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

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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.