血小板
计算生物学
微生物群
仿形(计算机编程)
代谢组学
肠道微生物群
血小板活化
生物
生物信息学
医学
免疫学
计算机科学
操作系统
作者
Nadira Vadaq,Melanie Schirmer,Rahajeng N. Tunjungputri,Hera Vlamakis,Cecilia Chiriac,Edwin Ardiansyah,Muhammad Hussein Gasem,Leo A. B. Joosten,Philip G. de Groot,Ramnik J. Xavier,Mihai G. Netea,André J. van der Ven,Quirijn de Mast
出处
期刊:Thrombosis and Haemostasis
[Georg Thieme Verlag KG]
日期:2021-06-30
卷期号:122 (04): 529-539
被引量:3
摘要
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.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.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.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.
科研通智能强力驱动
Strongly Powered by AbleSci AI