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

种族/民族对牙周炎炎症调节和微生物组相互作用的影响

基本信息

批准号：
10593396
负责人：
Chun-Teh Lee
金额：
$ 25.35万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-19 至 2024-09-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10593396
关键词：
16S ribosomal RNA sequencing Adult Affect African American population Alveolar Bone Loss Apoptosis Bacterial DNA Biological Biological Factors Black Populations Cardiovascular Diseases Cells Censuses Classification Clinical Cytokine Signaling Data Deposition Development Diabetes Mellitus Diagnosis Ethnic Origin Ethnic group Exhibits Failure Flow Cytometry G-Protein-Coupled Receptors Genes Gingiva Goals High Prevalence Hispanic Hispanic Americans Immune Immunofluorescence Immunologic Inflammation Inflammatory Link Measures Mechanics Mediator of activation protein Methods Mexican Americans Microbial Biofilms Minority Modeling Molecular Profiling National Health and Nutrition Examination Survey Neutrophil Infiltration Not Hispanic or Latino Omega-3 Fatty Acids Omega-6 Fatty Acids Pathway interactions Patients Periodontal Diseases Periodontitis Persons Phenotype Plasma Population Prevalence Production Proteins Quantitative Reverse Transcriptase PCR Race Regulation Resolution Reverse Transcription Role Sampling Severities Signal Transduction Specimen Stains Statistical Methods Stromal Cells Surveys Time Tissues Tooth structure United States Visit base biomarker discovery caucasian American chronic inflammatory disease data integration disease disparity dysbiosis federal poverty level health disparity lipid mediator macrophage microbiome microorganism monocyte multiple datasets neutrophil new therapeutic target novel therapeutics oral microbial community oral microbiome peripheral blood racial and ethnic racial and ethnic disparities receptor receptor expression recruit subgingival microbiome therapy development

项目摘要

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.

项目概要/摘要在美国，牙周炎的患病率在墨西哥裔美国人 (59.7%) 和非西班牙裔美国人中最高黑人（56.6%）在这些人群中也更常见；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。尽管患病率和严重程度不同，但缺乏令人信服的生物学因素证据来解释这些差异。专门的促消退介质 (SPM) 通过主动调节细胞来诱导炎症消退免疫细胞和基质细胞通过特定 G 蛋白偶联受体进行信号传导的活性。 SPM 诱导的炎症可逆转实验性牙周炎中口腔微生物群的失调变化 SPM 模型和 SPM 通路标记物与临床牙周炎和 SPM 异常相关。牙周炎形式的产生和功能不成比例地影响某些种族/族裔群体。尚未研究种族/民族对严重牙周炎炎症消退的影响。本研究旨在调查墨西哥裔美国人严重炎症消退的分子特征将招募患有严重牙周炎的四个受试者组；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促进炎症的脂质介质的独特特征，包括 SPM、SPM 通路标记物以及促炎脂质介质、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：描述本地和系统的特征。墨西哥裔美国人的 SPM、SPM 通路标记物、SPM 受体和龈下微生物组概况我们计划分析患有严重牙周炎的美国白人的内侧脂质水平、SPM 受体。多种生物样本中的表达和龈下微生物组，包括牙龈、血浆、血清、中性粒细胞、单核细胞和龈下菌斑之间的相关性脂质介质水平、受体表达。和相对细菌丰度将通过数据集成分析进行分析以发现生物标志物使用潜在成分（DIABLO）方法，可以识别相关的关键分子或微生物解决传统统计方法无法识别的牙周炎症。我们期望炎症特征和龈下成分的局部和全身解决墨西哥裔美国人的微生物组与美国白人的微生物组不同。这些受试者中脂质介质、SPM 受体和龈下微生物组之间的差异也将有所不同。结果将促进对炎症消退在疾病差异中的作用的理解。相关性分析中识别出的分子或微生物可以作为新疗法开发的目标。