Dataset Information

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

ABSTRACT: 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/m2). 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.

SUBMITTER: Mahfuz M

PROVIDER: S-EPMC5724211 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Mahfuz Mustafa M Das Subhasish S Mazumder Ramendra Nath RN Masudur Rahman M M Haque Rashidul R Bhuiyan Md Muzibur Rahman MMR Akhter Hasina H Sarker Md Shafiqul Alam MSA Mondal Dinesh D Muaz Syed Shafi Ahmed SSA Karim A S M Bazlul ASMB Borowitz Stephen M SM Moskaluk Christopher A CA Barratt Michael J MJ Petri William A WA Gordon Jeffrey I JI Ahmed Tahmeed T

BMJ open 20170811 8

<h4>Introduction</h4>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 dise ...[more]

PMID: 28801442

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Project description:OBJECTIVES:Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS:In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. RESULTS:EED prevalence (L:M?>?0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or ?-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and ?-1 antitrypsin (r?=?0.33, P?<?0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. CONCLUSIONS:Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Project description:Two emerging biomarkers of environmental enteric dysfunction (EED) include plasma citrulline (CIT), and the kynurenine (KYN): tryptophan (TRP)/ (KT) ratio. We sought to investigate the plasma concentration of CIT and KT ratio among the children having dehydrating diarrhea and examine associations between concentrations of CIT and KT ratio with concurrent factors. For this analysis, we used cross-sectional data from a total of 102, 6-36 months old male children who suffered from non-cholera acute watery diarrhea and had some dehydration admitted to an urban diarrheal hospital, in Bangladesh. CIT, TRP, and KYN concentrations were determined at enrollment from plasma samples using ELIZA. At enrollment, the mean plasma CIT concentration was 864.48 ± 388.55 µmol/L. The mean plasma kynurenine, tryptophan concentrations, and the KT ratio (× 1000) were 6.93 ± 3.08 µmol/L, 33.44 ± 16.39 µmol/L, and 12.12 ± 18.10, respectively. With increasing child age, KYN concentration decreased (coefficient: - 0.26; 95%CI: - 0.49, - 0.04; p = 0.021); with increasing lymphocyte count, CIT concentration decreased (coef.: - 0.01; 95% CI: - 0.02,0.001, p = 0.004); the wasted child had decreased KT ratio (coef.: - 0.6; 95% CI: - 1.18, - 0.02; p = 0.042) after adjusting for potential covariates. The CIT concentration was associated with blood neutrophils (coef.: 0.02; 95% CI: 0.01, 0.03; p < 0.001), lymphocytes (coef.: - 0.02; 95% CI: - 0.03, - 0.02; p < 0.001) and monocyte (coef.: 0.06; 95% CI: 0.01, 0.11; p = 0.021); KYN concentration was negatively associated with basophil (coef.: - 0.62; 95% CI: - 1.23, - 0.01; p = 0.048) after adjusting for age. In addition, total stool output (gm) increased (coef.: 793.84; 95% CI: 187.16, 1400.52; p = 0.011) and also increased duration of hospital stay (hour) (coef.: 22.89; 95% CI: 10.24, 35.54; p = 0.001) with increasing CIT concentration. The morphological changes associated with EED may increase the risk of enteric infection and diarrheal disease among children. Further research is critically needed to better understand the complex mechanisms by which EED biomarkers may impact susceptibility to dehydrating diarrhea in children.

Project description:BACKGROUND:Because Helicobacter pylori (H. pylori) infection and Environmental Enteric Dysfunction (EED) follow a similar mode of transmission, there can be a complex interplay between H. pylori infection and EED, both of which can influence childhood growth. We sought to investigate the factors associated with H. pylori infection and identify its relationship with the fecal biomarkers of EED including Myeloperoxidase (MPO), Neopterin (NEO), Calprotectin, Reg1B and Alpha-1 antitrypsin (AAT), and nutritional status of the children. METHODOLOGY:Data from an on-going community-based nutrition intervention study was used for this analysis. Total 319 children aged between 12-18 months were evaluated at enrolment and at the end of a 90-day nutrition intervention. Multivariable linear regression with generalized estimating equations was done to examine the association of H. pylori infection with stool biomarker of EED and nutritional status of the children. PRINCIPAL FINDINGS:One-fifth of the participants had H. pylori infection at both the time points, with 13.8% overall persistence. Children living in crowded households had higher odds of being infected by H. pylori (AOR = 2.02; 95% CI = 1.02, 4.10; p-value = 0.045). At enrolment, 60%, 99%, 69% and 85% of the stool samples were elevated compared to the reference values set for MPO, NEO, AAT and Calprotectin in the non-tropical western countries. The proportions reduced to 52%, 99%, 67%, and 77% for the same biomarkers after the nutrition intervention. Infection with H. pylori had significant positive association with fecal AAT concentrations (Coefficient = 0.26; 95% CI = 0.02, 0.49; p-value = 0.03) and inverse relationship with Reg1B concentrations measured in the stool samples (Coefficient = -0.32; 95% CI = -0.59, -0.05; p-value = 0.02). However, H. pylori infection was not associated with the indicators of childhood growth. CONCLUSIONS:The study findings affirmed that the acquisition and persistence of H. pylori infection in the early years of life may exert an adverse impact on intestinal health, induce gut inflammation and result in increased intestinal permeability.

Dataset Information

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

Publications

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

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