# Oral Microbiome, Nitric oxide Metabolism, and Oral and Cardiometabolic Health

> **NIH NIH R01** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2020 · $597,321

## Abstract

The oral microbiome has been gaining a lot of attention as a key player in nitric oxide (NO) metabolism, and
accordingly in cardiometabolic health. Commensal oral bacteria reduce exogenous (dietary) and endogenous
nitrate to nitrite, which is converted to NO, a signaling molecule that regulates vascular tone, inflammation and
insulin sensitivity. Randomized clinical trials have shown that eliminating the oral microbial flora through the use
of antiseptic mouthwash decreases systemic NO bioavailability with concomitant loss of insulin sensitivity and
increased blood pressure. Nitrite can also be further reduced by oral bacteria into inorganic nitrogen compounds,
such as ammonia via Dissimilatory Nitrate Reduction to Ammonia (DNRA) pathway, which can play important
biological roles in oral health; these pathways could also impact systemic NO bioavailability. Our recent
publication from the San Juan Overweight Adults Longitudinal Study (SOALS) shows that regular use of over-
the-counter mouthwash is significantly associated with increased risk of pre-diabetes/diabetes over a three-year
follow-up, independently of major diabetes risk factors. The oral microbiome has not yet been characterized in
direct relation to its nitrate reducing capacity and its role in NO bioavailability and related oral and cardiometabolic
health outcomes. Accordingly, we propose to evaluate the following specific aims. (1) To identify oral microbial
profiles associated with nitric oxide bioavailability (serum nitrite levels). (2) To evaluate the longitudinal
association of oral microbial profiles related to nitric oxide bioavailability with the development of hypertension,
pre-diabetes/diabetes, dental caries and progression of periodontitis. (3) To evaluate the impact of mouthwash
use on these microbial profiles and systemic NO bioavailability. In addition, we will also evaluate the association
of oral microbial profiles with other components of oral nitrate metabolism (salivary nitrate, nitrite, nitrate
reductase and DNRA activity). Modifiable lifestyle factors such as diet that may impact oral nitrate reducing
bacteria and pathways will be assessed. Over 1,000 SOALS participants have pertinent high quality data and
specimens available at baseline and 3-year follow-up visits (with 79% retention) to enable a timely cost-efficient
study. Saliva and blood samples, oral and cardiometabolic clinical measures, and key covariates including
detailed dietary, physical activity and oral hygiene measures have been collected. We will perform analysis of
the salivary microbiome using 16S rRNA sequencing, and we will measure key components of endogenous and
exogenous NO metabolism (nitrite and nitrate in serum and in saliva, nitrate reductase and DNRA activities in
saliva). The results from this study will help define the interrelationships between oral bacteria, NO metabolism,
cardiometabolic and oral health, and help understand pathways relating mouthwash use and cardiometabolic
condi...

## Key facts

- **NIH application ID:** 9886231
- **Project number:** 5R01DE028195-02
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** KAUMUDI J JOSHIPURA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $597,321
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886231

## Citation

> US National Institutes of Health, RePORTER application 9886231, Oral Microbiome, Nitric oxide Metabolism, and Oral and Cardiometabolic Health (5R01DE028195-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886231. Licensed CC0.

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