A microfluidics-based in vitro model of the gastrointestinal human–microbe interface

Abstract

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.

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

“…In the literature, few examples of impedance electrical monitoring integrated with organ-on-chip devices have been described 19,20 , and the electrode materials employed, for example, silver chloride (AgCl), are known to be a significant source of cytotoxicity if used for anything other than chronic measurements 60 . In a recent study of an in vitro model of the gastrointestinal-microbe interface, commercially available chopstick electrodes were employed for the measurement of the cell TER 16 . However, the insertion of these electrodes lead to the contamination of the microfluidic platform, thus limiting its employment as a true in-line sensing system, to say nothing of the issues related to irreproducibility of chopstick electrode readings 32 .…”

“…Several examples of organ-on-chip devices have already been described, such as a lung-on-a-chip array 9 , a human kidney proximal tubule-on-a-chip 10 , and a multi-organ-on-chip device platform for the co-culture of intestine, liver, skin, and kidney models 11 . The field is fast moving toward the development of novel and more complex microfluidic devices to host these organoid/tissue models [12][13][14][15][16][17][18] ; however, few existing research efforts have focused on the integration of in-line sensors, for example, monitoring of cell metabolites, or transepithelial resistance (TER), within the microfluidic environment, while maintaining compatibility with optical monitoring, despite the perceived demand 19,20 .…”

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

“…New types of dynamic models that are gaining increasing attention are microfluidic gut-on-a-chip models, which provide the potential to develop protocols where in vitro cellular models for absorption harbour intestinal microbiota. Microfluidic techniques have already been shown to allow long-term co-culturing of Caco-2 epithelial cells with microflora without compromising membrane integrity (Kim et al, 2012;Shah et al, 2016). The current use of in vitro methods for luminal degradation shows that these methods are occasionally included in the assessment of food chemicals (Fig.…”

Fabrication of nanocomposites and hybrid materials using microbial biotemplates

“…Another interesting example is that immobilized human and microbial cells can be utilized to build an in vitro model that can support the co-culturing of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. Thus, it will provide tools to explore a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease [40].…”