The intricate interrelationship between oral health, the number of teeth, oral microbiota, and frailty remains largely unexplored in clinical research. This study aimed to investigate the interrelationship between oral microbiome, the number of teeth, and frailty.

Data from 4518 participants in NHANES 2009–2012 were analyzed. Frailty was measured using the 48-item Frailty Index (FI). Multivariable logistic regression and restricted cubic spline (RCS) evaluated associations between alpha diversity and frailty. Mediation analysis was used to assess the role of number of teeth. The associations between oral microbiome diveristy and mortality were analyzed by Cox regression. Beta diversity was examined with PCoA and PERMANOVA.

The prevalence of frailty was 39.73 %. Univariate analysis showed that alpha diversity indices except for the Simpson index were significantly lower in frailty, and after adjusted for confounders, observed ASVs (adjusted OR: 0.80 [0.73, 0.87], p < 0.001), Faith's PD (adjusted OR: 0.81 [0.74, 0.88], p < 0.001) and Shannon-Weiner index (adjusted OR: 0.88 [0.81, 0.95], p = 0.002) were remained significantly associated with frailty. The reduced number of teeth partially mediated the relationship (for Faith's PD: βindirect = −0.001 [−0.003, 0.000], p = 0.036, proportion: 8.33 % [0.00 %, 37.50 %]; for Shannon-Weiner index, βindirect = −0.007 [−0.013, −0.002], p = 0.007, Proportion = 17.07 % [3.39 %, 65.00 %]). Univariable Cox proportional hazard regression showed that all alpha diversity indices were significantly associated with all-cause mortality in frail population, and in multivariable analysis, Shannon-Weiner index (HR: 0.72 [0.55, 0.94], p = 0.017) and Simpson index (HR: 0.71 [0.60, 0.83], p < 0.001) remained statistically significant. PCoA showed that beta diversity was also significantly associated with frailty.

Lower oral microbiome diversity is associated with higher frailty and mortality. The number of teeth partially mediates this link, emphasizing the importance of oral health in mitigating frailty and promoting healthy aging.