Gut microbiome evolution via nature verses nurture: the affect 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，其运作很像微生物器官，其功能是促进健康和预防疾病。了解肠道微生物群如何影响炎症性肠病等疾病易感性是我通过克罗恩病和结肠炎加拿大分部提供健康相关研究资金并提交给CIHR的基础。我的NSE相关工作的基础是理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，但也有人认为环境是肠道中通过水平传播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，在接下来的五年里，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。我未来5年的短期目标将集中在以下几个方面。目的1：了解环境对哺乳动物肠道微生物群发育的影响。目的2：了解环境诱导的肠道微生物群如何影响宿主免疫。意义：缺乏对宿主和环境因素对哺乳动物肠道内微生物变异的影响的了解，这是将微生物组知识转化为应用的障碍。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研究挑战，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。

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 a microbial organ that functions to promote health and prevent disease. Understanding how the gut microbiome affects disease susceptibility like inflammatory bowel disease is the basis of my health-related research funding through Crohn's and Colitis Canada and submitted to CIHR. The basis of my NSE-related work is understanding the basis of how the gut bacterial community structural assemblages form in the mammalian gut with a focus on the role of the environment. While there is evidence to support that the gut microbiota is vertically transmitted from the mother it is also believed 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, over the next five years I will examine factors that affect the gut microbiome and its impact on immune development. My short term goals of this research program over the next 5 years will focus on the following objectives. 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 how environment-primed gut microbiomes impact host immunity.  Significance: The lack of understanding about the impact of host and environmental factors on microbial variation within the mammalian gut is an obstacle for translating knowledge of the microbiome for application. 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.