Four-domain gut metagenomics reveals archaeal-centered cross-kingdom remodeling across coronary artery disease and acute myocardial infarction.

Cardiovascular microbiome research has focused mainly on bacterial taxa and pathways. We profiled stool archaea, bacteria, fungi, and viruses in patients with acute myocardial infarction (AMI) and healthy controls. Paired plasma metabolomics was examined in a subset. An independent angiography-defined cohort included angiographically normal controls, severe coronary artery disease (CAD), and AMI. No archaeal genus remained differentially abundant after multiple-testing correction. In the discovery cohort, archaeal-bacterial correlations were predominantly positive in healthy controls and negative in AMI, while archaeal-fungal rewiring was prominent. The extension cohort identified sign-flip archaeal-virome edges between severe CAD and AMI, while severe CAD showed the lowest archaeal-bacterial connectivity. Plasma metabolomics captured a broad AMI-associated systemic shift. These findings show that gut archaeal signals are expressed through multi-kingdom ecological organization across coronary disease states.