In new work that adds to the growing knowledge of precision heart care, a research team has developed a new atlas of the gut microbiome that highlights the bacteria and metabolites associated with an increased risk of cardiovascular disease.
The atlas, which was published in the European Heart Journal, maps out various metabolic by-products of amino acids linked to cardiovascular disease. It provides important details, including bacteria and metabolites’ routes and possible branching paths.
“The road map generated in the present studies acts as a ‘GPS’ to help guide clinicians and scientists in how to intelligently shift the gut microbiome output into one that makes more beneficial substances,” said study co-author Stanley Hazen, MD, Ph.D., Chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic.
Mapping bacteria and metabolites
Metabolites are the products from the processing of certain molecules known as precursors by bacteria located both in and on the body. These molecules can be found in diet constituents, such as protein, or other metabolized substances.
Researchers began this study honing in on a metabolite known as phenylacetylglutamine (PAG). The precursor of this substance is the amino acid phenylalanine, which is present in many foods from both plant and animal sources.
Previously, the team had found that this substance showed some connection to an increased risk of events such as heart attack or stroke.
In this study, the researchers also probed gut microbial metabolism of the amino acids tyrosine and tryptophan to get a broad view. These molecules share some metabolic pathways in common with phenylalanine.
The Cleveland Clinic team successfully mapped out multiple metabolic by-products linked to cardiovascular disease. Comparisons were made to patient data to measure the risk of disease in two large cohorts, one each in US and Europe.
This study presents vital information on the routes as well as the potential branching paths followed by bacteria and metabolites.
“In addition to PAG, microbes can generate a plethora of other metabolites starting from the same precursor,” said Dr. Ina Nemet, the study’s first author. “This inspired us to investigate these pathways to get a more comprehensive picture on how those metabolites interconnect and are associated with cardiovascular disease.”
A new technique for gauging blood metabolites
Nemet and her colleagues did not stop at finding out other metabolites that are linked to cardiovascular risk. They also developed an improved method for estimating the level of metabolites in the bloodstream.
Existing techniques show a tendency of supplying only relative metabolite levels when compared to other substances. They do not provide absolute amounts, which are crucial for determining a low or high risk.
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This work can go a long way in helping to prevent inadvertent effects of altering the human microbiome. It provides more information about precursors that bacteria produce metabolites from, thus potentially guiding a more helpful metabolite shift to prevent certain conditions.
For example, Nemet noted that microbes will start producing another thing if they are not making phenylacetic acid. It is important to know if the different metabolites have a link to benign or noxious effects to properly guide the development of new therapies, she added. This study has helped in that regard to some extent.
References
Nemet, I., Hazen, S. L., König, M., Haghikia, A., Landmesser, U., & Demuth, I. (2023). Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality. European Heart Journal. https://doi.org/10.1093/eurheartj/ehad333
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