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Environmental Enteric Dysfunction and the Fecal Microbiota in Malawian Children.

ABSTRACT: Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We performed 16S ribosomal RNA gene sequencing of fecal samples from 81 rural Malawian children with varying degrees of EED to determine which bacterial taxa were associated with EED. At the phyla level, Proteobacteria abundance is reduced with severe EED. Among bacterial genera, Megasphaera, Mitsuokella, and Sutterella were higher in EED and Succinivibrio, Klebsiella, and Clostridium_XI were lower in EED. Bacterial diversity did not vary with the extent of EED. Though EED is a condition that is typically believed to affect the proximal small bowel, and our focus was on stool, our data do suggest that there are intraluminal microbial differences that reflect, or plausibly lead to, EED.

SUBMITTER: Ordiz MI

PROVIDER: S-EPMC5303055 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Environmental Enteric Dysfunction and the Fecal Microbiota in Malawian Children.

Ordiz M Isabel MI Stephenson Kevin K Agapova Sophia S Wylie Kristine M KM Maleta Ken K Martin John J Trehan Indi I Tarr Phillip I PI Manary Mark J MJ

The American journal of tropical medicine and hygiene 20161212 2

Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We performed 16S ribosomal RNA gene sequencing of fecal samples from 81 rural Malawian children with varying degrees of EED to determine which bacterial taxa were associated with EED. At the phyla level, Prot ...[more]

PMID: 27956653

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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:BackgroundInterventions to decrease the burden of childhood malnutrition are urgently needed, as millions of children die annually owing to undernutrition and hundreds of millions more are left cognitively and physically stunted. Environmental enteric dysfunction (EED), a pervasive chronic subclinical inflammatory condition among children that develops when complementary foods are introduced, places them at high risk of stunting, malabsorption, and poor oral vaccine efficacy. Improved interventions to reduce the burden of EED and stunting are expected to markedly improve the nutritional status and survival of children throughout resource-limited settings.Methods/designWe will conduct, in parallel, two prospective randomized controlled clinical trials to determine whether common beans or cowpeas improve growth, ameliorate EED, and alter the intestinal microbiome during a high-risk period in the lives of rural Malawian children. Study 1 will enroll children at 6 months of age and randomize them to receive common beans, cowpeas, or a standard complementary food for 6 months. Anthropometry will be compared among the three groups; EED will be assessed using a dual-sugar absorption test and by quantifying human intestinal mRNA for inflammatory messages; and the intestinal microbiota will be characterized by deep sequencing of fecal DNA, to enumerate host microbial populations and their metabolic capacity. Study 2 will enroll children 12-23 months old and follow them for 12 months, with similar interventions and assessments as Study 1.DiscussionBy amalgamating the power of rigorous clinical trials and advanced biological analysis, we aim to elucidate the potential of two grain legumes to reduce stunting and EED in a high-risk population. Legumes have potential as an affordable and effective complementary food intervention, given their cultural acceptability, nutritional content, and agricultural feasibility in sub-Saharan Africa.Trial registrationClinicaltrials.gov NCT02472262 and NCT02472301 .

Dataset Information

Environmental Enteric Dysfunction and the Fecal Microbiota in Malawian Children.

Publications

Environmental Enteric Dysfunction and the Fecal Microbiota in Malawian Children.

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