Lifelong dietary omega-3 fatty acid suppresses thrombotic potential through gut microbiota alteration in aged mice

Seyed Soheil Saeedi Saravi; Nicole R Bonetti; Benoit Pugin; Florentin Constancias; Lisa Pasterk; Sara Gobbato; Alexander Akhmedov; Luca Liberale; Thomas F Lüscher; Giovanni G Camici; Jürg H Beer

doi:10.1016/j.isci.2021.102897

Lifelong dietary omega-3 fatty acid suppresses thrombotic potential through gut microbiota alteration in aged mice

iScience. 2021 Jul 22;24(8):102897. doi: 10.1016/j.isci.2021.102897. eCollection 2021 Aug 20.

Authors

Seyed Soheil Saeedi Saravi^{1

2}, Nicole R Bonetti^{1

2}, Benoit Pugin³, Florentin Constancias³, Lisa Pasterk¹, Sara Gobbato², Alexander Akhmedov⁴, Luca Liberale^{4

5}, Thomas F Lüscher^{4

6}, Giovanni G Camici^{4

7

8}, Jürg H Beer^{1

2}

Affiliations

¹ Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland.
² Department of Internal Medicine, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland.
³ Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.
⁴ Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland.
⁵ Department of Internal Medicine, University of Genoa, Genoa, Italy.
⁶ Royal Brompton and Harefield Hospitals and Imperial College, London, UK.
⁷ University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland.
⁸ Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.

Abstract

Aging is a major risk factor for cardiovascular diseases, including thrombotic events. The gut microbiota has been implicated in the development of thrombotic risk. Plant-derived omega-3 fatty acid ɑ-linolenic acid (ALA) confers beneficial anti-platelet and anti-inflammatory effects. Hence, antithrombotic activity elicited by ALA may be partly dependent on its interaction with gut microbiota during aging. Here, we demonstrate that lifelong dietary ALA decreases platelet hyperresponsiveness and thrombus formation in aged mice. These phenotypic changes can be partly attributed to alteration of microbial composition and reduction of its metabolite trimethylamine N-oxide and inflammatory mediators including TNF-α, as well as the upregulated production of short-chain fatty acid acetate. ALA-rich diet also dampens secretion of increased procoagulant factors, tissue factor and plasminogen activator inhibitor-1, in aged mice. Our results suggest long-term ALA supplementation as an attractive, accessible, and well-tolerated nutritional strategy against age-associated platelet hyperreactivity and thrombotic potential.

Keywords: Hematology; Microbiome; Nutrition.