Aim This study aimed to examine oral microbial features in the association between tooth loss and cognitive status in older adults from the US population and evaluate the role of oral microbiota in tooth loss and cognition. Methods and Results Eligible 568 participants from the National Health and Nutrition Examination Survey (Nhanes) 2011–2012 were recruited. Oral rinse sampleses were collected, and the 16S ribosomal RNA gene was sequenced. α‐diversity and β‐diversity was analyzed to depict microbiome profile. Mediation models were used to investigate the role of a‐diversity in the association between tooth loss and cognitive function. The co‐occurring group exhibited significantly reduced α‐diversity and distinct β‐diversity compared to CI (cognitive impairment) only group and the control group ( p < 0.001). Differential taxa analysis identified group‑specific microbial signatures, particularly enriched Lactobacillales in the co‐occurring group. Mediation analysis further revealed that observed amplicon sequence variants (ASVs) and phylogenetic diversity significantly affected the association between tooth loss and cognitive decline, whereas evenness indices did not. Conclusion This pioneering study investigated the oral microbiota composition in relation to varying levels of tooth loss and cognitive status. It revealed the complex role of mucosal colonization in both dental and cognitive health, thereby underscoring the need to integrate the oral microbiome into cognitive research.
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