Awards

Asad Ali of Aga Khan University in Pakistan and co-­investigators will test a selected group of candidate biomarkers to identify and monitor environmental enteropathy, which causes malnutrition and stunting. The biomarkers, which include markers of inflammation and enteric pathogens, will be tested in blood, urine and stools, and correlated with structural features of the small bowel using biopsies from malnourished children. They will also attempt to identify new candidate biomarkers in these biopsies using mRNA sequencing. Their results will provide important insight into disease pathophysiology and enable the development of evidence-­based interventions.

William Faubion of the Mayo Clinic in the U.S. and colleagues will develop a non-invasive test of small intestinal permeability to improve the reliability of detection of environmental enteropathy, which causes childhood growth failure. The test involves quantification of sugar absorption in urine samples using mass spectrometry, and will be validated in at risk infants in the developing world. The aim is to provide a simple, safe and inexpensive test to identify all cases of this condition on a global scale, and drive the development of preventative interventions.

Richard Guerrant of the University of Virginia in the U.S. and co-investigators will develop and validate non-invasive metabolic biomarkers of gut health to identify children at risk of environmental enteropathy and developmental impairment, in order to assess interventions. They will use ongoing MAL-ED (malnutrition and enteric diseases) and NIH-supported clinical studies in malnourished and control children, and their own studies in novel murine models, along with a nuclear magnetic resonance approach to perform metabolic profiling of urine, plasma and feces samples. Their goal is to improve the growth, nutrition and development of children at high risk of environmental enteropathy that can lead to morbidity and mortality.

Mark Manary of Washington University in the U.S. and colleagues will develop a strategy for the non-invasive diagnosis of environmental enteropathy, which causes malnutrition and growth failure in young children in the developing world. They will devise a robust protocol to isolate human RNA of the small bowel from samples of stool, and will test a broad panel of candidate biomarkers for their ability to identify environmental enteropathy with high sensitivity using samples from at risk Malawian children. These tools will be critical for studying disease etiology and for the development of effective intervention strategies.

Margaret Kosek of Johns Hopkins University in the U.S. and co-investigators will generate a new biomarker panel to assess disease activity in environmental enteropathy, which causes stunted growth and malnutrition. They will analyze markers related to immune system activation and growth factors in samples derived from the children enrolled in the MAL-ED (malnutrition and enteric diseases) study in Peru, and compare them with growth profiles and diarrheal disease burden as a proxy for disease activity. The identified biomarker panel will ultimately aid in evaluating interventions to prevent and treat enteric diseases.

Christopher Duggan of Children's Hospital Boston in the U.S. and his team will test whether known biomarkers of gut dysfunction can accurately predict impaired neurodevelopment and stunting, which reflects chronic malnutrition and is associated with increased morbidity and mortality in young children. The biomarkers will be validated in a well-characterized group of young Tanzanian children. The goal is to facilitate the identification of at risk children early in life, so that appropriate intervention strategies can be applied.

Paul Kelly of Queen Mary and Westfield College in the United Kingdom and the University of Zambia will work with colleagues to identify and evaluate candidate biomarkers of environmental enteropathy, which causes growth failure in children in the developing world. Possible markers of enteropathy in serum and gut secretions will be correlated with two severe clinical outcomes, impaired nutrient absorption, and loss of gut barrier function leading to bacteria entering the bloodstream. The aim is to drive the development of new treatments.