Microbiota post-transcriptional regulation of the intestinal barrier during postnatal life

本研究的目的是探讨肠道内微生物在出生后早期调节肠道屏障（肠道防御系统）的潜在机制。肠道中有数以万亿计的微生物组成一个群落，其结构是在出生后逐渐形成的。这一过程与肠道屏障的建立相似，表明两者之间存在联系。事实上，众所周知，肠道微生物通过影响基因表达来调节屏障。目前尚不清楚这是通过何种机制发生的，而这正是本研究项目旨在做出贡献的地方。我们将采用全球方法，允许分析数百种不同的基因表达调节因子，称为microRNA (miRNA)，以及出生后不同时间点小鼠体内数百种不同的微生物，我们将能够将两者联系起来。我们还将研究依赖于肠道常驻微生物群落组成和microRNA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（具有“正常”微生物群）和无菌（没有任何细菌）小鼠，以直接确认肠道微生物群落对调节屏障的基因和蛋白质表达的影响。这项工作将更好地了解肠道及其常驻微生物之间的相互作用。通过在快速发展的研究领域中使用尖端的分子技术，该研究项目为培养高素质人才提供了很好的机会，并将加强加拿大在该领域的研究地位。

The purpose of this research is to investigate the underlying mechanisms by which the microbes living within the gut regulate the intestinal barrier, which is the intestinal defense system, during early postnatal life. 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, 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, and this is where this research program aims at contributing. We will adopt global approaches that allow for the analysis of hundreds of different regulators of gene expression, called microRNA (miRNA), and hundreds of different microbes in parallel in mice at different time points after birth and 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 microRNA, affect the gut defense system. To this end, we will use use conventional (with a "normal" microbiota) and germ-free (without any bacteria) mice in order to directly confirm the impact of the gut microbial community on the expression of genes and proteins regulating the barrier.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.