Gut microbiome evolution via nature verses nurture: the iaffect of changing environments on the developing mammalian gut microbial ecosystem and immunity.

人类的胃肠道中有各种各样的共生细菌和其他微生物，统称为肠道微生物区系。这种微生物群体及其遗传物质被称为肠道微生物组。肠道微生物群与人类新陈代谢、肠道发育和正常生理、免疫成熟和耐受有关，最近还与大脑过程和行为有关。肠道微生物群是一个微生物生态系统，它的运作非常像一个器官，其功能是促进正常的人类生理。这项当前的计划将寻求了解肠道细菌群落结构组合如何在哺乳动物肠道中形成的基础，重点是环境和遗传的作用。虽然有证据支持肠道微生物区系是从母亲垂直传播的，但也认为环境是通过水平传播在肠道中获得的微生物的来源。然而，外界环境在肠道微生物群发育中的作用还知之甚少。在这个建议中，我们开始获得一个基本的理解，即先天和后天如何影响哺乳动物肠道内微生物的水平和垂直转移。总体而言，我的研究有助于了解外部环境、肠道微生物区系和肠道粘膜免疫之间的复杂关系。在很大程度上，我假设肠道微生物区系的定植是形成免疫耐受性的控制点，从而形成免疫成熟。因此，我将研究影响肠道微生物群的因素及其对免疫发育的影响。我的长期研究目标是在分子水平上了解微生物如何占据肠道中的特定生态位。在我对这一领域有所了解之前，我首先需要研究哪些因素影响组成肠道中群落组合的微生物类型。反过来，我试图了解这些群落的变化可能如何影响肠道中的免疫发展和耐受性。在接下来的5年里，我将集中在以下方面：*目标1：了解环境对哺乳动物肠道微生物群发育的影响。*目标2：了解环境对肠道微生物-宿主界面影响免疫的影响。*意义：这项研究将塑造我们对各种环境和遗传因素对肠道微生物区系组成、多样性和组装的作用的理解，确定自然与后天肠道微生物组研究的主要挑战，以及这如何影响肠道微生物-宿主动态。这将有助于描述微生物群如何影响肠道免疫成熟和免疫耐受背后的机制(S)，这对于了解肠道微生物区系如何影响局部和系统免疫结果非常重要。总体而言，我将培养2名硕士和3名博士生。

The human gastrointestinal tract is colonized with a diverse range of symbiotic bacteria and other microorganisms, collectively known as the gut microbiota. This population of microorganisms and their genetic material is referred to as the gut microbiome. The gut microbiome has been linked to human metabolism, gut development and normal physiology, immune maturation and tolerance, and more recently with brain processes and behavior. The gut microbiome is a microbial ecosystem that operates much like an organ, functioning to promote normal human physiology. This current program will seek to understand the basis of how the gut bacterial community structural assemblages form in the mammalian gut with a focus on the role of the environment and genetics. While there is evidence to support that the gut microbiota is vertically transmitted from the mother, it is also considered that the environment is a source of microbes that are acquired in the gut through horizontal transmission. Yet, the role of the external environment in gut microbiome development is poorly understood. In this proposal, we set out to gain a fundamental understanding of how nature vs. nurture influences horizontal and vertical transfer of microbes in the mammalian gut. Overall, my research serves to understand the complex relationship between the external environment, the intestinal microbiota and gut mucosal immunity. Largely, I hypothesize that intestinal colonization by the microbiota is a control point that shapes immune tolerance and consequently, immune maturation. Thus, I will examine factors that affect the gut microbiome and its impact on immune development. My long-term research goal is to understand how microbes occupy specific niches in the gut on a molecular level. Before I can gain understanding in this area, I first need to study what factors influence the types of microbes that make up community assemblages in the gut. In turn, I seek to understand how these community changes might affect immune development and tolerance in the gut. Over the next 5 years, I will focus on the following:******Objective 1: To understand the effects of the environment on the development of the gut microbiome in the mammalian gut.******Objective 2: To understand the effects of the environment on the gut microbe-host interface impacting immunity.******Significance: This research will shape our understanding about the role of various environmental and genetic factors on the gut microbiota composition, diversity and assembly, identify major research challenges for nature vs. nurture gut microbiome studies and how this effects the microbe-host dynamic in the gut. This will help delineate the mechanism(s) behind how the microbiome affects intestinal immune maturation and immunotolerance important for understanding how the gut microbiota influences not only local but also systemic immune outcomes. Overall, I will train 2 Masters and 3 PhD students.*****