Fig. 4: DSS-triggered liver inflammation mediates alterations of BA metabolism.

a Western blot of distal ileum FGF15 (WT, n = 3; Mdr2^−/−, n = 5; WT + DSS, n = 3; Mdr2^−/−+DSS, n = 5). b mRNA expression of liver Fxr and Shp (WT, n = 5; Mdr2^−/−, n = 10; WT + DSS, n = 7; Mdr2^−/−+DSS, n = 12); one-way ANOVA with Bonferroni’s multiple comparison test (Fxr & Shp: no statistical difference between Mdr2^−/− vs Mdr2^−/−+DSS). c Activated pathways in DSS-treated Mdr2^−/− liver identified by RNA-seq-based gene set enrichment analysis (n = 10 mice per group). d Heatmap of liver RNA-seq data demonstrates upregulated inflammatory genes (n = 10 mice per group). e Spleen to body weight ratio (WT, n = 5; Mdr2^−/−, n = 10; WT + DSS, n = 7; Mdr2^−/−+DSS, n = 12); one-way ANOVA with Bonferroni’s multiple comparison test (WT vs Mdr2^−/−, 95% CI −0.4801 to −0.007131, P = 0.0412; Mdr2^−/− vs Mdr2^−/−+DSS, 95% CI −0.5723 to −0.2025, P < 0.0001). f Spearman correlation heatmap reveals negative correlation between liver inflammatory genes and BA metabolism genes(Mdr2^−/−, n = 10; Mdr2^−/−+DSS, n = 10). g Heatmap of differentially expressed genes from microarray analysis of co-cultured human primary hepatocytes and Kupffer cells treated with or without LPS in 3-dimentional Human Liver Microtissues (MT) (n = 3 samples per group). h Serum ALT, AP and AST levels (n = 7 mice per group); unpaired two-tailed Student’s t-test (ALT: Mdr2^−/−+PBS vs Mdr2^−/−+LPS, P = 0.0494; AP: Mdr2^−/−+PBS vs Mdr2^−/−+LPS, P = 0.0186; AST: Mdr2^−/−+PBS vs Mdr2^−/−+LPS, P = 0.0432). i The percentage of liver neutrophils to CD45⁺ leukocytes (n = 7 mice per group); unpaired two-tailed Student’s t-test (Mdr2^−/−+PBS vs Mdr2^−/−+LPS, P < 0.0001). j Western blot of liver phosphorylated NF-κB P65 (n = 7 mice per group). k mRNA expression of hepatic genes responsible for bile acid synthesis (n = 7 mice per group); unpaired two-tailed Student’s t-test (Mdr2^−/−+PBS vs Mdr2^−/−+LPS: Cyp27a1, P = 0.0247); Two-tailed Mann–Whitney test (Mdr2^−/−+PBS vs Mdr2^−/−+LPS: Cyp7a1, P = 0.007; Cyp8b1, P = 0.0111). l mRNA expression of hepatic genes associated with bile acid transporter (n = 7 mice per group); unpaired two-tailed Student’s t-test (Mdr2^−/−+PBS vs Mdr2^−/−+LPS: Mrp3, P = 0.0011); Two-tailed Mann–Whitney test (Mdr2^−/−+PBS vs Mdr2^−/−+LPS: Ntcp, P = 0.0111; Oatp2, P = 0.0175; Bsep, P = 0.0006; Mrp2, P = 0.0111). All data are mean ± SEM and considered significant at *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. Source data are provided as a Source Data file.