Drug-induced gastrointestinal toxicity (GIT) is a common treatment-emergent adverse event that can negatively impact dosing, thereby limiting efficacy and treatment options for patients. An in vitro assay of GIT is needed to address patient variability, mimic the microphysiology of the gut, and accurately predict drug-induced GIT. Primary human ileal organoids (termed ‘enteroids’) have proven useful for stimulating intestinal stem cell proliferation and differentiation to multiple cell types present in the gut epithelium. Enteroids have enabled characterization of gut biology and the signaling involved in the pathogenesis of disease. Here, enteroids were differentiated from four healthy human donors and assessed for culture duration-dependent differentiation status by immunostaining for gut epithelial markers lysozyme, chromogranin A, mucin, and sucrase isomaltase. Differentiated enteroids were evaluated with a reference set of 31 drugs exhibiting varying degrees of clinical incidence of diarrhea, a common manifestation of GIT that can be caused by drug-induced thinning of the gut epithelium. An assay examining enteroid viability in response to drug treatment demonstrated 90% accuracy for recapitulating the incidence of drug-induced diarrhea. The human enteroid viability assay developed here presents a promising in vitro model for evaluating drug-induced diarrhea.

药物诱发的胃肠道毒性（GIT）是常见的治疗紧急不良事件，会对剂量产生负面影响，从而限制了患者的疗效和治疗选择。一种在体外需要进行GIT检测以解决患者的变异性，模仿肠道的微生理学并准确预测药物诱导的GIT。已证明人类主要回肠类器官（称为“类固醇”）可用于刺激肠道干细胞增殖和分化为肠道上皮中存在的多种细胞类型。肠类固醇能​​够表征肠道生物学和参与疾病发病机制的信号传导。在这里，从四个健康的人类供体中区分出类固醇，并通过对肠上皮标记物溶菌酶，嗜铬粒蛋白A，粘蛋白和蔗糖异麦芽糖酶的免疫染色，评估了培养时间依赖性的分化状态。参照一组31种药物的差异性肠溶素进行评估，这些药物表现出不同程度的腹泻临床发病率，GIT的常见表现，可能是药物引起的肠道上皮变薄所致。一项针对药物治疗的肠样生存力检测方法表明，重现药物性腹泻的发生率可达到90％的准确性。此处开发的人类肠样生存力测定法显示出令人鼓舞的前景评估药物性腹泻的体外模型。