DEVICES, SYSTEMS AND METHODS FOR THE PRODUCTION OF HUMANIZED GUT COMMENSAL MICROBIOTA
One embodiment provides a commensal gut production platform for ex vivo production of human gut commensal microbiota. Another embodiment provides devices, systems and methods for ex vivo culturing of gut microflora in a system that mimics the human gut environment. The culturing of the commensal microbiota in the disclosed systems produces gut microbiota having defined characteristics and properties that can be exploited to treat various conditions in a subject.
1 . A system for the ex vivo production of human gut microbiota, comprising:
a tortious, anaerobic, tubular ex vivo culture network comprising inner and outer surfaces for culturing human gut microbiota, wherein the inner surface is coated with a matrix for promoting adhesion of human gut microbiota to the inner surface;
hollow cartridges for culturing human gut microbiota, wherein the hollow cartridges are in the fluid communication and removably attached to the tortious tubular ex vivo culture network;
a humidifying system in fluid communication with the tortious tubular ex vivo culture network to maintain physiological humidity inside the tortious tubular ex vivo culture network;
a temperature regulation system in contact with the tortious tubular ex vivo culture network to regulate the temperature inside the tortious tubular ex vivo culture network to physiological temperature; and
a hollow functional screening portal comprising extracellular matrix proteins, human cells, and a line for receiving metabolites generated by the microbiota in the tortious tubular ex vivo culture network, wherein the screening portal receives oxygen and other gases for culturing the human cells from a gas system in fluid communication with the tortious tubular ex vivo culture network.
2 . The system of claim 1 , wherein the gas system comprises an oxygen sensor in fluid communication with the culture network.
3 . The system of claim 1 , further comprising a nutrient medium for culturing human gut microbiota in the tortious tubular culture network.
4 . The system of claim 1 , wherein the hollow cartridges have an interior surface coated with extracellular matrix proteins.
5 . The system of claim 4 , wherein the extracellular proteins are covered with a layer of cells of the intestine.
6 . The system of claim 4 , wherein the extracellular matrix proteins comprise one or more proteins selected from the group consisting of collagens, elastins, fibronectins, laminins and combinations thereof.
7 . The system of claim 1 , wherein the cartridge further comprises a substrate.
8 . The system of claim 7 , wherein the substrate is selected from the group consisting of glass wool, rockwool, porous sponge, perforated sponge, or combinations thereof.
9 . The system of claim 3 , wherein the nutrient medium comprises: organic nitrogen sources, protein sources, carbohydrate sources, metal salts, intestinal secretions, enzymes, vitamins, and trace minerals maintained at a slightly neutral to acidic pH.
10 . The system of claim 1 , wherein the functional screening portal comprises a cell-growing surface with a cell culture media, and a semi-permeable membrane that allows diffusion of only metabolites from the plurality of cartridges.
11 . The system of claim 1 , wherein an interior environment of the tortious tubular culture network mimics the interior environment of human intestine.
12 . The system of claim 1 , wherein the hollow cartridge comprises a sample of gut microbiota suitable for transplant into a subject in need thereof.
13 .- 30 . (canceled)
31 . The system of claim 1 , wherein the hollow cartridge comprises a sample of probiotic bacteria suitable for transplant into a subject in need thereof.