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

口腔微生物组、一氧化氮代谢以及口腔和心脏代谢健康

• 批准号: 10377933
• 负责人: EVANGELIA MOROU-BERMUDEZ
• 金额: $ 42.97万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10377933
• 关键词: 16S ribosomal RNA sequencing; Affect; Ammonia; Anti-Bacterial Agents; Attention; Attenuated; Bacteria; Biological; Biological Availability; Blood Circulation; Blood Vessels; Blood specimen; Cardiometabolic Disease; Clinical; Clinical Trials; Consumption; Data; Deglutition; Dental Hygiene; Dental caries; Development; Diabetes Mellitus; Diet; Ecology; Epidemiology; Future; Health; Hypertension; Individual; Inflammation; Inorganic Nitrogen Compounds; Insulin Resistance; Intervention; Lead; Local Anti-Infective Agents; Longitudinal Studies; Measures; Mediator of activation protein; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Modification; Mouth Diseases; Mouthwash; Nitrate Reductases; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Nitrogen Dioxide; Oral; Oral health; Outcome; Overweight; Participant; Pathway interactions; Periodontitis; Physical activity; Play; Population; Prediabetes syndrome; Prevention; Preventive; Public Health; Publications; Randomized Clinical Trials; Risk; Risk Factors; Role; Saliva; Salivary; Serum; Signal Transduction; Signaling Molecule; Smoking; Source; Specimen; Testing; Time; Tissues; Visit; adult obesity; blood pressure elevation; blood pressure regulation; cardiometabolic risk; cardiometabolism; cost efficient; denitrification; diabetes risk; dietary; dietary nitrate; endothelial dysfunction; follow-up; high risk; improved; insulin sensitivity; lifestyle factors; microbial; microbiome; microbiota; modifiable lifestyle factors; novel; novel strategies; oral bacteria; oral commensal; oral microbiome; overweight adults; psychosocial; saliva sample

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 conditions. This study has a high potential public health impact, as the results will likely inform development of novel interventions for the modulation of the oral microbiome, which could be important for the prevention and control of oral and cardiometabolic diseases.

作为一氧化氮（NO）代谢和 因此，在心脏代谢健康中。共生口服细菌减少外源性（饮食）和内源性 硝酸盐转化为NO的亚硝酸盐，一种调节血管张力，炎症和的信号分子 胰岛素灵敏度。随机临床试验表明，通过使用消除口腔微生物菌群 杀菌性漱口水会降低全身性无生物利用度，随之而来的胰岛素敏感性丧失和 血压升高。亚硝酸盐也可以通过口服细菌进一步降低到无机氮化合物中， 例如通过降低硝酸盐减少到氨（DNRA）途径的氨，可以发挥重要作用 在口腔健康中的生物学作用；这些途径也可能影响全身无生物利用度。我们最近 圣胡安超重成年人纵向研究（SOALS）的出版物表明，定期使用过度使用 口气清洗与三年内糖尿病/糖尿病的风险增加显着相关 随访，独立于主要的糖尿病风险因素。口服微生物组尚未在 与其硝酸盐降低能力的直接关系及其在无生物利用度和相关口服和心脏代谢中的作用 健康结果。因此，我们建议评估以下特定目标。 （1）识别口腔微生物 与一氧化氮生物利用度（血清亚硝酸盐水平）相关的轮廓。 （2）评估纵向 与一氧化氮生物利用度有关的口腔微生物谱与高血压的发展相关， 糖尿病前/糖尿病，龋齿和牙周炎的进展。 （3）评估漱口水的影响 用于这些微生物概况和全身性无生物利用度。此外，我们还将评估协会 口服微生物剖面具有其他口服硝酸盐代谢的成分（唾液硝酸盐，亚硝酸盐，硝酸盐 还原酶和DNRA活性）。可修改的生活方式因素，例如饮食，可能会影响口服硝酸盐减少 将评估细菌和途径。超过1,000个肥皂剧参与者拥有相关的高质量数据，并且 在基线和3年随访（保留79％）时可用的标本可及时成本效益 学习。唾液和血液样本，口服和心脏代谢临床措施以及关键协变量包括 已经收集了详细的饮食，体育锻炼和口腔卫生措施。我们将进行分析 使用16S rRNA测序的唾液微生物组，我们将测量内源性和 外源无代谢（血清和唾液中的亚硝酸盐和硝酸盐，硝酸盐还原酶和DNRA活性 唾液）。这项研究的结果将有助于定义口腔细菌之间的相互关系，没有代谢， 心脏代谢和口腔健康，并有助于了解与使用漱口水有关的途径和心脏代谢 状况。这项研究具有很大的公共卫生影响，因为结果可能会为开发提供信息 调节口腔微生物组的新干预措施，这对于预防和 控制口服和心脏代谢疾病。