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

口腔微生物群是全身健康的重要组成部分。许多口腔细菌种类是相关的 有口腔疾病，也有全身疾病。牙周病(PD)是一种常见疾病，其特征是 对某些细菌的慢性炎症反应，破坏牙齿的支撑结构。 帕金森病与其他系统性疾病有关，特别是糖尿病。患有糖尿病的成年人处于更高的 帕金森病和帕金森病的风险会加剧血糖控制和糖尿病并发症。两种牙周 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冠状动脉钙化治疗1型糖尿病(仙人掌)队列 表明自我报告的帕金森病持续时间与冠状动脉进展显著相关 1型糖尿病(T1D)受试者的钙化，但非糖尿病受试者不存在。这些结果 提示PD和T1D的同时存在可能加速了CVD过程。这个 该项目的中心假设是口腔病原体与T1D和T1D显著相关 亚临床心血管疾病，并采取行动改变这些疾病之间的联系。因此，这个项目的目标是 目的是描述T1D患者的牙龈下微生物群的特征，并研究 龈下微生物群、炎症、T1D和亚临床脑血管病。我们的长期目标是阐明 涉及口腔和全身健康之间关系的生物学机制。其基本原理是 对于这个项目来说，增加对这些关系和机制的理解可能会导致治疗 以口腔为目标，这将对全身有益。我们将用三个例子来验证我们的中心假设 具体目标：1)确定与T1D相关的龈下微生物群的分类和功能特征 和PD；2)确定牙周炎患者的龈下微生物群与亚临床心血管疾病之间的关系。 在没有T1D的情况下；3)确定炎症是否在龈下微生物群之间起中介作用 和亚临床脑血管病。我们将利用从仙人掌采集的被动口水样本和牙菌斑。 参与者对龈下微生物组进行16S核糖体RNA测序并测量唾液 炎性细胞因子。这种方法是创新的，因为我们能够全面地研究 龈下微生物群与糖尿病之间关系的相关性、介体和糖尿病特异性效应 亚临床脑血管病。尽管研究表明PD、T1D和心血管疾病之间存在关联，但到目前为止还没有研究表明 描述了与T1D相关的牙龈下微生物群，或重点研究了这些微生物群之间的关系 三种疾病均发生在龈下微生物群水平。这项研究具有重要意义，因为这些疾病 如果患者中有很大一部分人受到这种疾病的折磨，增加了解就可以改进治疗方法。

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.