(A) C57BL/6 mice were given water containing 2.5% DSS (w/v) for 11 days and treated with suspension of bile acid or vehicle control (VE) per rectum on days 4, 6 and 8 with 150 μL of either 1 mg (1X), 5 mg (5X), or 10 mg (10X) of bile acid. LCA and DCA treatment result in dose-dependent protection, evident by an improvement in (B, C) body weight and (D) histopathology. LCA and DCA-treated mice maintained (E) higher body weights, (F) healthier gross colon morphology and longer colon lengths compared to VE or CDCA-treated mice. (G) LCA and DCA reduced distal colon inflammation and histopathology score. Scale bar = 20 m. (H) Luminex heat map data shows a decrease of pro-inflammatory associated cytokines in colon homogenate isolated from LCA and DCA-treated mice. Colon homogenate from mice untreated with DSS was used as a control. Data represented as mean ± SEM, analyzed by one-way ANOVA with Tukey’s post-hoc (B, C, D, F, G) or two-way ANOVA with Bonferroni’s post-hoc (E), and significance reported as * P<.05, ** P<.01, *** P<.001, and **** P<0.0001 (B) VE n=23, LCA 1X n=20, LCA 5x n=10, LCA 10x n=9, (C) VE n=23, DCA 1X n=17, DCA 5x n=9, DCA 10x n=9 (D) VE n=5, LCA 1X n=3, LCA 5x n=5, LCA 10x n=4, DCA 1X n=4, DCA 5x n=4, DCA 10x n=4, (E-F) VE, LCA, DCA n=14, CDCA n=13, (G) All groups n=10, (H) All groups n=5.