Bangladesh Environmental Enteric Dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction

INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting. METHODS AND ANALYSIS: The BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12–18 months (length for age Z-score (LAZ) <−2), at risk of stunting children aged 12–18 months (LAZ <−1 to −2) and malnourished adults aged 18–45 years (body mass index <18.5 kg/m(2)). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure. ETHICS AND DISSEMINATION: Ethics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.