Role of iron as an detrimental influence on inflammatory bowel disease -analysis based on enteric microbiota and iron-related molecules

• Project/Area Number: 23590940
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: MATSUURA MINORU 京都大学, 医学(系)研究科(研究院), 助教 (30402910)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症性腸疾患 / 環境因子 / 鉄 / 腸内細菌

Research Abstract

Diet is a potential environmental influence in inflammatory bowel diseases (IBD). Enteric bacteria are required to induce and perpetuate intestinal inflammation in IBD, and iron is essential for the growth and virulence of bacteria. IL-10 deficient mice were fed normal- or low-iron diets. Histologic inflammation in the low-iron diet group was ameliorated and colonic IL-12p40 and MLN IL-17 secretion was lower in mice fed low-iron diet. There was no significant difference in concentrations of cultivable cecal bacteria, while T-RFLP analysis revealed distinct difference in the profile between two groups. The intracellular survival of iron-loaded E. coli in J774 macrophage cells was significantly enhanced compared to non-iron-loaded E. coli. TNF secretion from J774 cells phagocytosing iron-loaded E. coli was higher than J774 cells phagocytosing non-iron-loaded E. coli. Dietary iron potentiates intestinal inflammation by alteration of growth and virulence of enteric microbiota.

Research Products

• [Journal Article] Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease (2014)
  • Author(s): Honzawa Y, Nakase H, Shiokawa M, Yoshino T, Imaeda H, Matsuura M, Kodama Y, Ikeuchi H, Andoh A, Sakai Y, Nagata K, Chiba T
  • Journal Title: Gut Volume: 63 Issue: 12 Pages: 1902-12
  • DOI: 10.1136/gutjnl-2013-305632
  • Peer Reviewed
• [Journal Article] Efficacy and safety of granulocyte and monocyte adsorption apheresis for ulcerative colitis : a meta-analysis (2014)
  • Author(s): Yoshino T, Nakase H, Minami N, Yamada S, Matsuura M, Yazumi S, Chiba T
  • Journal Title: Dig Liver Dis Volume: 46 Issue: 3 Pages: 219-26
  • DOI: 10.1016/j.dld.2013.10.011
  • NAID: 120005385891
  • Peer Reviewed
• [Journal Article] Refractoriness of intestinal Behçet's disease with myelodysplastic syndrome involving trisomy 8 to medical therapies - our case experience and review of the literature (2013)
  • Author(s): Toyonaga T, Nakase H, Matsuura M, Minami N, Yamada S, Honzawa Y, Hukata N, Yoshino T, Chiba T, Okazaki K
  • Journal Title: Digestion Volume: 88 Issue: 4 Pages: 217-21
  • DOI: 10.1159/000355341
  • NAID: 120005385869
  • Peer Reviewed
• [Journal Article] Establishment of a novel mouse model of ulcerative colitis with concomitant cytomegalovirus infection : in vivo identification of cytomegalovirus persistent infected cells (2013)
  • Author(s): Matsumura K, Nakase H, Kosugi I, Honzawa Y, Yoshino T, Matsuura M, Kawasaki H, Arai Y, Iwashita T, Nagasawa T, Chiba T
  • Journal Title: Inflamm Bowel Dis Volume: 19 Pages: 1951-63
  • DOI: 10.1097/mib.0b013e318293c5bf
  • Peer Reviewed
• [Journal Article] Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling (2013)
  • Author(s): Yamamoto S, Nakase H, Matsuura M, Honzawa Y, Matsumura K, Uza N, Yamaguchi Y, Mizoguchi E, Chiba T
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 305 Issue: 3 Pages: G241-G249
  • DOI: 10.1152/ajpgi.00480.2012
  • Peer Reviewed
• [Journal Article] Prior use of immunomodulatory drugs improves the clinical outcome of endoscopic balloon dilation for intestinal stricture in patients with Crohn's disease. (2013)
  • Author(s): Honzawa Y
  • Journal Title: Digestive Endoscopy Volume: (印刷中) Issue: 5 Pages: 535-43
  • DOI: 10.1111/den.12029
  • Peer Reviewed
• [Journal Article] Effect of intensive granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis positive for cytomegalovirus (2013)
  • Author(s): Fukuchi T, Nakase H, Matsuura M, Yoshino T, Toyonaga T, Ohmori K, Ubukata S, Ueda A, Eguchi T, Yamashita H, Ito D, Ashida K
  • Journal Title: J Crohns Colitis Volume: 7 Issue: 10 Pages: 803-11
  • DOI: 10.1016/j.crohns.2012.12.003
  • NAID: 120005341874
  • Peer Reviewed
• [Journal Article] Involvement of Mycobacterium avium subspecies para tuberculosis with TNF-αproduction from Macrophage-possible link between MAP and immune response in Crohn's disease-Inflammatory Bowel Disease (2011)
  • Author(s): Nakase H, Tamaki H, Matsuura M, Chiba T, Okazaki K
  • Journal Title: Inflamm Bowel Dis Volume: 17 Issue: 11 Pages: 140-2
  • DOI: 10.1002/ibd.21750
  • Peer Reviewed
• [Journal Article] Rapid induction of mucosal healing by intensive granulocyte and monocyte adsorptive aphaeresis in active ulcerative colitis patients without concomitant corticosteroid therapy (2011)
  • Author(s): Fukuchi T, Nakase H, Ito D, Yamashita H, Matsuura M, Nagatani Y, Koga H, Senda K, Eguchi T, Ubukata S, Kawaguchi S, Ueda A, Tanaka T, Ohashi R, Otzuka M, Ashida K
  • Journal Title: Aliment Pharmacol Ther Volume: 34 Issue: 5 Pages: 583-5
  • DOI: 10.1111/j.1365-2036.2011.04768.x
  • Peer Reviewed
• [Journal Article] SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation (2011)
  • Author(s): Uza N, Nakase H, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Inoue S, Mikami S, Matsuura M, Shimaoka T, Kume N, Minami M, Yonehara S, Ikeuchi H, Chiba T
  • Journal Title: Gut Volume: 60 Issue: 11 Pages: 1494-1505
  • DOI: 10.1136/gut.2010.221879
  • NAID: 120003497105
  • Peer Reviewed
• [Presentation] Microbial balances altered by restriction of dietary iron ameliorated immune-mediated colitis (2014)
  • Author(s): Toyonaga T, Nakase H, Matsuura M, Yamada S, Minami S, Honzawa Y, Yoshino T, Okazaki K, Chiba T
  • Organizer: ECCO
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-02-21
• [Presentation] Microbial balances altered by restriction of dietary iron ameliorated immune-mediated colitis (2014)
  • Author(s): Takahiko Toyonaga, Hiroshi Nakase, Minoru Matsuura, Satoshi Yamada, Naoki Minami, Yusuke Honzawa, Takuya Yoshino, Kazuichi Okazaki, Tsutomu Chiba
  • Organizer: 9th Congress of European Crohn´s and Colitis Organisation
  • Place of Presentation: Bella Center Copenhagen, Denmark
• [Presentation] Fecal lipocalin2 reflects colonic inflammation in murine colitis model : A possible role of measuring fecal lipocalin2 as a biomarker of IBD (2013)
  • Author(s): Toyonaga T, Matsuura M, Yamada S, Minami S, Honzawa Y, Yoshino T, Nakase H, Okazaki K, Chiba T
  • Organizer: UEGW
  • Place of Presentation: Berlin
  • Year and Date: 2013-10-16
• [Presentation] Importance of magnifying colonoscopy for evaluation of mucosal healing and prediction of disease relapse in quiescent ulcerative colitis (2013)
  • Author(s): Matsuura M, Nakase H, Yoshino T, Chiba T
  • Organizer: AOCC
  • Place of Presentation: Tokyo
  • Year and Date: 2013-06-14
• [Presentation] Characteristics of colonoscopic features in patients with ulcerative colitis concomitant cytomegalovirus infection (2013)
  • Author(s): Matsuura M, Nakase H, Yoshino T, Chiba T
  • Organizer: AOCC
  • Place of Presentation: Tokyo
  • Year and Date: 2013-06-13
• [Presentation] Long-term follow-up in patients with ulcerative colitis treated with tacrolimus : early and long-term data from a retrospective observational study (2013)
  • Author(s): Matsuura M, Nakase H, Yoshino T, Chiba T
  • Organizer: ECCO
  • Place of Presentation: Wienna
  • Year and Date: 2013-02-15
• [Presentation] 炎症性腸疾患の病態における鉄の関与-腸内細菌からの解析 (2011)
  • Author(s): 松浦稔, 仲瀬裕志, R. Balfour Sartor
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13