Multiomics reveals gut dysbiosis links to fatty acid dysmetabolism in early phase of acute myocardial infarction

Abstract

Background:Acute myocardial infarction (AMI) remains a major cause of death, with limited understanding of its early risk stratification. While late-stage AMI has recognized associations with gut microbiome disturbances, the connection to eAMI is less explored.Methods:Using metabolomics and metagenomics, we analyzed 56 samples, comprising 30 eAMI patients (within 12 hours of onset) and 26 age- and gender-matched healthy controls, to discern the influence of gut microbes and their metabolites.Results:We found the eAMI plasma is dominated by increased long-chain fatty acids (LCFAs), 14 of which provide differentiating power of eAMI patients from HCs. Multiomics analysis reveals up to 70% of the variance in LCFAs of eAMI patients can be explained by altered gut microbiome. Higher-resolution profiling of gut bacterial species demonstrated that bacterial structural variations are mechanistically linked to LCFAs dysregulation. Byin silicomolecular docking andin vitrothrombogenic assay in isolated human platelets, we highlighted that eAMI-associated LCFAs contribute to platelet aggregation, a driving factor for AMI initiation.Conclusions:LCFAs hold significant potential as early biomarkers of AMI and gut microbiome contributes to altered LCFAs in eAMI. Further studies are imperative to expand upon these observations to better leverage LCFAs as a potential biomarker for eAMI and as a therapeutic target for inhibition of platelet aggregation in eAMI.