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.

最近对肠脑轴 (GBA) 的研究表明，肠腔环境，包括饮食成分和共生微生物群，可能会影响大脑的行为、情绪和认知能力。肠道和大脑之间存在多种信号通路，一些研究表明外泌体可以介导这种交流。目前对 GBA 的研究严重依赖动物模型，使研究具有挑战性。器官芯片技术的最新进展可能成为大湾区研究的解决方案。在目前的工作中，我们开发了一种模块化微流控芯片，其中肠道上皮细胞和脑内皮细胞共同培养以形成肠道上皮屏障和通过微流控通道互连的血脑屏障 (BBB)。这些模块可以很容易地组装和拆卸，当在适当的流体流动下共培养时，细胞屏障形成良好。对微生物副产物的反应与先前已知的肠道上皮和 BBB 之间相互作用的观察结果一致。我们观察到荧光标记的外泌体穿过肠道屏障向 BBB 的转运。我们的研究结果表明，该模型可用作 GBA 的新型体外模型，用于研究肠道和大脑之间的相互作用。