The trimethylamine/TMAO pathway likely represents only one of many microbe-dependent pathways that will ultimately be linked to cardiovascular disease pathogenesis, and proven to be an important diagnostic and therapeutic target for cardiovascular diseases. Key to the discovery of this pathway were untargeted metabolomics studies in large patient cohorts to demonstrate reproducibility of associations and then, more important, performance of animal model studies to test for causal connections beyond associations. Such approaches will be critical to understanding new microbial participants and pathways linked to the development of atherosclerosis and thrombosis.

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