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.

口服微生物组是系统健康的重要组成部分。许多口腔细菌是相关的 与口腔，以及全身性疾病。牙周疾病（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破坏了牙齿的支撑结构。 PD与其他全身性疾病，尤其是糖尿病有关。糖尿病的成年人处于较高的状态 PD的风险，而PD疾病加剧了血糖控制和糖尿病并发症。两个牙周 疾病和糖尿病与心血管疾病（CVD）的风险增加有关。以前的工作 在科罗拉多大学使用1型糖尿病（仙人掌）队列中的冠状动脉钙化 证明自我报告的PD持续时间与冠状动脉进展显着相关 患有1型糖尿病（T1D）的受试者的钙化，但没有糖尿病的受试者。这些结果 表明同时存在PD和T1D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 亚临床CVD并采取行动来修改这些疾病之间的关联。因此，该项目的目的 是为了表征T1D中的次命微生物组，并研究 亚gingival微生物组，炎症，T1D和亚临床CVD。长期目标是阐明 与口腔健康和系统健康之间关系有关的生物学机制。理由 因为这个项目是，对这些关系和机制的越来越多可能导致疗法 针对具有系统性益处的口腔。我们将用三个 具体目的：1）确定与T1D相关的subgingival微生物组的分类学和功能分布 和PD； 2）确定在患有的人群中的下属微生物组和亚临床CVD之间的关联 没有T1D； 3）确定炎症是否充当尺寸微生物组之间的介体 和亚临床CVD。我们将利用从仙人掌收集的被动口水样本和尺寸 参与者进行16S核糖体RNA测序，并测量唾液 炎症细胞因子。这种方法具有创新性，因为我们能够全面检查 尺寸微生物组与 亚临床CVD。尽管研究表明PD，T1D和CVD之间的关联，但迄今为止尚无工作 描述了与T1D相关的子木腔微生物组 在尺寸微生物组水平上的三种疾病。这项研究很重要，因为这些疾病 折磨很大一部分人口和增加的理解可能会导致疗法的改善。