Multikingdom oral microbiome interactions in early-onset cryptogenic ischemic stroke

Although knowledge of the role of the oral microbiome in ischemic stroke is steadily increasing, little is known about the multi-kingdom microbiota interactions and their consequences. We enrolled participants from a prospective multicentre case-control study and investigated multi-kingdom microbiome differences using saliva metagenomic datasets (n=308) from young patients diagnosed with cryptogenic ischemic stroke (CIS) and age- and sex-matched stroke-free controls. Differentially abundant taxa were identified using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC2). Functional potential was inferred using HUMANn3. Our findings revealed significant differences in the composition and functional capacity of the oral microbiota associated with CIS. We identified 51 microbial species, including 47 bacterial, 3 viral, and one fungal species associated with CIS in the adjusted model. Co-abundance network analysis highlighted a more intricate microbial network in CIS patients, indicating potential interactions and co-occurrence patterns among microbial species across kingdoms. The results of our metagenomic analysis reflect the complexity of the oral microbiome, with high diversity and multi-kingdom interactions, which may play a role in health and disease.