Transcriptomic Interrogation of the Duodenal Mucosa of Dogs with Chronic Enteropathy

Abstract: Background – Canine chronic enteropathy (CE) is a complex and incompletely understood syndrome. Bulk transcriptomic (RNA-seq) analysis offers characterization of thousands of genes simultaneously. Application of this technique to intestinal biopsies enables determination of the molecular signatures of enteric diseases. Hypothesis/Objectives – To use RNA-seq to define canine duodenal gene expression and compare transcriptomic programs in health and disease. Animals – Four healthy (3 research colony, 1 client-owned) and 11 client-owned dogs with CE and serum albumin concentrations > 2.5 g/dL. Methods – Descriptive case-control study. Duodenal biopsies were collected during GI endoscopy and RNA was isolated using a commercial kit. mRNA sequencing was completed. Gene expression in CE samples were compared to healthy using DESeq2 and pathway analysis using GSEA. Results – Transcriptional profiling revealed heterogeneity within both populations. Differential gene expression analysis highlighted 783 significantly upregulated and 1496 down-regulated genes in the CE group compared to healthy. This included enhanced expression of cytochrome P450 family 1 subfamily A member 1 (CYP1A1), glutathione peroxidase 2, and ATPase phospholipid transporting 10B (ATP10B) and diminished expression of cell migration inducing hyaluronidase 1 (CEMIP) and POU class 2 homeobox associating factor 1 within the CE group. GSEA highlighted enhancement of mitochondrial oxidative phosphorylation and electron transport pathways, with diminished epithelial to mesenchymal transition and cytokine receptor interaction pathways in CE samples. Conclusions and Clinical Importance – RNA sequencing of duodenal tissues provides comprehensive data highlighting molecular contributions to canine CE. This approach will support hypothesis-based investigations and advance mechanistic understanding of disease.