Modeling gut inflammation using intestinal organoids: Advances, challenges, and future perspectives

Intestinal organoids have emerged as powerful in vitro system for studying epithelial biology in a tissue-relevant context. Derived from adult stem cells or patient-specific induced pluripotent stem cells, these three-dimensional structures recapitulate key features of the intestinal epithelium, including crypt-villus architecture, cellular diversity, and functional barrier properties. Recent advances have enabled the modeling of gut inflammation using organoids through defined cytokine stimulation, co-culture with immune cells, and exposure to microbial components. These approaches have provided insights into epithelial barrier dysfunction, immune-epithelial crosstalk, and disease-specific responses, particularly in inflammatory bowel disease. Innovations such as gene-editing technologies, single-cell and spatial transcriptomics, and microengineered platforms like organoid-on-chip systems have advanced organoid-based research in various contexts, laying a strong foundation for their future application in modeling inflammation. Despite these advances, challenges remain in achieving long-term immune co-culture, media compatibility, and standardized readouts. This article highlights current strategies, key limitations, and future directions for using intestinal organoids to model gut inflammation and guide translational research.