Highlights •Elevated TMAO levels predict incident risk for thrombotic events in human subjects •TMAO enhances sub-maximal stimulus-dependent platelet activation •Dietary choline, gut microbes, and TMAO are linked to thrombotic potential in vivo •Microbial transplantation shows that thrombosis potential is a transmissible trait
TMAO – gut byproduct of animal-rich diets – encourages over-reactive platelet function, increasing thrombosis risk. In a combination of both clinical studies of over 4,000 patients and animal model studies, Cleveland Clinic researchers have demonstrated – for the first time – that gut microbes alter platelet function and risk of blood clot-related illnesses like heart attack and stroke.
When the nutrient choline –which is abundant in animal products like meat and egg yolk – is ingested, gut microbes play a role in breaking it down and producing the compound TMAO. High levels of TMAO have been linked to heart disease in recent studies. Blood TMAO levels are associated with heightened risk of heart attacks and strokes in humans, even after adjusting for traditional cardiac risk factors, renal function, markers of inflammation, medication use, and cardiovascular disease status.TMAO directly alters platelet function, increasing thrombosis potential.
Stanley Hazen, M.D., Ph.D. said; “The results of the studies suggest potential new therapeutic targets and possible nutritional interventions for preventing cardiovascular events and improving heart health.” This latest discovery further adds to the growing body of data showing a link between TMAO, gut microbes, and heart disease. It also shows lowering TMAO may represent a potential new way to reduce the formation of blood clots, and therefore decrease the risk of cardiovascular events. Heart disease is the No. 1 killer in the world of both men and women.
The link between TMAO, gut microbes and heart disease was first discovered 5 years ago by the team, led by Dr. Hazen. Subsequent studies with both human platelets and animal models confirmed that TMAO makes platelets over-reactive, heightening thrombosis potential and accelerating clotting rates. Enhanced platelet responsiveness and clot formation is the culminating event that causes a heart attack or stroke.
“We have shown that TMAO fundamentally alters calcium signaling within platelets; when TMAO is elevated, platelet responsiveness to known triggers like thrombin, collagen or ADP is heightened,” Hazen said. “In general, there’s a broad range for how quickly different people will form clots. However, across the board, when TMAO is elevated, platelet responsiveness jumps to the hyper-reactive side of normal.”
Microbial transplantation studies showed TMAO production and thrombosis potential are transmissible traits, building on the recent demonstration that atherosclerosis susceptibility similarly can be transmitted from donor to recipient with transfer of gut microbes via TMAO production potential. According to the Centers for Disease Control and Prevention, heart disease kills about 610,000 in the United States annually, accounting for 1 in 4 deaths. http://my.clevelandclinic.org/about-cleveland-clinic/newsroom/releases-videos-newsletters/2016-3-10-cleveland-clinic-study-shows-gut-microbes-influence-platelet-function-heart-attack-stroke http://www.cell.com/cell/abstract/S0092-8674(16)30113-1?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867416301131%3Fshowall%3Dtrue
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