neuroHuMiX: a gut-on-chip model to investigate gut microbiome-nervous system axis
The human gut microbiome (GM) is a significant contributor to human health and disease. This emphasized by the notion that GM alterations are not solely related to gastrointestinal diseases, but also to neurological diseases. However, the exact interactions between the GM with the enteric nervous system (ENS) are still not unknown, as the ENS is not easily accessible. Therefore, a representative model to understand and characterize the GM-ENS interactions is needed. Our personalised gut-on-chip in vitro model will enable proximal co-culture of ENS cells with microbial cells.
Our project involves a two-pronged approach, i.e. (i) to further develop the human-microbial crosstalk (HuMiX) gut-on-chip model by introducing induced pluripotent stem cell (iPSC)-derived ENS cells inside the device. (ii) Upon successful introduction of the ENS cells, the resulting model, neuroHuMiX, will be used to investigate the GM-ENS axis by leveraging multi-omic analyses which will allow for the identification of specific microbial and/or molecular markers.
Furthermore, the overarching goal focuses on the personlization of neuroHuMiX is another goal, where we aim to establish the different cell types within the device originating from the same individual.
To date, we have co-cultured iPSC-differentiated ENS with epithelial cells in HuMiX for up to 14 days. Characterization by immunofluorescence staining, gene expression and presence of specific neurotransmitter has demonstrated that the ENS keep their molecular characteristics in co-culture. Currently, we are co-culturing the ENS and epithelial cells together with microbial cells. Subsequently, we will determine whether the neuronal cells retain their distinctive molecular features.
NeuroHuMiX will provide a platform to unravel previously unaddressed questions regarding the role of the GM in neurological disease etiology.