Grant: Project Grant

Malnutrition is a major problem worldwide in both developed and developing countries with one in four children under five (25%) being malnourished. This results in diminished physical and mental development resulting in children that do poorly in school and with increased susceptibility to disease. Malnutrition accounts for half of all deaths in children <5 years of age worldwide. In Canada, 1 in 6 children are malnourished. The intestinal inflammation and dysfunction associated with environmental enteropathy (EE) remains a major problem in a large percentage of malnutrition cases, and is thought to be responsible for the insufficiency of dietary interventions to fully reverse malnutrition symptoms. Furthermore, there are currently no approved or effective medical interventions to reverse features of EE. In this application, we will explore the hypothesis that both diet and the microbiota synergistically affect malnutrition and EE. This will include further characterization of the underlying mechanisms using the novel murine model, developing a "humanized" murine model utilizing microbiota grown from malnourished children, and explore possible novel interventions including fecal transfers, probiotics and antibiotics. Collectively, results from both children and humanized murine models will lead to a desperately needed increase in our knowledge about this globally important but poorly studied area of malnutrition, especially in the area of host-microbial interactions in the gut. In addition, it will test the validity of various interventions that could be developed and used in the future to counter this global child health issue.