Antibacterial effect of alcohol abstinence in alcholics

• Project/Area Number: 16K09949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Osaka Medical College
• Principal Investigator: Asai Akira 大阪医科大学, 医学部, 准教授 (30622146)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アルコール依存症患者 / 感染抵抗性 / マクロファージ / アルコール依存症 / Pre-Pro-B細胞 / M2bマクロファージ / アルコール / IMC

Outline of Final Research Achievements

In alcoholics, bacterial translocation from the gut microbiota causes septic death. M2b monocyte/Mφ do not have of the bactericidal activity and suppress the other antibacterial effector cells (M1Mφ, CTL and neutrophils). These M2b monocytes/φ disappeared in peripheral blood of alcoholics.after 2 weeks of abstinence. Furthermore, it was revealed that humanized chimeric mice using monocytes from patients with alcoholic abstinence have improved antibacterial activity against the orally infection of Enterococcus faecalis. From these results, it is considered that the treatment of alcohol abstinence in alcoholics has an effect of improving the bacterial resistance against gut microbiota.

Academic Significance and Societal Importance of the Research Achievements

アルコール過剰摂取患者は、免疫不全状態であり様々な感染症から敗血症を起こし死に至る。抗生剤を使用しても耐性菌の出現等により感染が改善しないことも多く、根本的な治療が必要視されている。本研究は、断酒治療による感染抵抗性の改善効果を明らかにすることを目的とした。断酒治療は、腸内細菌叢からのBacterial translocationによる敗血症に対する治療のみならず、アルコール過剰摂取者に起こりうる他の全ての感染症に対する感染抵抗性や、感染に対する予防的効果も見込まれており、結果的には感染による死亡を減らせる可能性がある。以上より断酒治療は、今後のアルコールに対する治療において非常に有用である。

Research Products

• [Int'l Joint Research] University of Texas Medical Branch/Intermal Medicine/Infectious diseases(米国)
• [Int'l Joint Research] University of Texas Medical Branch/Department of Internal Medicine/Infectious diseases(米国)
• [Int'l Joint Research] University of Texas Medical Branch/Department of Internal Medicine/Makiko Kobayashi, Fujio Suzuki(U.S.A.)
• [Int'l Joint Research] University of Texas Medical Branch/Department of internal medicine/Makiko Kobayashi, Fujio Suzuki(USA)
• [Presentation] Suppressive role on bacterial resistance of CD10+Pax5+ cells in alcohol use disorder patients (2019)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Hideko Ohama, Shinya Fukunishi, Kazuhide Higuchi
  • Organizer: Immunology 2019
  • Int'l Joint Research
• [Presentation] 短期間の断酒治療により、アルコール依存症モデルマウスの消化管における感染抵抗性は回復する (2019)
  • Author(s): 朝井 章、岡本 紀夫、大濱 日出子、土本 雄亮、福西 新弥、樋口 和秀
  • Organizer: 第55回日本肝臓学会
• [Presentation] Suppressive role on bacterial resistance of CD10+Pax5+ cells in alcohol use disorder patients. (2019)
  • Author(s): Yusuke Tsuchimoto, Akira Asai, Hideko Ohama, Shinya Fukunishi, Kazuhide Higuchi.
  • Organizer: Immunology 2019
  • Int'l Joint Research
• [Presentation] アルコール摂取過剰マウスに対する短期間断酒のKupffer細胞への影響. (2018)
  • Author(s): 朝井 章、福西 新弥, 樋口 和秀
  • Organizer: 第54回日本肝臓学会
• [Presentation] The Antibacterial Resistance of Both Hepatic Macrophages in Mice with Alcohol Abstinence. (2018)
  • Author(s): Norio Okamoto, Akira Asai, Masahiro Matsui, Hidetaka Yasuoka, Tomohiro Nishikawa, Keisuke Yokohama,Ken Nakamura, Hideko Ohama, Yusuke Tsuchimoto, Shinya Fukunishi, Yasuhiro Tsuda, Kazuhide Higuchi.
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] Antibacterial resistance against MRSA oral infection on alcohol fed mice recovered 7 days after alcohol abstinence (2017)
  • Author(s): Akira Asai
  • Organizer: DDW2017
  • Int'l Joint Research
• [Presentation] Immature myeloid cells (IMCs) increased in the peripheral blood of patients with alcohol use disorder (AUD) suppress the bactericidal activity of monocytes (2017)
  • Author(s): Akira Asai, Hidetaka Yasuoka, Yusuke Tsuchimoto, Shinya Fukunishi, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki
  • Organizer: Immunology 2017
  • Place of Presentation: Washington
  • Int'l Joint Research