Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy.
INTRODUCTION:Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. METHODS:We studied 49 adults with environ...
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ftdoajarticles:oai:doaj.org/article:c67b43c61eab4a92a43bc3deeaff0e54 2023-05-15T15:10:59+02:00 Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. Paul Kelly Ellen Besa Kanekwa Zyambo John Louis-Auguste James Lees Themba Banda Rose Soko Rosemary Banda Beatrice Amadi Alastair Watson 2016-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004600 https://doaj.org/article/c67b43c61eab4a92a43bc3deeaff0e54 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4822862?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004600 https://doaj.org/article/c67b43c61eab4a92a43bc3deeaff0e54 PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004600 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004600 2022-12-31T11:54:57Z INTRODUCTION:Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. METHODS:We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. RESULTS:CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. CONCLUSIONS:Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 4 e0004600 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Paul Kelly Ellen Besa Kanekwa Zyambo John Louis-Auguste James Lees Themba Banda Rose Soko Rosemary Banda Beatrice Amadi Alastair Watson Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
INTRODUCTION:Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. METHODS:We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. RESULTS:CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. CONCLUSIONS:Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE. |
format |
Article in Journal/Newspaper |
author |
Paul Kelly Ellen Besa Kanekwa Zyambo John Louis-Auguste James Lees Themba Banda Rose Soko Rosemary Banda Beatrice Amadi Alastair Watson |
author_facet |
Paul Kelly Ellen Besa Kanekwa Zyambo John Louis-Auguste James Lees Themba Banda Rose Soko Rosemary Banda Beatrice Amadi Alastair Watson |
author_sort |
Paul Kelly |
title |
Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
title_short |
Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
title_full |
Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
title_fullStr |
Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
title_full_unstemmed |
Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy. |
title_sort |
endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004600 https://doaj.org/article/c67b43c61eab4a92a43bc3deeaff0e54 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004600 (2016) |
op_relation |
http://europepmc.org/articles/PMC4822862?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004600 https://doaj.org/article/c67b43c61eab4a92a43bc3deeaff0e54 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004600 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
4 |
container_start_page |
e0004600 |
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1766341908928397312 |