Oral microbiome perturbations link periodontal health to cognitive ageing in a large community cohort

BACKGROUND: Emerging evidence implicates the oral-brain axis in neurodegeneration, yet large community-based studies remain limited. This study aimed to examine associations between periodontal health, oral microbiome, and cognitive performance, and to explore potential biological pathways underlying these relationships. METHODS: We conducted a cross-sectional analysis of 1157 participants from the community-based Taizhou Imaging Study, all of whom underwent comprehensive periodontal examinations, salivary microbiome profiling, and cognitive assessments. Periodontal health and microbiome features were treated as exposures, and cognitive performance as the outcome. Associations between periodontal indices and cognitive scores were assessed using beta regression models adjusted for relevant confounders. Cognition-related microbial features were identified using Multivariate Associations with Linear Models (MaAsLin3), followed by mediation analyses to explore potential pathways linking periodontal health to cognitive function. FINDINGS: Five clinical periodontal indices were found to be inversely associated with cognitive performance. Ten microbial genera (e.g., Haemophilus), 21 functional pathways (e.g., FoxO signalling), and two co-abundance modules, including a Treponema module, were significantly related to cognitive function. Mediation analysis suggested that 11 features, including nitrate-reducing taxa and a Treponema-driven inflammatory module, may partially mediate the relationship between periodontal health and cognition. INTERPRETATION: These community-based findings reveal microbiome-mediated links along the oral-brain axis and highlight periodontal health and oral microbial homoeostasis as potential targets for early prevention of cognitive decline. FUNDING: This work was supported by the National Key R&D Program of China (2023YFC3606300), National Natural Science Foundation of China (82373658), Clinical Research General Project of the Shanghai Municipal Health Committee (202240355), Clinical Research General Project of Shanghai Municipal Health Commission (202440188), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0510000), Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project (2022ZD0211600).