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Untargeted Plasma Metabolomics and Gut Microbiome Profiling Provide Novel Insights into the Regulation of Platelet Reactivity in Healthy Individuals

N. Vadaq, M. Schirmer, RN. Tunjungputri, H. Vlamakis, C. Chiriac, E. Ardiansyah, MH. Gasem, LAB. Joosten, PG. de Groot, RJ. Xavier, MG. Netea, AJ. van der Ven, Q. de Mast

. 2022 ; 122 (4) : 529-539. [pub] 20210630

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/bmc22019073

BACKGROUND: Considerable variation exists in platelet reactivity to stimulation among healthy individuals. Various metabolites and metabolic pathways influence platelet reactivity, but a comprehensive overview of these associations is missing. The gut microbiome has a strong influence on the plasma metabolome. Here, we investigated the association of platelet reactivity with results of untargeted plasma metabolomics and gut microbiome profiling. METHODS: We used data from a cohort of 534 healthy adult Dutch volunteers (the 500 Functional Genomics study). Platelet activation and reactivity were measured by the expression of the alpha-granule protein P-selectin and the binding of fibrinogen to the activated integrin αIIbβ3, both in unstimulated blood and after ex vivo stimulation with platelet agonists. Plasma metabolome was measured using an untargeted metabolic profiling approach by quadrupole time-of-flight mass spectrometry. Gut microbiome data were measured by shotgun metagenomic sequencing from stool samples. RESULTS: Untargeted metabolomics yielded 1,979 metabolites, of which 422 were identified to play a role in a human metabolic pathway. Overall, 92/422 (21.8%) metabolites were significantly associated with at least one readout of platelet reactivity. The majority of associations involved lipids, especially members of eicosanoids, including prostaglandins and leukotrienes. Dietary-derived polyphenols were also found to inhibit platelet reactivity. Validation of metabolic pathways with functional microbial profiles revealed two overlapping metabolic pathways ("alanine, aspartate, and glutamate metabolism" and "arginine biosynthesis") that were associated with platelet reactivity. CONCLUSION: This comprehensive overview is an resource for understanding the regulation of platelet reactivity by the plasma metabolome and the possible contribution of the gut microbiota.

Citace poskytuje Crossref.org

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$a BACKGROUND: Considerable variation exists in platelet reactivity to stimulation among healthy individuals. Various metabolites and metabolic pathways influence platelet reactivity, but a comprehensive overview of these associations is missing. The gut microbiome has a strong influence on the plasma metabolome. Here, we investigated the association of platelet reactivity with results of untargeted plasma metabolomics and gut microbiome profiling. METHODS: We used data from a cohort of 534 healthy adult Dutch volunteers (the 500 Functional Genomics study). Platelet activation and reactivity were measured by the expression of the alpha-granule protein P-selectin and the binding of fibrinogen to the activated integrin αIIbβ3, both in unstimulated blood and after ex vivo stimulation with platelet agonists. Plasma metabolome was measured using an untargeted metabolic profiling approach by quadrupole time-of-flight mass spectrometry. Gut microbiome data were measured by shotgun metagenomic sequencing from stool samples. RESULTS: Untargeted metabolomics yielded 1,979 metabolites, of which 422 were identified to play a role in a human metabolic pathway. Overall, 92/422 (21.8%) metabolites were significantly associated with at least one readout of platelet reactivity. The majority of associations involved lipids, especially members of eicosanoids, including prostaglandins and leukotrienes. Dietary-derived polyphenols were also found to inhibit platelet reactivity. Validation of metabolic pathways with functional microbial profiles revealed two overlapping metabolic pathways ("alanine, aspartate, and glutamate metabolism" and "arginine biosynthesis") that were associated with platelet reactivity. CONCLUSION: This comprehensive overview is an resource for understanding the regulation of platelet reactivity by the plasma metabolome and the possible contribution of the gut microbiota.
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$a Vlamakis, Hera $u Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States $u Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, Massachusetts, United States
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$a Chiriac, Cecilia $u National Institute of Research and Development for Biological Sciences, Institute of Biological Research, Cluj-Napoca, Romania $u Department of Aquatic Microbial Ecology, Institute of Hydrobiology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic
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$a Ardiansyah, Edwin $u Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands $u Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
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$a Xavier, Ramnik J $u Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States $u Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, Massachusetts, United States
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