Metabolic Syndrome, Periodontal Health, and the Oral Microbiome

项目摘要 代谢综合征（MetS）是一种全球流行病，影响超过1/3的美国成年人 人群，是一组生化和生理异常，易患型 2糖尿病（T2D）和心血管疾病（CVD）。新出现的证据表明， 代谢综合征（MetS），肥胖的不良后果，与增加 牙周炎的程度和严重程度。牙周炎是一种由微生物引起的慢性 一种破坏牙齿支撑结构的炎症性疾病，最终导致牙齿 这种疾病的严重形式影响了约10%的美国成年人。虽然有 叙述性评论和一些横断面研究表明， MetS和牙周炎患病率增加，这些关联背后的机制 还没有被调查。 口腔环境中的菌群失调导致牙周病，然而， 代谢综合征患者口腔微生物组的这些破坏和随后的功能改变 仍然未定义。因此，我们的中心假设是，代谢综合征造成了一个危险的伤害， 环境，甚至在临床牙周病发作之前，通过改变微生物 功能和代谢物。我们将通过实现两个目标来检验我们的假设： 1、通过比较和定量的方法，确定MetS对口腔宏基因组的影响， 微生物基因丰度的变化和MetS与 对照组，使用多臂，横断面研究设计与全宏基因组测序。在 具体目标2我们将绘制微生物来源的代谢产物（最终产物）， MetS患者龈下环境的气相色谱/质谱分析 (GC/MS）分析。拟议研究的预期成果是确定 MetS对龈下环境的功能和代谢景观的影响。我们 预计我们的综合系统生物学方法与临床流行病学相结合， 为今后的机理研究奠定了基础。在惊人的统计数据的推动下， 经济和健康负担造成的MetS在流行的背景下， 牙周病在美国成年人口，我们提出了一个急需的研究， 严重未被探索的领域：代谢综合症对口腔健康的影响。我们长久以来- 长期目标是确定个性化的，实验验证的生物标志物/潜在指标， 健康和未来的牙周病在这个高风险的队列。

Project Summary Metabolic syndrome (MetS), a global epidemic that affects more than 1/3rd of the US adult population, is a cluster of biochemical and physiological abnormalities that predisposes to Type 2 Diabetes (T2D) and Cardiovascular Diseases (CVD). Emerging evidence indicates that Metabolic Syndrome (MetS), an adverse consequence of obesity, is associated with an increase in the extent and severity of periodontitis. Periodontitis is a microbially induced chronic inflammatory disease that destroys the supporting structures of teeth, eventually leading to tooth loss and the severe form of the disease affects ~10% of the American adults. Although there are narrative reviews and a handful of cross-sectional studies that suggest the association between MetS and increased prevalence of periodontitis, the mechanism(s) behind these associations have not been investigated. Dysbiosis in the oral environment leads to periodontal disease, however, the mechanisms of these disruptions and subsequent functional alterations in the oral microbiome of MetS patients remain undefined. Therefore, our central hypothesis is that MetS creates an at-risk-for-harm environment, even before the onset of clinical periodontal disease by altering the microbial functions and metabolites. We will test our hypothesis by carrying out two aims: In Specific Aim 1, we will determine the effects of MetS on the oral metagenome, by comparing and quantifying changes in microbial gene abundances and associated functional pathways between MetS and controls, using a multi-arm, cross-sectional study design with whole-metagenome sequencing. In Specific Aim 2 we will map the microbially-derived metabolites (the end products) in the subgingival environment of patients with MetS using gas chromatography/mass spectrometry (GC/MS) analysis. The expected outcomes of the proposed studies are the determination of effects of MetS on the functional and metabolic landscape of the subgingival environment. We anticipate that our integrative systems biology approach combined with clinical epidemiology will lay the foundation for future mechanistic investigations. Driven by the startling statistics of economic and health burden caused by the MetS in the backdrop of the prevalence of the periodontal disease in the US adult population, we are proposing a much-needed study in a severely under-explored area: the impact of Metabolic Syndrome on oral health. Our long- term goal is to identify personalized, experimentally validated biomarkers/potential indicators of health and future periodontal disease in this high-risk cohort.