The human gut microbiome plays an integral role in the development, maintenance, and function of the host immune system. Together, these interactions shape the balance between health and disease states, however, when disrupted can drive the development of infectious and inflammatory diseases. Advances in culturing and sequencing tools have paved way for comprehensive analysis of the intestinal ecosystem and microbial composition in the gut to functionally validate the microbiome. Despite numerous efforts to identify novel keystone species in health and disease, there is an unmet need to dissect the specific functions of host-microbiome interactions through experimental validation. Although extensive research has established various host-microbial factors that contribute to chronic immune disorders of the gut such as inflammatory bowel disease (IBD), further work is essential to fully understand the complex pathophysiology of IBD and determine causation of the microbiome. Through culturing and sequencing approaches, we have isolated novel bacteria from IBD patients that are associated with non-inflamed and inflamed intestinal states. However, the distinct functions of these bacterial isolates have yet to be characterised. Advancements in bioengineering has allowed the emergence of microfluidic organ-on-a-chip systems, which has revolutionised the ability to model organ physiology and function at a cell and tissue interface. Here, we describe the ability to functionally validate and characterise host-microbiome interactions based on the organ-on-a-chip system that mimics the intestinal niche and model diseases such as IBD. Intestinal epithelial cells, endothelial and immune cells are cultured in distinct nutrient-filled compartments on a multichannel, polymeric chip and can be co-cultured with bacteria or molecules of interest. This system will advance our current understanding of microbiome function and host responses, and will ultimately facilitate the development of high-throughput screening platforms and personalised precision medicine.