The Oral Microbiome in Type 1 Diabetes and Sub-Clinical Cardiovascular Disease

1 型糖尿病和亚临床心血管疾病中的口腔微生物组

• 批准号: 10059142
• 负责人: Amy Christine Alman
• 金额: $ 53.6万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-12 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059142
• 关键词: 16S ribosomal RNA sequencing; Adult; Affect; Atherosclerosis; Attenuated; Bacteria; Biological; Blood Vessels; Cardiovascular Diseases; Carotid Endarterectomy; Child; Chronic; Clinical; Colorado; Complications of Diabetes Mellitus; Control Groups; Data; Development; Diabetes Mellitus; Disease; Firmicutes; Gingiva; Goals; Health; Human Microbiome; Inflammation; Inflammatory; Inflammatory Response; Insulin-Dependent Diabetes Mellitus; Intervention; Knowledge; Lead; Lesion; Longitudinal Studies; Measurable; Measures; Mediating; Mediator of activation protein; Metabolic; Mission; Modeling; Oral; Oral cavity; Participant; Patient Self-Report; Periodontal Diseases; Periodontium; Physiologic pulse; Population; Process; Prospective cohort study; Public Health; Publishing; Research; Saliva; Salivary; Sampling; Severities; Site; Structure; Systemic disease; Taxonomy; Testing; United States National Institutes of Health; Universities; Visit; Whole-Genome Shotgun Sequencing; Work; calcification; cardiovascular disorder risk; cohort; coronary artery calcification; cytokine; dysbiosis; follow-up; glycemic control; high risk; illness length; improved; inflammatory marker; innovation; microbial; microbiome; microbiota; next generation; non-diabetic; oral microbiome; oral pathogen; periodontopathogen; recruit; subgingival microbiome; subgingival microbiota; targeted treatment

The oral microbiome is an important component of systemic health. Many oral bacterial species are associated with oral, as well as systemic diseases. Periodontal disease (PD) is a common condition characterized by a chronic inflammatory response to certain types of bacteria that destroys the supporting structures of the teeth. PD has been associated with other systemic diseases, particularly diabetes. Adults with diabetes are at higher risk of PD and, in turn, PD disease exacerbates glycemic control and diabetic complications. Both periodontal disease and diabetes have been associated with increased risk of cardiovascular disease (CVD). Previous work using the Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort at the University of Colorado demonstrated that self-reported PD duration was significantly associated with progression of coronary artery calcification in subjects with type 1 diabetes (T1D), but not in subjects without diabetes. These results suggest that the simultaneous presence of PD and T1D may accelerate CVD processes. The central hypothesis of this project is that oral pathogens are significantly associated with both T1D and subclinical CVD and act to modify the association between these diseases. As such, the objective of this project is to characterize the subgingival microbiome in T1D and to investigate longitudinal relationships between the subgingival microbiome, inflammation, T1D, and subclinical CVD. The long-term goal is to elucidate the biological mechanisms that are involved in the relationships between oral and systemic health. The rationale for this project is that increasing understanding of these relationships and mechanisms could lead to therapies targeted at the oral cavity that would have systemic benefits. We will test our central hypothesis with three specific aims: 1) Identify taxonomic and functional profiles of the subgingival microbiome associated with T1D and PD; 2) Determine the associations between the subgingival microbiome and subclinical CVD in those with and without T1D; 3) Determine whether inflammation acts as a mediator between the subgingival microbiome and subclinical CVD. We will utilize passive drool samples and subgingival plaque collected from CACTI participants to perform 16S ribosomal RNA sequencing of the subgingival microbiome and to measure salivary inflammatory cytokines. The approach is innovative because we are able to comprehensively examine correlates, mediators, and diabetes-specific effects of the relationship between the subgingival microbiome and subclinical CVD. Despite studies showing associations between PD, T1D, and CVD, no work to date has described the subginigval microbiome associated with T1D or has focused on the relationships between these three diseases at the level of the subgingival microbiome. This research is significant because these diseases afflict a large proportion of the population and increased understanding could lead to improved therapies.

口腔微生物组是全身健康的重要组成部分。许多口腔细菌种类都与之相关 患有口腔疾病以及全身疾病。牙周病 (PD) 是一种常见疾病，其特征是 对某些类型细菌的慢性炎症反应会破坏牙齿的支撑结构。 PD 与其他全身性疾病有关，特别是糖尿病。成人糖尿病患者发病率较高 帕金森病的风险，反过来，帕金森病会加剧血糖控制和糖尿病并发症。两者牙周 疾病和糖尿病与心血管疾病（CVD）风险增加有关。以前的工作 使用科罗拉多大学 1 型糖尿病患者冠状动脉钙化 (CACTI) 队列 证明自我报告的 PD 持续时间与冠状动脉的进展显着相关 1 型糖尿病 (T1D) 受试者会出现钙化，但非糖尿病受试者不会出现钙化。这些结果 表明 PD 和 T1D 同时存在可能会加速 CVD 过程。这 该项目的中心假设是口腔病原体与 T1D 和 T1D 显着相关。 亚临床 CVD 并采取行动改变这些疾病之间的关联。因此，该项目的目标 旨在描述 T1D 龈下微生物组的特征并研究之间的纵向关系 龈下微生物组、炎症、T1D 和亚临床 CVD。长期目标是阐明 涉及口腔和全身健康之间关系的生物机制。理由 对于这个项目来说，增加对这些关系和机制的了解可能会带来治疗方法 针对口腔，这将带来全身益处。我们将用三个方面来检验我们的中心假设 具体目标：1) 确定与 T1D 相关的龈下微生物组的分类和功能特征 和PD； 2) 确定患有以下疾病的患者龈下微生物组与亚临床 CVD 之间的关联 并且没有 T1D； 3) 确定炎症是否作为龈下微生物组之间的介质 和亚临床CVD。我们将利用从 CACTI 收集的被动口水样本和龈下菌斑 参与者对龈下微生物组进行 16S 核糖体 RNA 测序并测量唾液 炎症细胞因子。该方法是创新的，因为我们能够全面检查 龈下微生物群与糖尿病之间关系的相关性、中介因素和糖尿病特异性影响 亚临床CVD。尽管研究表明 PD、T1D 和 CVD 之间存在关联，但迄今为止还没有任何研究表明 描述了与 T1D 相关的龈下微生物组或重点关注了这些微生物组之间的关系 龈下微生物组水平的三种疾病。这项研究意义重大，因为这些疾病 困扰很大一部分人口，增加了解可能会导致治疗方法的改进。