Development of an innovative method for reducing colon-cancer-inducing secondary bile acid formation through enhancement of anaerobic respiration of the intestinal bacteria

• Project/Area Number: 23658064
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: Hokkaido University
• Principal Investigator: YOKOTA Atsushi 北海道大学, 大学院・農学研究院, 教授 (50220554)
• Co-Investigator(Kenkyū-buntansha): ISHIZUKA Satoshi 北海道大学, 大学院・農学研究院, 准教授 (00271627)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 二次胆汁酸 / デオキシコール酸 / リトコール酸 / フマル酸 / 嫌気呼吸 / 腸内細菌 / 大腸癌 / 腸溶性カプセル

Research Abstract

Some secondary bile acids formed in the large intestine are known as a riskfactor of colon cancer. In this study a novel method that reduces such secondary bile acids formed by thereductive metabolism of gut microbes were investigated. We tested if the enhancement of oxidativemetabolism of the responsible gut microbes by the introduction of anaerobic respiration can reduce thetarget secondary bile acids. Thus, rats were fed sodium fumarate-supplemented diet to enhanceanaerobic respiration of the gut microbes. Although the results suggested a possibility of decreasingrelative abundance of deoxycholic acid, a representative colon-cancer-inducing secondary bile acid, theobserved effects were not practically applicable, because high dose of fumarate was required (5~10% ofthe diet), which resulted in the diarrhea in rats experiments. Therefore, improved method of fumaratefeeding, e.g. encapsulation, might be necessary to achieve this goal.

Research Products

• [Presentation] Bile acid is a host factor that regulates the composition of the cecal microbiota in rats (2012)
  • Author(s): Atsushi Yokota
  • Organizer: The 5th Korea-Japan-China International Symposium to promote Industry-Academia-Government Cooperation "Contribution of Lactic acid Bacteria to Preventive and Pre-symptomatic Medicine
  • Place of Presentation: Catholic University of Korea, Seoul, Korea
  • Year and Date: 2012-12-04
• [Presentation] 胆汁酸と腸内フローラ (2012)
  • Author(s): 横田篤
  • Organizer: 第21回腸内フローラシンポジウム腸内フローラとエコロジー-食事・栄養・環境因子
  • Place of Presentation: 東京
  • Year and Date: 2012-11-02
• [Presentation] Is bile acid a determinant of the gut microbiota on a high-fat diet (2012)
  • Author(s): Atsushi Yokota
  • Organizer: Symposium on Recent Researches on GUT Microbiota
  • Place of Presentation: 大同大学,台北市,Taiwan,R.O.C
  • Year and Date: 2012-06-29
• [Presentation] Bile acid is a host factor that regulates the composition of the cecal microbiota in rats (2012)
  • Author(s): K.B.M. S. Islam, S. Fukiya, M. Hagio, N.Fujii, S. Ishizuka, T. Ooka, Y. Ogura, T.Hayashi, A. Yokota
  • Organizer: The 2nd ENGIHR Workshop
  • Place of Presentation: VTT, Helsinki, Finland
  • Year and Date: 2012-05-24
• [Presentation] 新規ウルソデオキシコール酸生成腸内細菌Ruminococcus gnavus N53 由来の 7 β-hydroxysteroid dehydrogenaseの発現と機能解析 (2012)
  • Author(s): 李慈英,吹谷智,和田大,横田篤
  • Organizer: 2012年度日本乳酸菌学会泊まり込みセミナー講演要旨集
  • Place of Presentation: 別府湾ロイヤルホテル(大分県)
  • Year and Date: 2012-05-10
• [Presentation] 新規ウルソデオキシコール酸生成腸内細菌 Ruminococcus gnavus N53由来の 7β-hydroxysteroid dehydrogenaseの発現と機能解析 (2012)
  • Author(s): 李 慈英,荒井尚志,吹谷智,和田大,横田篤
  • Organizer: 2012年度日本農芸化学会大会講演要旨集
  • Place of Presentation: 京都女子大学(京都市)
  • Year and Date: 2012-03-24