The Impact of Race/Ethnicity on Inflammation Regulation and Microbiome Interactions in Periodontitis

项目摘要/摘要 在美国，墨西哥裔美国人(59.7%)和非西班牙裔美国人患牙周炎的比例最高 黑人(56.6%)。重度牙周炎在这些人群中也更为普遍；非西班牙裔黑人(14.7%) 和墨西哥裔美国人(13.4%)。尽管种族和民族与牙周病有关 尽管发病率和严重程度不同，但缺乏令人信服的证据来解释这种差异的生物因素。 特殊的促分解介质(SPM)通过主动调节细胞来诱导炎症的消退 免疫细胞和基质细胞通过特定的G蛋白偶联受体传递信号。解决方案 SPMS诱导的炎症逆转实验性牙周炎患者口腔微生物区系的失调 模特们。SPM和SPM途径标记物与临床牙周炎和SPM异常相关 牙周炎的生产和功能对某些种族/民族群体的影响不成比例。这个 种族/民族在解决严重牙周炎炎症中的影响尚未被调查。 这项研究旨在研究墨西哥裔美国人重症患者炎症消退的分子特征。 牙周炎。将招募四个受试组；墨西哥裔美国人和患有严重疾病的美国白人 牙周炎(全身性，III/IV期，B/C级)，墨西哥裔美国人和美国白人健康对照。 我们的初步数据支持的假设是，患有严重牙周炎的墨西哥裔美国人将 表现出不同的促进炎症的脂质介质的特征，包括SPM，SPM途径标记物 以及促炎脂质介体、SPM受体和相关的龈下微生物群失调， 与美国白人相比。提出了以下具体目标：突出地方性和系统性 墨西哥裔美国人SPM、SPM途径标志物、SPM受体和龈下微生物群的分布 以及患有严重牙周炎的美国白人。我们计划分析脂质介体水平，SPM受体 牙周、血浆、血清、血清等多种生物标本的表达及龈下微生物群 中性粒细胞、单核细胞和龈下菌斑。脂类介质水平与受体表达的相关性 并将利用生物标志物发现的数据集成分析来分析相对细菌丰度 使用潜在成分(Diablo)方法，该方法可以识别相关的关键分子或微生物 牙周炎症消退，这是传统统计学方法无法识别的。 我们预计局部和全身炎症的消退和牙龈下组织的成分 墨西哥裔美国人的微生物群将不同于美国白人的微生物群。相关签名 在这些受试者中，脂质介体、SPM受体和龈下微生物群之间也将是不同的。这些 结果将促进对炎症消退在疾病差异中的作用的理解。这个 相关分析中确定的分子或微生物可以作为新疗法开发的靶点。

Project Summary/ Abstract In the United States, the prevalence of periodontitis is greatest in Mexican Americans (59.7%) and non-Hispanic Blacks (56.6%). Severe periodontitis is also more prevalent in these populations; non-Hispanic Blacks (14.7%) and Mexican Americans (13.4%). Although race and ethnicity are associated with periodontal disease prevalence and severity, there is lack of convincing evidence of biological factors explaining the differences. Specialized pro-resolving mediators (SPMs) induce resolution of inflammation by actively regulating cellular activity of immune cells and stromal cells signaling through specific G protein–coupled receptors. Resolution of inflammation induced by SPMs reverses dysbiotic shifts of the oral microbiota in experimental periodontitis models. SPMs and SPM pathway markers are associated with clinical periodontitis and abnormalities in SPM production and function in forms of periodontitis disproportionately affecting certain racial/ethnic groups. The impact of race/ethnicity in resolution of inflammation in severe periodontitis has not been investigated. This study aims to investigate molecular profiles of resolution of inflammation in Mexican Americans with severe periodontitis. Four subject groups will be recruited; Mexican Americans and White Americans with severe periodontitis (generalized, stage III/ IV, grade B/C), Mexican American and White American healthy controls. The hypothesis, supported by our preliminary data, is that Mexican Americans with severe periodontitis will exhibit distinct profiles of lipid mediators that promote inflammation, including SPMs, SPM pathway markers as well as pro-inflammatory lipid mediators, SPM receptors, and an associated subgingival microbiome dysbiosis, compared to White Americans. The following specific aim is proposed: Characterize the local and systemic profiles of SPMs, SPM pathway markers, SPM receptors and the subgingival microbiome in Mexican Americans and White Americans with severe periodontitis. We plan to analyze lipid mediator levels, SPM receptor expression and the subgingival microbiome in multiple biological specimens including gingiva, plasma, serum, neutrophils, monocytes and subgingival plaque. Correlations between lipid mediator levels, receptor expression and relative bacterial abundance will be analyzed with the Data Integration Analysis for Biomarker discovery using a Latent compOnents (DIABLO) method, which can identify key molecules or microorganisms associated with resolution of periodontal inflammation which cannot be identified by traditional statistical methods. We expect that local and systemic resolution of inflammation profiles and composition of the subgingival microbiome in Mexican Americans will be different from those in White Americans. The correlation signatures between lipid mediator, SPM receptor and subgingival microbiome in these subjects will also be distinct. These results will advance the understanding of the role of resolution of inflammation in disease disparities. The identified molecules or microorganisms in the correlation analysis can be targeted for novel therapy development.