Metabolomic profiles of an atherogenic TMAO-dietary pattern among postmenopausal women

We previously identified a dietary pattern (DP) associated with plasma trimethylamine n-oxide (TMAO) and choline, the TMAO-DP, where higher scores represent more atherogenic potential of the diet. The mechanisms linking dietary intake to the presence of choline and TMAO in the plasma, and by which TMAO may influence atherosclerosis in humans require further clarification. The objective was to evaluate associations between the TMAO-DP and metabolomic profiles in postmenopausal women from the Women's Health Initiative (WHI). This cross-sectional analysis used baseline WHI data. Dietary intake was assessed using a modified Block food frequency questionnaire. Liquid chromatography-mass spectrometry was used to measure 446 metabolites from plasma samples. Linear regression models were used to evaluate associations between the TMAO-DP and metabolites. Metabolites associated with the TMAO-DP were first identified in a Discovery Sample (WHI Hormone Trials participants; n = 1117) and then were replicated in an independent sample, the Replication Sample (WHI Observational Study participants; n = 870). Pathway enrichment analysis was used to identify overrepresented metabolic pathways in our set of significant metabolites. There were 132 metabolites associated with the TMAO-DP in the Discovery Sample, and 83 of those were replicated. In the Replication Sample, metabolite classes positively associated with the TMAO-DP included phosphatidylcholine plasmalogen, phosphatidylethanolamine plasmalogen, and acyl carnitine, and the metabolite classes negatively associated included phosphatidylcholine and cholesterol ester. Overrepresented pathways included pathways of lipid metabolism. This study provides insights into the metabolic processes linking dietary intake to TMAO production, and TMAO to atherosclerosis, among postmenopausal women.