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 (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.

Keywords: epidemiology; high blood pressure; insulin resistance; nitrate; oral microbiome.

Figure 1

The prevalence (%) and mean relative abundance (%) of the 20 nitrate‐reducing taxa measured in subgingival plaque samples among the 281 participants in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study).

Figure 2

Natural log‐transformed homeostatic model assessment of insulin resistance (HOMA‐IR) values, plasma glucose, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (95% CI) across increasing SD intervals of nitrate‐reducing taxa summary score (NO ₃ TSS). Adjusted for age, sex, race, education, body mass index (BMI), smoking, percentage of probing sites with attachment loss ≥3 mm, and dietary pattern. Note: <−1 SD (n=43); ≥−1 to 0 SD (n=99); ≥0 to 1 SD (n=96); and ≥1 SD (n=43).