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

> **NIH NIH R21** · WAKE FOREST UNIVERSITY · 2024 · $223,916

## Abstract

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.

## Key facts

- **NIH application ID:** 10846606
- **Project number:** 5R21DE032197-02
- **Recipient organization:** WAKE FOREST UNIVERSITY
- **Principal Investigator:** DANIEL B KIM-SHAPIRO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $223,916
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846606

## Citation

> US National Institutes of Health, RePORTER application 10846606, Identification of bacterial strains for development of an oral probiotic aimed at increasing nitric oxide bioavailability (5R21DE032197-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10846606. Licensed CC0.

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