The microbiome, a complex community of microorganisms that includes bacteria, viruses, archaea and fungi residing in the human intestine, plays a crucial role in colon cancer. Recent research indicates that the intestinal microbiome also plays a crucial role in predicting the potential for the disease. Researchers at La Paz University Hospital Research Institute (IDIPAZ) in Madrid discovered a correlation between specific groups of bacteria and the prognosis of colorectal tumors. “Based on our findings, it’s evident that there are two bacteria associated with a negative prognosis in patients with localized colorectal cancer. Conversely, we observed one bacteria that exhibits a protective effect against the condition. Therefore, certain bacteria play distinct roles, some of which confer protection while others contribute to increased risk,” said Daniel Martínez, an oncologist at the Central University Hospital of Asturias (Spain) and co-author of the study he recently presented at the annual meeting of the Spanish Society of Medical Oncology (SEOM) in Barcelona.
The scientific community has been studying the intestinal microbiome for some time to understand its role in the development of colorectal tumors. Researchers from Yale University have found that certain strains of bacteria, like Morganella morganii, produce toxic molecules that can cause tumors in mice. A study by Martina Rebersk from Ljubljana Oncology Institute (Slovenia) found that individuals with colorectal cancer have a distinct bacterial ecosystem in their intestines compared to those who are healthy; specific strains like Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Parvimonas, Peptostreptococcus, Porphyromonas and Prevotella.
“A lot of research is underway,” said Martínez, but there are still many unanswered questions. One thing everyone agrees on is that bacteria in the digestive tract plays a crucial role in the development of colorectal cancer. “Certain bacteria can cause inflammation in human tissues which, as you already know, is linked to cell deregulation and increases the risk of cancer,” he said. Colorectal cancer ranks as the third most prevalent cancer globally. In 2020 alone, approximately 1.9 million new cases were diagnosed worldwide, making it the second-deadliest type of cancer.
The IDIPAZ study presented at the annual SEOM meeting, which has not yet been published in a scientific journal, focused on the role of the microbiome in predicting the prognosis of a colorectal tumor. To identify bacteria in the microbiome that raised the risk of relapse in specific patients with localized colorectal cancer, researchers examined the proteins in tumor samples from 158 stage II and III patients (IV being the most advanced stage of cancer). They discovered that the abundance or scarcity of specific bacteria correlated with disease-free survival. “Studying the microbiome is complex due to the vast number of organisms in the digestive tract and their interdependencies,” said Martínez. “Understanding the individual roles of each organism is challenging. The study aimed to identify the most influential bacteria and develop a prognostic signature. By using data from these bacteria, we can detect different levels of risk in patients.”
The bacteria identified by the IDIPAZ researchers are well-known to scientists. “Previous studies have indicated a potential connection between certain bacterial species and the risk of colorectal cancer. Multiple studies show a consistent pattern regarding specific bacteria with varying levels of risk,” said Martínez. The protective profile belonged to the genus Bacterioides, while Fusobacterium and Faecalibacterium increased the risk of cancer.
Since their study only analyzed 15 bacterial species, the IDIPAZ researchers haven’t ruled out the possibility of other microorganisms that play a key role in the prognosis of colon cancer. “It’s possible that there are more species we don’t yet know about,” said Martínez. According to Jaime Feliú, the head of oncology at the La Paz University Hospital in Madrid and co-author of the IDIPAZ study, other factors besides bacteria may play a role. “We are also investigating whether viruses and fungi species can play a role in the development of cancer.”
Martínez says the next step is to “validate the results [of the study] in another cohort. And if they are confirmed, perhaps chemotherapy could be adjusted based on the specific microbiome [of each patient].” However, extensive research and clinical trials are still necessary. If successful, the prognostic signature could be integrated into decision-making and have a significant impact on patient management.
When it comes to modulating the presence of bacteria in the microbiome, such as through stool transplants or other therapies, Martínez acknowledges that research is ongoing. However, there are established risk factors that contribute to an unhealthy or favorable microbiome for colon cancer, including obesity, a sedentary lifestyle, an unhealthy diet and diabetes. “Obesity and diabetes have been found to disrupt the intestinal microbiome, a condition known as dysbiosis. Individuals affected by obesity or diabetes are at a higher risk of developing colorectal cancer, and there appears to be a connection with the microbiome. Ongoing research continues to shed light on this correlation.”
Colorectal cancer is on the rise. The World Health Organization predicts a 63% increase in cases by 2040, with 3.2 million new cases per year and a 73% increase in deaths. In order to address this, researchers emphasize the importance of focusing on modifiable risk factors in children, such as diet. This is particularly important in light of rising rates of colon cancer at younger ages. “It’s not an epidemic, but we do see a little more incidence in young adults,” said Feliú.
Feliú stresses the importance of “good nutrition during childhood and adolescence. All the crash diets and ultra-processed foods are having a notable influence on dietary patterns.” The doctor recalls a study presented at the annual meeting of the American Society of Clinical Oncology (ASCO). “Young adults diagnosed with colon cancer have a distinct microbiome compared to older individuals with the same condition,” said Feliú. “However, it remains unclear whether these differences in the microbiome are a result of lifestyle habits during childhood, leading to colonization by these germs, or if it is the other way around and these germs contribute to the development of colon cancer at a young age. The cause-and-effect relationship is still unknown.”
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