胃肠道（GI）上皮在营养吸收、屏障形成和先天免疫中起着重要作用。器官体系的发展方法对GI上皮的研究有着重要影响，特别是在黏膜生物学、免疫学和宿主-微生物相互作用领域。各种对GI上皮的影响，如遗传和营养等，影响患者并改变疾病状态。因此，将这些因素纳入器官体系模型中将有助于更好地理解疾病进展并提供评估治疗候选药物的机会。一种对GI上皮有重要影响的情况是营养不良，研究营养不良的机制影响将加强我们对多种病理学的理解。因此，本研究的目标是开始开发生成可行的营养不良器官体系的方法，使用可获取的技术和资源，为广泛的机制研究提供基础。通过有选择地限制器官体系培养基中不同的宏量营养成分，我们成功地培养和评估了营养不良器官体系。采用基因和蛋白质分析验证了该方法，并确认了已知营养不良生物标志物的存在。此外，作为概念验证，我们利用营养不良器官体系衍生的单层细胞模型评估了营养不良对屏障形成以及细菌致病菌志贺氏菌感染GI上皮的影响。这项工作为改变器官体系的营养状态以及对GI上皮的相关影响研究提供了新的和令人兴奋的技术基础。

The gastrointestinal (GI) epithelium plays a major role in nutrient absorption, barrier formation, and innate immunity. The development of organoid-based methodology has significantly impacted the study of the GI epithelium, particularly in the fields of mucosal biology, immunity, and host-microbe interactions. Various effects on the GI epithelium, such as genetics and nutrition, impact patients and alter disease states. Thus, incorporating these effects into organoid-based models will facilitate a better understanding of disease progression and offer opportunities to evaluate therapeutic candidates. One condition that has a significant effect on the GI epithelium is malnutrition, and studying the mechanistic impacts of malnutrition would enhance our understanding of several pathologies. Therefore, the goal of this study was to begin to develop methodology to generate viable malnourished organoids with accessible techniques and resources that can be used for a wide array of mechanistic studies. By selectively limiting distinct macronutrient components of organoid media, we were able to successfully culture and evaluate malnourished organoids. Genetic and protein-based analyses were used to validate the approach and confirm the presence of known biomarkers of malnutrition. Additionally, as proof-of-concept, we utilized malnourished organoid-derived monolayers to evaluate the effect of malnourishment on barrier formation and the ability of the bacterial pathogen Shigella flexneri to infect the GI epithelium. This work serves as the basis for new and exciting techniques to alter the nutritional state of organoids and investigate the related impacts on the GI epithelium.