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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.

项目摘要糖尿病会增加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潜在机制是，糖尿病导致转变为更致病性的细菌负担，这是由于促进某些细菌生长的底物，如葡萄糖或炎症产物。研究已经确定，糖尿病通过致病性增加了对感染的易感性。在几个目标器官中的细菌，糖尿病导致肠道微生物群的转变。是否糖尿病创造了一个环境，支持更多的致病性细菌群落，牙周组织尚未解决的部分原因是以前的研究技术的限制。随着研究复杂细菌群落动态方法的进步，可以将健康个体的微生物群与糖尿病患者进行比较。我们计划获得逆转之前和之后的高通量Illumina DNA-seq分析的微生物概况糖尿病，并通过RNA-Seq检查功能性细菌差异。最近的发展提供了一个机会，比较糖尿病和血糖正常相关的龈下细菌群落腹腔镜袖状胃切除术可快速解决糖尿病在大多数患者中糖尿病的逆转提供了新的见解，糖尿病对肠道微生物的影响。我们将利用这个机会进行两项研究。一种是横断面分析，以比较糖尿病患者与非糖尿病患者的微生物组。的二是在相同的被试中进行纵向比较，考察逆转的效果糖尿病由于糖尿病的逆转是迅速的，它有助于检查因果关系关系。所采用的两种方法（基线和纵向）各有其独特的优势所以我们可以确定糖尿病是否改变了龈下微生物组，牙周炎该项目汇集了两个领先的减肥手术计划在坦普尔大学和宾夕法尼亚大学，以确保有足够的患者人群，计划招生人数。它还汇集了来自坦普尔的糖尿病专家大学和宾夕法尼亚大学的口腔和口腔细菌专家，宾夕法尼亚和俄亥俄州州立大学。