Subgingival microbiota composition is associated with brain health in the general population-the PAROMIND study.

BACKGROUND: Periodontitis has gained attention as a key factor associated with cognitive decline and Alzheimer's dementia. However, the relationship between periodontitis-related oral microbiota shifts and brain health in the general population remains unclear. METHODS: We investigated the oral microbiome-brain axis in 1026 participants from the population-based PAROMIND Study. Using 16S rRNA gene amplicon sequencing of subgingival crevicular fluid, we inferred via topological data analysis a microbiota similarity network. This network, which distills the complex high-dimensional data into an interpretable map of microbial similarity, revealed a continuous disease gradient mirroring the microbial pathogenicity spectrum, from taxa of low periodontal pathogenicity (e.g., Streptococcus) to periodontitis-associated taxa (e.g., Porphyromonas, Fusobacterium). Leveraging this network, we systematically examined associations between periodontal microbiota profiles and 40 brain health-related phenotypes, including cognition, brain structure, mental health, inflammatory biomarkers, diet, vascular risk factors, and demographics. FINDINGS: Higher abundance of periodontitis-related bacterial taxa was associated with poorer cognitive performance, elevated leucocyte counts, and lower MIND diet adherence after covariate adjustment. Complementary forward model selection analysis supported the links to cognitive performance and inflammation, and additionally identified a significant association with brain structure (cortical thickness and subcortical volume). We identified associations with both established genera (Porphyromonas) and taxa not previously implicated in brain health (Fretibacterium, Tannerella, Dialister). INTERPRETATION: These findings from a large cohort advance the understanding of the oral microbiome-brain axis, highlighting specific microbial profiles linked to subclinical cognitive, structural, and inflammatory brain health markers. By demonstrating these links in a non-demented population, our study suggests that monitoring the oral microbiome could inform early risk assessment for cognitive decline, positioning periodontal health as an accessible target for early intervention strategies. FUNDING: Deutsche Forschungsgemeinschaft.