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

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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.