Outer Membrane Vesicles Secreted by Bacteroides fragilis Inhibit CFTR Chloride Secretion by Human Colon Organoids

The goals of this study were to develop a model to study host pathogen interactions in primary human colon cells and to test the hypothesis that Bacteroides fragilis toxin (BFT) secreted in outer membrane vesicles (OMVs) modulates mucosal immunity and CFTR Cl^- secretion. Since Bacteroides species often resides in mucus, OMVs are likely to represent a mechanism of communication between Bacteroides and the host. Two strains of Bacteroides were studied, Enterotoxigenic Bacteroides fragilis (ETBF), which produces BFT, and the non-toxigenic Bacteroides fragilis strain NCTC 9343 (NTBF) that does not express bft. We also utilized two additional strains of Bacteroides fragilis: one in which bft was knocked out (ETBF Δbft), and one that was engineered to contain bft (NTBF+bft). We report that most Bacteroides fragilis OMVs reduced forskolin-stimulated CFTR Cl ^- secretion, but had no effect on tight junction or cell adhesion structure, transepithelial resistance or the innate immune response of primary human colon monolayers. BFT did have an adverse effect on CFTR Cl^- secretion, but other factors in OMVs also inhibited CFTR Cl^- secretion. We conclude that OMVs secreted by Bacteroides can be an important mechanism of host pathogen interactions in the colon by reducing CFTR Cl^- secretion.