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Mucosa-associated bacteria in ulcerative colitis before and after new antibiotic combination therapy : DNA polymorphism analysis

Research Project

Project/Area Number 20591209
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

OHKUSA Toshifumi  Jikei University School of Medicine, 医学部, 教授 (50160445)

Co-Investigator(Renkei-kenkyūsha) KOIDO Shigeo  東京慈恵会医科大学, 医学部, 准教授 (70266617)
ODAHARA Shunichi  東京慈恵会医科大学, 医学部, 助教 (50445673)
KOMITA HIDEO  東京慈恵会医科大学, 医学部, 助教 (90534561)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords潰瘍性大腸炎 / 粘膜細菌フローラ / 細菌DNA / T-RFLP法 / メタゲノム解析
Research Abstract

We examined the efficacy of three-antibiotics combination therapy against F. varium, and investigated the mucosa-associated bacteria before and after the therapy using a molecular approach. Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline, and metronidazole for 2 weeks) of 12 patients and placebo group of 8 patients. Colonoscopic biopsy was performed at 0, 3 and 12 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism (T-RFLP) with the restriction enzyme HhaI, and quantified the change in the number of Fusobacterium varium by real-time PCR. After the treatment, profile changes of T-RFLP were found after treatment in 10 of 12 patients in the antibiotic group and none of 8 patients in the placebo group (p=0.0007). Based on the real time PCR study, F. varium/actin ratio was reduced after treatment in 8 of 12 patients (67%) in the antibiotic group and 4 of 8patients (50%) in the placebo group. Mucosal RNA extracts were also analyzed by Nextera RNA sequencing system. The number of Bacteroides, Acidaminococcus, Prevotella, Parabacteroides were decreased in the antibiotic group. Some number of mucosa-associated bacteria significantly decreased after the antibiotics combination therapy.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (53 results)

All 2011 2010 2009 2008

All Journal Article (33 results) (of which Peer Reviewed: 8 results) Presentation (15 results) Book (5 results)

  • [Journal Article] Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis.2011

    • Author(s)
      Terao S, Yamashiro K, Tamura I, Hirano T, Ohkusa T, Kato K
    • Journal Title

      Digestion. 83(3)

      Pages: 198-203

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎の新知見2011

    • Author(s)
      大草敏史
    • Journal Title

      日本薬剤師会雑誌 63(4)

      Pages: 401-405

    • Related Report
      2010 Final Research Report
  • [Journal Article] 炎症性腸疾患・大腸癌の病態と肥満の影響2011

    • Author(s)
      大草敏史
    • Journal Title

      BIO Clinica 26(2)

      Pages: 130-134

    • Related Report
      2010 Final Research Report
  • [Journal Article] Fusobacterium variumと潰瘍性大腸炎2011

    • Author(s)
      大草敏史
    • Journal Title

      臨床と微生物 38(1)

      Pages: 33-38

    • Related Report
      2010 Final Research Report
  • [Journal Article] Peroxisome proliferator-activated receptor gamma 2 mutation may cause a subset of ulcerative colitis.2010

    • Author(s)
      Aoyagi Y, Nagata S, Kudo T, Fujii T, Wada M, Chiba Y, Ohtsuka Y, Yamashiro Y, Shimizu T, Ohkusa T
    • Journal Title

      Pediatr Int. 52(5)

      Pages: 729-34

    • Related Report
      2010 Final Research Report
  • [Journal Article] Efficacy of antibiotic combination therapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases.2010

    • Author(s)
      Uehara T, Kato K, Ohkusa T, Sugitani M, Ishii Y, Nemoto N, Moriyama M
    • Journal Title

      J Gastroenterol Hepatol. 25 Suppl 1

    • Related Report
      2010 Final Research Report
  • [Journal Article] N-3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease.2010

    • Author(s)
      Uchiyama K, Nakamura M, Odahara S, Koido S, Katahira K, Shiraishi H, Ohkusa T, Fujise K, Tajiri H
    • Journal Title

      Inflamm Bowel Dis. 16(10)

      Pages: 1696-707

    • Related Report
      2010 Final Research Report
  • [Journal Article] Comparison of several activity indices for the evaluation of endoscopic activity in UC : inter- and intraobserver consistency.2010

    • Author(s)
      Osada T, Ohkusa T, Yokoyama T, Shibuya T, Sakamoto N, Beppu K, Nagahara A, Otaka M, Ogihara T, Watanabe S
    • Journal Title

      Inflamm Bowel Dis. 16(2)

      Pages: 192-7

    • Related Report
      2010 Final Research Report
  • [Journal Article] Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis : A Double-Blind Placebo-Controlled Multicenter Trial.2010

    • Author(s)
      Ohkusa T, Kato K, Terao S, Chiba T, Mabe K, Murakami K, Mizokami Y, Sugiyama T, Yanaka A, Takeuchi Y, Yamato S, Yokoyama T, Okayasu I, Watanabe S, Tajiri H, Sato N
    • Journal Title

      Am J Gastroenterol. 105(8)

      Pages: 1820-9

    • Related Report
      2010 Final Research Report
  • [Journal Article] 根治を目指した潰瘍性大腸炎に対する抗菌薬多剤併用療法2010

    • Author(s)
      大草敏史
    • Journal Title

      日本医事新報 4509

      Pages: 45-50

    • NAID

      40017280569

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎の内視鏡スコア2010

    • Author(s)
      大草敏史、内山幹、渋谷智義、長田太郎
    • Journal Title

      IBD Research 4(3)

      Pages: 160-166

    • Related Report
      2010 Final Research Report
  • [Journal Article] 腸内細菌をターゲットとした潰瘍性大腸炎に対する新規抗菌薬多剤併用療法2010

    • Author(s)
      大草敏史、月永真太郎、小田原俊一、松平浩、内山幹、古谷徹、荒川廣志、小井戸薫雄
    • Journal Title

      消化器内科 51(4)

      Pages: 318-324

    • Related Report
      2010 Final Research Report
  • [Journal Article] 抗菌薬の組み合わせ、特集・潰瘍性大腸炎の最新の治療2010

    • Author(s)
      大草敏史
    • Journal Title

      消化器の臨床 13(1)

      Pages: 45-51

    • Related Report
      2010 Final Research Report
  • [Journal Article] Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis : A Double-Blind Placebo-Controlled Multicenter Trial2010

    • Author(s)
      Ohkusa T, Kato K, Terao S, et al.
    • Journal Title

      Am J Gastroenterol.

      Volume: 105 Pages: 1820-1829

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease.2010

    • Author(s)
      Uchiyama K, Nakamura M, Odahara S, et al.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: 16 Pages: 1696-1707

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of antibiotic combination therapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases.2010

    • Author(s)
      Uehara T, Kato K, Ohkusa T, et al.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 25,Suppl 1

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial changes of cytokines in active ulcerative colitis : effects of antibiotic combination therapy.2009

    • Author(s)
      Sato K, Chiba T, Ohkusa T
    • Journal Title

      Hepatogastroenterology. 56(93)

      Pages: 1016-21

    • Related Report
      2010 Final Research Report
  • [Journal Article] Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion : a possible pathogenic mechanism of ulcerative colitis.2009

    • Author(s)
      Ohkusa T, Yoshida T, Sato N, Watanabe S, Tajiri H, Okayasu I
    • Journal Title

      J Med Microbiol. 58(Pt 5)

      Pages: 535-45

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎と抗菌薬療法2009

    • Author(s)
      大草敏史
    • Journal Title

      感染症 39(4)

      Pages: 19-23

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎における腸内細菌の役割2009

    • Author(s)
      大草敏史
    • Journal Title

      日本臨床腸内微生物学会誌 11

      Pages: 12-14

    • Related Report
      2010 Final Research Report
  • [Journal Article] 炎症性腸疾患と腸内細菌2009

    • Author(s)
      大草敏史
    • Journal Title

      無菌生物 39

      Pages: 19-24

    • NAID

      10025405199

    • Related Report
      2010 Final Research Report
  • [Journal Article] Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion : a possible pathogenic mechanism of ulcerative colitis.2009

    • Author(s)
      Ohkusa T, Yoshida T, et al
    • Journal Title

      J Med Microbiol 58

      Pages: 535-45

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial changes of cytokines in active ulcerative colitis : effects of antibiotic combination therapy.2009

    • Author(s)
      Sato K, Chiba T, Ohkusa T, et al.
    • Journal Title

      Hepatogastroenterology. 56

      Pages: 1016-21

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Colonic Mucosal Lesions Associated with Long-Term or Short-Term Administration of Nonsteroidal Anti-inflammatory Drugs2009

    • Author(s)
      Shibuya T, Ohkusa T, et al.
    • Journal Title

      Colorectal Dis. 2(Epub ahead of print)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis.2008

    • Author(s)
      Osada T, Ohkusa T, Okayasu I, Yoshida T, Hirai S, Beppu K, Shibuya T, Sakamoto N, Kobayashi O, Nagahara A, Terai T, Watanabe S
    • Journal Title

      J Gastroenterol Hepatol. 23 Suppl 2

    • Related Report
      2010 Final Research Report
  • [Journal Article] Identification of Bacteria from Blood in Febrile Patients with Ulcerative Colitis by Terminal Restriction Fragment Length Polymorphism Profile Analysis of 16S rRNA Gene.2008

    • Author(s)
      Harada A, Ohkusa T, Kushima K, Sakamoto M, Benno Y, Beppu K, Shibuya T, Sakamoto N, Watanabe S
    • Journal Title

      Scand J Gastroenterol 43

      Pages: 423-30

    • Related Report
      2010 Final Research Report
  • [Journal Article] 嫌気性菌と炎症性腸疾患2008

    • Author(s)
      大草敏史,内山幹,小田原俊一,光永眞人,小井戸薫雄,山根建樹
    • Journal Title

      臨床と微生物 35(4)

      Pages: 321-7

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎の内視鏡(病理組織)指標の相互比較2008

    • Author(s)
      内山幹,小田原俊一,亀岡佳彦,澁谷智義,長田太郎,大草敏史
    • Journal Title

      IBD Research 2

      Pages: 222-230

    • Related Report
      2010 Final Research Report
  • [Journal Article] 症候からみた腸疾患へのアプローチ,炎症性腸疾患と機能性腸疾患-病態の理解と求められる対応,腸疾患の診断と鑑別のポイント2008

    • Author(s)
      長田太郎,大草敏史,渡辺純夫
    • Journal Title

      Medicina 45

      Pages: 791-795

    • Related Report
      2010 Final Research Report
  • [Journal Article] 潰瘍性大腸炎の抗菌薬多剤併用療法の有用性2008

    • Author(s)
      大草敏史,渡辺純夫
    • Journal Title

      Medical Practice 25

      Pages: 671-672

    • Related Report
      2010 Final Research Report
  • [Journal Article] Identification of Bacteria from Blood in Febrile Patients with Ulcerative Colitis by Terminal Restriction Fragment Length Polymorphism Profile Analysis of 16S rRNA Gene.2008

    • Author(s)
      Harada A. Ohkusa T., et al
    • Journal Title

      Scand J Gastroenterol. 43

      Pages: 423-30

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis.2008

    • Author(s)
      Osada T. Ohkusa T., et al.
    • Journal Title

      J Gastroenterol Hepatol. 23Suppl 2

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 潰瘍性大腸炎の内視鏡(病理組織)指標の相互比較2008

    • Author(s)
      内山幹, 小田原俊一, 亀岡佳彦, 澁谷智義, 長田太郎, 大草敏史
    • Journal Title

      IBD Research 2

      Pages: 222-230

    • Related Report
      2008 Annual Research Report
  • [Presentation] 潰瘍性大腸炎に対する新規抗菌薬多剤併用AFM療法2010

    • Author(s)
      月永真太郎、大草敏史、及川紘太郎、湯川豊一、小田原俊一、永妻啓介、込田英夫、内山幹、佐藤憲一、天野克之、古谷徹、小井戸薫雄、田尻久雄
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟
    • Related Report
      2010 Final Research Report
  • [Presentation] 潰瘍性大腸炎に対する新規抗菌薬多剤併用AFM療法2010

    • Author(s)
      月永真太郎、大草敏史, ほか
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟県民会館
    • Related Report
      2010 Annual Research Report
  • [Presentation] 潰瘍性大腸炎は腸内細菌感染症かー明らかになってきた発症のメカニズム2009

    • Author(s)
      大草敏史
    • Organizer
      スポンサードシンポジウム「感染症としての潰瘍学」第37回日本潰瘍学会
    • Place of Presentation
      東京
    • Year and Date
      2009-11-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 腸内細菌をターゲットとした潰瘍性大腸炎に対する新規抗菌薬多剤併用療法2009

    • Author(s)
      大草敏史、加藤公敏、田尻久雄
    • Organizer
      第51回日本消化器病学会大会
    • Place of Presentation
      京都、グランドプリンスホテル京都
    • Year and Date
      2009-10-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 潰瘍性大腸炎における腸内細菌の役割2009

    • Author(s)
      大草敏史
    • Organizer
      第11回日本臨床腸内微生物学会総会
    • Place of Presentation
      東京(教育講演II)
    • Year and Date
      2009-09-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 潰瘍性大腸炎における腸内細菌の役割と抗菌薬多剤併用ATM療法2009

    • Author(s)
      大草敏史
    • Organizer
      第57回日本化学療法学会総会
    • Place of Presentation
      東京(教育講演9)
    • Year and Date
      2009-06-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 潰瘍性大腸炎に対する新規抗菌薬多剤併用療法-A Double-Blind Placebo-Controlled Multicenter Trial-,シンポジウム6「潰瘍性大腸炎の治療の進歩-ガイドラインを超えて」2009

    • Author(s)
      大草敏史,加藤公敏,田尻久雄
    • Organizer
      第77回日本消化器内視鏡学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-05-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 炎症性腸疾患と腸内細菌2009

    • Author(s)
      大草敏史
    • Organizer
      第42回日本無菌生物ノートバイオロジー学会総会
    • Place of Presentation
      大阪(特別講演II)
    • Year and Date
      2009-01-24
    • Related Report
      2010 Final Research Report
  • [Presentation] Seasonal varidations in onset and relapse of ulcerative colitis in Japan.2009

    • Author(s)
      Saito H, Ohkusa T, Yokoyama T, Harada A, Naoe K, Beppu K, Shibuya T, Sakamoto N, Osada T, Nagahara A, Watanabe S
    • Organizer
      The 13th Taishotoyama International Symposium on Gastroenterology.
    • Related Report
      2010 Final Research Report
  • [Presentation] Factors associated with incomplete total colonoscopy in a university hospital in Japan.2009

    • Author(s)
      Naoe K, Ohkusa T, Yokoyama T, Harada A, Saitou H, Beppu K, Shibuya T, Sakamoto N, Osada T, Nagahara A, Watanabe S
    • Organizer
      The 13th Taishotoyama International Symposium on Gastroenterology.
    • Related Report
      2010 Final Research Report
  • [Presentation] ANTIBIOTIC-INDUCED ULCERATIVE COLITIS REMISSIONS : A DOUBLE-BLIND PLACEBO-CONTROLLED MULTICENTRE TRIAL.2008

    • Author(s)
      Ohkusa T, Kato K, Terao S, Chiba T, Mabe K, Murakami K, Mizokami Y, Sugiyama T, Kudo T, Yanaka A, Takeuchi Y, Yamato S, Yokoyama T, Okayasu I, Sato N, Watanabe S, Tajiri H
    • Organizer
      16th United European Gastroenterology Week (UEGW) Vienna 2008
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2008-10-21
    • Related Report
      2010 Final Research Report
  • [Presentation] ANTIBIOTIC-INDUCED ULCERATIVE COLITIS REMISSIONS : A DOUBLE-BLIND PLACEBO-CONTROLLED MULTICENTRE TRIAL.2008

    • Author(s)
      Ohkusa T. Kato K., et al.
    • Organizer
      16th United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2008-10-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Interobserver and Intra-observer consistency in the endoscopic agreement of ulcerative colitis activities using various classification.2008

    • Author(s)
      Osada T, Ohkusa T, Yokoyama T, Shibuya T, Sakamoto N, Beppu K, Shimada Y, Takada M, Tamaki K, Nagahara A, Ogihara T, Watanabe S
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      San Diego, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] 潰瘍性大腸炎(UC)の臨床症状およびinter-observer agreementからみた新たな内視鏡診断スコアの試み2008

    • Author(s)
      長田太郎,大草敏史,澁谷智義,坂本直人,玉城久美子,笠原桂子,森広樹,斉藤紘昭,大高道郎,永原章仁,荻原達雄,渡辺純夫
    • Organizer
      第76回日本消化器内視鏡学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 全大腸内視鏡検査における全大腸到達阻害要因の分析2008

    • Author(s)
      中江弘三郎、大草敏史、原田章、斉藤紘昭、高橋泰治、森広樹、松本健史、別府加寿子、渋谷智義、坂本直人、長田太郎、永原章仁、大高道郎、荻原達雄、渡辺純夫
    • Organizer
      第75回日本消化器内視鏡学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Book] 消化器内科学(渡辺純夫編)(潰瘍性大腸炎)2010

    • Author(s)
      大草敏史
    • Publisher
      シュプリンガージャパン、東京
    • Related Report
      2010 Final Research Report
  • [Book] 消化器内科学(医学スーパーラーニングシリーズ)2010

    • Author(s)
      大草敏史
    • Total Pages
      349
    • Publisher
      シュプリンガー・ジャパン
    • Related Report
      2010 Annual Research Report
  • [Book] 専門医のための薬物療法Q&A消化器(渡辺純夫,三輪洋人編)(潰瘍性大腸炎)2008

    • Author(s)
      大草敏史,齋藤紘昭,渡辺純夫
    • Publisher
      中外医学社,東京
    • Related Report
      2010 Final Research Report
  • [Book] 消化器内科レジデントハンドブック(渡辺純夫,北條麻理子編)(A2潰瘍性大腸炎)2008

    • Author(s)
      大草敏史
    • Publisher
      中外医学社,東京
    • Related Report
      2010 Final Research Report
  • [Book] A2 潰瘍性大腸炎, 消化器内科レジデントハンドブック2008

    • Author(s)
      大草敏史
    • Publisher
      中外医学社
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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