Figure 7
From: Nitrate as a potential prebiotic for the oral microbiome

Overview of potential effects of nitrate inside the oral cavity. This graphical summary of the discussion is based on this study and current literature. Nitrate (NO3−) from food, such as vegetables (e.g., leafy greens, beetroots and carrots) and fruits, enters the blood stream and plasma nitrate is concentrated into saliva by sialin transporters in the salivary glands. There is also a direct effect of nitrate when the foods are chewed or pass through the mouth. Nitrate is reduced into nitrite (NO2−) and further to nitric oxide (NO) by denitrifying oral bacteria. Nitric oxide is an antimicrobial molecule that could limit the growth of certain species (e.g., periopathogenic species have been shown to be sensitive to NO) and thereby affecting the composition of oral biofilms. Additionally, at a pH of 5 and lower, acidic decomposition of nitrite to nitric oxide takes place (orange arrow), which could stimulate the antimicrobial effect when the pH drops due to sugar fermentation. Nitrite can also be reduced to ammonia (NH3) by the bacterial Dissimilatory Nitrate Reduction to Ammonium (DNRA) pathway, increasing the local pH. Additionally, nitrate-reducing species can use lactate as a carbon source, which further prevents a drop in pH. Other bacterial enzymes that lead to ammonia production are ureases using urea as a substrate and arginine deiminase system (ADS) enzymes using arginine. Denitrification is more energy efficient than sulfate reduction and, therefore, the presence of nitrate should limit hydrogen sulfide (H2S) production. In our study, we observed an increase of the health-associated genera Neisseria and Rothia, while caries-associated genera Streptococcus, Veillonella and Oribacterium decrease, as well as the anaerobic periodontal diseases- and halitosis-associated genera Porphyromonas, Fusobacterium, Leptotrichia, Prevotella, and Alloprevotella. It should be noted that these genera may also contain health-associated representatives. However, generally, the total abundance of these genera increases in the associated diseases. *assoc. associated genera, ADS arginine deiminase system.