Abstract
Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis patients were related to immune functions. The ileal changes in the inactive ulcerative colitis subjects converged into the maintenance of the intestinal barrier through increased mitochondrial function and dampened immune functions. In conclusion, we identified molecular changes in the non-inflamed ileum of ulcerative colitis that are dependent on colonic inflammation.
Highlights
Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) [1] and Crohn’s disease (CD), are chronic disorders of the gastrointestinal tract, characterized by relapsing gut inflammation [2].UC is limited to the colon and is characterized by a continuous mucosal inflammation, whereas CD can affect all parts of the gastrointestinal tract and is determined by a non-continuous transmural inflammation [2]
We found molecular alterations in the non-inflamed ileum of UC patients, which were dependent on the presence of colonic inflammation and disease extent, and point to a cross-talk between colon and ileum
While patients with inactive colitis showed a similar gene expression profile in the ileum as non-IBD controls, more alterations in ileal gene expression were seen in patients with active colitis at the time of endoscopy
Summary
Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) [1] and Crohn’s disease (CD), are chronic disorders of the gastrointestinal tract, characterized by relapsing gut inflammation [2]. UC is limited to the colon and is characterized by a continuous mucosal inflammation, whereas CD can affect all parts of the gastrointestinal tract and is determined by a non-continuous transmural inflammation [2]. Been reported in UC [3]. Histological alterations including structural alterations of villi and inflammatory cell infiltration [1,4,5,6,7], and increased intestinal permeability, have been detected in the small bowel of patients with UC [8,9]. There is experimental evidence of small bowel dysfunction from animal
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