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

Abstract

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 ( NO 3 TSS ) for each participant. Natural log‐transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on NO 3 TSS in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on NO 3 TSS using modified Poisson regression models. Nitrate‐reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1‐ SD increase in NO 3 TSS , 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. NO 3 TSS was associated with systolic BP only among patients without hypertension; 1‐ SD increase in NO 3 TSS 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.