Host, pathogen and pathogen interaction determinants of Environmental Enteric Dysfunction

James Nataro of the University of Virginia in the U.S. is developing new mouse models of environmental enteric dysfunction (EED) to explore how enteric pathogens commonly found among children in developing countries can affect intestinal function and cause growth retardation. In Phase I, they developed mouse models for five of the common pathogens and found that, as in humans, malnutrition (protein or zinc deficiency) enhanced the severity of infection, associated growth retardation, or the presence of intestinal inflammation. In Phase II, they will study the molecular mechanisms involved and analyze human candidate EED-associated biomarkers and metabolic states in their new mouse models to better compare them to the human disease. They will also test the effect of simultaneous and repeat infections on growth, and treat one of the models with alanine-glutamine to determine whether they can be used to evaluate new drugs.