Effect of Intestinal microbiota on inflammation induced colon cancer

• Project/Area Number: 26670194
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Narushima Seiko 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (80578336)
• Co-Investigator(Renkei-kenkyūsha): OGURA Yoshio 神戸女子大学, 家政学部, 教授 (00135849) ; HONDA Kenya 国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (60334231) ; ATARASHI Koji 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 客員研究員 (60546787)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腸内細菌 / マウスモデル / 大腸発癌 / ノトバイオート / 大腸腫瘍 / モデル動物 / 胆汁酸

Outline of Final Research Achievements

It ha been reported that chronic inflammation in the colon results in an increased risk for the development of colorectal cancer. In this study we aimed to confirm the hypothesis that intestinal microflora are required for the development of adenocarcinoma in the colon of the Interleukin 10 (IL-10) and p53 double-deficient mouse. The germ-free double deficient mice on C57BL background were produced and observed the development of colitis and colon tumor. Animals of both groups were subjected to histopathological examination. There was no development of adenocarcinoma of the colon among the germ-free mice, whereas in the mice housed under specific pathogen free conditions, high percentage of colonic inflammation and tumor development was observed. These results indicate that intestinal microflora play an important role in the development of colitis-associated cancer in this animal model, and that cancers can be prevented by controlling intestinal microflora.

Research Products

• [Journal Article] Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. (2015)
  • Author(s): Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, et al.
  • Journal Title: Cell Volume: 163 Pages: 367-380
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Induction of Th17 cells by segmented filamentous bacteria in the murine intestine (2015)
  • Author(s): Farkas AM, Panea C, 後藤義幸, 中藤学, Galan-Diez M, 成島聖子, 本田賢也, Ivanov II
  • Journal Title: J Immunol Methods Volume: 421 Pages: 104-111
  • DOI: 10.1016/j.jim.2015.03.020
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Induction of intestinal Th1 cells by human salivary microbiota. (2015)
  • Author(s): Atarashi K, Narushima S, Tanoue T, Nagano U, Honda K.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: 札幌コンベンションセンター・札幌・北海道
  • Year and Date: 2015-11-20
• [Presentation] SFB-mediated TH17 cell induction is influenced by mouse genetic background. (2015)
  • Author(s): Tanoue T, Atarashi K, Nagano U, Watanabe E, Narushima S, Umesaki Y, Honda K.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: 札幌コンベンションセンター・札幌・北海道
  • Year and Date: 2015-11-20