Impacts of Molecular Oxygen on the Structure and Function of the Intestinal Micro

复杂的微生物群落与人体密切相关，是人体不可或缺的组成部分。 健康与病原体因其扩散而造成损害不同， 微生物对宿主的正常功能至关重要。在胃肠道中，微生物在消化道中起着关键作用。 维持肠道内稳态，包括与摄入的病原体竞争（“定植抗性”）， 解毒摄入的化合物，维持粘膜免疫和产生短链脂肪酸， 酸-结肠肠细胞的优选能量来源和有效的免疫调节信号。虽然共同- 微生物和它们的人类宿主的进化导致肠道中微生物的遗传多样性群落， 宿主的微环境塑造了这些群落。在本提案中，我们将重点讨论以下因素的影响： 氧梯度对微生物群落结构和功能的影响。在哺乳动物的胃肠道中，氧气 从宿主扩散到管腔中，导致微氧区，其中低氧浓度 影响微生物群落和宿主细胞的潜力。长期以来的假设 支持呼吸所需的氧气浓度最近受到了以下发现的挑战， 种群E.大肠杆菌生长和呼吸的氧气浓度低于3纳米-超过2个数量级的 低于先前的估计。我们建议测试低氧环境对 哺乳动物胃肠道微生物群落的结构和功能。 我们将研究氧梯度在控制微生物群落结构和活性方面的作用， 我们致力于以下具体目标：1）确定人体内细菌的多样性和丰度 和具有高亲和力细胞色素氧化酶的小鼠肠道微生物组，并评估竞争性 这些微需氧菌的适应性; 2）使用体外空间结构化微环境，具有氧传感 元素，以评估氧气在确定微生物竞争适应性中的作用;和3）测量 无菌小鼠和定植有或微生物的小鼠粘膜表面的体内氧浓度 社区.此外，我们还将确定处理氧气的策略是否存在差异， 对某些生物体的生态优势。了解氧气在形成结构中的作用， 微生物群落的功能将提高我们建立微生物之间相互作用的预测模型的能力。 宿主和微生物群，不仅在胃肠道中，而且在身体的任何地方，生物膜产生氧气梯度。

Complex communities of microbes are intimately associated with the human body and integral to human health. Unlike pathogens that inflict damage as a consequence of their proliferation, communities of mutualistic microbes are essential for the normal functioning of the host. In the GI tract, microbes play critical roles in the maintenance of gut homeostasis, including competition against ingested pathogens ("colonization resistance"), detoxification of ingested compounds, maintenance of mucosal immunity and production of short-chain fatty acids - the preferred energy source of colonic enterocytes and a potent immunomodulatory signal. While co- evolution of microbes and their human host has led to a genetically diverse community of microbes in the gut, microenvironments in the host shape these communities. In this proposal we will focus on the influence of oxygen gradients on the structure and function of microbial communities. In the mammalian GI tract, oxygen diffuses into the lumen from the host, resulting in a microoxic zone where the low oxygen concentrations have the potential to impact both microbial communities and host cells. Long-held assumptions about the concentration of oxygen required to support respiration have been challenged recently by the finding that populations of E. coli grow and respire at oxygen concentrations less than 3 nM - more than 2 orders of magnitude below previous estimates. We propose to test the impact OF low oxygen environments on the structure and function of microbial communities in the mammalian GI tract. We will study the role of oxygen gradients in governing the structure and activity of microbial communities as we address the following specific aims: 1) Determine the diversity and abundance of bacteria in the human and murine intestinal microbiomes that have high-affinity cytochrome oxidases, and assess the competitive fitness of these microaerobes; 2) Use in vitro spatially-structured microenvironments, with oxygen sensing elements, to assess the role of oxygen in determining the competitive fitness of microaerobes; and 3) Measure in vivo oxygen concentrations at the mucosal surface in germ free mice and mice colonized with or microbial communities. Additionally, we will determine if differences in strategies for dealing with oxygen gives a relative ecologic advantage to certain organisms. Understanding the role of oxygen in shaping the structure and function of microbial communities will advance our ability to build predictive models of interactions between the host and microbiota, not only in the GI tract, but anywhere on the body where biofilms create oxygen gradients.