Gut microbiome diversity and host immunity during early life

*无论是热带森林还是北极冻土带，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群落(微生物群)构成了一个生态系统，其中的生产力不仅反映了微生物群落的功能，而且还反映了微生物群衍生的提高宿主适合度的功能。然而，缺乏这种联系的实验证据。此外，驱动α()多样性建立的生态基础，以及α多样性对宿主免疫发育(宿主适合性的关键决定因素)的影响，在大多数情况下是未知的。*我的NSERC项目的长期目标是阐明解释早期肠道微生物多样性的生态过程，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微生物多样性和多王国Keystone分类群的存在，而不是分类多样性(物种本身的丰富度)。*我们将(I)对102名婴儿从出生到18个月的纵向研究中研究微生物定植的生态过程；(Ii)确定芽囊原虫的影响。和其他真核生物的共生体对肠道微生物群和宿主免疫成熟的影响；以及(Iii)揭示分类多样性与功能多样性在生物多样性-生态系统功能实验中的作用。*影响：我的研究项目的创新依赖于：(1)依赖微生物生态学、统计学、生物信息学、免疫学和肠道生物学的一系列跨学科项目；(2)生态信息框架；(3)建立合作，从同类中迄今最大的婴儿纵向队列中获得样本；(4)多组学技术，向我们提供肠道微生物组的分类(扩增)和功能(元基因组学和代谢组学)方面的信息；以及(5)最先进的灵知生菌装置，允许在世界上最大和最复杂的无菌设施中利用预先定义的微生物群落进行定居。通过研究多王国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。我的研究计划将在一个跨学科的环境中培训加拿大科学家，让他们接触不同的学科和科学思维，并将为他们提供在学术界和工业中高度可雇用的技能，范围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。

***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 ()-diversity establishment, as well as the influence of -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 -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.*****