The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human “Gut-on-a-Chip” that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage.
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