Environmental Enteropathy

A long-term goal is to elucidate underlying mechanisms of diarrhea and undernutrition and improve therapies to break their vicious cycle in low-resource settings. Both conditions remain major causes of childhood deaths in the developing world. With partners at the Aga Khan University in Pakistan and the Federal University of Ceará in Brazil, we are engaged in field studies of childhood diarrhea, undernutrition, and environmental enteric dysfunction (EED). These include clinical trials of repair nutrients and observational, tissue-based studies of EED.

Dr. Sana Syed is studying small intestinal structure and function in children who experience growth and vaccine failure in low- and middle-income countries around the world. Her research focuses on understanding why a subset of children living in in low- and middle-income countries around the world develop growth and vaccine failure, an entity known as Environmental Enteric Dysfunction (EED). As a member of the Moore Lab, working along with collaborators at the Aga Khan University in Karachi, Pakistan, her work involves: 1) development of a histopathologic score based on morphometric characteristics of intestinal tissue from these children; 2) understanding differences in key epithelial transporters and binding protein expression among children with EED versus healthy and diseased controls; 3) deriving and validating case definitions for environmental enteropathy for use in interventional studies; 4) estimating associations between non-invasive biomarkers as well as specific enteropathogens with growth and immune outcomes in children with EED; and 5) development of directed nutrient and other interventions for environmental enteropathy in children.

Proposed schematic progression of Environmental Enteric Dysfunction resulting from a hyperstimulated enteric immune system: (i) chronic recurrent exposure to abnormally high concentrations of ingested enteropathogens in the small intestinal lumen, (ii) mucosal inflammation with infiltration of the lamina propria by plasma cells and lymphocytes, (iii) spectrum of villous blunting, altered barrier integrity, and reduced intestinal absorptive capacity (e.g., malabsorption of small sugars such as lactulose). The bidirectional arrow points out the fact that the lesion may improve or worsen over time
(Illustration © 2015 Haderer & Muller Biomedical Art).