Duodenal mucosal RNA-Seq identifies coordinated bile acid-axis transcriptional alterations in food-responsive enteropathy in dogs.

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.