Towards a gut-microbiome-on-a-chip

Project

Towards a gut-microbiome-on-a-chip

This project aims to develop a gut-on-a-chip allowing the co-culture of human gut microbiota, intestinal epithelium cells and local immune cells to study host-microbe interactions.

Our intestinal tract is host to trillions of micro-organisms, which are involved in major processes such as food digestion, energy metabolism and immune regulation. Because of the high abundance of and large variation in species among human individuals, the molecular mechanisms underlying host-microbe interactions remain largely unsolved. This project aims to unravel these molecular pathways using a gut-on-a-chip, in which the interactions can be closely mimicked and tightly controlled.

Organ-on-chips are microfluidic devices designed to closely mimic organ – in this case the gut – in vitro. Due to their opportunity to fine-tune physiological and mechanical parameters, organ-on-chips allow the long-term co-culture of multiple types of human cells or cell lines and, moreover, micro-organisms.

This project is part of an overarching project involving multidisciplinary partners all over the country. The part at Microbiology focusses particularly on the design of the microbial gut community that will ‘colonize’ the gut-on-a-chip. This community will involve core species of the human gut microbiome, starting with mucin-degrader A. muciniphila and cross-feeders. The microbial community will be gradually extended from bottom-up while monitoring host-microbe interactions. Particular attention will be paid to the role of short-chain fatty acids and effects on intestinal inflammatory responses. The latter will be done in close collaboration with the sub-department of Toxicology (WUR).