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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761650
• 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.

人类胃肠道定植有各种各样的共生细菌和其他微生物，统称为肠道微生物群。这群微生物及其遗传物质被称为肠道微生物组。肠道微生物组与人体代谢，肠道发育和正常生理，免疫成熟和耐受性有关，最近与大脑过程和行为有关。肠道微生物组是一种微生物生态系统，其运作方式与促进健康和预防疾病的微生物器官非常相似。了解肠道微生物组如何影响炎症性肠病等疾病的易感性是我通过克罗恩病和结肠炎加拿大健康相关研究资金的基础，并提交给CIHR。我的NSE相关工作的基础是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，重点是环境的作用。虽然有证据支持肠道微生物群是从母亲垂直传播的，但人们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组发育中的作用知之甚少。在这项提案中，我们着手从根本上了解先天与后天如何影响哺乳动物肠道中微生物的水平和垂直转移。总的来说，我的研究有助于了解外部环境，肠道微生物群和肠道粘膜免疫之间的复杂关系。最后，我假设微生物群的肠道定植是形成免疫耐受并因此形成免疫成熟的控制点。因此，在接下来的五年里，我将研究影响肠道微生物组的因素及其对免疫发育的影响。我在未来5年的研究计划的短期目标将集中在以下目标。 目的1：了解环境对哺乳动物肠道微生物组发育的影响。 目标二：了解环境致敏的肠道微生物组如何影响宿主免疫力。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群组成，多样性和组装的作用的理解，确定天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。这将有助于阐明微生物组如何影响肠道免疫成熟和免疫耐受的机制，这对于理解肠道微生物群如何影响局部和全身免疫结果至关重要。