Cardiovascular diseases remain a leading cause of death worldwide, with platelet hyperactivity and subsequent thrombosis playing a pivotal role in these conditions. While intermittent fasting has long been recognized for its metabolic benefits, including improvements in metabolic diseases, weight loss, and even lifespan extension, its effect on platelet activation and thrombosis formation remains less understood.
A recent study by Professor Junbo Ge team at Fudan University unveiled a novel mechanism by which intermittent fasting can significantly reduce the risk of platelet hyperactivity and thrombosis. That is, intermittent fasting elevates levels of the metabolite indole-3-propionic acid (IPA) by modulating gut microbiota (Figure 1), which in turn suppresses platelet activation — a critical factor in cardiovascular events such as heart attacks and strokes.
IPA was previously known as a tryptophan-derived metabolite with anti-inflammatory properties. By integrating clinical data from patients with coronary artery disease and experimental ApoE knockout mice, as well as utilizing metabolomic and transcriptomic analyses, the present study reported a novel role of gut microbiota-derived IPA in modulating platelet activation by binding to the pregnane X receptor (PXR), thereby decreasing the phosphorylation of Src, Lyn, Syk, LAT, PLCγ, and PKC, as well as reducing Ca2+ influx. The findings reveal a previously unknown relationship between dietary patterns and platelet activation and thrombosis, which suggests that nonpharmacological interventions could substantially lower the risk of life-threatening cardiovascular events.
