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

L'Heureux, Joanna E.; Jones, Andrew M.; Vanhatalo, Anni; Blackwell, Jamie R.; Williams, David W.; Smith, Ann; Kelly, James; Winyard, Paul G.; van der Giezen, Mark


Joanna E. L'Heureux

Andrew M. Jones

Anni Vanhatalo

Jamie R. Blackwell

David W. Williams

Ann Smith

James Kelly

Paul G. Winyard

Mark van der Giezen


© 2018 The Author(s) 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.


L'Heureux, J. E., Jones, A. M., Vanhatalo, A., Blackwell, J. R., L’Heureux, J. E., Williams, D. W., …van der Giezen, M. (2018). Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans. Free Radical Biology and Medicine, 124, 21-30.

Journal Article Type Article
Acceptance Date May 21, 2018
Online Publication Date May 25, 2018
Publication Date Aug 20, 2018
Deposit Date Oct 2, 2019
Publicly Available Date Oct 4, 2019
Journal Free Radical Biology and Medicine
Print ISSN 0891-5849
Electronic ISSN 1873-4596
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 124
Pages 21-30
Keywords Physiology (medical); Biochemistry
Public URL
Additional Information This article is maintained by: Elsevier; Article Title: Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans; Journal Title: Free Radical Biology and Medicine; CrossRef DOI link to publisher maintained version:; Content Type: article; Copyright: © 2018 The Author(s). Published by Elsevier Inc.


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