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，是人类不可或缺的组成部分 健康。与因其扩散而造成损害的病原体不同，互惠互利的群落 微生物对宿主的正常运作是必不可少的。在胃肠道中，微生物在肠道中起着关键作用 维持肠道内环境平衡，包括与摄入的病原体竞争(“殖民抵抗”)； 摄取化合物的解毒、维持粘膜免疫和短链脂肪的产生 酸-结肠肠道细胞的首选能源和强大的免疫调节信号。而联合- 微生物及其人类宿主的进化导致了肠道内微生物群落的遗传多样性， 宿主的微环境塑造了这些群落。在这份提案中，我们将重点关注 氧气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，导致微氧区，在那里低氧浓度 影响微生物群落和宿主细胞的潜力。长期持有的关于 支持呼吸所需的氧气浓度最近受到了挑战，因为发现 大肠杆菌种群在氧气浓度低于3 NM的情况下生长和呼吸-超过2个数量级 比之前估计的要低。我们建议测试低氧环境对生物多样性的影响。 哺乳动物胃肠道微生物群落的结构和功能。 我们将研究氧气梯度在控制微生物群落结构和活动中的作用，如 我们致力于以下具体目标：1)确定人类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群，并评估竞争性 这些微氧菌的适合性；2)使用体外空间结构的微环境，具有氧气传感功能 元素，以评估氧气在确定微生物的竞争适合性中的作用；以及3)测量 无菌小鼠和细菌定植小鼠粘膜表面的活体氧浓度 社区。此外，我们将确定处理氧气的策略的差异是否会给相对 对某些生物具有生态优势。了解氧在塑造结构和结构中的作用 微生物群落的功能将提高我们建立预测模型的能力 宿主和微生物区系，不仅在胃肠道，而且在身体上任何生物膜产生氧气梯度的地方。

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.