Food-responsive enteropathy (FRE) is a common form of chronic inflammatory enteropathy in dogs. Its underlying molecular mechanisms remain incompletely characterized. Increasing evidence from human studies and emerging canine data suggests that bile acids (BAs) influence intestinal homeostasis and inflammation. Duodenal mucosal biopsies from dogs with FRE ( n = 8) and healthy controls ( n = 4) were analyzed by bulk RNA sequencing. Differential expression analysis (DESeq2), KEGG and Reactome pathway enrichment, and GSEA were performed with a specific focus on BA transport, sensing, and metabolic pathways. FRE samples showed a distinct BA-associated transcriptional signature, including a non-significant decreasing trend of the BA receptor NR1H4 (FXR) expression (padj = 0.057), and significant upregulation of the nuclear receptor RXRA, together with increased expression of downstream mediators NR0B2 (SHP) and FGF19. BA transport components such as SLC51A (OSTα) and ABCC3 (MRP3) were differentially regulated, and the BA-synthetic enzyme HSD3B7 was increased. Bile secretion was among the top enriched KEGG pathways (ranked 9th; NES = 1.935; padj = 0.005). This study provides, to our knowledge, the first focused mucosal transcriptomic evidence of coordinated BA-axis alterations in canine FRE. The findings align with mechanisms described in human inflammatory bowel disease and support further investigation of bile acid signaling in canine chronic enteropathy. Findings should be interpreted as exploratory due to cohort heterogeneity.

Bile acid (BA) dysmetabolism is implicated in canine chronic inflammatory enteropathy (CIE), but fasting serum profiles across treatment-response groups remain poorly characterized. This exploratory observational study analyzed pretreatment serum from dogs subsequently classified as food-responsive enteropathy (FRE; n = 8) or immunosuppressant-responsive enteropathy (IRE; n = 5), with four unmatched purpose-bred Beagle controls. Targeted LC–MS/MS, performed using a published canine serum method, provided results for 15 BA species. All samples were analyzed in one batch by an analyst blinded to subsequent group assignment. Eight species quantifiable in every dog and ten derived variables were compared using Kruskal–Wallis tests with Benjamini–Hochberg correction across 18 omnibus tests. Cholic acid and unconjugated primary BA concentrations were higher in IRE than in controls and FRE. The total primary-to-secondary BA ratio showed a monotonic group ordering (control < FRE < IRE; H = 13.76, p = 0.0010, q = 0.0092; epsilon-squared = 0.840), with all Bonferroni-corrected pairwise comparisons significant. A post hoc four-scenario sensitivity analysis comprising the submitted zero-substitution analysis and three LOD/LOQ-based alternatives reproduced the same 18-test FDR-significant set and the same ratio inference. This analysis tests robustness to censored-value handling but is not independent validation. The findings suggest group-associated serum BA patterns, but the small sample, clinical heterogeneity, and unmatched controls preclude diagnostic or treatment-predictive interpretation.