A Microfluidic-Based Model for Spatially Constrained Culture of Intestinal Microbiota

Perturbation of the microbiome is implicated in the pathogenesis of many human ailments, including inflammatory bowel diseases such as Crohn's disease (CD). Recapitulating the microbiome associated with health and disease necessitates controlling the composition of multiple bacterial species. This is difficult to achieve in vitro due to the overgrowth of bacterial species over time. Here, a microfluidic-based model incorporating bacteria-embedded hydrogel microfibers for the coculture of human enteric bacteria is introduced. Employing bacterial species and strains associated with CD, it is shown that the hydrogel-based bacteria-embedded microfiber model is physically and mechanically robust, and tunable. Metabolite analysis of the medium in both mono- and coculture revealed the interfiber exchange of soluble mediators and their impact on the growth of different bacterial species. This novel approach should enhance the ability to decipher contact-independent cross-talk within the polymicrobial intestinal luminal environment, and its impact on the intestinal epithelium.