Adherent Invasive E. coli and colitis

粘附性侵袭性大肠杆菌和结肠炎

• 批准号: 8662700
• 负责人: Andreas J Baumler
• 金额: $ 19.25万
• 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/8662700
• 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）：人类大肠寄托着一个以巨大厌氧菌细菌为主的复杂微生物群落。然而，肠道炎症的条件导致兼性厌氧肠杆菌科的相对丰度，例如大肠杆菌。与健康对照组相比，粘附的浸润性大肠杆菌（AIEC）更常见于克罗恩病个体的肠粘膜。我们的中心假设是，末端呼吸电子受体是作为炎症反应的副产品产生的，并使大肠杆菌能够有效地摆脱竞争性的强制性厌氧菌细菌，这一过程可以为AIC增添一花，从而进一步刺激了肠道粘膜。我们将通过确定厌氧呼吸促进的AIC的绽放是否维持并加剧肠道炎症（AIM 1）来检验假设的关键方面。提出的工作具有创新性，因为它是最早阐明一种分子机制来控制宿主与其微生物群之间平衡的人之一。这项工作的成功完成将在肠道炎症条件下通过建立厌氧呼吸作为控制肠道大肠杆菌增长的基本原理之一，这将在理解微生物群落结构的变化方面具有广泛的意义。