Changes to 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. Furthermore, given the current propensity for the generation of big data in human microbiome science, several hypotheses arise from the analysis of this data for which high-throughput experimental systems are called for. Lack of representative models is slowing down the progress towards validating these hypotheses.
In order to address these challenges, we have developed a new model called HuMiX. HuMiX (human microbial cross-talk) device allows the co-culture of human intestinal cells and bacteria under conditions representative of the gastrointestinal human-microbe interface. HuMiX comprises of three chambers - The top chamber is the supply level, from which nutrients continuously flow to the cell cultures below. Human cells grow on a very thin membrane in the middle chamber, while bacteria grow in the lowest chamber. The engineered microfluidic system allows the tight control of culture conditions in each chamber. Thereby, human cells are supplied with oxygen-rich medium whereas microbial cells grow under anaerobic conditions mimicking the overall in vivo situation.
We performed carefully designed validation experiments involving pure cultures of various bacterial strains together with human epithelial and immune cells. Using these experiments, we demonstrated that HuMiX has the ability 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 showed that 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. Comparison of HuMiX-derived transcriptomic results to two human clinical studies show high degree of concordance providing validation for the HuMiX model.
From these initial proof-of-concept experiments it follows that HuMiX allows systematic 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."