Serum bile acid analysis of patients with Clostridium difficile -associated diarrhea

• Project/Area Number: 18K07920
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Iwamoto Junichi 東京医科大学, 医学部, 教授 (10384950)
• Co-Investigator(Kenkyū-buntansha): 本多 彰 東京医科大学, 医学部, 教授 (10468639) ; 宮崎 照雄 東京医科大学, 医学部, 准教授 (60532687)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: クロストリジウム・ディフィシル / 胆汁酸代謝 / Clostridium difficile / 胆汁酸 / CD-associated diarrhea / CD 関連下痢症 / Clostridium XIVa / Clostridium difficile 腸炎

Outline of Final Research Achievements

To clarify the pathophysiology and predicting factors of Clostridium difficile -associated diarrhea (CDAD), new LC-MS/MS methods were developed for bile acid analysis of patients’ serum. By use of the methods, we analyzed serum from patients with CDAD and high risk group of CDAD. (DCA)/(DCA＋CA)ratio was decreased in the CDAD patients compared with non-CD patients after using antibiotics. The decrease of (DCA)/ (DCA＋CA)ratio were shown in patients with CDAD before using antibiotics or before the development of CDAD. Thses results indicate that evaluation of bile acid profilesuch as (DCA)/ (DCA＋CA)ratio is usuful for predicting the development CDAD in high risk group.

Academic Significance and Societal Importance of the Research Achievements

近年、病院・老人施設等におけるクロストリジウム・ディフィシル腸炎が増加して欧米型の様に難治性の傾向となっている。今回の研究で抗生剤投与を行った症例でクロストリジウム・ディフィシル腸炎発症例と非発症例で胆汁酸代謝が異なることを証明した。血液検査で胆汁酸測定を行い解析することで、クロストリジウム・ディフィシル腸炎発症予測、発症リスク、また難治性になる可能性を予測することができる。

Research Products

• [Journal Article] Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn’s disease (2021)
  • Author(s): Shigeki Bamba, Osamu Inatomi, Atsushi Nishida,Masashi Ohno, Takayuki Imai,Kenichiro Takahashi, Yuji Naito, Junichi Iwamoto, Akira Honda, Naohiro Inohara, Akira Andoh
  • Journal Title: Intestinal Research Volume: ー Issue: 3 Pages: 370-380
  • DOI: 10.5217/ir.2021.00054
  • Peer Reviewed / Open Access
• [Journal Article] Current states of prevention of drug-induced gastroduodenal ulcer in real clinical practice: a cross-sectional study (2020)
  • Author(s): Iwamoto J, Murakami M, Monma T, Ueda H, Tamamushi M, Konishi N, Yara SI, Hirayama T, Ikegami T, Honda A, Mizokami Y
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 66 Issue: 2 Pages: 158-162
  • DOI: 10.3164/jcbn.19-66
  • NAID: 130007804498
  • ISSN: 0912-0009, 1880-5086
  • Year and Date: 2020-03-01
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial (2020)
  • Author(s): Uchiyama K, Takami S, Suzuki H, Umeki K, Mochizuki S, Kakinoki N, Iwamoto J, Hoshino Y, Omori J, Fujimori S, Yanaka A, Mizokami Y, Ohkusa T
  • Journal Title: PLoS One Volume: 15 Issue: 11 Pages: e0241337-e0241337
  • DOI: 10.1371/journal.pone.0241337
  • Peer Reviewed / Open Access
• [Journal Article] Regulations of bile acid metabolism in mouse models with hydrophobic bile acid composition. (2020)
  • Author(s): Honda A, Miyazaki T, Iwamoto J, Hirayama T, Morishita Y, Monma T, Ueda H, Mizuno S, Sugiyama F, Takahashi S, Ikegami T.
  • Journal Title: Journal of Lipid Research Volume: 61 Issue: 1 Pages: 54-69
  • DOI: 10.1194/jlr.ra119000395
  • Peer Reviewed
• [Journal Article] The comparison of the intensity of human intestinal spirochetes between <i>Brachyspira pilosicoli</i> and <i>Brachyspira aalborgi</i> infections (2019)
  • Author(s): Iwamoto J, Adachi Y, Honda A, Monma T, Matsuzaki Y
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 64 Issue: 1 Pages: 86-90
  • DOI: 10.3164/jcbn.18-68
  • NAID: 130007542267
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Simultaneous isolation of two species, <i>Brachyspira pilosicoli</i> and <i>Brachyspira aalborgi</i>, from a patient with ulcerative colitis (2018)
  • Author(s): Kanazawa T, Takezawa T, Iwamoto J, Adachi Y
  • Journal Title: Journal of Veterinary Medical Science Volume: 80 Issue: 9 Pages: 1416-1419
  • DOI: 10.1292/jvms.18-0220
  • NAID: 130007482580
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Detection of Gut Dysbiosis due to Reduced Clostridium Subcluster XIVa Using the Fecal or Serum Bile Acid Profile. (2018)
  • Author(s): Murakami M, Iwamoto J, Honda A, Tsuji T, Tamamushi M, Ueda H, Monma T, Konishi N, Yara S, Hirayama T, Miyazaki T, Saito Y, Ikegami T, Matsuzaki Y.
  • Journal Title: Inflamm Bowel Dis Volume: 24 Issue: 5 Pages: 1035-1044
  • DOI: 10.1093/ibd/izy022
  • Peer Reviewed
• [Presentation] 腸内環境と腎臓病治療薬 腸内細菌叢と胆汁酸代謝の関連性 (2020)
  • Author(s): 岩本淳一
  • Organizer: 第51日本消化吸収学会総会
  • Invited
• [Presentation] 胆汁酸研究の新たな臨床展開:自己免疫性肝疾患からウイルス肝炎、生活習慣病まで 血清胆汁酸分析を用いたdysbiosisの診断と消化器疾患診療への応用 (2019)
  • Author(s): 村上 昌, 門馬 匡邦, 岩本 淳一
  • Organizer: JDDW2019
• [Presentation] ヒト型胆汁酸マウスにおける胆汁酸代謝 (2019)
  • Author(s): 本多 彰、宮崎照雄、岩本淳一、平山 剛、池上 正
  • Organizer: 第41回胆汁酸研究会
• [Presentation] 血中胆汁酸分析による腸管内Clostridium subcluster XIVa比率の簡易評価 (2018)
  • Author(s): 村上 昌,岩本淳一,本多 彰
  • Organizer: 第49回日本消化吸収総会