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, and most of these microorganisms are located in the gut. Though the interplay between the gut microbiome and the host has been extensively studied, how the gut microbiome interacts with the enteric nervous system remains largely unknown. To date, a physiologically representative in vitro model to study gut microbiome-nervous system interactions does not exist. To fill this gap, we further developed the human-microbial crosstalk (HuMiX) gut-on-chip model by introducing induced pluripotent stem cell-derived enteric neurons into the device. The resulting model, 'neuroHuMiX', allows for the co-culture of bacterial, epithelial, and neuronal cells across microfluidic channels, separated by semi-permeable membranes. Despite separation of the different cell types, the cells can communicate with each other through soluble factors, simultaneously providing an opportunity to study each cell type separately. This setup allows for first insights into how the gut microbiome affects the enteric neuronal cells. This is a critical first step in studying and understanding the human gut microbiome-nervous system axis.

Toward hypothesis-driven, personalized microbiome screening.

The human gut microbiome is crucial for human health and disease but exhibits extensive individual-level strain variation. Distinct strains encode and express different functions. The resulting emergent properties therefore differentially affect human health and disease in a personalized manner. Pryszlak et al. have made strides in tackling the challenge of genome-based microbiome screening which will ultimately yield strain-level understanding of the functional roles played by the human gut microbiome.