| Project/Area Number |
18K08567
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Ogawa Eri 京都大学, 医学研究科, 助教 (30440506)
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| Co-Investigator(Kenkyū-buntansha) |
八木 真太郎 京都大学, 医学研究科, 講師 (60447969)
長尾 美紀 京都大学, 医学研究科, 教授 (80523993)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝移植 / bacterial translocation / 免疫 / 生体肝移植 / 腸内細菌 / 拒絶 / 門脈圧 / 腸管粘膜 |
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| Outline of Final Research Achievements |
The present study suggests that the mechanism of bacterial translocation (BT) is not the transfer of bacteria but the transfer of toxins, such as LPS, as the main pathogen. Although humans are exposed to BT on a daily basis, it is unlikely to affect us if our immune system is normal. However, if the host immunity is impaired due to liver failure or uncompensated cirrhosis, BT may develop into severe infections. Under the condition of severe hepatic dysfunction associated with end-stage liver failure or post-transplant rejection, systemic/intestinal immunity and barrier function were impaired, which lead to dysbiosis of the gut microbiota, increase or decrease of particular strains of bacteria, and increased incidence of BT. This study successfully presented the importance of "gut-liver axis" in the clinical curse of liver transplantation in both humans and small animals.
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| Academic Significance and Societal Importance of the Research Achievements |
小動物モデルとヒトの双方において，肝不全下での腸内細菌の変動にある一定の普遍性を確認できたことは本研究の重要な新規性の一つである．また，BTのメカニズムの重要な一端を明らかにできたことと肝機能が低下すると特定の菌の増減が観察されることを同定できたことは今後の肝移植周術期の治療戦略（抗生剤治療やシンバイオティクス治療の適応）の確立へとつながることが期待される．
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