Pathways Linking Oral Bacteria, Nitric Oxide Metabolism, and Health

Nitrate-reducing oral bacteria have gained a lot of interest due to their involvement in nitric oxide (NO) synthesis and its important cardiometabolic outcomes. Consortia of nitrate-metabolizing oral bacteria associated with cardiometabolic health and cognitive function have been recently identified. Longitudinal studies and clinical trials have shown that chronic mouthwash use is associated with increased blood pressure and increased risk for prediabetes/diabetes and hypertension. Concurrently, recent studies are beginning to shed some light on the complexity of nitrate reduction pathways of oral bacteria, such as dissimilatory nitrate reduction to ammonium (DNRA), which converts nitrite into ammonium, and denitrification, which converts nitrite to NO, nitrous oxide, and dinitrogen. These pathways can affect the composition and metabolism of the oral microbiome; consequently, salivary nitrate and nitrite metabolism have been proposed as targets for probiotics and oral health. These pathways could also affect systemic NO levels because NO generated through denitrification can be oxidized back to nitrite in the saliva, thus facilitating flux along the NO₃^--NO₂^--NO pathway, while DNRA converts nitrite to ammonium, leading to reduced NO. It is, therefore, important to understand which pathway predominates under different oral environmental conditions, since the clinical consequences could be different for oral and systemic health. Recent studies show that oral hygiene measures such as tongue cleaning and dietary nitrate are likely to favor denitrifying bacteria such as Neisseria, which are linked with better cardiometabolic health. A vast body of literature demonstrates that redox potential, carbon-to-nitrate ratio, and nitrate-to-nitrite ratio are key environmental drivers of the competing denitrification and DNRA pathways in various natural and artificial ecosystems. Based on this information, a novel behavioral and microbial model for nitric oxide metabolism and health is proposed, which links lifestyle factors with oral and systemic health through NO metabolism.