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While antiplatelet drugs are used, residual ischemic risk remains. Intermittent fasting (IF), a dietary pattern characterized by alternating periods of eating and fasting, has shown cardiovascular benefits, but its effect on platelet activation is unclear. This study demonstrates that IF inhibits platelet activation and thrombosis in both patients with coronary artery disease and apolipoprotein E (ApoE) knockout (ApoE\u2212\/\u2212) mice, by enhancing intestinal flora production of indole-3-propionic acid (IPA). Mechanistically, elevated IPA in plasma directly attenuates platelet activation by binding to the platelet pregnane X receptor (PXR) and suppressing downstream signaling pathways, including Src\/Lyn\/Syk and LAT\/PLC\u03b3\/PKC\/Ca2+. Importantly, IF alleviates myocardial and cerebral ischemia\/reperfusion injury in ApoE\u2212\/\u2212 mice. These findings suggest that IF mitigates platelet activation and thrombosis risk in coronary atherosclerosis by enhancing intestinal flora production of IPA, which subsequently activates the platelet PXR-related signaling pathways.<\/jats:p>","DOI":"10.1093\/lifemeta\/loaf002","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T14:37:10Z","timestamp":1738161430000},"source":"Crossref","is-referenced-by-count":17,"title":["Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite indole-3-propionate"],"prefix":"10.1093","volume":"4","author":[{"given":"Zhiyong","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]},{"name":"National Clinical Research Center for Interventional Medicine , 180 Fenglin Road, Shanghai 200032 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