2007 Fiscal Year Final Research Report Summary
Involvement of intestinal flora in the pathogenesis of chronic'colitis
| Project/Area Number |
17590677
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
INOUE Nagamu Keio University, School of Medicine, Assistant Professor (00232546)
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| Co-Investigator(Kenkyū-buntansha) |
HIBI Toshifumi Keio University, Department of Medicine, Professor (50129623)
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| Project Period (FY) |
2005 – 2007
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| Keywords | inflammatory bowel disease / ulcerative colitis / Crohn's disease / intestinal microflora / interleulcin-10 gene deficient mice / DSS coliti |
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| Research Abstract |
Intestinal bacteria play important roles in the maintenance of the gut environment and initiation or amplification of intestinal inflammation. However, the precise mechanism of the interaction between intestinal bacteria and mucosal immune system remains unclear. The aim of this study is to elucidate the role of intestinal bacteria in inflammatory bowel disease (IBD) using human-flora associated (HFA) mouse models. Human faces suspensions from healthy controls (HC) and patients with ulcerative colitis CO were orally inoculated into germ-free wild-type BaIb/c mice and then they were kept in isolators for 2 weeks to stabilization of intestinal flora. After stabilization, each group of mice was sacrificed and assessed macro- and microscopically to evaluate the influence of UC flora and intestinal bacteria of these mice were analyzed by culture techniques. lb elucidate the role of bacteria in IBD, colitis was induced by administration of 2.5% dextran sodium sulfate (DSS) for 7days followed
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by 3 days of water. Mice were sacrificed at day 10 and assessed macro- and microscopically. Fecal samples were also administrated to germ-free interleukin-10 gene deficient(11-10-/-)mice. In this model, mice were kept for 4 weeks after administration to stabilize the intestinal flora. After 4 weeks, each group of mice was sacrificed and inflammatory parameters same as those in DSS colitis model were assessed.
Flora analysis indicated that derangement of intestinal flora with UC was reproduced in HFA mice model. However, intestinal inflammation was not induced by administration of UC flora in wild-type mice. In contrast, mice colonized with UC flora presented severe inflammation compared with mice colonized with HC flora upon DSS administration. Moreover, in IL-10-/- mice, several inflammatory parameters were also severer in UC flora mice than those in HC flora mice. These results suggested that breakdown of intestinal bacterial balance increased the susceptibility of intestinal inflammatory stimuli. Less
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