Microbial Ecology of Helicobacter-induced Colitis

描述(申请人提供)：炎症性肠病(IBD)的特征是 胃肠道异常炎症反应的发展。这个 肠道微生物区系，部分通过与宿主上皮和 免疫系统被认为是驱动这种促炎状态的因素。肠道微生物区系 代表了一个复杂的细菌群落，直到最近才部分地 特色化的。使用与培养无关的技术检查复杂的微生物 社区已经开始揭示关于肠道的结构和组成的细节 微生物区系。到目前为止，只做了很少的工作来定义 肠道粘膜相关微生物区系继发于肠道的改变 宿主免疫系统、病原体的存在、抗生素治疗或 有益的(益生菌)生物。在这份提案中，现有的合作 对微生物生态学和传染病/细菌感兴趣的科学家 利用一口井研究肠道微生物区系在IBD中的作用的发病计划 建立IL-10-/-小鼠IBD动物模型 肝螺杆菌。 具体地说，我们建议1)确定宿主免疫系统的影响 关于塑造与粘膜相关的肠道微生物区系的群落结构2 确定肝包虫感染和结肠炎的发展如何改变 与粘膜相关的肠道微生物区系和3)确定抗生素是否可以改变 肝炎病毒感染IL-10-/-动物IBD的发生发展拟议中的实验 将提供对感染性病原体触发 导致寄主异常反应和疾病状态的本土微生物区系。这 信息将直接影响炎症性肠病患者，导致 更好地了解潜在的疾病机制和发展 新的治疗方式。 相关性：人类炎症性肠病被认为是由一种异常的 免疫系统与通常居住在肠道中的微生物之间的相互作用。 该项目旨在定义肠道微生物群落中的异常现象 易患炎症性肠病，指明方向 这种慢性疾病的新疗法在发达国家每1000人中就有1人受到影响 国家。

DESCRIPTION (provided by applicant): Inflammatory bowel disease (IBD) is characterized by the development of an abnormal inflammatory response in the gastrointestinal tract. The microbiota of the intestinal tract, in part via interactions with the host epithelium and immune system are thought to drive this proinflammatory state. The gut microbiota represents a complex community of bacteria that until recently has only been partly characterized. The use of culture-independent techniques to examine complex microbial communities has started to reveal details about the structure and composition of the gut microbiota. To date, minimal work has been done to define differences in the structure of the mucosa-associated microbiota of the intestinal tract secondary to alterations in the host immune system, the presence of pathogens, antibiotic treatment or the presence of beneficial (probiotic) organisms. In this proposal, an existing collaboration between scientists with interests in microbial ecology and infectious diseases/bacterial pathogenesis plan to investigate the role of the intestinal microbiota in IBD utilizing a well developed murine model of IBD in IL-10-/- mice triggered by the presence of the bacterium Helicobacter hepaticus. Specifically we propose to 1) determine the influence of the host immune system on shaping the community structure of the mucosa-associated intestinal microbiota 2) determine how H. hepaticus infection and the development of colitis changes the mucosa-associated intestinal microbiota and 3) determine if antibiotics can modify the development of IBD in H. hepaticus-infected IL-10-/- animals. The proposed experiments will provide insight into the mechanism by which infectious agents can trigger shifts in the indigenous microbiota that lead to aberrant host responses and disease states. This information will directly impact patients with inflammatory bowel disease, leading to a greater understanding of the underlying disease mechanisms and the development of novel treatment modalities. Relevance: Inflammatory bowel disease in humans is thought to arise from an abnormal interaction between the immune system and the microbes that normally inhabit the gut. This project intends to define abnormalities in the community of gut microbes that predispose to the development of inflammatory bowel disease, pointing the way towards new therapies for this chronic disease that affects 1 in 1000 people in developed countries.