Abstract
Although the gut microbiome is recognized as crucial for human health, its combined effects with microbial metabolites on acute myocardial infarction (AMI) remain poorly understood. This study investigated gut microbiome composition using 16 S rRNA sequencing and untargeted LC-MS metabolomics profiles from 24 AMI patients and 24 healthy individuals to identify microbial biomarkers, metabolite signatures, and key functional pathways. No significant difference was observed in alpha diversity, whereas beta diversity differed significantly between AMI patients and controls. At the taxonomic level, Bacteroidota, Proteobacteria, Escherichia_Shigella, Collinsella, and Klebsiella were increased, while Firmicutes, Actinobacteriota, and Bifidobacterium were decreased in the AMI group compared with controls. Metabolomic profiling identified seven metabolites with strong discriminatory power for AMI, with area under the curve (AUC) values ranging from 0.91 to 0.99. Among these, S‑adenosyl‑L‑homocysteine, Cyanidin 3‑[6‑(4‑glucosylcoumaryl)sophoroside] 5‑glucoside, and 5‑Methyltetrahydrofolate were found to be upregulated, whereas Prostaglandin J2, Leukotriene A4, and 5‑HEPE were downregulated. Based on these findings, the upregulated metabolites S‑Adenosyl‑L‑homocysteine, Cyanidin 3‑[6‑(4‑glucosylcoumaryl)sophoroside] 5‑glucoside, 5‑Methyltetrahydrofolate, and the downregulated metabolites Prostaglandin J2, Leukotriene A4, and 5‑HEPE represent candidate non‑invasive biomarkers for AMI that warrant further validation. Functional pathway analysis highlighted pronounced disruptions in arginine biosynthesis and the folate-mediated one-carbon metabolism. Spearman correlation analysis showed that specific gut microbial taxa were significantly associated with clinical parameters and metabolites implicated in AMI-related pathways. These findings revealed distinct microbial and metabolic profiles in Chinese patients with AMI compared to healthy controls. Future research should investigate causal mechanisms and evaluate microbiota-targeted approaches for cardiovascular disease prevention and therapy.