Image by Andre E.X. Brown
New research indicates that gut microbes alter platelet function, which affects the risk of thrombosis and related events 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.
Recent studies have shown that blood TMAO levels are associated with a heightened risk of heart attack and stroke.
The new study, published in Cell, suggests that TMAO encourages hyper-reactive platelet function, thereby increasing the likelihood of thrombosis.
Researchers said this could be the mechanism by which TMAO increases the risk of heart attack and stroke. And these findings reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.
“It is remarkable that gut microbes produce a compound that alters platelet function and thrombotic heart attack and stroke risk,” said study author Stanley Hazen, MD, PhD, of the Cleveland Clinic in Ohio.
“This new link helps explain how diet-induced TMAO generation is mechanistically linked to development of lethal adverse complications of heart disease.”
Dr Hazen and his colleagues first discovered a link between TMAO, gut microbes, and heart disease 5 years ago.
For the current study, the researchers analyzed blood levels of TMAO in more than 4000 patients and saw a significant correlation between higher TMAO and thrombosis potential. This led to the hypothesis that TMAO may directly impact platelet function.
Subsequent studies with both human platelets and animal models confirmed that TMAO makes platelets hyper-reactive, heightening thrombosis potential and accelerating clotting rates.
“We have shown that TMAO fundamentally alters calcium signaling within platelets,” Dr Hazen said. “When TMAO is elevated, platelet responsiveness to known triggers like thrombin, collagen, or ADP is heightened.”
“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.”
Dr Hazen and his colleagues said these results suggest that lowering TMAO—via dietary manipulation, alteration in microbial community with a probiotic or prebiotic, or direct pharmacological inhibition of microbial enzymes involved in TMA production—may be a way to reduce the risk of thrombotic events.
They noted that, unlike current antiplatelet therapies, targeting TMAO would likely reduce platelet hyper-responsiveness to the normal range and not induce impairment in overall platelet function. So the intervention could attenuate pro-thrombotic tendencies without increasing the risk of bleeding complications.
