Dietary omega-3 fatty acid suppresses age-associated thrombotic potential via gut microbiota modulation
Aging is a strong independent risk factor for the development of cardiovascular diseases, including atherothrombosis, and associates with platelet hyperreactivity and thrombotic events. Aging also contributes to altering the diversity of gut microbiota and related cardiometabolic disease. Previous studies have shown that plant-derived omega-3 ɑ-linolenic acid (ALA) confers beneficial anti-platelet and anti-inflammatory effects in patients with myocardial infarction and sudden cardiac death. We therefore evaluated whether long-term ALA-rich diet beneficially affects age-dependent platelet hyperreactivity and enhanced thrombosis risk, which is mediated by the gut microbiota in aged mice. We showed that ALA supplementation inhibits age-associated platelet hyperreactivity and increased thrombotic potential; this effect is mediated via modulation of the gut microbiota and its metabolites, including trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), and suppression of exacerbated coagulation factors. Collectively, our results reveal a previously unrecognized mechanistic link between dietary ALA, gut microbiota, and age-associated platelet hyperresponsiveness and subsequent thrombotic potential.