The mouth of America: the oral microbiome profile of the US population.

Importance: The oral microbiome is increasingly recognized to play key roles in human health and disease; yet, population-representative characterizations are lacking.

Objective: Characterize the composition, diversity, and correlates of the oral microbiome among US adults.

Design: Cross-sectional population-representative survey.

Setting: The National Health and Nutrition Examination Survey (NHANES, 2009-2012), a stratified multistage probability sample of the US population.

Participants: NHANES participants aged 18-69 years (n=8,237, representing 202,314,000 individuals).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes: Oral microbiome, characterized through 16S rRNA sequencing. Microbiome metrics were alpha diversity (number of observed Amplicon Sequence Variants [ASV], Faith's Phylogenetic diversity, Shannon-Weiner Index, and Simpson Index); beta diversity (unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity); and prevalence and relative abundance at taxonomic levels (phylum through genus). Analyses accounted for the NHANES complex sample design.

Results: Among US adults aged 18-69 years, the oral microbiome encompassed 37 bacterial phyla, 99 classes, 212 orders, 446 families, and 1,219 genera. Five phyla- Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria and six genera- Veillonella, Streptococcus, Prevotella7, Rothia, Actinomyces, and Gemella , were present in nearly all US adults (weighted-prevalence >99%). These genera also were the most abundant, accounting for 65.7% of abundance. Observed ASVs showed a quadratic pattern with age (peak at 30 years), was similar by sex, significantly lower among non-Hispanic White individuals, and increased with higher body mass index (BMI) categories, alcohol use, and periodontal disease severity. All covariates together accounted for a modest proportion of oral microbiome variability, as measured by beta diversity (unweighted UniFrac=8.7%, weighted UniFrac=7.2%, and Bray-Curtis=6.3%). By contrast, relative abundance of a few genera explained a high percentage of variability in beta diversity (weighted UniFrac: Aggregatibacter =22.4%, Lactococcus =21.6%, Haemophilus =18.4%). Prevalence and relative abundance of numerous genera were significantly associated (Bonferroni-corrected Wald-p<0.0002) with age, race and ethnicity, smoking, BMI categories, alcohol use, and periodontal disease severity.

Conclusions: We provide a contemporary reference standard for the oral microbiome of the US adult population. Our results indicate that a few genera were universally present in US adults and a different set of genera explained a high percentage of oral microbiome diversity across the population.