Microbial Ecology of Helicobacter-induced Colitis

描述（由申请人提供）：炎症性肠病（IBD）的特征在于 胃肠道中出现异常炎症反应。的 肠道微生物群，部分通过与宿主上皮细胞的相互作用， 免疫系统被认为驱动这种促炎状态。肠道微生物群 代表了一个复杂的细菌群落，直到最近， 表征了使用非培养技术检测复杂微生物 已经开始揭示肠道的结构和组成的细节 微生物群到目前为止，在确定结构差异方面所做的工作很少。 肠道的粘膜相关微生物群继发于 宿主免疫系统、病原体的存在、抗生素治疗或 益生菌（probiotic）在这项提案中， 对微生物生态学和传染病/细菌感兴趣的科学家 发病机制计划调查肠道微生物群在IBD中的作用， 在IL-10-/-小鼠中开发了IBD的鼠模型， 肝螺杆菌 具体来说，我们建议1）确定宿主免疫系统的影响 塑造粘膜相关肠道微生物群的群落结构2） 确定H.肝感染和结肠炎的发展改变了 粘膜相关的肠道微生物群和3）确定抗生素是否可以改变 H.肝感染的IL-10-/-动物。拟议的实验 将提供深入了解感染因子可以触发转变的机制， 导致异常宿主反应和疾病状态的固有微生物群。这 信息将直接影响炎症性肠病患者， 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 免疫系统和肠道内的微生物之间的相互作用。 该项目旨在确定肠道微生物群落的异常， 易患炎症性肠病，指出了 这种慢性疾病的新疗法影响了1000人中的1人， 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.