Microbiota-gut-brain axis multi-organ chip construction and applications in drug evaluation

The theoretical framework of the microbiota-gut-brain axis (MGBA) elucidates the influence of gut microbiota (GM) on the central nervous system (CNS) and offers novel approaches for diagnosing and treating neurological disorders. The application of microfluidic organ chips to study this axis represents an innovative methodology, enabling multidisciplinary assessment of drug effects. Bionic microphysiological systems based on these chips establish a groundbreaking paradigm for analyzing cross-organ interaction mechanisms within the MGBA. This technology facilitates systematic evaluation of pharmacokinetics, host-microbe coevolution, and neuroendocrine regulation, thereby supporting multimodal cross-validation in pharmacodynamics, toxicology, and translational medicine. This review summarizes the conceptual foundation and mechanistic insights of the MGBA, highlights recent advances in its constituent Multiorgan components, including gut-on-a-chip, blood-brain barrier-on-a-chip, and brain-on-a-chip models, alongside multiorgan chip cascade technologies, and underscores their applications in drug evaluation. Additionally, it discusses future challenges and developmental directions for the MGBA multiorgan chip technologies in this field.