The interaction between the gut and the liver, often known as the gut-liver axis, play crucial roles in modulating the body’s responses to the xenobiotics as well as progression of diseases. Dysfunction of the axis can cause metabolic disorders as well as obesity, diabetes, and fatty liver disease. During the progression of such diseases, inflammatory responses involving the immune system also play an important part. In this study, we developed a three-tissue microphysiological system (MPS) that can accommodate three different cell types in separated compartments connected via fluidic channels in a microfluidic device. Using computational fluid dynamics, geometry of fluidic channels and flow conditions were optimized for seeding and culturing different cell types in the three-tissue MPS. Caco-2 (gut), RAW264.7 (immune), and HepG2 (liver) cells were seeded and cultured in the chip. Stimulation of the gut cells in the MPS with lipopolysaccharide (LPS) resulted in induction of inflammatory response and production of nitric oxide (NO) in all connected chambers. The anti-inflammatory effect of luteolin was demonstrated. Our study demonstrates that the three-tissue MPS can recapitulate the inflammatory responses involving the gut, liver and immune cells.

肠道和肝脏之间的相互作用，通常称为肠-肝轴，在调节人体对异生素的反应以及疾病进展方面发挥着至关重要的作用。轴功能障碍会导致代谢紊乱以及肥胖、糖尿病和脂肪肝疾病。在此类疾病的进展过程中，涉及免疫系统的炎症反应也发挥着重要作用。在这项研究中，我们开发了一种三组织微生理系统（MPS），可以在通过微流体装置中的流体通道连接的独立隔室中容纳三种不同的细胞类型。使用计算流体动力学，优化了流体通道的几何形状和流动条件，以在三组织 MPS 中接种和培养不同的细胞类型。 Caco-2（肠道）、RAW264.7（免疫）和 HepG2（肝脏）细胞在芯片中接种和培养。用脂多糖 (LPS) 刺激 MPS 中的肠道细胞会诱导炎症反应，并在所有相连的腔室中产生一氧化氮 (NO)。木犀草素的抗炎作用得到了证实。我们的研究表明，三组织 MPS 可以重现涉及肠道、肝脏和免疫细胞的炎症反应。