Intestinal Organoid-on-a-Chip: A new frontier in deciphering the mechanisms of absorption and transport of traditional Chinese medicine

Traditional Chinese medicine (TCM), refined over millennia, embodies distinctive therapeutic principles rooted in the concept of harmony with nature. The oral efficacy of TCM is critically dependent upon the precise absorption and efficient intestinal transport of its complex constituents. However, the underlying mechanisms remain poorly understood, posing a significant challenge to the modernization and global advancement of TCM research. Intestinal organoid technology, which enables three-dimensional in vitro culture of intestinal tissues, accurately recapitulates the cellular heterogeneity, structural organization, and key physiological functions of the native intestine. Recently, the integration of organoids with microfluidic platforms to form “Intestinal Organoid-on-a-Chip” systems has further advanced this field by dynamically recapitulating intestinal peristalsis, absorption, and metabolic activities. These systems provide a more physiologically relevant platform for investigating the transmembrane transport and spatiotemporal dynamics of TCM constituents. This review summarizes the principles, construction strategies, and functional characteristics of intestinal organoid technology, highlights its emerging applications in elucidating the absorption and transport mechanisms of TCM, and discusses current challenges, including standardization, experimental complexity, and clinical translation. Furthermore, it envisions future directions involving multiomics, artificial intelligence, and other cutting-edge approaches, aiming to provide novel strategies to accelerate the modernization and internationalization of TCM research.