Host-Flora interactions: Susceptibility to colitis

宿主-菌群相互作用：结肠炎易感性

基本信息

批准号：
7340173
负责人：
Abigail Henderson
金额：
$ 1.68万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-01-27 至 2008-07-11
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7340173
关键词：
Acetic Acid Acetic Acids Address Adoptive Transfer Affect Animal Model Animals Antibiotics Antibody Formation Antigens B-Lymphocytes Bacteria Blood Body Weight decreased CD4 Positive T Lymphocytes Carrageenan Categories Cecum Cells Chemicals Chronic Clinical Colitis Colon Condition Crohn&apos s disease Data Defect Development Dextran Sulfate Diarrhea Disease Disease model Disruption Dose Ecology Edema Enterobacteriaceae Enterocolitis Environmental Risk Factor Epithelial Epithelial Cells Epithelium Esophagus Ethanol Etiology Event Experimental Animal Model Feces Gene Targeting Genetic Genetic Predisposition to Disease Genus Cola Gnotobiotic Goals Gossypium HLA-B27 Antigen Helicobacter Histologic Housing Human Hyperplasia IL2 gene Immune Immune response Immunity Immunodeficient Mouse Indomethacin Infiltration Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory disease of the intestine Injury Interleukin-10 Interleukin-12 Interleukin-2 Intestinal Mucosa Intestines Irritants Laboratories Lamina Propria Lesion Lymphocyte Measures Mediating Medical Methods Modeling Mononuclear Mucosal Immune Responses Mucosal Immunity Mucositis Mucous Membrane Multidrug Resistance Gene Mus Mutation N-Cadherin Nature Nausea and Vomiting Neutrophil Infiltration One-Step dentin bonding system Oxazolone Pathogenesis Peptidoglycan Polysaccharides Population Predisposition Production Reagent Rectum Relative (related person)Reporting Research Resistance Rodent SCID Mice Saguinus Score Secondary to Severities Severity of illness Site Sodium Sodium Dextran Sulfate Spleen Symptoms T-Lymphocyte TNF gene Testing Th1 Cells Tonsil Transgenic Model Trinitrobenzenesulfonic Acid Ulcer Ulcerative Colitis United States Weight Work career chemokine cost crypt cell cytokine gastrointestinal genetic manipulation immunoregulation intraepithelial member microbial mouse model prevent response retinal rods size trefoil factor wasting

项目摘要

Gastrointestinal (Gl) diseases affect over 70 million people in the United States annually. In 1992, the collective medical costs of Gl diseases was reported to be in excess of $100 billion in the US alone. Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease of the Gl tract and the etiology is unknown. Resident intestinal bacteria have been implicated in the pathogenesis of IBD as evidenced by the resistance of germfree mice to many forms of colitis in comparison to colitis observed in mice bearing a conventional microflora. Preliminary data shows that colonization of gnotobiotic mice with Helicobacter bilis induces antigen-specific responses to members of the resident flora. We propose that a disruption of the microbial ecology of the Gl tract induces aberrant immune responses directed at luminal antigens, resulting in an increased susceptibility to colitis. To test this hypothesis, we will inoculate gnotobiotic mice with H.bilis and evaluate their susceptibility to a colitic insult (low dose dextran sulfate sodium, DSS). Comparisons in disease severity and immune responses will be assessed between groups. Results from these studies will add to our understanding of the host-flora interactions that contribute to the susceptibility to colitis.

胃肠道 (GI) 疾病每年影响美国超过 7000 万人。 1992 年，据报道，仅在美国，胃肠道疾病的集体医疗费用就超过 1000 亿美元。炎症性肠病（IBD）是一种胃肠道慢性炎症性疾病，其病因是未知。肠道常驻细菌与 IBD 的发病机制有关，证据如下：与在无菌小鼠中观察到的结肠炎相比，无菌小鼠对多种形式的结肠炎具有抵抗力常规微生物区系。初步数据表明，胆汁螺杆菌定植于无菌小鼠诱导对常驻菌群成员的抗原特异性反应。我们建议中断胃肠道的微生物生态诱导针对管腔抗原的异常免疫反应，从而导致结肠炎的易感性增加。为了验证这一假设，我们将用 H.bilis 给无菌小鼠接种并评估他们对结肠炎损伤（低剂量葡聚糖硫酸钠，DSS）的敏感性。比较将在组之间评估疾病的严重程度和免疫反应。这些研究的结果将增加我们对导致结肠炎易感性的宿主菌群相互作用的理解。