Adherent Invasive E. coli and colitis

描述（由申请人提供）：人类大肠是一个以专性厌氧细菌为主的复杂微生物群落的宿主。然而，肠道炎症的条件导致兼性厌氧肠杆菌科的相对丰度增加，如大肠杆菌。粘附性侵袭性大肠杆菌（AIEC）通常从克罗恩病患者的肠黏膜中分离出来，而不是从健康对照中分离出来。我们的中心假设是，终端呼吸电子受体作为炎症反应的副产品产生，使大肠杆菌能够有效地淘汰竞争的专性厌氧细菌，这一过程可以促进AIEC的繁殖，这反过来又进一步刺激肠粘膜。我们将通过确定由厌氧呼吸推动的AIEC爆发是否会维持和加剧肠道炎症来验证我们假设的关键方面（目的1）。这项提议的工作是创新的，因为它是第一个阐明控制宿主及其微生物群之间平衡的分子机制。这项工作的成功完成将对理解肠道炎症条件下微生物群落结构的变化具有广泛的意义，因为厌氧呼吸是控制肠道内大肠杆菌生长的基本原理之一。

DESCRIPTION (provided by applicant): The human large intestine is host to a complex microbial community dominated by obligate anaerobic bacteria. However, conditions of intestinal inflammation lead to an increased relative abundance of facultative anaerobic Enterobacteriaceae, such as Escherichia coli. Adherent- invasive E. coli (AIEC) are isolated more commonly from the intestinal mucosa of individuals with Crohn's disease than from healthy controls. Our central hypothesis is that terminal respiratory electron acceptors are generated as a by-product of the inflammatory response and enable E. coli to efficiently edge out competing obligate anaerobic bacteria, a process that can fuel a bloom of AIEC, which in turn further irritates the intestinal mucosa. We will test key aspects of our hypothesis by determining whether a bloom of AIEC fueled by anaerobic respiration sustains and exacerbates intestinal inflammation (Aim 1). The proposed work is innovative because it is among the first to elucidate a molecular mechanism that controls the balance between the host and its microbiota. Successful completion of this work will have broad relevance for understanding changes in the microbial community structure during conditions of intestinal inflammation by establishing anaerobic respiration as one of the fundamental principles that governs growth of E. coli in the gut lumen.