"Role of the Microbiota in Asthma and Malnutrition"
The past decade has seen an explosion in knowledge about the microbes that live in and on us, and their role in human health and disease. Asthma is an inflammatory disease of the lungs whose incidence is increasing rapidly, making it a major problem worldwide. Although the exact cause is not known, environmental conditions such as the use of antibiotics, mode of delivery, etc. impact on asthma. We have shown that early life microbiota is critical for determining asthma outcome. Using clinical cohorts of children from Canada and Ecuador, we have identified particular microbiota, including a yeast, that play a profound impact asthma susceptibility. A subclinical chronic inflammatory disease of the small intestine called environmental enteropathy (EE) is now recognized as the major contributor to childhood malnutrition. Features of EE include growth stunting, intestinal permeability, villous blunting and intestinal inflammation independent of any known infectious etiology. EE has a profound impact on the persistence of childhood malnutrition even after dietary intervention, yet to date no preclinical models of EE exist. We found that, in mice, early life consumption of a malnourished diet, in combination with exposure to a cocktail of Bacteroidales and E. coli species, remodels the small intestine to resemble the major features of EE observed in humans. We also found that the brain microglial cells are affected in this model. Collectively, these studies demonstrate that early life microbiota play major roles in childhood health, including malnutrition and asthma.