the prognosis of colon cancer. In their study, they only analyzed 15 species of bacteria. “There may be other species that we don’t know about yet,” admits Martínez. And not just bacteria, says Jaime Feliú, head of oncology at La Paz Hospital in Madrid and also responsible for this research: “We are also working to find out whether the virome [la diversidad de virus presentes en el ser humano] “It may also be involved in the development of cancer or even fungal species.”
After this study, Martínez assures that it is now time to “validate the results in another cohort”. “And if they are confirmed, chemotherapy could be modulated more or less intensively depending on the microbiome,” he suspects. However, this still requires a lot of research and clinical trials. If successful, he emphasizes, this prognostic signature could be incorporated into decision-making and “change the way patients are treated.”
Regarding the possibility of modulating the presence of these bacteria within this complex microbiome, for example through possible fecal transplants or other therapeutic approaches, Martínez limits himself to pointing out that everything is being studied. One advance is that there are known risk factors that promote a less healthy or more favorable microbiome for colon cancer. For example: obesity, lack of exercise, unhealthy diet or diabetes. “Obesity and diabetes are known to alter the human gut microbiome, which we call dysbiosis. It is known that these patients with obesity or diabetes have a higher risk of colon cancer, and it appears that there is a common connection with the microbiome, although research is still ongoing.
Nutrition in childhood
Given the rise in colorectal cancer – the World Health Organization estimates that cases will increase by 63% to 3.2 million per year and deaths by 73% (1.6 million deaths per year) by 2040 – researchers are calling for modifiable influences Risk factors, such as diet, from childhood. Especially due to the increase in cases of colorectal cancer, historically linked to age, in younger years: “It is not that it is an epidemic, but we are seeing a slightly higher incidence in young adults,” says Feliú.
The oncologist from La Paz emphasizes the importance of “nutrition in childhood and adolescence, more than after the age of 30”. “And there are more and more fast diets, highly processed foods… and all of that has an influence,” he argues. The doctor recalls a study presented at the American Congress of Oncology (ASCO) that specifically “showed that young adults who developed colorectal cancer had a different microbiome than another older population with colorectal cancer.” “What we don’t know is whether this different microbiome is due to the lifestyle habits they had throughout their childhood that caused this colonization by these germs, or whether it is the other way around and they develop young colon cancers thanks to these germs.” . . “We don’t know if it’s cause-effect or effect-cause.”
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