Interactions of Candida albicans with non-pathogenic gut bacteria

The yeast Candida albicans is a commensal colonizer of mucosal surfaces in humans. Under certain circumstances, the fungus can cause superficial infections like oropharyngeal or vulvovaginal candidiasis, but also invasive and disseminated infections. Predispositions for this opportunistic pathogen to cause disease include antibiotic treatment, immunosuppression, and a compromised epithelial barrier. The intestine is the main reservoir from which the fungus can translocate across the intestinal barrier, invade the bloodstream, and disseminate when predisposing conditions permit. Since intestinal colonization with C. albicans is a prerequisite for infection, research on the fungus in this biological niche is of specific importance to understand the pathogenesis of candidiasis and provide fundamental knowledge for novel therapeutic strategies. As the natural microbiota in the healthy intestine limits fungal overgrowth, this thesis aimed to investigate interactions between C. albicans, intestinal epithelial cells, and intestinal bacteria and to dissect the fungal commensal-to-pathogen shift. Therefore, a static in vitro gut model was established that includes intestinal epithelial cells and mucus-secreting goblet cells, which were colonized with Lactobacillus spp. as a single species artificial microbiota before C. albicans infection. Using this model, Lactobacillus spp. colonization was observed to mediate a time-, dose-, and species-dependent protection against C. albicans pathogenicity. Particularly L. rhamnosus was identified to exhibit a potent protection compared to other tested Lactobacillus species. The bacterial antagonism was related to a reduction of C. albicans cytotoxicity, hypha-length, and translocation. These results were verified in a perfused intestine-on-chip model that contains two compartments separated by a porous membrane to mimic the gut lumen with intestinal epithelial cells and the vasculature with endothelial cells...