The HuMiX model. (a) Conceptual diagram of the HuMiX model for the representative co-culture of human epithelial cells with gastrointestinal microbiota. (b) Annotated exploded view of the HuMiX device. The device is composed of a modular stacked assembly of elastomeric gaskets (thickness: 700 μm) sandwiched between two polycarbonate (PC) enclosures, and each gasket defines a distinct spiral-shaped microchannel with the following characteristics: length of 200 mm, width of 4 mm and height of 0.5 mm, amounting to a total volume of 400 μl per channel. Semi-permeable membranes affixed to the elastomeric gaskets demarcate the channels. The pore sizes of the membranes were chosen for their intended functionality. A microporous membrane (pore diameter of 1 μm), which allows diffusion-dominant perfusion to the human cells, is used to partition the perfusion and human microchambers. A nanoporous membrane (pore diameter of 50 nm) partitions the human and microbial microchambers to prevent the infiltration of microorganisms, including viruses, into the human microchamber. (c) Photograph of the assembled HuMiX device (scale bar, 1 cm). (d) Diagram of the experimental set-up of the HuMiX model with provisions for the perfusion of dedicated oxic and anoxic culture media as well as the monitoring of the oxygen concentration and transepithelial electrical resistance. The oxygen concentration in the anoxic medium is maintained at 0.1% by continuously bubbling the medium with dinitrogen gas. (e) Diagrammatic overview of the HuMiX co-culture protocol.
Scientists have now proven that a model of the human gut they have developed and patented – HuMiX – is representative of the actual conditions and processes that occur within our intestines. With HuMiX, they can analyse complex interactions between human cells and bacteria, predict their effects on health or disease onset, and study the action of probiotics and drugs.
In HuMiX, the “Human Microbial Cross-talk” model, human intestinal cells and bacteria can be cultivated together in a very small space under representative conditions. The apparatus, no bigger than a beer mat, has 3 chambers. The top chamber is the supply level, from which nutrients continuously flow down to the cell cultures below. Human cells grow on a very thin membrane in the middle chamber, while bacteria grow in the lowest chamber. “With HuMiX, we can observe interaction of bacteria in real-time as they communicate with human intestinal cells,” says Prof. Paul Wilmes.
For tests confirming validity of HuMiX experiments, they used pure cultures of various bacterial strains. “Using cutting-edge analytical methods established at the LCSB, we then studied how the gene activity and metabolism of intestinal epithelial cells change depending on the bacterial strain used in HuMiX,” Wilmes explains. “A comparison of our data with results from other research groups who obtained theirs from humans or animals showed strong agreement.” That means HuMiX delivers a very accurate portrayal of the cellular and molecular processes taking place in the human gut. “With HuMiX we can also study processes so far inaccessible by existing experimental methods,” Wilmes adds.
In vitro co-culture of human and microbial cells inside the HuMiX device.
Dr. Pranjul Shah said as an example: “In a co-culture of intestinal cells and a certain strain of the bacterial species Lactobacillus rhamnosus, we determined that production of …GABA, is stimulated in intestinal cells, indicating a mechanism by which the intestine may be communicating with the brain.” Scientists had already seen evidence of this effect several years earlier in the brain of mice born with a completely sterile gut (which was devoid of all intestinal flora), when their gut was inoculated with similar Lactobacillus strains.
Paul Wilmes said. “There are clues, for example, that inflammatory processes can play a role in the onset of neurodegenerative diseases such as Parkinson’s. In HuMiX, we can introduce distinct bacterial species or whole communities into the artificial gut model whether these organisms trigger or slow down inflammation, or even introduce immune cells and neurons together with the bacteria.” http://wwwen.uni.lu/university/news/slideshow/gut_model_humix_works_like_the_real_thing
http://www.nature.com/ncomms/2016/160511/ncomms11535/full/ncomms11535.html
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