Fig. 5.

Acetate production by Il22ra2^–/– microbiota promotes protection against C. difficile infection. (A) Schematic representation of WT and Il22ra2^–/– mice treatment with different types of fiber diet. Mice were fed a conventional rodent diet or a low-fiber or 10% inulin (high-fiber) diet for 3 wk. Mice were subsequently returned to a conventional rodent diet, received antibiotics, and were infected with C. difficile. (B and C) Mice were monitored during infection for body weight (B) and clinical score (C), and comparisons were calculated against the WT group. (D) GC-MS quantification of acetate levels in proximal colonic contents. (E) Schematic representation of SCFA treatment of WT and Il22ra2^–/– mice before C. difficile infection. Mice received acetate (150 mM) in the drinking water for 3 wk. SCFA supplementation was subsequently discontinued and mice received antibiotics for 4 d followed by infection with C. difficile on day 0. (F and G) Mice were monitored daily after infection for changes in body weight (F) and clinical scores (G). Comparisons were conducted against the WT group. (A–C) n = 10; (D) n = 4 to 5; and (E–G) n = 8 to 9 mice per group. (B, C, F, and G) One representative experiment is shown. Data for the second experiment are reported in Dataset S3. The asterisks (*) indicate the statistical significance of the same color group they refer to when compared to the control. Black only (*) indicates that the significance of all groups is the same compared to the control. Error bars represent mean ± SD. Normality was assessed by D’Agostino–Pearson test. Statistical analysis was performed using a one-way ANOVA with post hoc Tukey test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns = not significant.