neuroHuMiX: a gut-on-a-chip model to study the gut microbiome-nervous system axis

The human body is colonized by at least the same number of microbial cells as it is composed of human cells, whereby most of these microorganisms are located in the gut. In this context, the human gut microbiome plays an essential role in human health and disease. Dysbiosis, an imbalanced microbial community state, is associated with diseases and functionally contributes to the aetiology, diagnosis, or treatment of them. It has been linked to different diseases, from gastrointestinal tract infections to neurodegenerative diseases. As more and more evidence points towards a role for the gut microbiome in neurological disorders, interactions between the gut microbiome and the nervous system can be implied. Though studies have shown that the gut communicates with the brain via the vagus nerve, it still remains largely unknown how the gut microbiome interacts with the enteric nervous system. In order to close this knowledge gap, a physiologically representative in
vitro model is required to study the linked gut microbiome-nervous system interactions. In this project, I adapted the Human Microbial Crosstalk (neuroHuMiX) gut-on-chip by including induced pluripotent stem cell-derived enteric neurons in the model and thus developed ‘neuroHuMiX’. The resulting model, ‘neuroHuMiX’, allows the co-culture of bacterial, epithelial, and neuronal cells across microfluidic channels, separated by semi-permeable membranes. Despite the separation of the
different cell types, the cells are able to communicate with each other via soluble factors, simultaneously providing an opportunity to study each cell type separately. neuroHuMiX not only allows for first insights into the gut microbiome-nervous system interactions but may also serve as a model for therapeutic testing. This is a critical first step in studying the human gut-brain axis which can be further expanded to personalized models for neurological disorders research.