A Gut-Brain Axis-on-a-Chip for studying transport across epithelial and endothelial barriers

Recent research on Gut-Brain Axis (GBA) has suggested that the gut luminal environment, including the dietary components and commensal microbiota, could affect behavior, emotion, and cognitive abilities in the brain. Various signaling pathways exist between the gut and the brain, and several studies have implied exosomes could mediate the communication. Current research on GBA has relied heavily on animal models, making the research challenging. Recent advances in organ-on-a-chip technology could be a solution for GBA research. In present work, we have developed a modular microfluidic chip, where gut epithelial and brain endothelial cells were co-cultured to form the gut epithelial barrier and the Blood-Brain Barrier (BBB) interconnected via microfluidic channels. These modules can be easily assembled and disassembled, and cell barriers were well formed when co-cultured under appropriate fluidic flow. Responses to microbial byproducts were consistent with previously known observations of interaction between gut epithelium and BBB. We observed the transport of fluorescently labeled exosomes across the gut barrier towards the BBB. Our results suggest this model can be used as a novel in vitro model of GBA for studying the interaction between the gut and the brain.