Multi-omic analysis and platelet function distinguish treatment responses to hydroxytyrosol in cardiovascular risk

Many phenolic compounds, 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 of high-CV risk patients -HT responders and non-responders. The suppression of platelet reactivity and agonist-induced platelet activation observed after HT intervention were measured by CD61/CD62P expression and apoptotic microparticles with flow cytometry. Microbiota analysis revealed that HT treatment significantly increased and decreased the abundance of <i>Ruminiclostridium</i> sp. and <i>Desulfovidrio</i> sp., respectively. Lipid metabolism and proteomic responses were heterogeneous within the two distinct subgroups, associated mainly with thrombotic and hemostatic signals. The metabolomic analysis further confirmed the differentially expressed metabolites within these two subgroups, highlighting improved glutathione metabolism after HT treatment. The omics datasets integration offers a more comprehensive representation of the glutathione and coagulation pathways affected by the HT treatment. Even though the translation of multi-omics technologies into the clinical landscape is slow, the current interventional study provides an overview of their utility in developing novel therapeutic opportunities to prevent CV diseases, such as suppression of platelet reactivity. Registration number of Clinical Trial: NCT06319417.