[HTML][HTML] Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk

W Zhu, JC Gregory, E Org, JA Buffa, N Gupta, Z Wang… - Cell, 2016 - cell.com
W Zhu, JC Gregory, E Org, JA Buffa, N Gupta, Z Wang, L Li, X Fu, Y Wu, M Mehrabian…
Cell, 2016cell.com
Normal platelet function is critical to blood hemostasis and maintenance of a closed
circulatory system. Heightened platelet reactivity, however, is associated with
cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut
microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to
platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects
(n> 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk …
Summary
Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.
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