HuMiX, an in vitro model to study the human gut microbiome and immune system
LIH’s Department of Infection and Immunity collaborated in a research project led by the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg to develop an ‘organ-on-a-chip’ model for the human gastrointestinal tract. The model named HuMiX, a device of the size of a beer met, allows the in vitro study of the human-microbial cross-talk taking place in the gut. The technology was published on 11th May 2016 in the scientific open access journal Nature Communications.
HuMiX, which stands for “Human-Microbial X(cross)-talk” is a modular, microfluidics-based apparatus, in which human and microbial cells can be co-cultured under conditions representative of the gastrointestinal human-microbe interface. It consists of three chambers: The top chamber is the supply level, from which nutrients continuously flow down to the cell cultures below. Human cells grow on a thin membrane in the middle chamber, while bacteria grow in the lowest chamber.
‘The model delivers a very accurate portrayal of the cellular and molecular processes taking place in the human gut’, states project leader Prof Paul Wilmes from LCSB. It allows to dissect molecular mechanisms of host-microbiome interactions in a controlled manner that is not possible using existing in vitro systems or animal models. HuMiX is well positioned to become an enabling technology in the field of drug discovery. It is known that the pharmacokinetics of drugs largely depend on the gut microbiome, therefore HuMiX could serve for pre-clinical drug testing. The technology may also be used to analyse how probiotics and dietary compounds affect human physiology.
The design of the device allows the addition of a third layer of cells to address further research questions. LIH contributed to the HuMiX technology by showing that it is possible to introduce immune cells, which are critical players in gut homeostasis, as a third cell type. Dr Carole Devaux, Head of the HIV Clinical and Translational Research Group at the Department of Infection and Immunity and postdoctoral researcher Dr Joëlle Fritz, jointly supervised by Dr Devaux and Prof Wilmes, could show that CD4+ T lymphocytes are viable in the HuMiX system. LIH greatly reinforced the HuMiX project by providing its knowhow in human immune cells isolation and phenotyping with flow cytometry.
The collaboration with LIH will be intensified in a follow-up project to establish “ImmunoHuMiX”. The researchers will test whether gut-specific immune cell populations can be introduced into the system. Those cells shall be infected with HIV in order to mimic HIV infection of the gastrointestinal associated lymphoid tissue (GALT), which is the largest immune compartment in the human body and plays an important role in driving HIV pathogenesis.
The development of the HuMiX model was achieved through support from different research grants of the National Research Fund Luxembourg. Preliminary experiments performed to test the suitability of the model for the study of HIV infection were in addition supported by the Luxembourg AIDS Foundation.
Link to publication: A microfluidics-based in vitro model of the gastrointestinal human-microbe interface