Diabetes reversal and the subgingival microbiota

糖尿病逆转和龈下微生物群

基本信息

批准号：
10413264
负责人：
DANA T GRAVES
金额：
$ 38.18万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-07 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10413264
关键词：
Address Adopted Affect Bacteria Bacterial Genes Body Weight decreased Categories Clinical Complex Cross-Sectional Studies DNA sequencing Data Development Diabetes Mellitus Enrollment Ensure Environment Etiology Experimental Designs Gastrectomy Gene Amplification Gene Dosage Gene Expression Gene Expression Profiling Genes Gingival Crevicular Fluid Glucose Growth Human Hyperglycemia Individual Infection Inflammation Inflammatory Insulin Resistance Matched Group Measures Messenger RNA Metabolic Methods Modernization Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Ohio Operative Surgical Procedures Oral Oral cavity Organ Outcome Outcome Measure Pathogenicity Pennsylvania Periodontal Diseases Periodontitis Periodontium Population Predisposition Prevalence Procedures Resolution Ribosomal RNA Risk Severities Techniques Testing Type 2 diabetic Universities Weight bacterial community bariatric surgery base clinically significant comorbidity cytokine diabetic diabetic patient gut microbiome gut microbiota in vivo insight mRNA Expression microbial microbial community microbial composition microbiome microbiome research microbiota next generation sequencing non-diabetic obese person oral bacteria oral microbial community oral microbiome pathogenic bacteria patient population programs rRNA Genes secondary analysis subgingival microbiome subgingival microbiota transcriptome sequencing

项目摘要

Project Summary Diabetes mellitus increases the prevalence and severity of periodontal diseases. Periodontitis has a complex bacterial etiology, and the relationship of the bacterial community to diabetes remains unclear. A potential mechanism for the interaction of periodontitis and diabetes is that diabetes causes a shift to a more pathogenic bacterial burden as the result of alterations in substrates such as glucose or inflammatory products that promote growth of certain bacteria. Studies have established that diabetes enhances susceptibility to infection by pathogenic bacteria in several target organs, and that diabetes causes a shift in the gut microbiota. Whether diabetes creates an environment that supports a more pathogenic bacterial community in the periodontium has not been settled in part because of technical limitations of previous studies. With advances in approaches to study the dynamics of complex bacterial communities, it is now possible to compare the microbiota in healthy individuals to diabetics. We plan to obtain microbial profiles by high throughput Illumina DNA-seq analysis before and after reversal of diabetes and to examine functional bacterial differences by RNA-Seq. A recent development has provided an opportunity to compare diabetes and normoglycemia-associated subgingival bacterial communities. Laparoscopic sleeve gastrectomy surgery produces a rapid resolution of diabetes in most recipients. The reversal of diabetes has provided new insights into the impact of diabetes on the gut microbiome. We will advantage of this opportunity to conduct two studies. One is a cross-sectional analysis to compare the microbiome in diabetics with nondiabetics. The second is a longitudinal comparison in the same subjects to examine the effect of reversing diabetes. Because the reversal of diabetes is rapid it facilitates examination of cause and effect relationships. The two approaches taken (baseline and longitudinal) each has distinct strengths so we can determine whether diabetes alters the subgingival microbiome to enhance the risk of periodontitis. This project brings together two leading bariatric surgery programs at Temple University and the University of Pennsylvania to ensure an adequate patient population to reach the planned enrollment figures. It also brings together experts in diabetes from Temple University and University of Pennsylvania, and experts in the oral cavity and oral bacteria from Penn and Ohio State University.

项目概要糖尿病增加了牙周病的患病率和严重程度。牙周炎具有复杂的细菌病因学，以及细菌群落与糖尿病的关系仍不清楚。牙周炎和糖尿病相互作用的一个潜在机制是糖尿病由于以下因素的改变而导致致病性细菌负荷增加：促进某些细菌生长的底物，例如葡萄糖或炎症产物。研究表明，糖尿病会增加病原菌感染的易感性多个目标器官中的细菌，糖尿病会导致肠道微生物群的变化。无论糖尿病创造了一个支持更多致病菌群落的环境由于先前研究的技术限制，牙周病尚未得到解决。随着复杂细菌群落动态研究方法的进步，现在可以将健康个体与糖尿病患者的微生物群进行比较。我们计划获得通过高通量 Illumina DNA-seq 分析逆转前后的微生物概况糖尿病并通过 RNA-Seq 检查功能性细菌差异。最近的一项进展是提供了比较糖尿病和血糖正常相关龈下的机会细菌群落。腹腔镜袖状胃切除手术可快速解决大多数接受者患有糖尿病。糖尿病的逆转提供了对其影响的新见解糖尿病对肠道微生物群的影响。我们将利用这个机会进行两项研究。一种是横断面分析，比较糖尿病患者与非糖尿病患者的微生物组。这第二是对同一受试者进行纵向比较，以检验逆转的效果糖尿病。由于糖尿病的逆转很快，因此有利于因果关系的检查关系。采取的两种方法（基线和纵向）各有不同的优势因此我们可以确定糖尿病是否会改变龈下微生物群从而增加患糖尿病的风险牙周炎。该项目汇集了天普大学两个领先的减肥手术项目大学和宾夕法尼亚大学确保有足够的患者群体到达计划的入学人数。它还汇集了天普大学的糖尿病专家大学和宾夕法尼亚大学，以及口腔和口腔细菌方面的专家宾夕法尼亚大学和俄亥俄州立大学。