Abstract:
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.
摘要:
人体的微生物细胞数量至少与人类细胞相同,这些微生物大多位于肠道。虽然肠道微生物组和宿主之间的相互作用已被广泛研究,肠道微生物组如何与肠神经系统相互作用在很大程度上仍然未知。迄今为止,研究肠道微生物组-神经系统相互作用的生理代表性体外模型不存在。为了填补这个空白,我们通过将诱导的多能干细胞来源的肠神经元引入设备中,进一步开发了人类-微生物串扰(HuMiX)芯片上肠道模型。由此产生的模型,\'neuroHuMiX\',允许细菌的共培养,上皮,和穿过微流体通道的神经元细胞,被半透膜隔开。尽管不同的细胞类型分离,细胞可以通过可溶性因子相互交流,同时提供了一个机会,分别研究每个细胞类型。这种设置允许首次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-神经系统轴的关键的第一步。