Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans
van der Giezen, M
Free Radical Biology and Medicine
© 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)
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- (12mmol/d) and placebo supplementation in young (18-22yrs) and old (70-79yrs) 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 (70-79yrs), but not young (18-22yrs), 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.
The Exeter Sequencing Service and Computational Centre are core facilities at the University of Exeter. We are grateful for funding from a Medical Research Council Clinical Infrastructure award (MR/M008924/1), the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), a Wellcome Trust Multi User Equipment Award (WT101650MA) and a BBSRC LOLA award (BB/K003240/1). Data collection on the nine older adults included in this study was supported by the Dunhill Medical Trust (R269/1112).
This is the final version of the article. Available from the publisher via the DOI in this record.
Vol. 124, pp. 21–30
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