@article{1e9488548edf4e138c64a44c61c04dd7,
title = "Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction",
abstract = "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.",
author = "Amir Bein and Fadel, {Cicely W.} and Ben Swenor and Wuji Cao and Powers, {Rani K.} and Camacho, {Diogo M.} and Arash Naziripour and Andrew Parsons and Nina LoGrande and Sanjay Sharma and Seongmin Kim and Sasan Jalili-Firoozinezhad and Jennifer Grant and Breault, {David T.} and Junaid Iqbal and Asad Ali and Denson, {Lee A.} and Moore, {Sean R.} and Rachelle Prantil-Baun and Girija Goyal and Ingber, {Donald E.}",
note = "Funding Information: This research was sponsored by funding from the Bill and Melinda Gates Foundation (independent support to D.E.I), NIH award DK119488 (to D.T.B), the Anne London Fellowship (to C.W.F), and the Wyss Institute for Biologically Inspired Engineering. This work was conducted with the support of a KL2 award (an appointed KL2 award to C.W.F.) from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR002542). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, or the National Institutes of Health. Funding Information: This research was sponsored by funding from the Bill and Melinda Gates Foundation (independent support to D.E.I), NIH award DK119488 (to D.T.B), the Anne London Fellowship (to C.W.F), and the Wyss Institute for Biologically Inspired Engineering. This work was conducted with the support of a KL2 award (an appointed KL2 award to C.W.F.) from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR002542). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = nov,
doi = "10.1038/s41551-022-00899-x",
language = "English",
volume = "6",
pages = "1236--1247",
journal = "Nature Biomedical Engineering",
issn = "2157-846X",
publisher = "Nature Publishing Group",
number = "11",
}
