Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults
Background:: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acut...
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doaj-2ee0bb3bdf0247f984493b9054739d8f2021-07-31T04:40:09ZengElsevierEBioMedicine2352-39642021-08-0170103509Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adultsPaul Kelly0Beatrice Amadi1Kanta Chandwe2Ellen Besa3Kanekwa Zyambo4Mubanga Chama5Phillip I. Tarr6Nurmohammad Shaikh7I Malick Ndao8Chad Storer9Richard Head10Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, 4 Newark Street, London, UK; Corresponding author at: Blizard Institute, Barts & The London School of Medicine, Queen Mary, University of London, 4 Newark Street, London E1 2AT, UK.Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, ZambiaTropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, ZambiaTropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, ZambiaTropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, ZambiaTropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, ZambiaDepartments of Paediatrics, Washington University School of Medicine, St Louis, MO, United StatesDepartments of Paediatrics, Washington University School of Medicine, St Louis, MO, United StatesDepartments of Paediatrics, Washington University School of Medicine, St Louis, MO, United StatesDepartments of Genetics, Washington University School of Medicine, St Louis, MO, United StatesDepartments of Genetics, Washington University School of Medicine, St Louis, MO, United StatesBackground:: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. Methods:: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. Findings:: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. Interpretation:: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study. Funding:: Bill & Melinda Gates Foundation (OPP1066118)http://www.sciencedirect.com/science/article/pii/S2352396421003029Environmental enteropathyEnvironmental Enteric DysfunctionmalnutritionRNA sequencingintestinal transportintestinal digestion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paul Kelly Beatrice Amadi Kanta Chandwe Ellen Besa Kanekwa Zyambo Mubanga Chama Phillip I. Tarr Nurmohammad Shaikh I Malick Ndao Chad Storer Richard Head |
spellingShingle |
Paul Kelly Beatrice Amadi Kanta Chandwe Ellen Besa Kanekwa Zyambo Mubanga Chama Phillip I. Tarr Nurmohammad Shaikh I Malick Ndao Chad Storer Richard Head Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults EBioMedicine Environmental enteropathy Environmental Enteric Dysfunction malnutrition RNA sequencing intestinal transport intestinal digestion |
author_facet |
Paul Kelly Beatrice Amadi Kanta Chandwe Ellen Besa Kanekwa Zyambo Mubanga Chama Phillip I. Tarr Nurmohammad Shaikh I Malick Ndao Chad Storer Richard Head |
author_sort |
Paul Kelly |
title |
Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults |
title_short |
Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults |
title_full |
Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults |
title_fullStr |
Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults |
title_full_unstemmed |
Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults |
title_sort |
gene expression profiles compared in environmental and malnutrition enteropathy in zambian children and adults |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-08-01 |
description |
Background:: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. Methods:: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. Findings:: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. Interpretation:: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study. Funding:: Bill & Melinda Gates Foundation (OPP1066118) |
topic |
Environmental enteropathy Environmental Enteric Dysfunction malnutrition RNA sequencing intestinal transport intestinal digestion |
url |
http://www.sciencedirect.com/science/article/pii/S2352396421003029 |
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