Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting
Data files
Mar 01, 2021 version files 142.07 KB
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BEECHbiomarkersarchival.csv
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BEECHpathogensarchival.csv
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README_file.docx
Abstract
Environmental enteropathy is a major contributor to growth faltering in millions of children in Africa and South Asia. We carried out a longitudinal, observational and interventional study in Lusaka, Zambia, of 297 children with stunting (aged 2–17 months at recruitment) and 46 control children who had good growth (aged 1–5 months at recruitment). Control children contributed data only at baseline. Children were provided with nutritional supplementation of daily cornmeal-soy blend, an egg and a micronutrient sprinkle, and were followed up to 24 months of age. Children whose growth did not improve over 4–6 months of nutritional supplementation were classified as having non-responsive stunting. We monitored microbial translocation from the gut lumen to the bloodstream in the cohort with non-responsive stunting (n = 108) by measuring circulating lipopolysaccharide (LPS), LPS-binding protein and soluble CD14 at baseline and when non-response was declared. We found that microbial translocation decreased with increasing age, such that LPS declined in 81 (75%) of 108 children with non-responsive stunting, despite sustained pathogen pressure and ongoing intestinal epithelial damage. We used confocal laser endomicroscopy and found that mucosal leakiness also declined with age. However, expression of brush border enzyme, nutrient transporter and mucosal barrier genes in intestinal biopsies did not change with age or correlate with biomarkers of microbial translocation. We propose that environmental enteropathy arises through adaptation to pathogen-mediated epithelial damage. Although environmental enteropathy reduces microbial translocation, it does so at the cost of impaired growth. The reduced epithelial surface area imposed by villus blunting may explain these findings.
Methods
Two datasets are provided. The first contains data on pathogens present. in stool samples, analysed by Luminex xTAG GPP. The second contains analysis of plasma biomarkers, analysed by commercial ELISA kits. These biomarkers include lipolpolysaccharide (LPS), LPS-binding protein (LBP), soluble CD14, and intestinal fatty acid binding protein (iFABP).
Usage notes
The ID numbers used are not the ID numbers used for each child in the study, but allow the two databases to be cross-linked. There are missing values where, for example, the plasma was insufficient to do all assays. In the pathogens file, avpos is adenovirus positive, nvpos is norovirus, rvapos is rotavirus A positive, etecpos is positive for Enterotoxigenic Escherichia coli (ETEC), salmo1pos is positive for Salmonella spp, shigpos is positive for Shigella spp., campypos is positive for Campylobacter spp., giardiapos is positive for Giardia intestinalis, and cryptopos is positive for Cryptosporidium spp.