MULTI-OMIC ANALYSIS AND PLATELET FUNCTION DISTINGUISH TREATMENT RESPONSES TO HYDROXYTYROSOL IN CARDIOVASCULAR RISK
Many polyphenols, such as hydroxytyrosol (HT), have been recognized for their antioxidant and cardiovascular (CV) health benefits. To address the efficacy of HT, the present study aimed to identify the relevant mechanisms, associated with high-CV risk.  Plasma unbiased multi-omics data were compared among two subgroups -HT responders and non-responders patients- and in a mice model. The suppression of platelet reactivity and agonist-induced platelet activation observed after HT intervention were measured by CD61/CD62P expression and apoptotic microparticles in high-CV risk patients. Microbiota analysis revealed HT treatment significantly increased and decreased the abundance of Ruminiclostridium sp. and Desulfovidrio sp., respectively. Proteomic and metabolomic responses were heterogeneous within two distinct  ? responder and non-responder ?  subgroups, associated mainly with thrombotic and hemostatic signals. Metabolomic analysis further confirmed the differentially expressed metabolites within these two subgroups, highlighting improved glutathione metabolism after HT treatment, and was later validated through the mice study. The correlations between classical CV biomarkers, proteins, and metabolites offer a more comprehensive representation of the glutathione and coagulation pathways affected by HT treatment. Even though the translation of multi-omics technologies into the clinical landscapes is slow, these in vivo studies provide an overview of their utility in developing novel therapeutic strategies to prevent CV diseases and integrate data in the search for novel biomarkers and therapeutic opportunities.