| International Session (Symposium) 1 (JSGE・JGES) |
| Thu. November 1st 9:00 - 12:00 Room 13: Kobe International Conference Center International Conference Room |
| Gankyrin in the small intestine controls colonic microbiota and attenuates colitis | |||
| Toshiharu Sakurai1, Tomoyuki Nagai1, Masatoshi Kudo1 | |||
| 1Department of Gastroenterology and Hepatology, Kindai University | |||
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| ackground: Gankyrin (GK) regulates the inflammatory responses, and inhibition of GK is considered as a possible anti-inflammatory therapy for inflammatory bowel disease (IBD). However, mice with a targeted deletion of GK in the epithelial cells were found to be more susceptible to dextran sodium sulfate (DSS)-induced colitis than control mice. Methods: To investigate the role of GK in epithelial cells, we used mice with intestinal epithelial cell-specific GK deletion in (i) the entire small intestine and colon (Villin-Cre;Gankyrinf/f) and (ii) the distal intestine and colon (Cdx2-Cre;Gankyrinf/f). Results: GK-deficiency in the upper small bowel, but not in the lower small bowel or colon, augmented the inflammatory activity, leading to a worse survival outcome. Bacterial taxa such as Bilophila and Helicobacter which contain the species that are potentially deleterious to intestinal homeostasis were significantly over-represented in Villin-Cre;Gankyrinf/f, but not in Cdx2-Cre;Gankyrinf/f, when compared with control mice. We performed co-housing experiments and found that the enhanced inflammation observed in Villin-Cre;Gankyrinf/f mice was dependent on the alterations in microbiota. In line with this relation between GK and microbiota, GK-deficiency led to the reduced expression of antimicrobial peptides, a-Defensin-5 and -6, in the upper small bowel. Intriguingly, the reduced GK expression in the small bowel was associated with colonic involvement in human Crohn’s disease. Conclusion: These results highlight the distinct site dependence of the pro- and anti-inflammatory functions of GK and provide important insights into the pathogenesis of IBD. |
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Index Term 1: microbiota Index Term 2: crohn's disease |
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