Microbiota-generated metabolites associated with major CV adverse events

A new study by Ina Nemet and team found a number of gut microbial metabolites that are linked to serious adverse cardiovascular events within three years, suggesting prospective therapeutic targets. The findings of this study were published in European Heart Journal.

Precision microbiome regulation as a cutting-edge therapeutic approach is a fast developing and sought-after objective. In order to pinpoint potential targets for individualized treatment interventions, correlations between systemic gut microbial metabolite levels and incident cardiovascular disease risks were investigated in this investigation.

Sequential subjects undergoing elective diagnostic cardiac evaluation were examined using stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites in two separate cohorts with longitudinal outcome data [US (n = 4,000) and EU (n = 833) cohorts]. Additionally, it was utilized to inhibit the gut microbiota in plasma from people and animals before and after taking a combination of poorly absorbed antibiotics.

The key findings of this study were:

1. Several aromatic amino acid-derived metabolites, at least partially derived from gut bacteria, are associated with an increased risk of incident (3-year) major cardiovascular adverse events (MACE) (myocardial infarction, stroke or death) and any independent mortality of traditional risk factors.

2. The main gut microbiota-derived metabolites associated with incident MACE and worse survival risk are: (i) phenylacetylglutamine and phenylacetylglycine (from phenylalanine); (ii) p-cresol (from tyrosine) giving p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) to give 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan), which gives indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan), which gives indole-3-lactic acid and indole-3-acetylglutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan).

Future research on gut-microbial metabolic outputs important to host cardiovascular health will benefit from the identification of key gut microbiota-generated metabolites derived from aromatic amino acids that are independently related with incident poor cardiovascular outcomes.

Reference:

Nemet, I., Li, X. S., Haghikia, A., Li, L., Wilcox, J., Romano, K. A., Buffa, J. A., Witkowski, M., Demuth, I., König, M., Steinhagen-Thiessen, E., Bäckhed, F., Landmesser, U., & Hazen, S. L. (2023). Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality. European Heart Journal, ehad333. https://doi.org/10.1093/eurheartj/ehad333