Fig. 4: PPARα/γ dual agonists ameliorate Citrobacter rodentium-induced infectious colitis in mice.

a Schematic summarizing the workflow for testing PPARα/γ-targeted therapeutics in C. rodentium-induced colitis. Mice were gavaged with C. rodentium on day 0 and subsequently treated daily with PPAR agonists. Fecal pellets were collected to test viable bacterial burden, as determined by dilution plating and colony counting. Colons were excised on day 7 and 18 and analyzed using the indicated readouts. b–d Line graphs (b) display time series of the burden of viable bacteria in feces. Scatter plots with bar graphs (c) compare the peak burden of viable bacteria in feces on day 7. Scatter plots with bar graphs (d) display the area under the curve (AUC) for the line graph in b. CFU, colony forming units. Data points were plotted as black or white simply to improve visibility. e Images display representative fields from H&E-stained colon tissues of 4–5 mice in each group. Mag = 100x (top) and 200x (bottom); Scale bars, 100 μm. White arrowheads point to immune cell infiltrates. f–j Bar graphs display four parameters of inflammation that were quantified in H&E stained colon tissues in (e). Statistics: All results are displayed as mean ± SEM. Significance was tested on the cumulative histological score using one-way ANOVA followed by Tukey’s test for multiple comparisons. Significance: n.s., not significant, p-value < 0.05 was considered significant. k Violin plots (left) display the deviation of expression of genes in Clusters #1-2-3 in the IBD network, as determined by RNA Seq on murine colons. Bar plot (right) displays the rank ordering of the samples. Welch’s t-test was used to determine statistical significance. Significance: n.s., not significant, p-value < 0.05 was considered significant. l Pre-ranked GSEA based on pairwise differential expression analyses (DMSO vs PAR5359 groups) are displayed as enrichment plots for epithelial tight (top) and adherens (middle) junction signatures and balanced macrophage processes (bottom). See also Supplementary Fig. 8 for the day #7 results in the C. rodentium-induced colitis model, Supplementary Fig. 9 for extended GSEA analyses, and Supplementary Fig. 10 for the effect of PAR5359 on DSS-induced colitis in mice.