The human gut-on-a-chip contains two microchannels that are separated by the flexible porous Extracellular Matrix (ECM)-coated membrane lined by the gut epithelial cells: Caco-2, which has been used extensively as the intestinal barrier. Caco-2 cells are cultured under spontaneous differentiation of its parental cell, a human colon adenocarcinoma, that represent the model of protective and absorptive properties of the gut. The microchannels are fabricated from polydimethylsiloxane (PDMS) polymer. In order to mimic the gut microenvironment, peristalsis-like fluid flow is designed. By inducing suction in the vacuum chambers along both sides of the main cell channel bilayer, cyclic mechanical strain of stretching and relaxing are developed to mimic the gut behaviors.  Furthermore, cells undergo spontaneous villus morphogenesis and differentiation, which generalizes characteristics of intestinal cells. Under the three-dimensional villi scaffold, cells not only proliferate, but metabolic activities are also enhanced. Another important player in the gut is the microbes, namely gut microbiota. Many microbial species in the gut microbiota are strict anaerobes. In order to co-culture these oxygen intolerant anaerobes with the oxygen favorable intestinal cells, a polysulfone fabricated gut-on-a-chip is designed. The system maintained the co-culture of colon epithelial cells, goblet-like cells, and bacteria Faecalibacterium prausnitzii, [https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=39491 Eubacterium rectale], and Bacteroides thetaiotaomicron.
Oral administration is one of the most common methods for drug administration. It allows patients, especially out-patients, to self-serve the drugs with minimal possibility of experiencing acute drug reactions and in most cases: pain-free. However, the drug's action in the body can be largely influenced by the first pass effect. The gut, which plays an important role in the human digestive system, determines the effectiveness of a drug by absorbing its chemical and biological properties selectively. While it is costly and time consuming to develop new drugs, the fact that the gut-on-a-chip technology attains a high level of throughput has significantly decreased research and development costs and time for new drugs.
Even though the cause for inflammatory bowel disease (IBD) is elusive, its pathophysiology involves the gut microbiota. Current methods of inducing IBD are using inflammatory cues to activate Caco-2. It was found that the intestinal epithelium experienced a reduction in barrier function and increased cytokine concentrations. The gut-on-a-chip allowed for the assessment on drug transport, absorption and toxicity as well as potential developments in studying pathogenesis and interactions in the microenvironment overall. Immune cells are essential in mediating inflammatory processes in many gastrointestinal disorders, a recent gut-on-a-chip system also includes multiple immune cells, e.g., macrophages, dendritic cells, and CD4+ T cells in the system. Additionally, the gut-on-a-chip allows the testing of anti-inflammatory effects of bacterial species.
The chip was used to model human radiation-induced injury to the intestine in vitro as it recapitulated the injuries at both cellular and tissue levels. Injuries include but not limited to: inhabitation of mucus production, promotion of villus blunting, and distortion of microvilli.