Examining the Associations Between Oral Nitrate-Reducing Bacteria and Cardiometabolic Outcomes

teeth with plaque, gingivitis
teeth with plaque, gingivitis
A greater quantity of oral nitrate-reducing bacteria was found to be associated with reduced plasma glucose and insulin resistance in young to middle-aged adults.

A greater quantity of oral nitrate-reducing bacteria was found to be associated with reduced plasma glucose and insulin resistance in young to middle-aged adults, as well as a drop in the mean systolic blood pressure (SBP) of normotensive individuals, according to a study published in the Journal of the American Heart Association.

The oral microbiome, via the enterosalivary nitrate-nitrite-nitric oxide (NO) pathway and NO generation, may affect BP and insulin resistance by modulating the bioavailability of systemic NO.

As part of the Oral Infections, Glucose Intolerance, and Insulin Resistance Study (ORIGINS), 281 patients without diabetes mellitus (mean age, 34 years; aged, 20-55; 78% women), comprising 187 (66.6%) normotensive (mean age, 32 years; 82% women) and 93 (33.1%) hypertensive (mean age, 37 years; 72% women) individuals, were enrolled between 2011 and 2013. There were 50 (18%) and 93 (33%) participants who carried diagnoses of prediabetes mellitus and hypertension, respectively, at baseline.

Subgingival dental plaque was used to extract microbial DNA, and 20 nitrate-reducing species were selected a priori for sequencing of the V3-V4 regions of the 16s rRNA gene to assess relative abundances. The summation of the standardized scores of the relative abundance of all the taxa yielded a nitrate-reducing taxa summary score (NO3TSS) specific to each participant.

Multivariable linear regression was used to conduct natural log-transformed homeostatic model assessments (HOMAs) of plasma glucose, insulin resistance, and SBP and diastolic BP on NO3TSS. Modified Poisson regression models were used to conduct a regression analysis of hypertension and prediabetes mellitus prevalences on NO3TSS.

The mean total relative abundance of nitrate-reducing bacteria was 20%. Rothia dentocariosa and Propionibacterium acnes had the highest (7.9%) and lowest (0.0002%) mean relative abundances, respectively. The mean HOMA plasma glucose and insulin resistance for the cohort were 85 mg/dL and 1.75, respectively, and the mean SBP and diastolic BP were 117 and 75 mm Hg, respectively.

After multivariable adjustment for potential confounders (age, race, sex, and smoking status), each 1 standard deviation (SD) NO3TSS increase was associated with reductions of −1.03 mg/dL (95% CI, −1.903 to −0.16 mg/dL) and −0.09 (95% CI, −0.15 to −0.03) in HOMA plasma glucose and HOMA-insulin resistance, respectively. In normotensive patients, an increase in NO3TSS by 1 SD was found to be associated with a −1.53 mm Hg (95% CI, −2.82 to −0.24 mm Hg) change in mean SBP. The prevalence of prediabetes mellitus tended to decrease with increasing NO3TSS levels (0.79; 95% CI, 0.61-1.03).

Study strengths include the use of the latest sequencing techniques, a young cohort relatively free of major cardiometabolic conditions, and robust risk factor data to control for potential confounders.

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Study limitations include its cross-sectional design, the possible inability to identify the full array of relevant nitrate-reducing species, uncertainty regarding the quality of subgingival plaque, the lack of accounting for gut-based pathways, and the inability to control for mouthwash use.

“If this relationship proves to be causal, oral microbial risk factors for cardiometabolic outcomes may be identified, and further research could yield useful treatments that manipulate the oral microbiome to improve cardiometabolic health,” noted the authors.

This research was supported by National Institutes of Health (NIH) grants R00 DE018739, R21 DE022422, and R01 DK102932 to Dr Demmer. This publication was also supported by the National Center for Advancing Translational Sciences, NIH, through grant number UL1TR001873.


Goh CE, Trinh P, Colombo PC, et al. Association between nitrate‐reducing oral bacteria and cardiometabolic outcomes: results from ORIGINS. J Am Heart Assoc. 2019;8(23):e013324.