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），溃疡性结肠炎（DC）和克罗恩病（CD）是慢性，终身复发性疾病，影响近100万美国人。尽管有许多线索表明IBD中可能存在营养不良，但IBD患者菌群的特定变化在很大程度上尚不清楚。扩增子长度异质性（ALH）是一种基于PCR的精致技术，可用作筛选工具，以识别IBD患者细菌菌群的变化。因此，我们假设与正常的微生物相比，IBD中的回肠小结构菌群具有改变的微生物组成。我们收集了初步数据，这些数据显示了对照和IBD以及IBD患者之间的统计差异。因此，为了检验上述假设，我们提出了以下2个相互关联的科学目的：目标1。使用ALH确定与IBD相关的细菌指纹模式。 ALH模式将在总共160名IBD患者和健康对照中确定，并将使用多样性，多元减少分析和聚类分析来分析。与IBD相关的ALH模式将使用直方图，生态软件与自定义Perl脚本以及监督和无监督的自动化模式识别系统确定。 AIM 2.确定使用分子克隆和测序的IBD相关ALH指纹模式的细菌含量。靶向样品的克隆和测序将通过使用多种生物信息学工具与细菌身份联系起来。意义。该建议涉及首次使用复杂且高度可再现的分子生物学工具ALH在GL段中的微生物研究中。越来越多地认识到菌群在包括IBD在内的健康和疾病中的重要性。使用环境微生物学（例如ALH）的强大技术在人类中表征菌群的研究可以在理解GL道疾病方面取得重大进展。 ALH可以在医学上首次对微生物变化进行实时调查，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。