Human microbiome crosstalk with immune system on an organ-on-chip model

An individual's immune status is an essential factor affecting the efficacy of microbiome-based therapies. To enable representative studies of microbiome-immune system interactions, we co-cultured intestinal epithelial cells and human peripheral blood mononuclear cells (PBMC) in our microphysiological model of the human gut, immunoHuMiX, and assessed responses to a co-culture with a probiotic mixture comprised of 17 strictly anaerobic Clostridia strains. We demonstrate the ability to sustain metabolically active microbiota in immunoHuMiX, while maintaining human cell viability, and generate relevant read-outs for host-microbiome interaction studies. The composition of the strain mixture was not affected by the individual sources of PBMCs, and immune cell populations were comparable after 24 h in the system when incubated with or without the 17-mix, and between individuals. We observed increased cytokine production, PBMC viability, and PBMC cell counts upon co-culture with the 17-mix, thereby demonstrating immune sensing of the microbiota by the PBMCs. In summary, our immunoHuMiX model provides an important personalisable tool for screening microbiota-driven immune responses.