Figure 2

Conceptualization of an idealized in vitro gastrointestinal experimental model. An idealized in vitro co-culture model may include three distinct culture chambers, namely microbial, human epithelial and human immune cell culture chambers, each separated by semipermeable membranes allowing molecular cross-talk between the different contingents while preventing microbes from rapidly overtaking human cells due to pronounced differences in their respective growth rates. Furthermore, an idealized gastrointestinal in vitro model should reflect the biogeographical distribution of the gastrointestinal microbiota. Such a model should allow the culture of representative microbial communities for the individual sections of the gastrointestinal tract (GIT) including stomach, small intestine, ascending colon, transverse colon and descending colon. All the individual compartments should be connected in series and allow modulation of their respective environmental factors including pH, fluid retention times, growth medium and other physiological factors such as mucin (in green in the microbial chamber) compositions, which actively interact and alter the microbial communities. To represent the GIT in the most realistic way, the microbial growth chamber needs to be depleted of oxygen, which could be achieved by flushing this chamber with anaerobic microbial medium, whereas the human cell chambers need to be flushed with oxygenated medium. Finally, an idealized GIT in vitro model suitable for microbiome research must support high-throughput omic analyses and, thus, needs to allow probing of the individual contingents to perform dedicated analyses on the different cell contingents following a particular experimental regime and to relate particular measurements back to the cell populations of origin.