Does our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics

Abstract

Millions of microbes are found in the human gut, and are collectively referred as the gut microbiota. Recent studies have estimated that the microbiota genome contains 100-fold more genes than the host genome. These microbiota contribute to digestion by processing energy substrates unutilized by the host, with about half of the total genome of the gut microbiota being related to central carbon and amino acid metabolism as well as the biosynthesis of secondary metabolites. Therefore, the gut microbiome and its interaction with the host influences many aspects of health and disease, including the composition of biofluids such as urine and blood plasma. Metabolomics is uniquely suited to capture these functional host-microbe interactions. This review aims at providing an overview of recent metabolomics evidence of gut microbiota-host metabolic interactions with a specific focus on cardiovascular disease and related aspects of the metabolic syndrome. Furthermore, the emphasis is given on the complexities of translating these metabolite signatures as potential clinical biomarkers, as the composition and activity of gut microbiome change with many factors, particularly with diet, with special reference to trimethylamine-oxide.

Keywords: cardiovascular disease; diabetes mellitus; metabolomics; microbiome; obesity; trimethylamine-N-oxide.

Conflict of interest statement

Conflict of Interest Disclosures: None

© 2015 American Heart Association, Inc.

Figures

Figure 1

Choline metabolism: The figure shows key metabolic pathways involved in the degradation of choline and production of urinary amines, in part via the gut microbiome. Key: BHCMT: betaine-homocysteine methyl transferase (EC 2.1.1.5), CA: creatinase (EC 3.5.3.3), CHAT: choline O-acetyltransferase (EC 2.3.1.6), CHCD: Choline dehydrogenase (EC 1.1.99.1), CK: creatine kinase (EC 2.7.3.2), CNA: creatininase (EC 3.5.2.10), DMA: dimethylamine, DMDH: dimethylglycine dehydrogenase (EC 1.5.99.2), FMO3: flavin-containing monoxygenase, MTHFD: methylenetetrahydrofolate dehydrogenase(EC 1.5.1.5), MTHFR:Methylene-tetrahydrofolate reductase (EC 1.5.1.20), PD: phospholipase D (EC 3.1.4.4), PEMT: Phosphatidylethanolaminemethyltransferase (EC 2.1.1.17, 2.1.1.71), SDH: sarcosine dehydrogenase (EC 1.5.99.1), TMA: trimethylamine, TMAO: Trimethylamine-N-oxide. *Bacterial degradation of choline by the gut microbiome.