Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-β, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.
肠道类器官是指利用隐窝干细胞的增殖和自组装的特性，在体外重建出的多种小肠上皮细胞类型和类似生理结构，也被称为"微肠"。类器官研究起始于不同肠段中Lgr5阳性隐窝干细胞的发现，而小肠/结肠干细胞微环境中EGF、Wnt、BMP/TGF-β、Notch等信号通路对干细胞特性的体外维持同样起关键作用。"微肠"类器官不仅可以实现隐窝-绒毛极性结构的重建，也可以重现分化型细胞组分和上皮功能。自2009年Sato等构建起小肠类器官培养体系以来，相较于主要由遗传变异细胞所构成的常规细胞培养体系，肠道类器官展现出诸多优点，并成为胃肠道疾病研究领域的热点。此外，类器官研究通过与基因组学、材料学、工程学相结合，在各医学研究领域大放异彩。"微肠"类器官作为临床前模型已广泛应用于肠道发生、肠道转运生理、肠屏障、病原体-宿主相互作用等基础研究领域，以及囊性纤维化、感染性腹泻、溃疡性结肠炎、克罗恩病和肠道肿瘤等疾病的临床研究中。本综述主要讨论肠道类器官的构建方法及其在肠道疾病中的研究及应用进展。.
Keywords: Intestinal disease; Intestinal stem cell; Organoids; Pathogen-host interaction; Reconstitution.