2023-07-21 10:44:35
Updated Friday, July 21, 2023 – 10:44
Two metabolites present in the microbiome indicate the presence of precancerous lesions
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People with HIV, especially men who have sex with men, are at increased risk of developing canal. In these patients, early detection of precancerous lesions is essential to prevent the tumor from developing. However, the techniques that are commonly used for this purpose can be greatly improved.
An international team, led by Spanish researchers, has identified two new biomarkers that could significantly improve this detection of cancer precursor lesions (called high-grade squamous intraepithelial lesions) and, therefore, prevent the development of tumors. Details of his work have been published in the journal Nature Medicine.
Specifically, these researchers have discovered that in the anal microbiome there are two metabolites produced by bacteria that directly correlate with the aforementioned intraepithelial lesions.
As they were able to verify, the production of succinyl-coA and cobalamin is increased in the microbiome of patients with precancerous lesions. Therefore, these metabolites may serve as useful biomarkers in clinical practice.
“Our goal is to create a diagnostic kit that allows self-sampling to measure these markers. This would mean a great saving of resources and would increase the accessibility of the diagnosis. The ultimate goal is to improve our ability to diagnose and therefore treat high-grade anal dysplasia more efficiently and effectively,” he explains. Sergio Serranoresearcher at the Ramón y Cajal Health Research Institute (IRYCIS), member of the Infectious Diseases service of the Ramón y Cajal University Hospital in Madrid and first author of the paper.
Researchers from the CIBER of Infectious Diseases, the CSIC, the La Paz Hospital and the Jimnez Díaz Foundation, as well as the Universities of Hohenheim (Germany), Oslo (Norway), Bangor (United Kingdom) and Milan (Italy) have also participated in the research.
To carry out the research, the scientists studied 213 patients, who were already being followed up by anoscopies and anal biopsies as they presented a higher risk of developing anal cancer, a type of cancer that is linked to papillomavirus infection. Using different techniques, they analyzed their anal microbiome, as well as changes in the composition and metabolic activity of the bacteria.
“Our previous investigations led us to believe that we could identify a specific group of bacteria that would indicate the presence of lesions,” Serrano says by email. This was not the case and the team came to believe that it would have to end the investigation without significant results. “However, when analyzing the proteins expressed by the bacteria we discovered something fascinating. We found a powerful statistical signal in certain proteins. In addition, these proteins were linked to two previously described metabolic pathways in bacteria that adapt to cause infections and in tissue-invading tumor cells. In other words, there was a solid biological basis for our findings. These proteins guided us to study two metabolites derived from these metabolic pathways: cobalamin or vitamin B12, which only bacteria can produce; and succinyl CoA, a key compound in the reactions that generate energy in cells”, points out Serrano, who remembers that moment as a true moment “eureka”.
The research suggests that the combination of biomarkers is superior in diagnostic capacity to conventional anal cytologysince it improves the sensitivity, specificity and predictive values.
In addition to trying to develop a diagnostic kit, the researchers want to replicate the results in other populations, study whether these biochemical pathways represent potential treatment targets, and analyze the levels of these metabolites in other cancers originating in epithelia.
“Because of the parallels with that of the cervix, this will be the first one we investigate”advances Serrano.
Regarding the mechanisms involved in the relationship between metabolites and precancerous lesions, the researcher clarifies that “due to the design of the study that we have already carried out, we cannot establish the causes that lead to the induction of these biochemical pathways. But given the functions of the proteins associated with the presence of precancerous lesions, we believe that they are involved in the development of these lesions.”
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