考虑到传统的二维细胞培养和离体组织模型的重大限制，创建肠道器官样（organoids）已成为复制原生肠道上皮异质性的理想选择。肠道器官样可以从组织驻留成体干细胞（ADSs）或多能干细胞（PSCs）中发展，在诱导PSCs和胚胎干细胞两种形式下均可发展。在这里，我们回顾当前肠道器官样开发的最新进展，这些进展使得器官样更好地复制了肠道的复杂性、生理学、形态学、功能和微环境。我们讨论了肠道器官样的当前应用，重点关注疾病模型的应用。特别是，我们指出近期在人类肠道器官样中感染SARS-CoV-2的研究。我们还讨论了肠道器官样在表观遗传学中较少探索的应用，通过强调表观遗传修饰在肠道发育、稳态和疾病中的作用，以及器官样在模拟这些情况中表观遗传机制的调节作用和引入新的预测/诊断生物标志物的能力。最后，我们提出三维器官样模型，以评估新型表观遗传药物（表观药物）对胃肠疾病的治疗效果，在其中表观遗传机制在疾病发展和进展中发挥关键作用，特别是在结直肠癌治疗和表观遗传获得性耐药性中。 版权所有 © 2023 Elsevier Inc. 发表。

Considering the significant limitations of conventional 2D cell cultures and tissue in vitro models, creating intestinal organoids has burgeoned as an ideal option to recapitulate the heterogeneity of the native intestinal epithelium. Intestinal organoids can be developed from either tissue-resident adult stem cells (ADSs) or pluripotent stem cells (PSCs) in both forms induced PSCs and embryonic stem cells. Here, we review current advances in the development of intestinal organoids that have led to a better recapitulation of the complexity, physiology, morphology, function, and microenvironment of the intestine. We discuss current applications of intestinal organoids with an emphasis on disease modeling. In particular, we point out recent studies on SARS-CoV-2 infection in human intestinal organoids. We also discuss the less explored application of intestinal organoids in epigenetics by highlighting the role of epigenetic modifications in intestinal development, homeostasis, and diseases, and subsequently the power of organoids in mirroring the regulatory role of epigenetic mechanisms in these conditions and introducing novel predictive/diagnostic biomarkers. Finally, we propose 3D organoid models to evaluate the effects of novel epigenetic drugs (epi-drugs) on the treatment of GI diseases where epigenetic mechanisms play a key role in disease development and progression, particularly in colorectal cancer treatment and epigenetically acquired drug resistance.Copyright © 2023. Published by Elsevier Inc.