Gut Microbe-Generated Trimethylamine N -Oxide From Dietary Choline Is Prothrombotic in Subjects

We previously showed gut microbial production of trimethylamine N -oxide (TMAO) from dietary nutrients like choline, lecithin, and L -carnitine is linked to the development of cardiovascular diseases.1–3 We also recently reported that plasma TMAO levels are associated with incident thrombotic event risk in subjects, and that TMAO both enhances platelet responsiveness to multiple agonists by augmenting stimulus-dependent Ca2+ signaling and heightens thrombosis potential in animal models.4 Specifically, a role for TMAO and gut microbiota in transmitting heightened thrombosis potential in vivo was supported by both direct TMAO infusion and microbial transplantation studies.4 A Western diet, rich in choline, is associated with heightened thrombosis risk; however, the effect of dietary choline on TMAO and platelet hyperresponsiveness in human subjects has not yet been reported.We prospectively recruited healthy vegans/vegetarians (n=8) and omnivores (n=10) with no preceding (1-month) history of antibiotics or probiotics. This single-center study was approved by the Cleveland Clinic Institutional Review Board. After informed consent, subjects (46±5 years of age, …