Determination of the importance of colonization history in the assembly of the ga

描述（由申请人提供）：人类胃肠道由与其宿主密切相互作用的微生物（肠道微生物组）的高潮群体定殖。肠道微生物组与宿主代谢和免疫功能之间的联系是复杂而重要的;肠道微生物组的获取或最终组成的异常被认为是复杂疾病（如肥胖症，炎症性肠病和胃癌）的重要易感因素。与这些多因素疾病一样，肠道微生物组的组成本身是一种复杂的性状，受环境因素（机会、暴露、饮食）和许多宿主遗传因素（如影响粘膜免疫的因素）的影响。微生物种群组装过程中生态位相关、中性和历史过程的相对影响是目前群落生态学领域的一个热门话题，这些概念对于胃肠道中的微生物生态学也具有重大意义。通过一套综合的协同特定目标，我们将探索小鼠肠道微生物组组装的定植历史。我们进行这项研究的理由是，对肠道微生物群如何组装的精确理解是必要的，可以为重塑微生物群和抵消异常定植模式的成功策略提供信息。我们的工作假设是，历史过程，特别是殖民秩序，是肠道微生物群组装过程中的主要决定因素。我们目前的目标是表征肠道微生物群组装过程中定植顺序的重要性，测试适应性免疫系统是否影响这一过程，并确定定植顺序是否影响特定“益生菌”菌株的长期持久性。我们的创新实验利用了知生菌技术和我们在实验小鼠中创建和评估复杂微生物种群的广泛专业知识。该提案中所代表的团队已经建立了令人印象深刻的合作，以创造新的实验方法和有利的研究环境。

DESCRIPTION (provided by applicant): The human gastrointestinal tract is colonized by a climax population of microbes (the gut microbiome) that interacts intimately with its host. Linkages between the gut microbiome and host metabolic and immune functions are complex and vital; aberrations in the acquisition or ultimate composition of the gut microbiome are believed to be an important predisposition factor in complex diseases such as obesity, inflammatory bowel disease, and gastric cancers later in life. Like these multifactorial diseases, composition of the gut microbiome is in itself a complex trait, affected by both environmental factors (chance, exposure, diet) and a number of host genetic factors such as those influencing mucosal immunity. The relative influence of niche-related, neutral, and historical processes in the assembly of microbial populations is currently a topic of hot debate in the field of community ecology, and these concepts are also of major significance for the microbial ecology in the gastrointestinal tract. With an integrated set of synergistic specific aims, we will explore the roe of colonization history for the assembly of the gut microbiome in mice. Our rationale for this research is that a refined understanding of how the microbiota of the gut is assembled is necessary to inform successful strategies to reshape microbiotas and counteract aberrant patterns of colonization. Our working hypothesis is that Historic Processes, and especially colonization order, are major determinants during the assembly of the gut microbiota. Our current objectives are to characterize the importance of colonization order in the assembly process of the gut microbiota, test whether the adaptive immune system influences this process, and determine if colonization order affects long-term persistence of specific 'probiotic' strains. Our innovative experiments capitalize on gnotobiotic technology and our extensive expertise in creating and evaluating complex microbial populations in experimental mice. The team represented in this proposal has forged impressive collaborations to create a new experimental approach and favorable research environments.