Abstract
BACKGROUND AND AIMS: Knowledge about the association between oral microbiome diversity within individuals and cardiovascular disease (CVD) and non-CVD mortality is scarce. Besides, variation by sex and racial and ethnic groups, and the potential mediators of these associations remain unclear. We aimed to investigate the associations of oral microbiome alpha diversity with all-cause, CVD, and non-CVD mortality, and the interaction effects of sex and racial and ethnic groups and potential mediators in the associations. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used. RESULTS: Baseline mean ± standard deviation (SD) age was 42.1 ± 15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95 % confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality. CONCLUSIONS: Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.