Low-Molecular-Weight Compounds Produced by the Intestinal Microbiota and Cardiovascular Disease

Abstract

Cardiovascular disease is the main cause of mortality in industrialized countries, with over 500 million people affected worldwide. In this work, the roles of low-molecular-weight metabolites originating from the gut microbiome, such as short-chain fatty acids, hydrogen sulfide, trimethylamine, phenylacetic acid, secondary bile acids, indoles, different gases, neurotransmitters, vitamins, and complex lipids, are discussed in relation to their CVD-promoting or preventing activities. Molecules of mixed microbial and human hepatic origin, such as trimethylamine N-oxide and phenylacetylglutamine, are also presented. Finally, dietary agents with cardioprotective effects, such as probiotics, prebiotics, mono- and poly-unsaturated fatty acids, carotenoids, and polyphenols, are also discussed. A special emphasis is given to their gut microbiota-modulating properties.

Keywords: bile acids; hydrogen sulfide; phenylacetylglutamine; short-chain fatty acid; trimethylamine N-oxide.

Figure 1

Main metabolites that cause promotion (column “CVD Promotion”) and prevention (column “CVD Prevention”) of cardiovascular events.

Figure 2

Overview of TMAO biosynthesis.

Figure 3

Overview of known PAG biosynthetic pathways. L-AAD (L-amino acid deaminase), VOR (α-ketoisovalerate–ferredoxin oxidoreductase), PPFOR (phenylpyruvate–ferredoxin oxidoreductase), PPDC (phenylpyruvate decarboxylase), ACS (acetyl-CoA synthase), AldH (aldehyde dehydrogenase), GLYAT (glutamine phenylacetyltransferase).