Higher Trimethylamine- N -Oxide Plasma Levels with Increasing Age Are Mediated by Diet and Trimethylamine-Forming Bacteria

• DOI: 10.1128/msystems.00945-21
• Publication Date: 2021-09-14T14:46:56Z
• Authors: Silke Rath; Katharina Rox; Sven Kleine Barde...; Ulf Schminke; Marcus Dörr; Julia Mayerle; Fabian Frost; Markus M. Lerch; André Karch; Mark Brönstrup; Dietmar H. Pieper; Marius Vital
• Keywords: Trimethylamine N-oxide

The gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is linked to an increased risk for cardiovascular diseases. Trimethylamine (TMA), which subsequently oxidized TMAO in the liver, formed by intestinal bacteria via distinct biochemical routes from dietary precursors that are enriched animal product-based foods. To get a full picture of entire process diet > microbiota axis, we quantified potential TMA-forming and plasma metabolites using gene-targeted assays targeted metabolomics on subsample (n = 425) German population-based cohort study. We specifically compared persons reporting daily meat intake with those rarely or never consume meat. While did not predict levels our study, two major bacterial pathways were metabolite's concentration. Furthermore, advancing age was strongly associated TMAO. Construction structural equation model allowed us disentangle different promote higher increasing age, demonstrating, first time, functional role process, where specific food items augmented abundances concentrations. Analyses stratified showed association between carotid intima-media thickness only individuals >65 indicating this group particularly affected metabolite. IMPORTANCE Many studies have investigated link levels, incongruent results, while recently included into analyses. In these studies, taxonomic data recorded good proxy TMA formation, as members various taxa exhibit genes catalyzing reaction, demanding function-based technologies accurate quantification TMA-synthesizing bacteria. Using approach, demonstrated main components leading i.e., bacteria, uncoupled governed same (dietary) factors. Results emphasize all TMA(O) formation should be considered assessment, rejecting simple view diets rich directly lead hazardous compound. results can assist developing strategies reduce elderly, who prone TMAO-associated