Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction.
Nat Biomed Eng
; 6(11): 1236-1247, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35739419
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desnutrição
/
Enteropatias
Tipo de estudo:
Risk_factors_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Humans
Idioma:
En
Revista:
Nat Biomed Eng
Ano de publicação:
2022
Tipo de documento:
Article