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

通过自然与培育的肠道微生物组进化：环境变化对发育中的哺乳动物肠道微生物生态系统和免疫力的影响

• 批准号: RGPIN-2019-05181
• 负责人: Gibson, Deanna
• 金额: $ 2.4万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=715404
• 关键词: Gut; microbiome; evolution; via; nature

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.

人类胃肠道被多种共生细菌和其他微生物定植，统称为肠道微生物群。这种微生物及其遗传物质的种群称为肠道微生物组。肠道微生物组与人类代谢，肠道发育和正常生理学，免疫成熟和耐受性有关，最近与脑过程和行为有关。肠道微生物组是一个微生物生态系统，其运作非常类似于微生物器官，可促进健康和预防疾病。了解肠道微生物组如何影响疾病易感性（如炎症性肠病）是我通过加拿大克罗恩斯和结肠炎与健康相关的研究资金的基础，并提交给CIHR。我与NSE相关的工作的基础是了解肠道细菌社区结构组合在哺乳动物肠道中如何形成的基础，重点是环境的作用。虽然有证据表明肠道微生物群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，对外部环境在肠道微生物组发育中的作用知之甚少。在此提案中，我们着手对自然与养育如何影响哺乳动物肠道中微生物的水平和垂直转移的基本了解。总体而言，我的研究有助于了解外部环境，肠道菌群和肠粘膜免疫之间的复杂关系。在很大程度上，我假设微生物群的肠道定植是一个控制点，它塑造了免疫耐受性，从而塑造了免疫成熟。因此，在接下来的五年中，我将研究影响肠道微生物组及其对免疫发育的影响的因素。我在未来5年中的该研究计划的短期目标将集中在以下目标上。 目标1：了解环境对哺乳动物肠道肠道微生物组发展的影响。 目标2：了解环境染色的肠道微生物组如何影响宿主免疫。 意义：缺乏对宿主和环境因素对哺乳动物肠内微生物变化的影响的理解，这是转化用于应用的微生物组知识的障碍。这项研究将影响我们对各种环境和遗传因素在肠道菌群组成，多样性和组装方面的作用的理解，确定对自然与培养肠道微生物组研究的主要研究挑战，以及这如何影响肠道中的微生物 - 宿主动态。这将有助于描述微生物组如何影响肠道免疫成熟和免疫耐受的机制，对于理解肠道微生物群不仅影响局部，而且还影响全身免疫结果。