Gut‐on‐a‐chip platforms: Bridging in vitro and in vivo models for advanced gastrointestinal research

Abstract The gastrointestinal (GI) tract plays a critical role in nutrient absorption, immune responses, and overall health. Traditional models such as two‐dimensional cell cultures have provided valuable insights but fail to replicate the dynamic and complex microenvironment of the human gut. Gut‐on‐a‐chip platforms, which incorporate cells located in the gut into microfluidic devices that simulate peristaltic motion and fluid flow, represent a significant advancement in modeling GI physiology and diseases. This review discusses the evolution of gut‐on‐a‐chip technology, from simple cellular mono‐cultures models to more sophisticated systems incorporating bi‐cultures and tri‐cultures that enable studies of drug metabolism, disease modeling, and gut–microbiome interactions. Although challenges remain, including maintaining long‐term cell viability and replicating immune responses, these platforms hold great potential for advancing personalized medicine and improving drug discovery efforts targeting gastrointestinal disorders.