Assessment of Environmental Enteric Dysfunction in the SHINE Trial: Methods and Challenges

Andrew J Prendergast, Jean H Humphrey, Kuda Mutasa, Florence D Majo, Sandra Rukobo, Margaret Govha, Mduduzi N N Mbuya, Lawrence H Moulton, Rebecca J Stoltzfus, Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team, Andrew J Prendergast, Jean H Humphrey, Kuda Mutasa, Florence D Majo, Sandra Rukobo, Margaret Govha, Mduduzi N N Mbuya, Lawrence H Moulton, Rebecca J Stoltzfus, Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team

Abstract

Environmental enteric dysfunction (EED) is a virtually ubiquitous, but poorly defined, disorder of the small intestine among people living in conditions of poverty, which begins early in infancy and persists. EED is characterized by altered gut structure and function, leading to reduced absorptive surface area and impaired intestinal barrier function. It is hypothesized that recurrent exposure to fecal pathogens and changes in the composition of the intestinal microbiota initiate this process, which leads to a self-perpetuating cycle of pathology. We view EED as a primary gut disorder that drives chronic systemic inflammation, leading to growth hormone resistance and impaired linear growth. There is currently no accepted case definition or gold-standard biomarker of EED, making field studies challenging. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in Zimbabwe is evaluating the independent and combined effects of a package of infant feeding and/or water, sanitation, and hygiene interventions on stunting and anemia. SHINE therefore provides an opportunity to longitudinally evaluate EED in a well-characterized cohort of infants, using a panel of biomarkers along the hypothesized causal pathway. Our aims are to describe the evolution of EED during infancy, ascertain its contribution to stunting, and investigate the impact of the randomized interventions on the EED pathway. In this article, we describe current concepts of EED, challenges in defining the condition, and our approach to evaluating EED in the SHINE trial.

Keywords: IGF-1; environmental enteric dysfunction; infants; inflammation; stunting.

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Hypothesized causal pathway to stunting through environmental enteric dysfunction. Abbreviations: AGP, α-1 acid glycoprotein; CRP, C-reactive protein; I-FABP, intestinal fatty acid binding protein; IGF-1, insulin-like growth factor 1; L:M, lactulose mannitol ratio; LPS, lipopolysaccharide; REG-1B, regenerating gene 1B; sCD14, soluble CD14; sCD163, soluble CD163; sTFR, soluble transferrin receptor.

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