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

Free Radic Biol Med. 2018 Aug 20;124:21-30. doi: 10.1016/j.freeradbiomed.2018.05.078. Epub 2018 May 25.


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.

Keywords: 16S rRNA sequencing; Ageing; Cardiovascular health; Host-microbe symbiosis; Nitrite; Oral nitrate reduction; Prebiotic.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bacteria / drug effects
  • Blood Pressure*
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Homeostasis*
  • Humans
  • Male
  • Microbiota*
  • Middle Aged
  • Nitrates / metabolism
  • Nitric Oxide / metabolism*
  • Nitrites / metabolism
  • RNA, Ribosomal, 16S
  • Retrospective Studies
  • Saliva / drug effects
  • Saliva / metabolism
  • Saliva / microbiology*
  • Vascular Stiffness / drug effects*
  • Vascular Stiffness / physiology
  • Young Adult


  • Nitrates
  • Nitrites
  • RNA, Ribosomal, 16S
  • Nitric Oxide