Progress in human intestinal organoid research: applications to acute gastroenteritis viruses

Acute gastroenteritis viruses, such as rotavirus, human norovirus, human astrovirus, human adenovirus, human sapovirus, represent significant threats to global public health. Research on these pathogens has long been hampered by the limitations of conventional models. Animal and cell-based systems, widely used in virological studies, show limited efficiency in supporting rotavirus replication, while noroviruses remain largely non-cultivable in these settings. Organoids-complex, three-dimensional multicellular structures derived from stem cells-exhibit organ-specific characteristics and spatial organization, making them promising tools for viral research. Intestinal organoids, in particular, recapitulate key features of the gut epithelium and have emerged as versatile platforms for investigating viral pathogenesis and developing intervention strategies. This review systematically outlines the cultivation and functional properties of human intestinal organoids, as well as the evolution and progress of their application in studying acute gastroenteritis viruses. However, current intestinal organoid models are primarily composed of epithelial cells and lack immune and other non-epithelial components, thereby limiting their ability to fully simulate host-pathogen interactions and immune responses following infection. Future efforts should focus on incorporating emerging technologies, such as CRISPR/Cas9 gene editing, to develop more physiologically relevant intestinal models that better mimic in vivo conditions.