session

85 - Oral Communication
Mechanisms of Disease II
Feb. 26, 2021, 1:45 p.m. - 3:15 p.m., Lausanne

Abstract

3
Dietary omega-3 fatty acid reverses age-associated platelet hyperreactivity through modulation of gut microbiota
S. S. Saeedi Saravi1, 2, N. R. Bonetti1, 2, B. Pugin1, F. Constancias1, L. Pasterk1, S. Gobbato2, A. Akhmedov1, L. Liberale1, T. F. Lüscher1, G. G. Camici1, J. H. Beer2, 1, Presenter: S. S. Saeedi Saravi1, 2 (1Zurich, 2Baden)

Background and Objective
Background: Aging is associated with platelet hyperreactivity, which may contribute to thrombotic events. Aging also affects the gut microbiota and leads to altered metaorganismal metabolites including trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs), which directly contribute to the platelet hyperresponsiveness. Our previous studies have shown that plant-derived omega-3 ɑ-linolenic acid (ALA) confers beneficial anti-thrombotic effects in human and animal studies. Objective: We therefore hypothesized that a long-term ALA-rich diet could reverse age-linked platelet function and thrombosis potential via modulation of gut microbiota in our model of aged mice.
Methods
Methods: 8-12 week old wild-type C57BL/6J mice were fed a specific low (0.03%) or high (7.3%) ALA containing diet for >16 months. Blood samples were then taken for quantification of plasma TMAO levels, flow cytometric analysis of platelet receptors GPIb, GPIIb/IIIa and P-selection, platelet aggregometry (in response to stimulation with agonists ADP, collagen, and TRAP-6), and clot formation on von Willebrand factor (vWF) under high shear rates. In parallel, faecal samples were collected for 16S rRNA metabarcoding and SCFAs (acetate and propionate) analysis.
Results
Results: Our results show that long-term ALA supplementation inhibits aging-linked platelet hyperreactivity, increased platelet aggregation and enhanced clot formation on vWF, likely, through reduction of the abundance of TMAO-producing genera Desulfovibrio and Lachnospiraceae, and inflammation-promoting Clostridiaceae, as well as, restoration of health-promoting Rikenellaceae_RC9_gut group and Intestinimonas. Consistently with our hypothesis on the pathophysiology, ALA-rich diet could also both decline plasma levels of TMAO and increase faecal SCFAs acetate and propionate in aged mice.
Conclusion
Conclusion: Our studies reveal that dietary ALA modulates the aged microbial community towards the young enterotype, which leads to the reversal of the platelet hyperresponsiveness and the subsequent thrombosis risk. Hence, ALA-rich diet can be potentially exploited as a nutritional antithrombotic strategy in the aging.
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