Host-Flora interactions: Susceptibility to colitis

宿主-菌群相互作用：结肠炎易感性

• 批准号: 7064723
• 负责人: Abigail Henderson
• 金额: $ 2.94万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-27 至 2009-01-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064723
• 关键词: Helicobacter; T lymphocyte; bacteria infection mechanism; body weight; colitis; cytokine; dextrans; disease /disorder etiology; disease /disorder model; disease /disorder proneness /risk; enteric bacteria; germ free condition; host organism interaction; inflammation; inflammatory bowel diseases; laboratory mouse; mucosal immunity; pathologic process; predoctoral investigator; sodium; sulfates

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：胃肠道 (GI) 疾病每年影响美国超过 7000 万人。据报道，1992 年，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，病因尚不清楚。肠道常驻细菌与 IBD 的发病机制有关，与在携带传统微生物群的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就证明了这一点。初步数据显示，胆汁螺杆菌定植于限生小鼠中，可诱导针对常驻菌群成员的抗原特异性反应。我们提出，胃肠道微生物生态的破坏会诱导针对管腔抗原的异常免疫反应，导致对结肠炎的易感性增加。为了检验这一假设，我们将给无菌小鼠接种 H.bilis，并评估它们对结肠炎损伤（低剂量葡聚糖硫酸钠，DSS）的敏感性。将评估各组之间疾病严重程度和免疫反应的比较。这些研究的结果将加深我们对导致结肠炎易感性的宿主菌群相互作用的理解。