Gut microbiome diversity and host immunity during early life

生命早期肠道微生物组多样性和宿主免疫力

• 批准号: RGPIN-2018-04305
• 负责人: ArrietaMendez, MarieClaire
• 金额: $ 2.99万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=644160
• 关键词: Gut; microbiome; diversity; host; immunity

***Whether it is a tropical forest or the arctic tundra, biodiversity is considered an important determinant of ecosystem function. The gastrointestinal tract of vertebrates and its microbial inhabitants (microbiome) constitute an ecosystem, in which productivity reflects not only functions pertaining to the microbial community, but also microbiome-derived functions that increase the fitness of the host.***Microbiome diversity is consistently assumed to be beneficial for host fitness. However, experimental evidence for this association is lacking. Further, the ecological underpinnings that drive alpha (α)-diversity establishment, as well as the influence of α-diversity on host immune development (a key determinant of host fitness) are, for the most part, unknown. ******The long-term goal of my NSERC program is to elucidate the ecological processes that explain gut microbiome α-diversity during early life, as well as to understand how taxonomic and/or functional diversity influence host immune function. The general hypothesis is that the maturation of key immune functions depends on functional microbial diversity and the presence of multi-kingdom keystone taxa, rather than taxonomic diversity (species richness per se).******We will (i) study ecological processes of microbial colonization in a longitudinal study of 102 infants sampled monthly from birth until 18 months of age; (ii), determine the influence of Blastocystis sp. and other eukaryote commensals on the gut microbiome and host immune maturation; and (iii) disentangle the role of taxonomic vs. functional diversity in a biodiversity-ecosystem function experiment in gnotobiotic mice. ******Impact: My research program innovates by relying on: (1) an interdisciplinary array of projects that relies on microbial ecology, statistics, bioinformatics, immunology and gut biology; (2) an ecologically-informed framework; (3) established collaboration to receive samples from the largest infant longitudinal cohort of its class to date; (4) multi-omics technology to inform us on the taxonomic (amplicon) and functional (metagenomics and metabolomics) aspects of the gut microbiome; and (5) state-of-the-art gnotobiotic installations that allow colonization with a predefined microbial community in the largest and most sophisticated germ-free facility in the world. By examining multi-kingdom taxonomic and functional parameters to determine the contribution of richness vs. functional diversity in early immune development, my research program will produce novel knowledge at the leading edge of this field. My research program will train Canadian scientists in an interdisciplinary environment that exposes them to different disciplines and scientific mindsets, and will provide them highly employable skills in academia and industry, that range from gut physiology and immunology to bacterial genomics, big data analysis and systems biology.*****

***无论是热带森林还是北极苔原，生物多样性都被认为是生态系统功能的重要决定因素。脊椎动物的胃肠道及其微生物居民（微生物组）构成了一个生态系统，其中生产力不仅反映了与微生物群落有关的功能，还反映了微生物组衍生的功能，这些功能可以增加宿主的适应性。***微生物组的多样性一直被认为有利于宿主的适应性。然而，缺乏这种关联的实验证据。此外，驱动α (α)多样性建立的生态基础，以及α-多样性对宿主免疫发育（宿主适应性的关键决定因素）的影响，在很大程度上是未知的。******我的NSERC项目的长期目标是阐明在生命早期解释肠道微生物组α-多样性的生态过程，以及了解分类学和/或功能多样性如何影响宿主免疫功能。一般的假设是，关键免疫功能的成熟取决于功能性微生物多样性和多界关键分类群的存在，而不是分类多样性（物种丰富度本身）。******我们将(i)对102名婴儿进行纵向研究，从出生到18个月每月取样，研究微生物定植的生态过程；（ii）确定囊虫和其他真核生物共生体对肠道微生物群和宿主免疫成熟的影响；（iii）在生物多样性-生态系统功能实验中理清分类多样性与功能多样性的作用。******影响：我的研究项目依靠以下方面进行创新：(1)一系列跨学科的项目，这些项目依赖于微生物生态学、统计学、生物信息学、免疫学和肠道生物学；(2)生态知情框架；(3)建立合作，接收迄今同类最大的婴儿纵向队列样本；(4)多组学技术为我们提供肠道微生物组的分类（扩增子）和功能（宏基因组学和代谢组学）方面的信息；(5)最先进的无菌装置，允许在世界上最大和最先进的无菌设施中与预定义的微生物群落进行定植。通过检查多界分类和功能参数来确定丰富度与功能多样性在早期免疫发育中的贡献，我的研究计划将在该领域的前沿产生新的知识。我的研究项目将在一个跨学科的环境中培养加拿大科学家，使他们接触到不同的学科和科学思维，并为他们提供在学术界和工业界的高就业技能，从肠道生理学和免疫学到细菌基因组学，大数据分析和系统生物学。*****