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

描述(由申请人提供)：人类胃肠道被与其宿主密切互动的微生物(肠道微生物群)的高峰期占据。肠道微生物群与宿主代谢和免疫功能之间的联系是复杂和重要的；肠道微生物群获取或最终组成的异常被认为是复杂疾病的重要易感因素，如肥胖、炎症性肠病和以后的胃癌。与这些多因素疾病一样，肠道微生物群的组成本身是一个复杂的特征，既受环境因素(机会、暴露、饮食)和一些宿主遗传因素的影响，如那些影响粘膜免疫的因素。生态位相关的、中性的和历史的过程在微生物种群聚集中的相对影响是目前群落生态学领域争论的热点，这些概念对胃肠道微生物生态学也具有重要意义。通过一套整合的协同作用的特定目标，我们将探索在小鼠体内组装肠道微生物组的定殖史。我们这项研究的基本原理是，对肠道微生物区系如何组装的精细理解对于制定成功的战略来重塑微生物区系和对抗异常的殖民模式是必要的。我们的工作假设是，历史过程，特别是定居顺序，是肠道微生物区系组装过程中的主要决定因素。我们目前的目标是表征定植顺序在肠道微生物区系组装过程中的重要性，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。我们的创新实验充分利用了诺生菌技术和我们在实验小鼠身上创造和评估复杂微生物种群方面的广泛专业知识。这项提案中代表的团队已经建立了令人印象深刻的合作，以创造一种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.