Gut virome alterations in AMI pathogenesis

Background Atherosclerotic plaque rupture and coronary thrombosis are key causes of acute myocardial infarction (AMI), but recent evidence suggests that gut microbiota, particularly viral dysbiosis, may also contribute to its pathogenesis. Most research has focused on bacteria, with limited exploration of the gut virome. This study investigates gut virome alterations in AMI patients and their interactions with bacteria and metabolites. Purpose This study aimed to: (1) characterize gut virome changes in AMI patients, (2) investigate the interactions between gut viruses, bacteria, and host metabolites, and (3) explore potential mechanisms through which viral dysbiosis may contribute to AMI pathogenesis. Methods A prospective study was conducted on 38 patients with acute myocardial infarction (AMI) and were compared to a control group of 47 individuals (24 healthy and 23 with stable coronary artery disease). Fecal samples were collected from all participants, and metagenomic sequencing was performed to identify viral and bacterial species. Non-targeted metabolomic analysis was conducted using liquid chromatography-mass spectrometry (LC-MS). Correlations between viral taxa, bacterial populations, metabolites, and clinical parameters were assessed using Spearman correlation. Results AMI patients showed significant alterations in gut virome composition compared to controls, including an increase in s_uncultured_crAssphage and Erwinia_virus_Wellington. These viruses were associated with a disruption of beneficial bacterial populations, such as Faecalibacterium prausnitzii and Roseburia faecis, leading to gut dysbiosis. Metabolomic profiling revealed four upregulated metabolites (propylparaben, guanidinosuccinic acid, sphinganine, benzenebutanoic acid) and four downregulated metabolites (ecdysone, SPH(d17:1), 4-hydroxy-2-methylquinoline, inosine). Correlations between viral taxa and clinical indicators suggested that viral dysbiosis contributes to systemic inflammation, dysregulated lipid metabolism, and worsened cardiac function in AMI patients. Conclusion This study reveals that viral dysbiosis in the gut is associated with alterations in gut bacterial populations and metabolic pathways in AMI patients. While these findings suggest a potential role for viral dysbiosis in AMI pathogenesis, further research is required to establish causality and investigate the potential for virome-targeted therapeutic interventions.study protocol