Microphysiological models of human gastrointestinal diseases

Gastrointestinal (GI) diseases impose a growing global health burden, extending beyond localized pathology to disrupt systemic metabolism, immunity and cancer risk. Despite advances in conventional animal and cell models, critical mechanisms driving chronic inflammation, tumour initiation and host-microbiome dysregulation remain incompletely understood, limiting translational progress. Microphysiological systems, including organoids and organ-on-a-chip technologies, have transformed our ability to model human GI biology and pathology with increasing cellular, spatial and mechanical fidelity. Here we synthesize recent advances in organoid and organ-on-a-chip models of GI disease, highlighting their applications across inflammatory, infectious and neoplastic conditions throughout the GI tract. We integrate emerging engineering approaches with mechanistic and clinical insights, assessing how these systems advance disease modelling while identifying remaining gaps in complexity, translation and scalability. By bridging microengineering innovation with clinical gastroenterology, we outline how next-generation, human-relevant models can inform mechanistic discovery, guide targeted therapeutic development and support precision medicine in GI disease.