Exploring the oral microbiome diversity and genus signatures associated with a novel non-invasive metabolic...

To examine the associations between oral microbiome diversity and genus composition with the Zhejiang University Index (ZJU Index) and clinical biomarkers.

We included 2,490 eligible participants from the U.S. National Health and Nutrition Examination Survey (NHANES). Oral microbiome diversity was assessed using alpha and beta diversity, and genus-level analyses were based on abundance transformed using the centered log-ratio (CLR) method to account for compositionality. Weighted logistic regression models were used to assess the corresponding associations. Beta diversity disparities were evaluated through Principal Coordinate Analysis (PCoA) and Permutational Multivariate Analysis of Variance (PERMANOVA).

Alpha diversity metrics were positively correlated with the ZJU Index in males aged 30-44 years (Faith's Phylogenetic Diversity: unadjusted: β = 0.05, 95% CI: 0.006 to 0.094, p = 0.033; Model 1: β = 0.058, 95% CI: 0.011 to 0.104, p = 0.026; Model 2: β = 0.076, 95% CI: 0.032 to 0.120, p = 0.005; Model 3: β = 0.081, 95% CI: 0.035 to 0.128, p = 0.008) and in females aged 60-69 years (Observed ASVs: β = 1.242, 95% CI: 0.345 to 2.139, p = 0.042; Faith's Phylogenetic Diversity: β = 0.097, 95% CI: 0.025 to 0.168, p = 0.045). Significant differences in beta diversity metrics were observed among ZJU Index-defined subgroups (p < 0.05), confirmed with age- and sex-stratified analyses. Genera including Bulleidia, Senegalimassilia, Fretibacterium, and Hungatella exhibited significant associations with the ZJU Index and with clinical biomarkers (triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), insulin, and testosterone).

Higher oral microbiome alpha diversity was associated with higher ZJU Index in certain populations. Beta diversity demonstrated that ZJU Index-defined subgroups differed in oral microbial composition. Specific genera were identified to be significantly associated with the ZJU Index and clinical biomarkers.