Ecophysiolosical consequences of chronic ethanol consumption on human gut microbiota: implications for the pathogenesis of ethanol-related colorectal cancer

• Project/Area Number: 15K14682
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: Tohoku University
• Principal Investigator: Nakayama Toru 東北大学, 工学研究科, 教授 (80268523)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: acetaldehyde / alcoholism / gut microbiota / intestinal bacteria / 習慣的多量飲酒 / 大腸がん / 腸内細菌 / アセトアルデヒド / 酸化ストレス / 活性酸素 / 菌叢構造 / アルコール依存症

Outline of Final Research Achievements

To find roles of gut microbes and their acetaldehyde metabolism in the pathogenesis of ethanol-related colorectal cancer, the gut microbiota structures of non-alcoholics and alcoholics were analyzed and compared. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The acetaldehyde productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. Based on these results, a model has been proposed, in which oxidative dress induced upon chronic ethanol consumption serves as an important risk factor in the pathogenesis of ethanol-related colorectal cancer.

Research Products

• [Journal Article] Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake (2018)
  • Author(s): Hideki Okata et al.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum (2016)
  • Author(s): Atsuki Tsuruya, Akika Kuwahara, Yuta Saito, Haruhiko Yamaguchi, Natsuki Tenma, Makoto Inai, Seiji Takahashi, Eri Tsutsumi, Yoshihide Suwa, Yukari Totsuka, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Takeshi Mizukami, Akira Yokoyama, Takefumi Shimoyama, and Toru Nakayama
  • Journal Title: Alcohol and Alcoholism Volume: 未定 Issue: 4 Pages: 395-401
  • DOI: 10.1093/alcalc/agv135
  • Peer Reviewed / Open Access
• [Journal Article] Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer (2016)
  • Author(s): A. Tsuruya, A. Kuwahara, Y. Saito, H. Yamaguchi, T. Tsubo, S. Suga, M. Inai, Y. Aoki, S. Takahashi, E. Tsutsumi, Y. Suwa, H. Morita, K. Kinoshita, Y. Totsuka, W. Suda, K. Oshima, M. Hattori, T. Mizukami, A.Yokoyama, T. Shimoyama & T. Nakayama
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27923-27923
  • DOI: 10.1038/srep27923
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 習慣的多量飲酒と大腸発がんリスク： 微生物アルコール代謝から眺めたヒトと腸内細菌の相互作用 (2016)
  • Author(s): 中山 亨
  • Organizer: 日本農芸化学会2016年度大会 大会シンポジウム 「微生物メタボリズム研究の最前線」（3SY09）
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-03-29
  • Invited
• [Presentation] ヒト消化管常在微生物のエタノール代謝と発がん (2016)
  • Author(s): 中山 亨
  • Organizer: 第89 回日本生化学会大会 in 仙台
  • Place of Presentation: 東北大学（宮城県・仙台市）
  • Invited
• [Presentation] アルコール依存症患者の大腸内菌叢構造の再解析 (2016)
  • Author(s): 中山 亨
  • Organizer: 第444 回ビタミンB 研究協議会
  • Place of Presentation: 富山国際会議場（富山県・富山市）
• [Book] ヒトマイクロバイオーム研究最前線 常在菌 の解析技術から生態，医療分野，食品への応用研究まで (2016)
  • Author(s): 中山 亨，鶴谷 篤生
  • Total Pages: 429
  • Publisher: 株式会社エヌ・ティー・エス
• [Book] メタゲノム解析実験プロトコール (2016)
  • Author(s): 鶴谷 篤生，中山 亨
  • Total Pages: 229
  • Publisher: 羊土社
• [Book] 「ヒトマイクロバイオーム研究最前線常在菌の解析技術から生態、医療分野、食品への応用研究まで」第3編 第2章 第2節 (2016)
  • Author(s): 中山 亨，鶴谷 篤生
  • Total Pages: 472
  • Publisher: エヌ･ティー･エス