Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.

中文翻译：

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胃肠道人-微生物界面的基于微流体的体外模型。

人类胃肠道微生物组的变化与几种疾病有关。为了推断因果关系，必须在代表性模型中进行实验，但是广泛使用的动物模型存在局限性。在这里，我们提出了一个基于微流控的模块化模型（HuMiX，人与微生物的串扰），该模型允许在代表胃肠道人-微生物界面的条件下共培养人和微生物细胞。我们证明了HuMiX与共生的鼠李糖乳杆菌GG（LGG）在厌氧条件下共培养后，在人类肠道上皮细胞中概括体内转录，代谢和免疫应答的能力。此外，我们显示人类上皮细胞与专性厌氧细菌拟杆菌和LGG的共培养可导致转录反应，这与仅包含LGG的共培养物不同。HuMiX促进了宿主-微生物分子相互作用的研究，并提供了对将胃肠道微生物组与人类健康和疾病联系起来的一系列基础研究问题的见解。