Gut Microbial Associations to Plasma Metabolites Linked to Cardiovascular Phenotypes and Risk: A Cross-Sectional Study

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVD), but its functional links to host metabolism and immunity in relation to CVD development remain unclear.Objective: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts. Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based Lifelines-DEEP cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, gender and BMI, the gut microbiome could explain up to 11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a...