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.

环境性肠功能障碍 (EED) 是一种肠道慢性炎症，其特点是绒毛变钝、肠道屏障功能受损和营养吸收减少。在这里，我们表明，EED 相关肠道损伤的基本基因型和表型特征可以在人类芯片肠道中重建，该芯片由来自 EED 患者的类器官来源的肠上皮细胞排列，并在缺乏烟酰胺和烟酰胺的营养缺乏培养基中培养。色氨酸。将器官芯片暴露在这种营养缺乏的情况下，会导致前十个上调基因中的六个发生一致变化，这些变化与 EED 患者样本中观察到的变化相当。内衬健康上皮或暴露于营养缺乏的 EED 上皮的芯片会导致严重的绒毛变钝和屏障功能障碍，并导致脂肪酸摄取和氨基酸运输受损；带有 EED 上皮细胞的芯片表现出炎症细胞因子分泌增加。 EED 相关肠道损伤的器官芯片模型可能有助于分析该疾病的分子、遗传和营养基础，并测试其候选疗法。