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In this original article, Seyed Soheil Saeedi Saravi et al. exploited a lifelong omega-3 fatty acid alpha-linolenic acid (ALA) supplementation approach to prevent ageing-related thrombosis. The authors show that ageing is associated with an increase in the gut microbial metabolite trimethylamine N-oxide (TMAO), and a decrease in short-chain fatty acid (SCFA) acetate, accompanied by heightened thrombotic events, thereby enhancing the susceptibility to the development of atherothrombotic events. Indeed, ALA altered ageing gut microbiota towards a TMA-lowering, acetate-producing, and anti-inflammatory composition that suppressed both platelet hyperreactivity and thrombotic potential. These findings coincided with a significant decrease in inflammatory cytokine release and synthesis of procoagulant factors that may be due to reduced TMAO and increased acetate levels.