Colonization resistance against enteric pathogen by gut microbiota

• Project/Area Number: 17H05068
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including mycology)
• Research Institution: Keio University
• Principal Investigator: Kim Yun-Gi 慶應義塾大学, 薬学部(芝共立), 准教授 (00620220)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000); Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2017: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 腸内細菌 / 腸管病原細菌 / 食餌 / 代謝物 / 食餌因子

Outline of Final Research Achievements

In this study, two projects were conducted to clarify the effect of gut microbiota on enteropathogenic bacterial infection.
1) We assessed the growth mechanism in the intestine of Clostridia which strongly inhibit colonization of enteropathogenic bacteria. As a result, a metabolite (succinic acid) produced by the gut microbiota from infants promoteed the growth of Clostridia in the intestine.
2) Focusing on the diet that influences the composition and metabolism of gut microbiota, we assessed the effect of the diet on the colonization and growth of enteropathogenic bacteria via gut microbiota. As a result, the gut microbiota composition was changed by switching the diet, and that influenced the resistance against the enteric pathogen infection.

Academic Significance and Societal Importance of the Research Achievements

本研究により、乳幼児型から大人型への腸内細菌叢の成熟ステップが、腸管病原細菌に対する感染抵抗性を獲得するのに重要なプロセスであることが明らかとなった。また、食事因子が腸内細菌を介して腸管病原細菌感染に対する感受性に影響をすることも観察された。これらの成果は、腸内細菌を介した腸管病原細菌に対する感染予防薬開発のための基盤となる知見を提供するものであり、臨床応用への波及効果も大きいと考えている。

Research Products

• [Int'l Joint Research] University of Michigan/University of Chicago(米国)
• [Journal Article] Protection of gut microbiome from antibiotics: development of a vancomycin-specific adsorbent with high adsorption capacity (2020)
  • Author(s): 1.Yuzuriha K, Yakabe K, Nagai H, Li S, Zendo T, Zai K, Kishimura A, Hase K, Kim YG, Mori T, Katayama Y.
  • Journal Title: Biosci Microbiota Food Health Volume: accepted
  • Peer Reviewed
• [Journal Article] Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon. (2020)
  • Author(s): Junya Isobe, Shintarou Maeda, Yuuki Obata, Keito Iizuka, Yutaka Nakamura, Yumiko Fujimura, Tatsuki Kimizuka, Kouya Hattori, Yun-Gi Kim, Tatsuya Morita, Ikuo Kimura, Stefan Offermanns, Takahiro Adachi, Atsuhito Nakao, Hiroshi Kiyono, Daisuke Takahashi, Koji Hase
  • Journal Title: International Immunology Volume: 32 Issue: 4 Pages: 243-258
  • DOI: 10.1093/intimm/dxz078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens (2017)
  • Author(s): Kim, YG., Sakamoto, K., Seo, SU., Pickard, JM., Gillilland, M.G. 3rd, Pudlo, NA., Hoostal, M., Li, X., Feehley, T., Stefka, AT., Schmidt, TM., Martens, EC., Fukuda, S., Inohara, N., Nagler, CR., Nunez, G.
  • Journal Title: Science Volume: 356 Issue: 6335 Pages: 315-319
  • DOI: 10.1126/science.aag2029
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Neonatal Acquisition of Clostridia Species Controls Colonization Resistance Against Bacterial Pathogens (2018)
  • Author(s): Yun-Gi Kim
  • Organizer: IMKASID
  • Int'l Joint Research / Invited
• [Presentation] Role of gut microbiota in intestinal pathogen colonization (2018)
  • Author(s): Yun-Gi Kim
  • Organizer: International Meeting of the Federation of Korean Microbiological Societies
  • Int'l Joint Research / Invited
• [Presentation] 腸内細菌による腸管病原細菌の定着阻害作用 (2018)
  • Author(s): 金 倫基
  • Organizer: 第161回日本獣医学会学術集会
  • Invited