Gut microbiota regulation of the intestinal mucus layer during postnatal development

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The purpose of this research is to investigate the underlying mechanisms by which the gut resident microbiota regulates the postnatal establishment of the intestinal mucus layer. The mucus layer plays a critical role in the intestinal barrier function since it protects the epithelium from luminal pathogens and toxins. The mucus layer is located between the mucosa and the microbiota, a complex community of trillions of microorganisms. The gut microbiota is acquired after birth through a gradual diversification process ending after weaning, when an adult-type composition is achieved. This process parallels the establishment of the gut barrier and in particular of the mucus layer. While in the adult the composition of the microbiota regulates the expression of epithelial barrier-related genes, it is not known if it does so in early life. We will perform a global gene expression analysis in epithelial cells isolated from the intestine of conventional (with a "normal" microbiota) and germ-free (without any bacteria) mice at different times after birth in order to assess the impact of the evolving gut microbial community on the timely appropriate expression of genes regulating the establishment of the mucus layer. Given that alteration of mucus layer composition characterizes several gastro-intestinal diseases, such as inflammatory bowel disease and mucositis, understanding the molecular mechanisms of its establishment has implications for the understanding of these pathologies as well as for the design of new therapies and treatments. Furthermore, this research has implications for the development of dietary guidelines to improve human health through nutritional approaches targeting the maintenance of a healthy gut microbial community in the intestine.