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: 10221890
• 负责人: KAUMUDI J JOSHIPURA
• 金额: $ 22.49万
• 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 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221890
• 关键词: 2019-nCoV; Adult; Affect; Ammonia; Anti-Bacterial Agents; Antiviral Agents; Area; Asthma; Attenuated; Bacteria; Biological; Biological Availability; Biological Process; Blood Circulation; Blood Pressure; Blood Vessels; Bronchodilation; COVID-19; Chronic; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Consumption; Data; Deglutition; Dental Hygiene; Dental caries; Development; Diabetes Mellitus; Diagnosis; Diagnostic tests; Diet; Disease; Ecology; Endothelium; Epidemiology; Future; Grant; Health; Hypertension; Individual; Infection; Inflammation; Insulin Resistance; Interleukin-6; Interview; Lead; Longitudinal Studies; Lung; Lung diseases; Mediator of activation protein; Metabolic Diseases; Metabolic Pathway; Metabolism; Modification; Mouthwash; Movement; Nitrate Reductases; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Oral; Oral health; Oropharyngeal; Outcome; Overweight; Participant; Pathway interactions; Periodontitis; Physical activity; Play; Population; Prediabetes syndrome; Production; Public Health; Publications; Research; Respiratory System; Risk; Role; Saliva; Salivary; Sampling; Serum; Signal Transduction; Signaling Molecule; Smoking; Source; Symptoms; TNF gene; Testing; Time; Tissues; Vascular Cell Adhesion Molecule-1; Vasodilation; Viral Load result; Visit; adult obesity; cardiometabolic risk; cardiometabolism; cost efficient; cytokine; denitrification; dietary nitrate; endothelial dysfunction; follow-up; high risk; improved; inflammatory marker; insight; insulin sensitivity; lifestyle factors; microbial; microbiota; novel strategies; oral bacteria; oral commensal; oral microbiome; outcome forecast; parent grant; prevent; psychosocial; public health relevance; respiratory; respiratory health; transmission process

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. Our original grant aims to evaluate the role of this “entero-salivary pathway” and the related microbial profiles in cardiometabolic health in over 1,000 participants from the San Juan Overweight Adults Longitudinal Study (SOALS) who have pertinent high quality data and biospecimens available at baseline and 3-year follow-up visits (with 79% retention). Endogenous NO also plays important biological functions in the respiratory system such as bronchodilation, vasodilation of the pulmonary blood vessels, and modulation of cytokine production, which could be relevant to COVID-19 outcomes. Furthermore, NO could help prevent COVID-19 infection of the airways because it is involved in ciliary movement and has a demonstrated antiviral activity against SARS-CoV-2, the causative agent of COVID-19. Mouthwash has been recently proposed as a potential strategy for reducing the oral viral load, thus reducing transmission of SARS-CoV-2. However, regular mouthwash use could significantly disrupt the NO production from the entero-salivary nitrate pathway, and it could also possibly interfere with COVID-19 diagnostic tests that use oral or oropharyngeal samples. It is not known to what extent the NO produced exogenously via the entero-salivary pathway contributes to respiratory health and in COVID-19, or how could this be influenced by mouthwash use or other modulators of the oral microbiome. In this revision, we propose to expand the scope of the parent grant to additionally evaluate the role of this pathway, and a key modifiable factor, mouthwash use, in COVID-19 symptoms, diagnosis and outcomes. We propose three new specific aims: 1)To evaluate the association between regular over-the-counter mouthwash use (any mouthwash and few specific brands) and COVID-19 symptoms, diagnosis and outcomes; 2)To evaluate the association of nitric oxide metabolites (nitrate and nitrite) in the saliva with COVID-19 symptoms, diagnosis and outcomes; 3) to evaluate the association of mouthwash use and nitric oxide metabolism with systemic markers of inflammation (IL-6, TNF-a, CRP) and endothelial function (sICAM, VCAM), which may impact COVID-19 progression. As a secondary aim we will also evaluate the association of the salivary nitric oxide metabolites and the oral microbiome with chronic respiratory disease (asthma and chronic obstructive pulmonary disease). Data on COVID-19 and pertinent covariates will be assessed through two sets of interviews conducted over the calls. This supplement expands the scope of the parent grant into a highly relevant and urgent research area pertinent to the transmission, diagnosis and prognosis of COVID-19, and will also evaluate other respiratory outcomes. The additional analyses and insight obtained through this project, will enrich the parent grant, and is expected to have a high

共生口腔细菌将外源(饮食)和内源硝酸盐还原为亚硝酸盐，亚硝酸盐转化为NO，NO是一种调节血管张力、炎症和胰岛素敏感性的信号分子。我们最初的资助旨在评估这一“肠道-唾液途径”和相关微生物谱在心脏代谢健康中的作用，这些参与者来自圣胡安超重成年人纵向研究(SOALS)，他们在基线和3年随访(79%保留)时拥有相关的高质量数据和生物样本。内源性NO在呼吸系统中也发挥着重要的生物学功能，如支气管扩张、肺血管扩张和调节细胞因子的产生，这些可能与新冠肺炎的预后有关。此外，一氧化氮可以帮助预防新冠肺炎感染呼吸道，因为它参与纤毛运动，并对新冠肺炎的病原体SARS-CoV-2具有明显的抗病毒活性。漱口水最近被提出作为一种潜在的策略来减少口服病毒载量，从而减少SARS-CoV-2的传播。然而，经常使用漱口水可能会显著扰乱肠道-唾液硝酸盐途径产生NO，还可能干扰使用口腔或口咽样本的新冠肺炎诊断测试。目前尚不清楚通过肠道-唾液途径产生的NO在多大程度上有助于呼吸健康和新冠肺炎中的NO，也不知道漱口水的使用或口腔微生物群的其他调节剂如何影响这一点。在这次修订中，我们建议扩大父母资助的范围，以另外评估这一途径的作用，以及一个关键的可修改因素，即漱口水的使用，在新冠肺炎的症状、诊断和结果中。我们提出了三个新的具体目标：1)评估经常非处方药使用(任何含漱口水和少数特定品牌)与新冠肺炎症状、诊断和预后的关系；2)评估唾液中一氧化氮代谢产物(硝酸盐和亚硝酸盐)与新冠肺炎症状、诊断和预后的关系；3)评估漱口水使用和一氧化氮代谢与全身炎症标志物(IL-6、肿瘤坏死因子-α、C反应蛋白)和内皮功能(细胞间黏附分子、血管细胞间黏附分子)可能影响新冠肺炎进展的相关性。作为第二个目标，我们还将评估唾液一氧化氮代谢产物和口腔微生物群与慢性呼吸系统疾病(哮喘和慢性阻塞性肺疾病)的相关性。有关新冠肺炎和相关协变量的数据将通过在电话会议上进行的两组采访进行评估。这一补充方案将父母资助的范围扩大到一个与新冠肺炎的传播、诊断和预后相关的高度相关和紧迫的研究领域，并将评估其他呼吸结果。通过这个项目获得的额外分析和洞察力，将丰富父母的资助，并预计将有很高的