P820 Molecular changes in non-inflamed terminal ileum in patients with ulcerative colitis
H-S. Lee*1,2, M. Vancamelbeke3, S. Verstockt1, B. Verstockt3,4, G. Van Assche3,4, M. Ferrante3,4, S. Vermeire3,4, I. Cleynen1
1KU Leuven, Department of Human Genetics, Laboratory of Complex Genetics, Leuven, Belgium, 2University of Ulsan College of Medicine, Department of Biochemistry and Molecular Biology, Seoul, South Korea, 3KU Leuven, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium, 4University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine, typically confined to the mucosal layer of the colon. Small intestinal dysfunction has, however, been described in patients with UC, although the underlying mechanisms of these alterations in apparently intact ileum are currently unknown. We here evaluated molecular changes and biological networks in non-inflamed terminal ileum in UC, and their association with colonic inflammation.
Terminal ileum biopsies were obtained during endoscopy from 36 patients with UC (7 active (Mayo endoscopic subscore ≥2) and 29 inactive) and 16 healthy controls. Subjects with endoscopic or histological (backwash) ileitis were not included. Single-end RNA sequencing was performed using Illumina HiSeq4000. Gene expression differences were analysed using DESeq2, and corrected for age and gender. Weighted gene co-expression network analysis (WGCNA) was performed to find biological networks of genes that correlate with UC activity. Pathways and upstream regulators were identified using IPA.
When we compared ileal expression levels of active UC (71% male, median age 52 years) with controls (44% male, median age 57 years), we found 20 differentially expressed (adj.
Our transcriptome analysis identified significant alterations in non-inflamed ileum of UC patients, depending on colonic inflammation. Ileal changes in active UC are mainly related to immune function, but the causal and temporal relationship with colonic inflammation is unclear. Ileal changes in inactive UC on the other hand seem to be functioning to maintain the intestinal barrier with increased mitochondrial functions and dampened immune functions.