The Role of the Gut Microbiota in Ulcerative Colitis

项目摘要 胃肠道的固有微生物群是人类中最丰富的- 相关微生物群落的绝对生物量和相对多样性。 虽然肠道微生物群在维持肠道稳态中起着关键作用， 越来越多的证据表明，肠道微生物群落的紊乱（“生态失调”） 是许多胃肠道疾病状态的基础， 腹泻和炎症性肠病（IBD）。为了解决我们的假设，我们提出 以确定肠道微生物组与 溃疡性结肠炎患者的结肠黏膜炎症。我们将协调和整合 IBD患者研究的现有资源，宏基因组分析，分子生物学 微生物多样性分析和靶向序列辅助细菌培养， 用于研究复杂宿主相关微生物群落的研究管道。我们 将描述人类患者的肠道微生物群， 结肠切除回肠贮袋肛管吻合术治疗结肠癌 溃疡性结肠炎这些患者将在手术后进行临时随访，以监测 囊袋吻合术中粘膜炎症的发展（“囊袋炎”）。 将进行患者内随时间推移的比较和患者间的比较， 肠道微生物组的特定生态和功能特征， 结肠袋炎的发展。为了实现这些目标，我们组织了一个 来自不同学科的经验丰富的综合研究团队。我们将研究A 精心挑选的一组溃疡性结肠炎患者，这将使我们能够在- 和患者内比较。虽然使用高通量，成本- 有效的技术，该团队的成员在其中发挥了关键作用 我们打算证明肠道微生物组在肠道疾病中的关键作用。 发展失调的粘膜免疫应答，这是IBD的标志。 这一知识将引导新的方法来监测IBD患者， 开发新的预防和治疗干预措施。

Project summary 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.