Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans

Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO₃^-)-nitrite (NO₂^-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO₃^- to NO₂^-. NO (generated from both NO₂^- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO₃^- (12 mmol/d) and placebo supplementation in young (18-22 yrs) and old (70-79 yrs) normotensive humans (n = 18). NO₃^- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (-46%; P < 0.05). After NO₃^-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (-60%) and Veillonella (-65%) were lower than in the placebo condition (all P < 0.05). NO₃^- supplementation increased plasma concentration of NO₂^- and reduced systemic blood pressure in old (70-79 yrs), but not young (18-22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO₂^-] in response to NO₃^- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO₃^-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo.