Diabetes reversal and the subgingival microbiota

糖尿病逆转和龈下微生物群

• 批准号: 10189550
• 负责人: DANA T GRAVES
• 金额: $ 47.95万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-07 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189550
• 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

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 糖尿病增加了牙周病的患病率和严重程度。牙周炎 有复杂的细菌病原学，以及细菌群落与糖尿病的关系 目前仍不清楚。牙周炎和糖尿病相互作用的一个潜在机制是 糖尿病导致向致病性更强的细菌负担转变，这是由于 促进某些细菌生长的底物，如葡萄糖或炎症产物。 研究已经证实，糖尿病增加了感染的易感性， 细菌存在于几个靶器官中，糖尿病会导致肠道微生物区系发生变化。是否 糖尿病创造了一个支持更具致病性的细菌群落的环境 牙周组织尚未得到解决的部分原因是先前研究的技术限制。 随着研究复杂细菌群落动态的方法的进步，现在是 可以将健康人和糖尿病患者的微生物区系进行比较。我们计划获得 高通量Illumina DNA-seq分析逆转前后的微生物谱 用RNA-Seq法检测功能细菌的差异。最近的一项发展是 提供了一个比较糖尿病和正常血糖相关的牙龈下病变的机会 细菌群落。腹腔镜袖状胃切除手术可迅速解决 大多数受赠者都患有糖尿病。糖尿病的逆转为研究糖尿病的影响提供了新的见解 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，比较糖尿病患者和非糖尿病患者的微生物组。这个 二是在同一受试者中进行纵向比较，考察逆转的效果 糖尿病。因为糖尿病的逆转速度很快，所以便于检查因果关系。 两性关系。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，从而增加患牙周炎的风险 牙周炎。该项目汇集了坦普尔的两个领先的减肥手术项目 大学和宾夕法尼亚大学，以确保有足够的患者人数 计划招生人数。它还汇集了坦普尔的糖尿病专家 来自宾夕法尼亚大学和宾夕法尼亚大学的口腔和口腔细菌专家 宾夕法尼亚州立大学和俄亥俄州立大学。