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Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction
Environmental enteric dysfunction (EED)—a chronic inflammatory condition of the intestine—is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury ca...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652151/ https://www.ncbi.nlm.nih.gov/pubmed/35739419 http://dx.doi.org/10.1038/s41551-022-00899-x |
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author | Bein, Amir Fadel, Cicely W. Swenor, Ben Cao, Wuji Powers, Rani K. Camacho, Diogo M. Naziripour, Arash Parsons, Andrew LoGrande, Nina Sharma, Sanjay Kim, Seongmin Jalili-Firoozinezhad, Sasan Grant, Jennifer Breault, David T. Iqbal, Junaid Ali, Asad Denson, Lee A. Moore, Sean R. Prantil-Baun, Rachelle Goyal, Girija Ingber, Donald E. |
author_facet | Bein, Amir Fadel, Cicely W. Swenor, Ben Cao, Wuji Powers, Rani K. Camacho, Diogo M. Naziripour, Arash Parsons, Andrew LoGrande, Nina Sharma, Sanjay Kim, Seongmin Jalili-Firoozinezhad, Sasan Grant, Jennifer Breault, David T. Iqbal, Junaid Ali, Asad Denson, Lee A. Moore, Sean R. Prantil-Baun, Rachelle Goyal, Girija Ingber, Donald E. |
author_sort | Bein, Amir |
collection | PubMed |
description | Environmental enteric dysfunction (EED)—a chronic inflammatory condition of the intestine—is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan. Exposure of the organ chip to such nutritional deficiencies resulted in congruent changes in six of the top ten upregulated genes that were comparable to changes seen in samples from patients with EED. Chips lined with healthy epithelium or with EED epithelium exposed to nutritional deficiencies resulted in severe villus blunting and barrier dysfunction, and in the impairment of fatty acid uptake and amino acid transport; and the chips with EED epithelium exhibited heightened secretion of inflammatory cytokines. The organ-chip model of EED‐associated intestinal injury may facilitate the analysis of the molecular, genetic and nutritional bases of the disease and the testing of candidate therapeutics for it. |
format | Online Article Text |
id | pubmed-9652151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96521512022-11-15 Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction Bein, Amir Fadel, Cicely W. Swenor, Ben Cao, Wuji Powers, Rani K. Camacho, Diogo M. Naziripour, Arash Parsons, Andrew LoGrande, Nina Sharma, Sanjay Kim, Seongmin Jalili-Firoozinezhad, Sasan Grant, Jennifer Breault, David T. Iqbal, Junaid Ali, Asad Denson, Lee A. Moore, Sean R. Prantil-Baun, Rachelle Goyal, Girija Ingber, Donald E. Nat Biomed Eng Article Environmental enteric dysfunction (EED)—a chronic inflammatory condition of the intestine—is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan. Exposure of the organ chip to such nutritional deficiencies resulted in congruent changes in six of the top ten upregulated genes that were comparable to changes seen in samples from patients with EED. Chips lined with healthy epithelium or with EED epithelium exposed to nutritional deficiencies resulted in severe villus blunting and barrier dysfunction, and in the impairment of fatty acid uptake and amino acid transport; and the chips with EED epithelium exhibited heightened secretion of inflammatory cytokines. The organ-chip model of EED‐associated intestinal injury may facilitate the analysis of the molecular, genetic and nutritional bases of the disease and the testing of candidate therapeutics for it. Nature Publishing Group UK 2022-06-23 2022 /pmc/articles/PMC9652151/ /pubmed/35739419 http://dx.doi.org/10.1038/s41551-022-00899-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bein, Amir Fadel, Cicely W. Swenor, Ben Cao, Wuji Powers, Rani K. Camacho, Diogo M. Naziripour, Arash Parsons, Andrew LoGrande, Nina Sharma, Sanjay Kim, Seongmin Jalili-Firoozinezhad, Sasan Grant, Jennifer Breault, David T. Iqbal, Junaid Ali, Asad Denson, Lee A. Moore, Sean R. Prantil-Baun, Rachelle Goyal, Girija Ingber, Donald E. Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title | Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title_full | Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title_fullStr | Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title_full_unstemmed | Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title_short | Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
title_sort | nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652151/ https://www.ncbi.nlm.nih.gov/pubmed/35739419 http://dx.doi.org/10.1038/s41551-022-00899-x |
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