Oral microbiome profiles relate to periodontal disease and brain health - a microbiome network analysis in the Hamburg City Health Study

The relationship between oral microbiome composition and brain health in the general population remains poorly understood. In this study, we inferred a microbiome similarity network based on 16S rRNA sequencing data of crevicular fluid collected from 1,026 participants in the Hamburg City Health Study, which revealed a continuous disease gradient mirroring the microbial pathogenicity spectrum of periodontitis. Leveraging this network, we systematically examined associations between periodontal microbiome profiles and 37 brain health-related phenotypes, including cognitive function, brain structure, mental health, inflammatory biomarkers, diet, vascular risk factors, and demographics. We found that higher abundance of periodontitis-related microbial taxa was linked to poorer cognitive performance, lower cortical thickness and subcortical volumes, and elevated leukocyte counts, after adjusting for covariates. Notably, we identified both, previously known as well as novel microbial associations with brain health phenotypes. These findings advance the understanding of the oral microbiome-brain axis, suggesting mechanistic links between periodontal health and brain function with potential implications for future causal and interventional studies.