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: 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=763331
• 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 ()-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.

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.