Identification of bacterial strains for development of an oral probiotic aimed at increasing nitric oxide bioavailability

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Nitric oxide (NO) plays critical roles in a myriad of cellular and molecular mechanisms regulating physiology and function of various organs and systems. Depletion of NO and its reduced bioavailability contributes to the pathology of several human diseases including anemia, malaria, heart failure, obesity, diabetes and neurodegeneration. Recent reports suggest that oral microbiota regulate NO homeostasis through the action of some bacteria that have the ability to perform reduction of the nutrient anion nitrate to nitrite and NO. Several clinical trials have taken advantage of this nitrate-nitrite-NO cycle employing oral nitrate to deliver NO. However, many individuals do not respond to oral nitrate, and we hypothesize that this is due to a deficiency in nitrate to nitrite converting bacteria. Hence, developing microbiome modulators like probiotics to enhance and/or perform increased nitrate reduction and NO formation can potentially serve as a solution to recover diminished NO levels and bioavailability. The goal of this project is to test the role of oral bacteria in determining the extent of conversion of oral nitrate to plasma nitrite while developing novel human-origin probiotics of nitrate-nitrite-NO formation abilities and determine their adherence potential to colonize and form biofilms in epithelia. In Aim 1 we will use novel, high throughput screening assays to identify candidate bacterial strains with efficient nitrate to nitrite conversion abilities obtained from the oral cavity and characterize these strains. In Aim 2 we will determine the oral cavity colonizing capabilities of the nitrate to nitrite converting bacterial strains. In Aim 3, we will test the role of these bacterial strains’ in determining the extent of conversion of oral nitrate to plasma nitrite in a murine model. Successful completion of these studies could lead to probiotics against human diseases caused by NO homeostasis abrogation.