The Gut-Brain Axis on Chip to unravel Inter-Tissue Interactions

The gut, its microbiota and the brain communicate with each other via the microbiome-gut-brain axis (MGBA) which represents the bi-directional path for interaction between the gastrointestinal tract and the central nervous system. The vagus nerve offers a direct route of communication within the MGBA as many modulatory effects of gut microbiota are directly facilitated via vagal activation. Dysregulation of the relationship between the microbiota and the host is implicated in a large number of diseases and pathological conditions involving the MGBA. Increasing evidence demonstrated that, specifically, neurodegenerative diseases (NDs) are not only confined to the brain but are progressively viewed in the context of alterations in the intestinal physiology. However, the exact mechanisms underlying remain unclear. While current in vivo models lack transferability of results and raise ethical issues, in vitro models to study gut-brain interactions often have unilateral approaches and lack representativeness of the complex multi-organ system. This thesis describes our efforts into recreating various components of the microbiome-gut-brain axis as well as creating a custom microfluidic chip to enable parallel multi-organ culture. Our
aim is to gain a deeper understanding of processes underlying gut-brain communication.