Dataset Information

Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.

ABSTRACT: Intestinal damage in malnutrition constitutes a threat to the survival of many thousands of children globally. We studied children in Lusaka, Zambia, with severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy and analysis of markers and protective proteins in blood and intestinal secretions. We carried out parallel investigations in apparently healthy adults, and analyzed biomarkers only in apparently healthy children. Villus height and crypt depth did not differ in children with SAM and adult controls, but epithelial surface was reduced in children with SAM (median 445, interquartile range (IQR) 388, 562?m per 100?m muscularis mucosae) compared to adults (578, IQR 465,709; P=0.004). Histological lesions and disruptions of claudin-4 and E-cadherin were most pronounced in children with SAM. Circulating lipopolysaccharide, a marker of bacterial translocation, was higher in malnourished children (251, IQR 110,460EU/ml) than in healthy children (51, IQR 0,111; P=0.0001). Other translocation markers showed similar patterns. Anti-Deamidated Gliadin Peptide IgG concentrations, although within the normal range, were higher in children with SAM (median 2.7U/ml, IQR 1.5-8.6) than in adults (1.6, 1.4-2.1; P=0.005), and were inversely correlated with villus height (?=-0.79, n=13, P=0.001). Malnutrition enteropathy is associated with intestinal barrier failure and immune dysregulation.

SUBMITTER: Amadi B

PROVIDER: S-EPMC5552244 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.

Amadi Beatrice B Besa Ellen E Zyambo Kanekwa K Kaonga Patrick P Louis-Auguste John J Chandwe Kanta K Tarr Phillip I PI Denno Donna M DM Nataro James P JP Faubion William W Sailer Anne A Yeruva Sunil S Brantner Tricia T Murray Joseph J Prendergast Andrew J AJ Turner Jerrold R JR Kelly Paul P

EBioMedicine 20170719

Intestinal damage in malnutrition constitutes a threat to the survival of many thousands of children globally. We studied children in Lusaka, Zambia, with severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy and analysis of markers and protective proteins in blood and intestinal secretions. We carried out parallel investigations in apparently healthy adults, and analyzed biomarkers only in apparently healthy children. Villus height and crypt depth did not differ in chi ...[more]

PMID: 28750860

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Project description:BackgroundChildren with severe acute malnutrition (SAM), with or without diarrhoea, often have enteropathy, but there are few molecular data to guide development of new therapies. We set out to determine whether SAM enteropathy is characterised by specific transcriptional changes which might improve understanding or help identify new treatments.MethodsWe collected intestinal biopsies from children with SAM and persistent diarrhoea. mRNA was extracted from biopsies, sequenced, and subjected to a progressive set of complementary analytical approaches: NOIseq, Gene Set Enrichment Analysis (GSEA), and correlation analysis of phenotypic data with gene expression.FindingsTranscriptomic profiles were generated for biopsy sets from 27 children of both sexes, under 2 years of age, of whom one-third were HIV-infected. NOIseq analysis, constructed from phenotypic group extremes, revealed 66 differentially expressed genes (DEGs) out of 21,386 mapped to the reference genome. These DEGs include genes for mucins and mucus integrity, antimicrobial defence, nutrient absorption, C-X-C chemokines, proteases and anti-proteases. Phenotype - expression correlation analysis identified 1221 genes related to villus height, including increased cell cycling gene expression in more severe enteropathy. Amino acid transporters and ZIP zinc transporters were specifically increased in severe enteropathy, but transcripts for xenobiotic metabolising enzymes were reduced.InterpretationTranscriptomic analysis of this rare collection of intestinal biopsies identified multiple novel elements of pathology, including specific alterations in nutrient transporters. Changes in xenobiotic metabolism in the gut may alter drug disposition. Both NOIseq and GSEA identified gene clusters similar to those differentially expressed in pediatric Crohn's disease but to a much lesser degree than those identified in coeliac disease. FUND: Bill & Melinda Gates Foundation OPP1066118. The funding agency had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Project description:BackgroundThe burden of child under-nutrition still remains a global challenge, with greater severity being faced by low- and middle-income countries, despite the strategies in the Sustainable Development Goals (SDGs). Globally, malnutrition is the one of the most important risk factors associated with illness and death, affecting hundreds of millions of pregnant women and young children. Sub-Saharan Africa is one of the regions in the world struggling with the burden of chronic malnutrition. The 2018 Zambia Demographic and Health Survey (ZDHS) report estimated that 35% of the children under five years of age are stunted. The objective of this study was to analyse the distribution, and associated factors of stunting in Zambia.MethodsWe analysed the relationships between socio-economic, and remote sensed characteristics and anthropometric outcomes in under five children, using Bayesian distributional regression. Georeferenced data was available for 25,852 children from two waves of the ZDHS, 31% observation were from the 2007 and 69% were from the 2013/14. We assessed the linear, non-linear and spatial effects of covariates on the height-for-age z-score.ResultsStunting decreased between 2007 and 2013/14 from a mean z-score of 1.59 (credible interval (CI): -1.63; -1.55) to -1.47 (CI: -1.49; -1.44). We found a strong non-linear relationship for the education of the mother and the wealth of the household on the height-for-age z-score. Moreover, increasing levels of maternal education above the eighth grade were associated with a reduced variation of stunting. Our study finds that remote sensed covariates alone explain little of the variation of the height-for-age z-score, which highlights the importance to collect socio-economic characteristics, and to control for socio-economic characteristics of the individual and the household.ConclusionsWhile stunting still remains unacceptably high in Zambia with remarkable regional inequalities, the decline is lagging behind goal two of the SDGs. This emphasises the need for policies that help to reduce the share of chronic malnourished children within Zambia.

Dataset Information

Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.

Publications

Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.

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