Organ-on-chip is a novel technology harnessing advances in microengineering and fluid dynamics to reconstruct the physiological tissue microenvironment, including many features that cannot be achieved in conventional tissue culture (e.g. villi, differentiation of epithelial cell types, mucus secretion, peristalsis). The chips are a modular physical, biochemical, and optical sensing platform which are interfaced through a fluidics-routing breadboard with in situ, continual, and automated sensing of biophysical and biochemical parameters. Microbiome could be introduced to the chips and thei interaction with the gut model could be screened. With integration of biosensors enabling precise control of the microenvironment, this tool provides a novel platform to study host-microbiome interactions in a physiologically-relevant system.