Emerging advances in intestinal models for in vitro preclinical research

Traditional in vitro intestinal model systems frequently fail to accurately replicate human intestinal physiology for absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments. These limitations, coupled with the growing demand for faster drug discovery and high-throughput screening capabilities, have refined more physiologically relevant models. Recent advancements have led to the development of cell-based intestinal systems that better reflect in vivo conditions, ranging from monolayer and coculture models to complex three-dimensional (3-D) cell culture systems, microfluidic devices, and bioengineered models. This review provides a comprehensive overview of current progress, ongoing challenges, and future directions in developing and applying human in vitro intestinal models for chemical testing.