Association Between Nitrate-Reducing Oral Bacteria and Cardiometabolic Outcomes: Results From ORIGINS

Background: The enterosalivary nitrate-nitrite-nitric oxide pathway is an alternative pathway of nitric oxide generation, potentially linking the oral microbiome to insulin resistance and blood pressure (BP). We hypothesized that increased abundance of nitrate-reducing oral bacteria would be associated with lower levels of cardiometabolic risk cross-sectionally. Methods and Results: ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study) enrolled 300 diabetes mellitus–free adults aged 20 to 55 years (mean=34±10 years) (78% women). Microbial DNA was extracted from subgingival dental plaque (n=281) and V3–V4 regions of the 16S rRNA gene were sequenced to measure the relative abundances of 20 a priori–selected taxa with nitrate-reducing capacity. Standardized scores of each taxon's relative abundance were summed, producing a nitrate-reducing taxa summary score (NO₃TSS) for each participant. Natural log-transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on NO₃TSS in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on NO₃TSS using modified Poisson regression models. Nitrate-reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1-SD increase in NO₃TSS, was associated with a −0.09 (95% CI, −0.15 to −0.03) and −1.03 mg/dL (95% CI, −1.903 to −0.16) lower natural log-transformed homeostatic model assessment of insulin resistance and plasma glucose, respectively. NO₃TSS was associated with systolic BP only among patients without hypertension; 1-SD increase in NO₃TSS was associated with −1.53 (95% CI, −2.82 to −0.24) mm Hg lower mean systolic BP. No associations were observed with prediabetes mellitus and hypertension. Conclusions: A higher relative abundance of oral nitrate-reducing bacteria was associated with lower insulin resistance and plasma glucose in the full cohort and with mean systolic BP in participants with normotension.