Luxembourg Centre for Systems Biomedicine, University of Luxembourg.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg; Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg;
J Vis Exp. 2023 Jul 28(197). doi: 10.3791/64483.
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.
人体被微生物细胞定植的数量至少与人体细胞数量相同，而这些微生物大多数存在于肠道中。尽管肠道微生物组与宿主之间的相互作用已经得到了广泛研究，但肠道微生物组与肠神经系统的相互作用在很大程度上仍不清楚。迄今为止，还没有一种具有生理代表性的体外模型来研究肠道微生物组-神经系统的相互作用。为了填补这一空白，我们通过将诱导多能干细胞衍生的肠神经元引入设备，进一步开发了人类微生物相互作用（HuMiX）肠道芯片模型。由此产生的模型“neuroHuMiX”允许在微流控通道中对细菌、上皮和神经元细胞进行共培养，这些细胞被半透膜隔开。尽管不同细胞类型被分离，但它们可以通过可溶性因子相互通信，同时为分别研究每种细胞类型提供了机会。这种设置使我们能够首次深入了解肠道微生物组如何影响肠神经元细胞。这是研究和理解人类肠道微生物组-神经系统轴的关键第一步。
