Adherent Invasive E. coli and colitis

粘附性侵袭性大肠杆菌和结肠炎

• 批准号: 8569896
• 负责人: Andreas J Baumler
• 金额: $ 21.71万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-17 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8569896
• 关键词: Address; Anaerobic Bacteria; Bacteroidetes; Cells; Colitis; Communities; Complex; Crohn' s disease; Data; Development; Dimethyl Sulfoxide; Enterobacteriaceae; Equilibrium; Escherichia coli; Excision; Family; Fermentation; Funding Mechanisms; Goals; Growth; Human; Human body; Immune system; Individual; Inflammation; Inflammatory Response; Inflammatory disease of the intestine; Intestinal Mucosa; Knowledge; Laboratories; Large Intestine; Lead; Microbe; Modeling; Molecular; Mus; Nitrates; Nitrogen; Nutrient; Outcome; Oxidants; Oxygen; Process; Production; Proteobacteria; Relative (related person); Research; Resolution; Respiration; Science; Structure; System; Testing; Work; base; expectation; innovation; insight; microbial; microbial community; mouse model; mutant; prevent; public health relevance; research study; respiratory; trimethyloxamine

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.

描述（由申请人提供）：人体大肠是以专性厌氧菌为主的复杂微生物群落的宿主。然而，肠道炎症的状况导致兼性厌氧肠杆菌科（如大肠杆菌）的相对丰度增加。粘附-侵袭性E.大肠杆菌（AIEC）更常见地从克罗恩病个体的肠粘膜中分离，而不是从健康对照中分离。我们的中心假设是终末呼吸电子受体作为炎症反应的副产物产生，并使E。大肠杆菌，以有效地排挤竞争专性厌氧菌，这一过程可以燃料的AIEC，这反过来又进一步刺激肠粘膜的大量繁殖。我们将通过确定由无氧呼吸引起的AIEC激增是否会维持和加剧肠道炎症来测试我们假设的关键方面（目的1）。这项研究具有创新性，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的研究。这项工作的成功完成将有广泛的相关性，通过建立厌氧呼吸作为控制大肠杆菌生长的基本原则之一，了解肠道炎症条件下微生物群落结构的变化。大肠杆菌。