Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis
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...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1793 |
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| author | Ho-Su Lee Maaike Vancamelbeke Sare Verstockt Tom Wilms Bram Verstockt João Sabino Marc Ferrante Séverine Vermeire Isabelle Cleynen |
| author_facet | Ho-Su Lee Maaike Vancamelbeke Sare Verstockt Tom Wilms Bram Verstockt João Sabino Marc Ferrante Séverine Vermeire Isabelle Cleynen |
| author_sort | Ho-Su Lee |
| collection | DOAJ |
| description | 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: <i>REG1B</i>, <i>REG1A</i>, <i>MUC4</i>, <i>GRAMD2</i>, and <i>CASP10</i>. 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. |
| first_indexed | 2024-03-10T18:09:03Z |
| format | Article |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:09:03Z |
| publishDate | 2020-07-01 |
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| spelling | doaj.art-643c972982924518901db0a243086bf52023-11-20T08:13:15ZengMDPI AGCells2073-44092020-07-0198179310.3390/cells9081793Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative ColitisHo-Su Lee0Maaike Vancamelbeke1Sare Verstockt2Tom Wilms3Bram Verstockt4João Sabino5Marc Ferrante6Séverine Vermeire7Isabelle Cleynen8Laboratory of Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, 3000 Leuven, BelgiumLaboratory of Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumLaboratory of Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, 3000 Leuven, BelgiumLaboratory of Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumUlcerative 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: <i>REG1B</i>, <i>REG1A</i>, <i>MUC4</i>, <i>GRAMD2</i>, and <i>CASP10</i>. 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.https://www.mdpi.com/2073-4409/9/8/1793mucosal gene expressionRNA-Seqsmall bowel dysfunctionulcerative colitis |
| spellingShingle | Ho-Su Lee Maaike Vancamelbeke Sare Verstockt Tom Wilms Bram Verstockt João Sabino Marc Ferrante Séverine Vermeire Isabelle Cleynen Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis Cells mucosal gene expression RNA-Seq small bowel dysfunction ulcerative colitis |
| title | Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis |
| title_full | Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis |
| title_fullStr | Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis |
| title_full_unstemmed | Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis |
| title_short | Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis |
| title_sort | molecular changes in the non inflamed terminal ileum of patients with ulcerative colitis |
| topic | mucosal gene expression RNA-Seq small bowel dysfunction ulcerative colitis |
| url | https://www.mdpi.com/2073-4409/9/8/1793 |
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