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Roles of the microbiota in inflammatory bowel diseases.

机译:微生物群在炎症性肠病中的作用。

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摘要

Studying the roles of the microbial community structure as it relates to disease can give important insight into development of inflammation. This study employs concepts present in ecology to understand how altering bacterial communities in mammalian intestines affect inflammation at different stages of disease. The overall goal is to understand the role of the resident microbiota in initiation and progression of inflammatory bowel disease (IBD). Changes in the community can possibly act as a biomarker to diseases allowing preventative action to be taken or development of novel therapies.;Work was done on two different models of IBD, dextran sodium sulfate (DSS)-induced murine colitis and Helicobacter hepaticus triggered inflammation in IL-10-/- mice (model of Crohn's disease). Through culture independent techniques, changes in the microbiota were investigated, together with alterations in host mediators.;In the first model, whether DSS-induced colitis was associated with changes in the microbiota was investigated. DSS administration was associated with microbial changes in intestinal communities in mice and these changes were present at onset of inflammation and persisted through later stages of disease. In the second model, whether changes in microbial community structure affected disease severity was investigated. The H. hepaticus triggered disease model was used to explore this question, and it was found that H. hepaticus infection of mice with different microbial community structures resulted in similar disease outcomes. This indicated that disease severity was independent from antibiotic-induced changes in the microbial community in this model. We also show that the microbiota is essential in disease induction in mice in our colonies, as H. hepaticus monoassociated mice do not develop disease.;These experiments demonstrate that the microbiota has important roles at several stages of disease, and these roles can be affected by other factors that influence IBD. In investigating stages at which the microbiota plays a role in IBD, we can better understand stages along disease progression when prognosis or treatment can be most effective.
机译:研究与疾病有关的微生物群落结构的作用可以为炎症的发展提供重要的见识。这项研究利用生态学中存在的概念来了解哺乳动物肠道中细菌群落的变化如何在疾病的不同阶段影响炎症。总体目标是了解驻留微生物群在炎症性肠病(IBD)的发生和发展中的作用。社区的变化可能会成为疾病的生物标志物,从而可以采取预防措施或开发新的疗法。研究了两种不同的IBD模型,即右旋糖酐硫酸钠(DSS)诱发的小鼠结肠炎和肝炎引起的肝炎在IL-10-/-小鼠中(克罗恩病模型)。通过独立于培养的技术,研究了微生物群的变化以及宿主介体的变化。在第一个模型中,研究了DSS诱导的结肠炎是否与微生物群的变化有关。 DSS给药与小鼠肠道菌群的微生物变化有关,这些变化出现在炎症发作时,并持续到疾病的后期。在第二个模型中,研究了微生物群落结构的变化是否影响了疾病的严重程度。肝炎H.触发的疾病模型被用来探讨这个问题,并且发现具有不同微生物群落结构的小鼠感染H. HC会导致相似的疾病结果。这表明该模型中疾病的严重程度与抗生素诱导的微生物群落变化无关。我们还证明了微生物群在我们殖民地小鼠的疾病诱导中是必不可少的,因为肝单链肝炎相关小鼠不会发展疾病。这些实验表明微生物群在疾病的多个阶段都具有重要作用,并且这些作用可能会受到影响其他影响IBD的因素。在研究微生物群在IBD中起作用的阶段时,我们可以更好地了解疾病的发展过程,以便预测或治疗最有效。

著录项

  • 作者

    Nagalingam, Nabeetha Aarti.;

  • 作者单位

    Michigan State University.;

  • 授予单位 Michigan State University.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 209 p.
  • 总页数 209
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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