Lab-on-chip technologies for exploring the gut-immune axis in metabolic disease

The continued rise in metabolic diseases such as obesity and type 2 diabetes mellitus poses a global health burden, necessitating further research into factors implicated in the onset and progression of these diseases. Recently, the gut-immune axis, with diet as a main regulator, has been identified as a possible role player in their development. Translation of conventional 2D in vitro and animal models is however limited, while human studies are expensive and preclude individual mechanisms from being investigated. Lab-on-chip technology therefore offers an attractive new avenue to study gut-immune interactions. This review provides an overview of the influence of diet on gut-immune interactions in metabolic diseases and a critical analysis of the current state of lab-on-chip technology to study this axis. While there has been progress in the development of "immuno-competent" intestinal lab-on-chip models, with studies showing the ability of the technology to provide mechanical cues, support longer-term co-culture of microbiota and maintain in vivo-like oxygen gradients, platforms which combine all three and include intestinal and immune cells are still lacking. Further, immune cell types and inclusion of microenvironment conditions which enable in vivo-like immune cell dynamics as well as host-microbiome interactions are limited. Future model development should focus on combining these conditions to create an environment capable of hosting more complex microbiota and immune cells to allow further study into the effects of diet and related metabolites on the gut-immune ecosystem and their role in the prevention and development of metabolic diseases in humans.