Patient-Derived Organoids in Gastrointestinal Disease: Current Applications, Limitations, and Future Perspectives

The development of patient-derived organoids (PDOs) has substantially advanced the study of gastrointestinal diseases by providing three-dimensional human models that faithfully recapitulate the structural, molecular, and functional characteristics of native tissues. Unlike conventional two-dimensional cultures and animal models, intestinal organoids preserve epithelial architecture, cellular heterogeneity, and patient-specific genetic features, enabling more physiologically relevant investigations of gastrointestinal physiology and disease. Recent technological advances, including co-culture systems, organoid-derived monolayers, and organ-on-chip platforms, have further expanded their ability to model epithelial interactions with immune cells, stromal components, and the gut microbiota. These developments have facilitated mechanistic studies of epithelial barrier function, host–microbiota communication, microbial metabolites, and endocrine signaling, while also supporting translational applications in inflammatory bowel disease, infectious disorders, inherited gastrointestinal diseases, and gastrointestinal cancers. Moreover, patient-derived organoids have emerged as promising platforms for drug screening, biomarker discovery, precision medicine, and regenerative therapies. Despite these advances, several challenges remain, including limited representation of the native tissue microenvironment, lack of standardized culture protocols, scalability, and regulatory issues that currently restrict routine clinical implementation. This review summarizes recent progress in gastrointestinal organoid technology, highlighting current applications, emerging experimental platforms, and future perspectives for integrating organoid-based models into translational research and personalized medicine.