Effects of host associated microbial community composition on maturation of the i

宿主相关微生物群落组成对 i 成熟的影响

• 批准号: 8701879
• 负责人: ANNAH ROLIG
• 金额: $ 5.33万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701879
• 关键词: Address; Aeromonas; Affect; Bacteria; Bacterial Genes; Cardiovascular Diseases; Cells; Communities; Data; Development; Diabetes Mellitus; Disease; Ecology; Education; Equilibrium; Gene Expression; Gene Expression Profile; Genes; Gnotobiotic; Goals; Health; Health system; Human; Human Microbiome; Immune; Immune response; Immune system; Individual; Infection prevention; Inflammatory Bowel Diseases; Intestines; Libraries; Life; Microbe; Modeling; Mono-S; Natural Immunity; Neutrophil Infiltration; Obesity; Play; Probiotics; Research Design; Role; Scientist; Sum; System; Systems Biology; Systems Development; Testing; Therapeutic; Zebrafish; gene induction; gut microbiota; member; microbial community; mutant; public health relevance; response

DESCRIPTION (provided by applicant): The microbiota is imperative for the development of our immune system and thus critical for human health. Studies have identified a few specific members of the gut microbial community that have explicit functions in aiding immune system education, however these studies have been piecemeal. Unanswered questions remain regarding how both bacterial-bacterial interactions and bacterial-host interactions affect immune system development. I hypothesize that within microbial community bacterial-bacterial relations alter bacterial-host interactions that initiate and maintain a healthy immune system. I propose to apply a systems biology approach to examine host-microbe ecology in the simplified system of gnotobiotic zebrafish. The zebrafish is a well-established model for gnotobiotic studies, and possesses many advantages for examining bacterial-host interactions. Most importantly, their gut microbiota is well defined and cultureable, allowing a systematic, comprehensive examination of each species' individual role in immune response education. Specific aims: (1) Test the hypothesis that the immune response to a gut microbial community is different than the sum of the individual immune responses to each member. (2) Determine whether secreted bacterial products contribute to the induction of the innate immune response. (3) Identify Aeromonas veronii genes differentially required for survival within a microbial community compared to an A. veronii single species community. Research Design: To compare immune responses to single bacterial species with immune responses to microbial communities I will examine gut neutrophil infiltration and host transcriptomes in gnotobiotic studies with one or two-member communities. To examine whether secreted products are necessary and sufficient to induce innate immunity, I will examine gut neutrophil infiltration and innate immune gene induction in response to an A. veronii secretion system mutant and to A. veronii cell free supernatent. Finally, to identify A. veronii genes differentially required for survival in a microbal community I will employ the A.veronii transposon library developed in the Guillemin lab. I will focus on genes necessary for colonization that differ between a mono- association of A. veronii and a co-association with A. veronii and a second zebrafish gut microbe. This systematic approach will address the question of how collective activities of microbial communities educate the immune system. This data is vital for interpretation of Human Microbiome Project data, construction of probiotics, and application of microbiota manipulations as a therapeutic approach to treat disease.

描述（由申请人提供）：微生物群对于我们免疫系统的发育至关重要，因此对人类健康至关重要。研究已经确定了肠道微生物群落的一些特定成员，它们在帮助免疫系统教育方面具有明确的功能，但这些研究是零碎的。关于细菌-细菌相互作用和细菌-宿主相互作用如何影响免疫系统发育的问题仍然没有答案。我假设在微生物群落中，细菌-细菌关系改变了启动和维持健康免疫系统的细菌-宿主相互作用。我建议应用系统生物学的方法来研究宿主微生物生态学的简化系统的gnotobiotic斑马鱼。斑马鱼是一种成熟的模式生物研究，并具有许多优势，研究细菌-宿主相互作用。最重要的是，他们的肠道微生物群是明确定义和可培养的，允许系统，全面检查每个物种在免疫反应教育中的个体作用。具体目标：（1）检验对肠道微生物群落的免疫应答不同于对每个成员的个体免疫应答之和的假设。(2)确定分泌的细菌产物是否有助于诱导先天性免疫应答。(3)确定与A. veronii相比，Veronii气单胞菌在微生物群落中生存所需的差异基因。Veronii单种群落研究设计：为了比较对单一细菌物种的免疫反应与对微生物群落的免疫反应，我将在具有一个或两个成员群落的gnotobiotic研究中检查肠道中性粒细胞浸润和宿主转录组。为了检验分泌产物是否是诱导先天免疫所必需和充分的，我将检测肠道中性粒细胞浸润和先天免疫基因诱导对A。veronii分泌系统突变体和A.维罗纳无细胞上清液。最后，对A.在微生物群落中生存所需的差异veronii基因我将使用Guillemin实验室开发的A.veronii转座子文库。我将集中在定植所必需的基因上，这些基因与单联合的A. veronii和与A. veronii和第二种斑马鱼肠道微生物。这种系统的方法将解决微生物群落的集体活动如何教育免疫系统的问题。这些数据对于人类微生物组项目数据的解释，益生菌的构建以及微生物群操作作为治疗疾病的治疗方法的应用至关重要。