Role of microRNA in gut microbiome-host interaction in early life

microRNA 在生命早期肠道微生物组与宿主相互作用中的作用

• 批准号: RGPIN-2019-06100
• 负责人: Comelli, Elena
• 金额: $ 2.91万
• 依托单位: University of Toronto
• 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=714964
• 关键词: Role; microRNA; gut; microbiome; host

There are trillions of microbes in the gut, living as a community, the structure of which is gradually acquired after birth. This process parallels the establishment of the intestinal barrier (the intestinal defense system), suggesting a relationship between the two. Indeed, it is known that gut microbes regulate the barrier by impacting gene expression. It is unknown through which mechanisms this happens. We previously found that gut microbes affect the expression of small molecules that work as micro regulators of gene expression and are called microRNA. We have also shown that a beneficial bacterium (called Bifidobacterium bifidum) and an intestinal pathogen (called Citrobacter rodentium) affect intestinal microRNA, although in a different manner. These findings suggest that the composition of the microbiota may play a role in regulating intestinal microRNAs. Thus, the purpose of this research is to investigate the mechanisms by which the microbes living within the gut regulate the intestinal defense system, during early postnatal life, with a focus on microRNA. Our long term goal is to assess how this is important for intestinal epithelium protection throughout life. It is anticipated that this work will lead to the discovery of genes and microRNA the expression of which changes during intestinal maturation in response to changes in the gut microbial community. We will adopt global approaches that allow for the analysis of hundreds of different intestinal microRNAs, genes and microbes at different time points after birth; we will be able to correlate the two. We will also investigate how gene expression changes that depend on the composition of the gut resident microbial community and on the microRNAs, affect the gut defense system. To this end, we will use conventional (with a "normal" microbial community) and germ-free (without any microbes) mice, including microbes transplantation between the two, in order to directly confirm the impact of the gut microbial community on the expression of genes and proteins regulating intestinal defenses. This work will provide a better understanding of the interaction between the intestine and its resident microbes. By using cutting-edge molecular techniques in a rapidly evolving field of research, this research program offers a great opportunity for training highly-qualified personnel and will reinforce the position of Canadian research in the field.

肠道中有数以万亿计的微生物，作为一个群落生活，其结构是在出生后逐渐获得的。这一过程与肠道屏障(肠道防御系统)的建立平行，表明两者之间存在关系。事实上，已知肠道微生物通过影响基因表达来调节屏障。目前还不清楚这种情况是通过什么机制发生的。我们之前发现，肠道微生物会影响小分子的表达，这些小分子被称为microRNA，是基因表达的微调节器。我们还表明，一种有益的细菌(称为双歧双歧杆菌)和一种肠道病原体(称为轮状柠檬酸杆菌)影响肠道microRNA，尽管方式不同。这些发现表明，微生物区系的组成可能在调节肠道microRNAs方面发挥作用。因此，本研究的目的是研究肠道内的微生物在出生后早期调节肠道防御系统的机制，重点是microRNA。我们的长期目标是评估这对终生肠道上皮保护的重要性。预计这项工作将导致发现基因和microRNA，它们的表达在肠道成熟过程中随着肠道微生物群落的变化而变化。 我们将采用全球方法，在出生后的不同时间点分析数百种不同的肠道微RNA、基因和微生物；我们将能够将两者联系起来。我们还将研究依赖于肠道驻留微生物群落组成和microRNAs的基因表达变化如何影响肠道防御系统。为此，我们将使用常规(有“正常”微生物群落)和无菌(没有任何微生物)的小鼠，包括两者之间的微生物移植，以直接证实肠道微生物群落对调节肠道防御的基因和蛋白质表达的影响。 这项工作将更好地了解肠道与其驻留微生物之间的相互作用。通过在一个快速发展的研究领域使用尖端分子技术，该研究计划为培养高素质的人才提供了一个很好的机会，并将巩固加拿大在该领域的研究地位。