Fig. 4.

FimH blocker TAK-018 prevents Enterobacteriaceae adhesion and inflammation of gut explant. a Adhesion of different strains of E. coli to human primary intestinal epithelial cells, in the presence of increasing concentrations of TAK-018. Note that the 41CB2 strain did not express FimH. Bars represent the mean value of individual points which themselves correspond to biological replicates. ANOVA was performed for each group to identify the statistically significant effect of TAK-018 (***P < 0.001). b Number of intracellular colonies in epithelial cells from human ileal explant incubated with LF82 E. coli, in the presence of increasing concentrations of TAK-018. Bars represent the mean value of individual points which themselves correspond to biological replicates. ANOVA was performed to identify the statistically significant effect of TAK-018 (*P < 0.05). c TNF-α secretion of human ileal explant incubated for 4 h with 10⁹ LF82 E. coli, in the presence of increasing concentrations of TAK-018. IL-1β was used as a positive control to trigger inflammation. Bars represent the mean value of individual points which themselves correspond to biological replicates. A nonparametric Wilcoxon signed-rank paired test was used to identify the statistically significant differences between the LF82 and LF82 + TAK-018 1 µM groups (P = 0.031). A linear mixed model was used to identify the statistically significant differences between the groups LF82, LF82 + 500 nM, and LF82 + 1 µM (P = 0.07). d Variation of transepithelial electric resistance (TEER) of T84 cells incubated for 4 h with 10⁹ LF82 E. coli, in the presence of increasing concentrations of TAK-018. Note that FimH^−/− LF82 E. coli does not adhere to T84 cells and therefore does not affect TEER. Bars represent the mean value of individual points which themselves correspond to biological replicates. A nonparametric Kruskal–Wallis test was used to identify the statistically significant differences between the LF82 groups (P = 0.02). e Histopathologic effects of LF82 E. coli adhesion on human ileal explants from a patient with CD and respective countereffects in the presence of increasing concentrations of TAK-018. Note the characteristic mucosa desquamation upon 4-h incubation with LF82 E. coli, visibly reduced in the presence of increased concentrations of TAK-018