Sean Moore and colleagues at Cincinnati Children's Hospital in the U.S. will generate a mouse model of human environmental enteropathy, which is characterized by stunted growth and physiological defects in the gut, and is caused by malnutrition and repeated infections. The model will be used to test whether environmental enteropathy is affected by diet and contaminated water, and whether it reduces the effect of oral vaccines. In Phase I, they proved that feeding mice a nutritionally deficient diet mimicked at least some of the features of the human disease. To improve on this, in Phase II they will also modify DNA methylation in intestinal stem cells and induce inflammation. They will also test whether a rotavirus vaccine is less effective in these mice.
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