Dysbiosis in Inflammatory Bowel Disease

炎症性肠病的菌群失调

• 批准号: 7197734
• 负责人: ECE A. MUTLU
• 金额: $ 22.2万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197734
• 关键词: Affect; Age; Algorithms; American; Attention; Back; Bacteria; Bioinformatics; Biopsy Specimen; Bispecific Antibody 2B1; Celiac Disease; Chronic; Clinical; Cloning; Cluster Analysis; Colon; Colonoscopy; Colorectal; Complex; Computer software; Crohn' s disease; Custom; DNA; Data; Databases; Disease; Distal part of ileum; Effectiveness; Environment; Environmental Microbiology; Feces; Fingerprint; Flare; Flexible fiberoptic sigmoidoscopy; Future; Gender; Genus Cola; Hand; Health; Healthcare Systems; Heterogeneity; Human; Human body; Immunosuppressive Agents; Incidence; Individual; Infection; Inflammatory; Inflammatory Bowel Diseases; Intestines; Irritable Bowel Syndrome; Knowledge; Length; Link; Machine Learning; Maps; Medicine; Methods; Molecular Biology; Molecular Cloning; Morbidity - disease rate; Mucous Membrane; Newly Diagnosed; Numbers; Operative Surgical Procedures; Organ; Organism; Patients; Pattern; Pattern Recognition; Pattern Recognition Systems; Pharmaceutical Preparations; Polymerase Chain Reaction; Population; Probiotics; Procedures; Race; Reaction; Recruitment Activity; Relapse; Relative (related person); Research Personnel; Ribosomal RNA; Sampling; Schedule; Screening procedure; Soil; Surveys; Techniques; Technology; Testing; Time; Tissues; Toxic effect; Ulcerative Colitis; Visual; base; carcinogenesis; clinical application; computerized; cost; data mining; disabling disease; ileum; indexing; microbial; microbial community; neglect; novel; novel diagnostics; pathogen; prebiotics; programs; satisfaction; success; time use; tool; treatment effect

DESCRIPTION (provided by applicant): Inflammatory Bowel Diseases (IBDs), namely ulcerative colitis (DC) and Crohn's disease (CD), are chronic, lifelong, relapsing illnesses, affecting close to 1 million Americans. Despite the many clues that a dysbiosis may exist in IBD, the specific changes in the microflora of IBD patients are largely unknown. Amplicon length heterogeneity (ALH) is a sophisticated and well established PCR based technology that can be used as a screening tool to identify changes in the Bacterial microflora of IBD patients. We therefore have hypothesized that the ileocolonic microflora in IBD has an altered microbial composition compared to normal microflora. We have gathered preliminary data that shows statistical differences between controls and IBD as well as within IBD patients. Therefore, to test the above hypothesis, we are proposing the following 2 inter-related scientific aims: AIM 1. Identify bacterial fingerprint patterns associated with IBD using ALH. ALH patterns will be determined in a total of 160 IBD patients and health controls and will be analyzed using diversity indeces, multivariate reduction analysis and cluster analysis. ALH patterns associated with IBD will be determined using histograms, ecological software in conjunction with custom PERL scripts as well as supervised and unsupervised automated pattern recognition systems. AIM 2.Determine the bacterial contents of putatively IBD associated ALH fingerprint patterns using molecular cloning and sequencing. Cloning and sequencing of targeted samples will be linked to bacterial identities by employing multiple bioinformatics tools. Significance. This proposal involves the first time use of a sophisticated and highly reproducible molecular biology tool, ALH, in the study of microflora in the Gl tract. There is a growing recognition of the importance of microflora in health and disease, including IBD. Studies that characterized microflora in human using powerful techniques from environmental microbiology such as ALH can bring about significant advances in the understanding of Gl tract illnesses. ALH may enable a real-time survey of microfloral changes for the first time in medicine and may provide the first evidence linking IBD with specific microbial patterns.

描述（由申请人提供）： 炎症性肠病 (IBD)，即溃疡性结肠炎 (DC) 和克罗恩病 (CD)，是慢性、终生、复发性疾病，影响着近 100 万美国人。尽管有许多线索表明 IBD 可能存在菌群失调，但 IBD 患者微生物群落的具体变化在很大程度上尚不清楚。扩增子长度异质性 (ALH) 是一种复杂且完善的基于 PCR 的技术，可用作筛查工具来识别 IBD 患者细菌微生物群落的变化。因此，我们假设 IBD 中的回结肠微生物群与正常微生物群相比具有改变的微生物组成。我们收集的初步数据显示了对照和 IBD 之间以及 IBD 患者之间的统计差异。因此，为了检验上述假设，我们提出以下 2 个相互关联的科学目标： 目的 1. 使用 ALH 识别与 IBD 相关的细菌指纹模式。将确定总共 160 名 IBD 患者和健康对照者的 ALH 模式，并使用多样性指数、多变量还原分析和聚类分析进行分析。与 IBD 相关的 ALH 模式将使用直方图、生态软件结合定制 PERL 脚本以及监督和非监督自动模式识别系统来确定。目的 2. 使用分子克隆和测序确定假定的 IBD 相关 ALH 指纹模式的细菌含量。通过采用多种生物信息学工具，目标样本的克隆和测序将与细菌身份相关联。意义。该提案首次使用复杂且高度可重复的分子生物学工具 ALH 来研究胃肠道微生物区系。人们越来越认识到微生物群落对健康和疾病（包括炎症性肠病）的重要性。使用环境微生物学（例如 ALH）的强大技术来表征人类微生物群落的研究可以为对胃肠道疾病的理解带来重大进展。 ALH 可能首次在医学领域实现微生物变化的实时调查，并可能提供将 IBD 与特定微生物模式联系起来的第一个证据。