Cellular interplay to 3D in vitro microphysiological disease model: cell patterning microbiota–gut–brain axis

The microbiota–gut–brain axis(MGBA) has emerged as a key prospect in the bidirectional communication between two major organ systems: the brain and the gut. Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions. The most common communication paths are the microbial release of metabolites, soluble neurotransmitters, and immune cells. However, each pathway is intertwined with a complex one. With the emergence of in vitro models and the popularity of three-dimensional(3D) cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases. This paper briefly retraces the possible communication pathways between the gut microbiome and the brain. It further elaborates on three major diseases:autism spectrum disorder, Parkinson's disease, and Alzheimer's disease, which are prevalent in children and the elderly. These diseases also decrease patients' quality of life. Hence, understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases. Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances. Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers. Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal) while allowing physical and chemical cues between them. Cutting-edge technologies, such as bioprinting and microfluidic chips, might be the future of in vitro modeling, as they provide dynamicity.