The Role of the Gut Microbiota in Ulcerative Colitis

描述：就绝对生物量和相对多样性而言，胃肠道的本土微生物区系是人类相关微生物群落中最丰富的。虽然肠道微生物区系在维持肠道内环境平衡方面起着关键作用，但越来越多的证据表明，肠道微生物群落的紊乱(“生物失调”)是许多胃肠道疾病状态的基础，包括抗生素相关性腹泻和炎症性肠病(IBD)。为了解决我们的假设，我们建议确定肠道微生物群和溃疡性结肠炎患者黏膜炎症发展之间的关系。我们将协调和整合现有的IBD患者研究、元基因组分析、分子微生物多样性分析和靶向序列辅助细菌培养的资源，形成一个研究管道，用于研究复杂的宿主相关微生物群落。我们将通过构建回肠袋肛门吻合术治疗溃疡性结肠炎，对接受全结肠切除的人类患者的肠道微生物区系进行特征分析。术后将对这些患者进行临时随访，以监测膀胱术后吻合口黏膜炎症的发展(“膀胱炎”)。将进行患者内部和患者之间的比较，以将肠道微生物群的特定生态和功能特征与膀胱炎的发展联系起来。为了实现这些目标，我们组建了一支来自不同学科的经验丰富的综合研究团队。我们将研究一组精心挑选的溃疡性结肠炎患者，这将使我们能够随着时间的推移进行患者间和患者内的比较。虽然使用了高通量、成本效益高的技术，该团队的成员在开发这些技术方面发挥了关键作用，但我们打算证明肠道微生物组在IBD标志的失调粘膜免疫反应的发展中发挥关键作用。这一知识将为监测IBD患者的新方法以及开发新的预防和治疗干预措施开辟道路。与公共卫生相关：人们认为生活在肠道中的细菌在胃肠道健康中发挥着关键作用。我们将通过使用最先进的分子生物学技术和先进的培养技术来确定肠道细菌在人类炎症性肠病发展中的作用。

DESCRIPTION: The indigenous microbiota of the gastrointestinal tract is the richest of the human associated microbial communities in terms of absolute biomass and relative diversity. Although the gut microbiota play critical roles in the maintenance of gut homeostasis, evidence is accumulating that disturbances in the gut microbial community ("dysbiosis") underlie a number of gastrointestinal disease states including antibiotic-associated diarrhea and inflammatory bowel disease (IBD). To address our hypothesis we propose to determine the relationship between the gut microbiome and the development of mucosal inflammation in patients with ulcerative colitis. We will coordinate and integrate existing resources for the study of IBD patients, metagenomic analysis, molecular microbial diversity analysis and targeted sequence-aided bacterial culture into a research pipeline for the study of complex host-associated microbial communities. We will characterize the gut microbiota in human patients who have undergone total colectomy with the construction of an ileal pouch anal anastomosis for treatment of ulcerative colitis. These patients will be followed temporally after surgery to monitor for the development of mucosal inflammation in the pouch anastomosis ("pouchitis"). Comparison within patients over time and between patients will be done to associate specific ecologic and functional characteristics of the gut microbiome with the development of pouchitis. To accomplish these goals, we have assembled an experienced, integrated team of researchers from a variety of disciplines. We will study a carefully selected group of patients with ulcerative colitis that will permit us to make inter- and intra-patient comparisons over time. Though the use of high-throughput, cost effective technologies, which members of this team have played a key role in developing, we intend to demonstrate a critical role for the gut microbiome in the development of the dysregulated mucosal immune response that is the hallmark of IBD. This knowledge will lead the way to novel ways to monitor patients with IBD and to the development of novel preventative and therapeutic interventions. PUBLIC HEALTH RELEVANCE: The bacteria that live in the gut are felt to play a key role in the health of the gastrointestinal tract. We will determine the role of the gut bacteria in the development of human inflammatory bowel disease through the use of state-of-the-art molecular biology techniques and advanced culture techniques.