Abstract
BACKGROUND: The microbiome, especially the gut microbiome, contributes to the regulation, etiology, and pathogenesis of sleep disorder. However, limited evidence regarding the oral microbiome's role in sleep disorder. Therefore, this study aimed to investigate the association between sleep disorder and oral microbial diversity and whether oral microbiota is associated with all-cause mortality in people with sleep disorder. METHODS: The study included 4,729 individuals in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012 and mortality data until 2019. Sleep disorder was assessed by structured questionnaire. The oral microbiome was characterized by 16 S ribosomal RNA gene sequencing. Logistic regression models were conducted to quantify the association of α-diversity with different sleep status controlling for potential confounding variables, and principal coordinate analysis along with permutational multivariate analysis of variance for β-diversity. The association between the oral microbiome and all-cause mortality was assessed using Cox proportional hazard models. RESULTS: The α-diversity showed that a lower number of operational taxonomic units (OTUs) (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = 0.994-0.998), less Faith's phylogenetic diversity (aOR = 0.954, 95% CI = 0.934-0.975), and a lower Shannon-Weiner index (aOR = 0.854, 95% CI = 0.772-0.944) were associated with sleep disorder. β-diversity revealed different oral microbiome communities between the two groups, as measured by the Bray-Curtis dissimilarity (R(2) = 0.358%, P = 0.001), unweighted UniFrac distance (R(2) = 0.450%, P = 0.001) and weighted UniFrac distance (R(2) = 0.709%, P = 0.001). Furthermore, the OTUs (odds ratio [OR] = 0.999; 95% CI = 0.998-0.999; P < 0.05), Faith's phylogenetic diversity (OR = 0.987; 95% CI = 0.975-0.998; P < 0.05), Shannon-Weiner index (OR = 0.924; 95% CI = 0.873-0.979; P < 0.05), and the inverse Simpson index (OR = 0.553; 95% CI = 0.306-0.997; P < 0.05) were all associated with a significant increase in the risk of all-cause death in participants with sleep disorder. CONCLUSIONS: Intra-population richness, inter-population dispersion, and the phylogenetic diversity of the oral microbiome have all been linked to sleep disorder and all-cause mortality. Overall, these results will help to better understand the etiology and pathogenesis of sleep disorder. Further studies are required to determine the mechanisms underlying the role of microbiome in the pathogenesis of sleep disorder.