title: Assessment of Environmental Enteric Dysfunction in the SHINE Trial: Methods and Challenges.
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.
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe Blizard Institute, Queen Mary University of London, United Kingdom Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prendergast
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Jean H
authors.initials: JH
authors.lastname: Humphrey
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Kuda
authors.initials: K
authors.lastname: Mutasa
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Florence D
authors.initials: FD
authors.lastname: Majo
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rukobo
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Margaret
authors.initials: M
authors.lastname: Govha
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Mduduzi N N
authors.initials: MN
authors.lastname: Mbuya
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Stoltzfus
mesh_terms: D000740:Anemia; D015415:Biomarkers; D004435:Eating; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006130:Growth Disorders / Q000503:physiopathology; D006801:Humans; D006920:Hygiene; D007223:Infant; D007249:Inflammation; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D008297:Male; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D012424:Rural Population; D012499:Sanitation; D015030:Zimbabwe
chemical_list: D015415:Biomarkers
keywords: IGF-1; environmental enteric dysfunction; infants; inflammation; stunting